Pneumonia

Module 4.
2
Respiratory System
Pneumonia
INSTRUCTIONAL OBJECTIVES
TRIGGER.................................................................................................................................................. 1
PHYSICAL EXAMINATION OF THE CHEST AND LUNGS................................................................. 1
TECHNIQUES OF EXAMINATION..................................................................................................... 1
Examination of the Posterior Chest........................................................................................ 2
Examination of the Anterior Chest.......................................................................................... 6
DIFFERENTIATE RALES FROM OTHER ADVENTITIOUS SOUNDS........................................ 8
DIFFERENTIATE THE CAUSES OF DECREASED BREATH SOUNDS....................................10
CAUSES OF CHEST PAIN RELATED TO RESPIRATORY DISORDERS................................... 11
PNEUMONIA.........................................................................................................................................12
DEFINITION.......................................................................................................................................... 13
PATHOPHYSIOLOGY......................................................................................................................... 13
PATHOLOGY.........................................................................................................................................14
PULMONARY INFECTIONS..............................................................................................................15
PRIMARY DIAGNOSIS: COMMUNITY- ACQUIRED PNEUMONIA..........................................16
ETIOLOGY.............................................................................................................................................16
MORPHOLOGY (Bacterial pneumonia)......................................................................................... 19
MORPHOLOGY (Viral Pneumonia)................................................................................................ 23
EPIDEMIOLOGY..................................................................................................................................28
CLINICAL FINDINGS......................................................................................................................... 29
PROGNOSIS........................................................................................................................................ 30
DIAGNOSIS..........................................................................................................................................30
TREATMENT/MANAGEMENT..........................................................................................................33
RISK STRATIFICATION FOR COMMUNITY ACQUIRED PNEUMONIA................................. 40
EMPIRIC TREATMENT RECOMMENDATIONS FOR MANAGEMENT OF CAP....................40
DIFFERENTIAL DIAGNOSIS 1: PLEURAL EFFUSION.............................................................. 44
ETIOLOGY............................................................................................................................................ 44
DIAGNOSTIC APPROACH................................................................................................................44
PATHOGENESIS................................................................................................................................. 45
CLINICAL MANIFESTATIONS AND MANAGEMENT..................................................................47
DIFFERENTIAL DIAGNOSIS 2: LUNG ABSCESS..................................................................... 50
ETIOLOGY.............................................................................................................................................51
EPIDEMIOLOGY...................................................................................................................................51
PATHOGENESIS.................................................................................................................................. 51
MORPHOLOGY..................................................................................53
CLINICAL FINDINGS......................................................................................................................... 55
DIFFERENTIAL DIAGNOSIS............................................................. 55
DIAGNOSIS..........................................................................................................................................56
TREATMENT/MANAGEMENT......................................................................................................... 56
COMPLICATIONS.............................................................................. 57
PROGNOSIS AND PREVENTION..................................................... 57
APPROACH TO THE PATIENT.......................................................... 58
CASE RESOLUTION............................................................................................................................ 58
GRID...................................................................................................................................................... 59
REFERENCES
Respiratory System | Pneumonia
1. Harrison’s Principles of Internal Medicine, 21st ed, Chapter 126

2. Robbins and Cotran’s Pathologic Basis of Diseases, 10th ed
3. Bates’ Guide to Physical Examination and History Taking, 12th ed
4. Philippine Clinical Practice Guidelines: Diagnosis, Empiric Management
and Prevention of Community Acquired Pneumonia in Immunocompetent
Adults 2020 update
TRIGGER
Nico, a 44-yo/M, was seen at the ER because of cough and fever. Ten
days PTA, he noted onset of cough with sputum production. Five days ago, he
noted that his cough is now associated with sputum described as having
purulent-brownish discoloration. It was also during this time that he reported to
have fever that recorded at 37.8 to 38.80C relieved temporarily by Paracetamol.
He also self-medicated with Robitussin as recommended by his friends. Two days
PTA, he felt pain in his chest, more on the right side, worsened by coughing and
during inhalation. Persistence of fever and cough, with the latter now associated
with shortness of breath, prompted him to seek medical attention.
He has neither illnesses nor hospitalizations in the past. He is a cigarette
smoker of 20-pack years and a chronic alcoholic beverage drinker (mostly beer
and rum). He denied any illicit drug use. He is currently unemployed and lives with
his parents.
At the ER, Nico was noted to be unkempt, seated on a wheelchair,
tachypneic.
Vital signs of BP 110/80 mmHg, HR 120 bpm, RR 26 breaths per minute,
and Temp of 38.70C, O2sat 90% room air.
He was also noted to have poor dentition. Examination of the chest
revealed dullness on percussion of the right base and bronchial breath sound
heard on the right, mid-base. There was also a note of tachycardia but with a
regular rhythm. No murmurs were noted. The rest of the examination was normal.
Guide Questions:
1. Based on the initial information, what are your possible differential
diagnoses?
2. What other information would you like to ask to help you in narrowing
your differential diagnosis?
3. What are the possible causes of cough with purulent sputum production
and chest pain?
4. Identify the pertinent abnormal PE of the chest and its possible causes.
5. What other C/L physical examination techniques would you have wanted
to do if you have a dullness on percussion? How would you differentiate if
this is a fluid or mass/consolidation?
6. Based on his clinical manifestations, what is the most likely diagnosis?
What are the pathogenesis and pathophysiologic bases of his clinical
manifestations?
7. What diagnostic tests would you recommend in his case?
8. How would you manage the patient and what are the possible
complications?
9. Is his condition preventable? How?
PHYSICAL EXAMINATION OF THE CHEST AND LUNGS

Source: Bates’ Guide to Physical Examination and History Taking, Chapter 8 The Thorax and
Lungs
TECHNIQUES OF EXAMINATION
For best results, examine the posterior thorax and lungs while the patient
is sitting, and the anterior thorax and lungs with the patient supine. Be considerate
when draping the patient’s gown. For men, arrange the gown so that you can see
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the full chest. For women, cover the anterior chest when you examine the back;
for the anterior examination, drape the gown over each half of the chest as you
examine the other half. Begin with inspection, then palpate, percuss, and
auscultate. Try to visualize the underlying lobes and compare the right lung field
with the left, carefully noting any asymmetries.
● With the patient sitting, examine the posterior thorax and lungs. The
patient’s arms should be folded across the chest with hands resting, if
possible, on the opposite shoulders. This position swings the scapula
laterally and increases access to the lung fields. Then ask the patient to
lie down.
● With the patient supine, examine the anterior thorax and lungs. For
women, this position allows the breasts to be gently displaced. Some
clinicians examine both the posterior and anterior chest with the patient
sitting, which is also satisfactory.
● For patients who cannot sit up, ask for assistance so that you can examine
the posterior chest in the sitting position. If this is not possible, roll the
patient to one side and then to the other. Percuss and auscultate both
lungs in each position. Because ventilation is relatively greater in the
dependent lung, you are more likely to hear abnormal wheezes or
crackles on the dependent side (see p. 325).
Examination of the Posterior Chest

INSPECTION.
Standing in a midline position behind the patient, note the shape of the
chest and how the chest moves, including the following:
● Deformities or asymmetry in chest expansion
● Abnormal muscle retraction of the intercostal spaces during inspiration,
most visible in the lower intercostal spaces.
● Impaired respiratory movement on one or both sides or a unilateral lag (or
delay) in movement.
PALPATION.
As you palpate the chest, focus on areas of tenderness or bruising, respiratory
expansion, and fremitus.
● Identify tender areas. Carefully palpate any area where the patient
reports pain or has visible lesions or bruises. Note any palpable crepitus,
defined as a crackling or grinding sound over bones, joints, or skin, with
or without pain, due to air in the subcutaneous tissue.
● Assess any skin abnormalities such as masses or sinus tracts (blind,
inflammatory, tube-like structures
opening onto the skin).
● Test chest expansion.
1. Place your thumbs at about the
level of the 10th ribs, with your
fingers loosely grasping and
parallel to the lateral rib cage
(Fig. 8-14).
2. As you position your hands, slide
them medially just enough to
raise a loose fold of skin
between your thumbs over the
spine.
3. Ask the patient to inhale deeply.
4. Watch the distance between
your thumbs as they move apart
during inspiration, and feel for
the range and symmetry of the
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rib cage as it expands and contracts. This movement is

sometimes called lung excursion.
● Palpate both lungs for symmetric tactile fremitus (Fig. 8-15).
○ Fremitus refers to the palpable vibrations that are transmitted
through the bronchopulmonary tree to the chest wall as the
patient is speaking and is normally symmetric. Fremitus is
typically more prominent in the interscapular area than in the
lower lung fields and easier to detect over the right lung than the
left. It disappears below the diaphragm.
○ To detect fremitus, use either the ball (the bony part of the palm
at the base of the fingers) or the ulnar surface of your hand to
optimize the vibratory sensitivity of the bones in your hand. Ask
the patient to repeat the words “ninety-nine” or “one-oneone.”
○ Initially practice with one hand until you feel the transmitted
vibrations.
○ Use both hands to palpate and compare symmetric areas of the
lungs in the pattern shown in the photograph. Identify and locate
any areas of increased, decreased, or absent fremitus.
○ If fremitus is faint, ask the patient to speak more loudly or in a
deeper voice.
○ Tactile fremitus is a somewhat imprecise assessment technique,
but does direct your attention to possible asymmetries. Confirm
any disparities by listening for underlying breath sounds, voice
sounds, and whispered voice sounds. All these attributes should
increase or decrease together.
PERCUSSION.
Percussion is one of the most important techniques of physical
examination. Percussion sets the chest wall and underlying tissues in motion,
producing audible sound and palpable vibrations. Percussion helps you establish
whether the underlying tissues are air-filled, fluid-filled, or consolidated. The
percussion blow penetrates only 5 to 7 cm into the chest, however, and will not
aid in detection of deep-seated lesions.
The technique of percussion can be practiced on any surface. As you

practice, listen for changes in percussion notes over different types of materials or
different parts of the body. The key points for good technique, described for a
right handed person, are detailed below:
● Hyperextend the middle finger of your left
hand, known as the pleximeter finger. Press
its distal interphalangeal joint firmly on the
lung surface to be percussed (Fig. 8-16). Avoid
surface contact by any other part of the hand
because this dampens out vibrations. Note
that the thumb and second, fourth, and fifth
fingers are not touching the chest wall.
● Position your right forearm quite close to the
surface, with the hand cocked upward. The
middle finger should be partially flexed,
relaxed, and poised to strike.
● With a quick, sharp but relaxed wrist motion,
strike the pleximeter finger with the right
middle finger, called the plexor finger (Fig.
8-17). Aim at your distal interphalangeal joint.
Your goal is to transmit vibrations through the
bones of this joint to the underlying chest wall.
Use the same force for each percussion strike
and the same pleximeter pressure to avoid
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changes in the percussion note due to your technique rather than

underlying findings.
● Strike using the tip of the plexor finger, not the finger pad. The striking
finger should be almost at right angles to the pleximeter. A short fingernail
is recommended to avoid injuring your knuckle.
● Withdraw your striking finger quickly to avoid damping the vibrations you
have created (Fig. 8-18).
● In summary, the movement is at the wrist. It is directed, brisk, yet relaxed
and slightly bouncy.
Percussion Notes:
With your plexor or striking finger, use the lightest percussion that
produces a clear note. A thick chest wall requires a more forceful percussion blow
than a thin one. However, if a louder note is needed, apply more pressure with the
pleximeter finger.
When percussing the lower posterior chest, stand somewhat to the side
rather than directly behind the patient. In this position it is easier to place your
pleximeter finger more firmly on the chest, making your plexor strike more
effective by creating a better percussion note.
● When comparing two areas, use the same percussion technique in both
areas. Percuss or strike twice in each location and listen for differences in
the percussion notes at the two locations.
● Learn to identify five percussion notes. You can practice four of them on
yourself. These notes differ in their basic qualities of sound, intensity,
pitch, and duration. Train your ear by concentrating on one quality at a
time as you percuss first in one location, then in another. Review the
description of percussion notes on p. 323.
Healthy lungs are resonant. While the patient keeps both arms crossed in
front of the chest, percuss the thorax in symmetric
locations on each side from the apex to the base.
● Percuss one side of the chest and then the
other at each level in a ladder-like pattern,
as shown in (Figure 8-19). Omit the areas
over the scapulae— the thickness of
muscle and bone alters the percussion
notes over the lungs. Identify and locate
the area and quality of any abnormal
percussion note.
● Identify the descent of the diaphragm, or
diaphragmatic excursion. First, determine
the level of diaphragmatic dullness during
quiet respiration. Holding the pleximeter
finger above and parallel to the
expected level of dullness,
percuss downward in progressive
steps until dullness clearly
replaces resonance. Confirm this
level of change by percussing
downward from adjacent areas
both medially and laterally (Fig.
8-20).
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Note that with this technique, you are identifying the boundary between
the resonant lung tissue and the duller structures below the diaphragm. You are
not percussing the diaphragm itself. You can infer the probable location of the
diaphragm from the level of dullness.
Now, estimate the extent of diaphragmatic excursion by determining the

distance between the level of dullness on full expiration and the level of dullness
on full inspiration, normally about 3 to 5.5 cm.
AUSCULTATION
Auscultation is the most important examination technique for assessing
air flow through the tracheobronchial tree.
● Auscultation involves:
1. Listening to the sounds generated by breathing,
2. Listening for any adventitious (added) sounds
3. If abnormalities are suspected, listening to the sounds of the
patient’s spoken or whispered voice as they are transmitted
through the chest wall.
● Before beginning auscultation, ask the patient to cough once or twice to
clear mild atelectasis or airway mucus that can produce unimportant extra
sounds.
● Listen to the breath sounds with the diaphragm of your stethoscope after
instructing the patient to breathe deeply through an open mouth. Always
place the stethoscope directly on the skin. Clothing alters the
characteristics of the breath sounds and can introduce friction and added
sounds.
● Use the ladder pattern suggested for percussion, moving from one side to
the other and comparing symmetric areas of the lungs.
● Listen to at least one full breath in each location. If you hear or suspect
abnormal sounds, auscultate adjacent areas to assess the extent of any
abnormality. If the patient becomes lightheaded from hyperventilation,
allow the patient to take a few normal breaths.
● Use the ladder pattern suggested for percussion, moving from one side to
the other and comparing symmetric areas of the lungs. Listen to at least
one full breath in each location. If you hear or suspect abnormal sounds,
auscultate adjacent areas to assess the extent of any abnormality. If the
patient becomes light-headed from hyperventilation, allow the patient to
take a few normal breaths.
● Note the intensity of the breath sounds, which reflects the air flow rate at
the mouth, and may vary from one area to another. Breath sounds are
usually louder in the lower posterior lung fields. If the breath sounds seem
faint, ask the patient to breathe more deeply. Shallow breathing or a thick
chest wall can both alter breath sound intensity.
● Is there a silent gap between the inspiratory and expiratory sounds?
● Listen for the pitch, intensity, and duration of the inspiratory and
expiratory sounds. Are vesicular breath sounds distributed normally over
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the chest wall? Are breath sounds diminished, or are there

bronchovesicular or bronchial breath sounds in unexpected places? If so,
in what distribution?
Breath Sounds (Lung Sounds). Learn to identify breath sounds by their

intensity, their pitch, and the relative duration of their inspiratory and expiratory
phases. Normal breath sounds are:
● Vesicular, or soft and low pitched. They are heard throughout inspiration,
continue without pause through expiration, and then fade away about one
third of the way through expiration.
● Bronchovesicular, with inspiratory and expiratory sounds about equal in
length, at times separated by a silent interval. Detecting differences in
pitch and intensity is often easier during expiration.
● Bronchial, or louder, harsher and higher in pitch, with a short silence
between inspiratory and expiratory sounds. Expiratory sounds last longer
than inspiratory sounds.
● Tracheal, or loud harsh sounds heard over the trachea in the neck.
The characteristics of these four kinds of breath sounds are summarized below.
Examination of the Anterior Chest

When examined in the supine position, the patient should lie comfortably
with arms somewhat abducted. If the patient is having difficulty breathing, raise
the head of the examining table or the bed to increase respiratory excursion and
ease of breathing.
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INSPECTION.
Observe the shape of the patient’s chest and the movement of the chest
wall.
Note:
● Deformities or asymmetry of the thorax
● Abnormal retraction of the lower intercostal spaces during
inspiration, or any supraclavicular retraction
● Local lag or impairment in respiratory movement
PALPATION.
Palpate the anterior chest wall for the following purposes:
● Identification of tender areas
● Assessment of bruising, sinus tracts, or other skin changes
● Assessment of chest
expansion. Place your
thumbs along each
costal margin, your
hands along the lateral
rib cage (Fig. 8-22). As
you position your
hands, slide them
medially a bit to raise
loose skin folds
between your thumbs.
Ask the patient to
inhale deeply. Observe
how far your thumbs
diverge as the thorax expands, and feel for
the extent and symmetry of respiratory
movement.
● Assessment of tactile fremitus. If needed,
compare both sides of the chest, using the
ball or ulnar surface of your hand. Fremitus
is usually decreased or absent over the
precordium. When examining a woman,
gently displace the breasts as necessary
(Fig. 8-23).
PERCUSSION.
As needed, percuss the anterior and lateral
chest, again comparing both sides (Fig. 8-24). The
heart normally produces an area of dullness to the
left of the sternum from the 3rd to the 5th
interspaces.
In a woman, to enhance percussion, gently
displace the breast with your left hand while
percussing with the right, or ask the patient to move
the breast for you.
Identify and locate any area with an
abnormal percussion note.
Percuss for liver dullness and gastric tympany.

With your pleximeter finger above and parallel to the
expected upper border of liver dullness, percuss in
progressive steps downward in the right
midclavicular line (Fig. 8-25). Identify the upper
border of liver dullness. Later, during the abdominal
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examination, you will use this method to estimate the size of the liver. As you
percuss down the chest on the left, the resonance of normal lungs usually
changes to the tympany of the gastric air bubble.
AUSCULTATION.
Listen to the chest anteriorly and laterally as the patient breathes with
mouth open, and somewhat more deeply than normal. Compare symmetric areas
of the lungs, using the pattern suggested for percussion and extending it to
adjacent areas, if indicated.
● Listen to the breath sounds, noting their intensity and identifying any
variations from normal vesicular breathing. Breath sounds are usually
louder in the upper anterior lung fields. Bronchovesicular breath sounds
may be heard over the large airways, especially on the right.
● Identify any adventitious sounds, time them in the respiratory cycle, and
locate them on the chest wall. Do they clear with deep breathing?
● If indicated, listen for transmitted voice sounds.
DIFFERENTIATE RALES FROM OTHER ADVENTITIOUS SOUNDS

ADVENTITIOUS (ADDED) SOUNDS.
Listen for any added, or adventitious sounds that are superimposed on
the usual breath sounds. Detection of adventitious sounds—crackles (sometimes
called rales), wheezes, and rhonchi—is an important focus of your examination,
often leading to diagnosis of cardiac and pulmonary conditions. The most
common adventitious sounds are described below. Note that the American
Thoracic Society describes rhonchi as a low pitched wheeze (unrelated to airway
secretions), so some recommend not using the term “rhonchi.”
If you hear wheezes or rhonchi, note their timing and location. Do they
change with deep breathing or coughing? Beware of the silent chest, in which air
movement is minimal.
Note that tracheal sounds originating in the neck such as stridor and
vocal cord dysfunction can be transmitted to the chest and mistaken for wheezing,
leading to inappropriate or delayed treatment.
Note any pleural rubs, which are coarse, grating biphasic sounds heard
primarily during expiration.
CRACKLES.
Crackles are discontinuous nonmusical sounds that can be early
inspiratory (as in COPD), late inspiratory (as in pulmonary fibrosis), or biphasic (as
in pneumonia). They are currently considered to result from a series of tiny
explosions when small distal airways, deflated during expiration, pop open during
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inspiration. With few exceptions, recent acoustic studies indicate that the role of
secretions as a cause of crackles is less likely.
● Fine crackles are softer, higher pitched, and more frequent per breath
than coarse crackles. They are heard from mid to late inspiration,
especially in the dependent areas of the lung, and change according to
body position. They have a shorter duration and higher frequency than
coarse crackles. Fine crackles appear to be generated by the “sudden
inspiratory opening of small airways held closed by surface forces during
the previous expiration.”
Examples include pulmonary fibrosis (known for “Velcro rales”)
and interstitial lung diseases such as interstitial fibrosis and interstitial
pneumonitis.
● Coarse crackles appear in early inspiration and last throughout expiration
(biphasic), have a popping sound, are heard over any lung region, and do
not vary with body position. They have a longer duration and lower
frequency than fine crackles, change or disappear with coughing, and are
transmitted to the mouth. Coarse crackles appear to result from “boluses
of gas passing through airways as they open and close intermittently.”
○ Examples include COPD, asthma, bronchiectasis, pneumonia
(crackles may become finer and change from mid to late
inspiratory during recovery), and heart failure.
○ If you hear crackles, especially those that do not clear after
coughing, listen carefully for the following characteristics. These
are clues to the underlying condition:
● Loudness, pitch, and duration, summarized as fine or
coarse crackles
● Number, few to many
● Timing in the respiratory cycle
● Location on the chest wall
● Persistence of their pattern from breath to breath
● Any change after a cough or change in the patient’s
position
In some normal people, crackles may be heard at the anterior lung bases
after maximal expiration. Crackles in dependent portions of the lungs may also
occur after prolonged recumbency.
WHEEZES.
Wheezes are continuous musical sounds that occur during rapid airflow
when bronchial airways are narrowed almost to the point of closure. Wheezes can
be inspiratory, expiratory, or biphasic. They may be localized, due to a foreign
body, mucous plug, or tumor, or heard throughout the lung. Although wheezes are
typical of asthma, they can occur in a number of pulmonary diseases. Recent
studies suggest that as the airways become more narrowed, wheezes become
less audible, culminating finally in “the silent chest” of severe asthma requiring
immediate intervention.
RHONCHI.
Rhonchi are considered by some to be a variant of wheezes, arising from
the same mechanism, but lower in pitch. Unlike wheezes, rhonchi may disappear
with coughing, so secretions may be involved.
STRIDOR.
Stridor is a continuous, high-frequency, high-pitched musical sound
produced during airflow through a narrowing in the upper respiratory tract. Stridor
is best heard over the neck during inspiration, but can be biphasic. Causes of the
underlying airway obstruction include tracheal stenosis from intubation, airway
edema after device removal, epiglottitis, foreign body, and anaphylaxis. Immediate
intervention is warranted.
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PLEURAL RUB.
A pleural rub is a discontinuous, low-frequency, grating sound that arises
from inflammation and roughening of the visceral pleura as it slides against the
parietal pleura. This nonmusical sound is biphasic, heard during inspiration and
expiration, and often best heard in the axilla and base of the lungs.
MEDIASTINAL CRUNCH.
A mediastinal crunch is a series of precordial crackles synchronous with
the heartbeat, not with respiration. Best heard in the left lateral position, it arises
from air entry into the mediastinum causing mediastinal emphysema
(pneumomediastinum). It usually produces severe central chest pain and may be
spontaneous. It has been reported in cases of tracheobronchial injury, blunt
trauma, pulmonary disease, use of recreational drugs, childbirth, and rapid ascent
from scuba diving.
TRANSMITTED VOICE SOUNDS.

If you hear abnormally located bronchovesicular or bronchial breath
sounds, assess transmitted voice sounds using three techniques below. With the
diaphragm of your stethoscope, listen in symmetric areas over the chest wall for
abnormal vocal resonances suspicious for pneumonia or pleural effusion.
● Egophony. Ask the patient to say “ee.” You will normally hear a muffled
long E sound.
● Bronchophony. Ask the patient to say “ninety-nine.” Normally the sounds
transmitted through the chest wall are muffled and indistinct. Louder voice
sounds are called bronchophony
● Whispered pectoriloquy. Ask the patient to whisper “ninety-nine” or
“one-two-three.” The whispered voice is normally heard faintly and
indistinctly, if at all.
DIFFERENTIATE THE CAUSES OF DECREASED BREATH SOUNDS

The origins of breath sounds continue to be investigated. Acoustic studies
indicate that turbulent air flow in the pharynx, glottis, and subglottic region
produce tracheal breath sounds, which are similar to bronchial sounds. The
inspiratory component of vesicular breath sounds seems to arise in the lobar and
segmental airways; the expiratory component arises in the more central larger
airways. Normally, tracheal and bronchial sounds may be heard over the trachea
and mainstem bronchi; vesicular breath sounds predominate throughout most of
the lungs. When lung tissue loses airflow, there is increased transmission of
high-pitched sounds. If the tracheobronchial tree is open, bronchial breath sounds
may replace the normal vesicular sounds over airless areas of the lung. This
change occurs in lobar pneumonia when the alveoli get filled with fluid and
cellular debris—a process called consolidation. Other causes include pulmonary
edema or, rarely, hemorrhage. Bronchial breath sounds usually correlate with an
increase in tactile fremitus and transmitted voice sounds. These findings are
summarized below.
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CAUSES OF CHEST PAIN RELATED TO RESPIRATORY DISORDERS
PROBLEM PROCESS LOCATION QUALITY SEVERITY
Tracheobronchitis Inflammation of Upper sternal or Burning Mild-to-moderate

trachea and large on other side of
bronchi the sternum
Pleural pain Inflammation of Chest wall Sharp, knifelike Often severe

the parietal overlying the
pleura, process
pneumonia,
pulmonary
infarction or
neoplasm
Table 8-8: Physical Findings in Selected Chest Disorders

The red boxes in this table provide a framework for the clinical
assessment of common chest disorders. Start with the three boxes under
percussion. Note resonant, dull, and hyperresonant. Then move from each of
these to other boxes that emphasize some of the key differences among various
conditions. The changes described vary with the extent and severity of the
disorder. Abnormalities deep in the chest usually produce fewer signs than
superficial ones, and may cause no signs at all. Use the table for the direction of
typical changes, not for absolute distinctions.
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PNEUMONIA
Source: Harrison’s Principles of Internal Medicine 21st ed, Chapter 126 Pneumonia
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DEFINITION
Pneumonia is an infection of the pulmonary parenchyma. Despite

significant morbidity and mortality, it is often misdiagnosed, mistreated, and
underestimated. Pneumonia has usually been classified as community acquired
(CAP), hospital-acquired (HAP), or ventilator-associated (VAP). A fourth category,
health care–associated pneumonia (HCAP) was introduced to encompass cases
caused by multidrug-resistant (MDR) pathogens typically associated with HAP and
cases in unhospitalized individuals at risk of MDR infection. Unfortunately, this
Pneumonia Lionel A. Mandell, Michael S. Niederman category has not reliably
predicted infection with resistant pathogens and has been associated with
increased use of broad-spectrum antibiotics, particularly those employed for
treatment of methicillin resistant Staphylococcus aureus (MRSA) and
antipseudomonal β-lactams. Accordingly, use of the HCAP category should be
discontinued. Rather than relying on a predefined subset of pneumonia cases, it is
better to assess patients individually on the basis of risk factors for infection with a
resistant organism. Risk factors for infection with MRSA and Pseudomonas
aeruginosa include prior isolation of the organism, particularly from the respiratory
tract during the preceding year, and/ or hospitalization and treatment with an
antibiotic in the previous 90 days.
Pneumonia caused by macroaspiration of oropharyngeal or gastric

contents, usually referred to as aspiration pneumonia, is best thought of as a point
on the continuum that includes CAP and HAP. Estimates suggest that aspiration
pneumonia accounts for 5–15% of CAP cases, but reliable figures for HAP are
unavailable. The airways or pulmonary parenchyma may be involved, and patients
usually represent a clinical phenotype with risk factors for macroaspiration and
involvement of characteristic anatomic pulmonary locations.
PATHOPHYSIOLOGY
Pneumonia is the result of the proliferation of microbial pathogens at the

alveolar level and the host’s response to them. Until recently, it was thought that
the lungs were sterile and that pneumonia resulted from the introduction of
potential pathogens into this sterile environment. Typically, this introduction
occurred through microaspiration of oropharyngeal organisms into the lower
respiratory tract. Overcoming of innate and adaptive immunity by such
microorganisms could result in the clinical syndrome of pneumonia.
Recent use of culture-independent techniques of microbial identification

has demonstrated a complex and diverse community of bacteria in the lungs that
constitutes the lung microbiota. Awareness of this microbiota has prompted a
rethinking of how pneumonia develops. Mechanical factors, such as the hairs and
turbinates of the nares, the branching tracheobronchial tree, mucociliary
clearance, and gag and cough reflexes, all play a role in host defense but are
insufficient to effectively block bacterial access to the lower airways. In the
absence of a sufficient barrier, microorganisms may reach the lower respiratory
tract by a variety of pathways, including inhalation, microaspiration, and direct
mucosal dispersion.
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The constitution of the lung microbiota is determined by three factors:

microbial entry into the lungs, microbial elimination, and regional growth
conditions for bacteria, such as pH, oxygen tension, and temperature. The key
question, however, is how a dynamic homeostasis among bacterial communities
results in acute infection. Pneumonia therefore does not appear to be the result of
the invasion of a sterile space by a particular microorganism but is more likely an
emergent phenomenon dependent upon a number of mechanisms, including
self-accelerating positive feedback loops.
A possible model for pneumonia is as follows. An inflammatory event

resulting in epithelial and or endothelial injury results in the release of cytokines,
chemokines, and catecholamines, some of which may selectively promote the
growth of certain bacteria, such as Streptococcus pneumoniae and P. aeruginosa.
This cycle of inflammation, enhanced nutrient availability, and release of potential
bacterial growth factors may result in a positive feedback loop that further
accelerates inflammation and the growth of particular bacteria, which may then
become dominant. In cases of CAP and HAP, the trigger may be a viral infection
compounded by microaspiration of oropharyngeal organ isms. In cases of true
aspiration pneumonia, the trigger may simply be the macroaspiration event itself.
Once triggered, innate and adaptive immune responses can ideally help
contain potential pathogens and prevent the development of pneumonia.
However, in the face of continuing inflammation (and especially if a positive
feedback loop becomes sustainable), the process may proceed to a full-fledged
pneumonia syndrome. Inflammatory mediators such as interleukin 6 and tumor
necrosis factor result in fever, and chemokines such as interleukin 8 and
granulocyte 1010 colony-stimulating factors increase local neutrophil numbers.
Mediators released by macrophages and neutrophils may create an alveolar
capillary leak resulting in impaired oxygenation, hypoxemia, and radiographic
infiltrates. Moreover, some bacterial pathogens appear to interfere with the
hypoxic vasoconstriction that would normally occur with fluid-filled alveoli, and this
interference may result in severe hypoxemia. Decreased compliance due to
capillary leak, hypoxemia, increased respiratory drive, increased secretions, and
occasionally infection-related bronchospasm all lead to worsening dyspnea. If
severe enough, changes in lung mechanics secondary to reductions in lung
volume, compliance, and intrapulmonary shunting of blood may cause respiratory
failure.
Cardiovascular events with pneumonia, particularly in the elderly and
usually in association with pneumococcal pneumonia and influenza, are
increasingly recognized. These events, which may be acute or whose occurrence
may extend to at least 1 year, include congestive heart failure, arrhythmia,
myocardial infarction, or stroke and may be caused by a variety of mechanisms,
including increased myocardial load and/or destabilization of atherosclerotic
plaques by inflammation. In animal models, direct myocardial invasion by
pneumococci may result in scarring and impaired myocardial function and
conductivity.
PATHOLOGY
Classic pneumonia evolves through a series of stages. The initial stage is

edema with a proteinaceous exudate and often bacteria in the alveoli. Next is a
rapid transition to the red hepatization phase. Erythrocytes in the intra alveolar
exudate give this stage its name. In the third phase, gray hepatization, no new
erythrocytes are extravasating, and those already present have been lysed and
degraded. The neutrophil is the predominant cell, fibrin deposition is abundant,
and bacteria have disappeared. This phase corresponds with the successful
containment of the infection and improvement in gas exchange. In the final phase,
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resolution, the macrophage reappears as the dominant cell in the alveolar space
and the debris of neutrophils, and bacteria and fibrin have been cleared, as has
the inflammatory response. This pattern has been described best for lobar
pneumococcal pneumonia but may not apply to pneumonia of all etiologies. In
VAP, respiratory bronchiolitis may precede the development of a radiologically
apparent infiltrate. A bronchopneumonia pattern is most common in nosocomial
pneumonias, whereas a lobar pattern is more common in bacterial CAP. Despite
the radiographic appearance, viral and Pneumocystis pneumonias represent
alveolar rather than interstitial processes.
PULMONARY INFECTIONS
Source: Robbins and Cotran Pathologic Basis of Disease, 10th edition
Respiratory tract infections are more frequent than infections of any other
organ and account for the largest number of workdays lost in the general
population. The vast majority consist of upper respiratory tract infections caused
by viruses (common cold, pharyngitis), but bacterial, viral, mycoplasmal, and fungal
infections of the lung (pneumonia) account for an enormous amount of morbidity
and are responsible for 2.3% of all deaths in the United States. Pneumonia can be
very broadly defined as any infection of the lung parenchyma.
Pulmonary antimicrobial defense mechanisms are described in Chapter 8.

Pneumonia can result whenever these local defense mechanisms are impaired or
the systemic resistance of the host is lowered. Factors that impair resistance
include chronic diseases, immunologic deficiencies, treatment with
immunosuppressive agents, and leukopenia. Local pulmonary defense
mechanisms may also be compromised by many factors, including:
● Loss or suppression of the cough reflex, as a result of altered sensorium
(e.g., coma), anesthesia, neuromuscular disorders, drugs, or chest pain,
any of which may lead to aspiration of gastric contents.
● Dysfunction of the mucociliary apparatus, which can be caused by
cigarette smoke, inhalation of hot or corrosive gases, viral diseases, or
genetic defects of ciliary function (e.g., immotile cilia syndrome).
● Accumulation of secretions in conditions such as cystic fibrosis and
bronchial obstruction.
● Interference with the phagocytic and bactericidal activities of alveolar
macrophages by alcohol, tobacco smoke, anoxia, or oxygen intoxication.
● Pulmonary congestion and edema.
Defects in innate immunity (including neutrophil and complement defects) and

humoral immunodeficiency typically lead to an increased incidence of infections
with pyogenic bacteria. Germline mutations in MyD88 (an adaptor for several
Toll-like receptors [TLRs] that is important for activation of the transcription factor
nuclear factor kappa B [NF-κB]) are also associated with destructive bacterial
(pneumococcal) pneumonias. On the other hand, cell mediated immune defects
(congenital and acquired) lead to increased infections with intracellular microbes
such as mycobacteria and herpesviruses as well as with microorganisms of very
low virulence, such as the fungus Pneumocystis jiroveci.
Defects in innate immunity (including neutrophil and complement defects) and

humoral immunodeficiency typically lead to an increased incidence of infections
with pyogenic bacteria. Germline mutations in MyD88 (an adaptor for several
Toll-like receptors [TLRs] that is important for activation of the transcription factor
nuclear factor kappa B [NF-κB]) are also associated with destructive bacterial
(pneumococcal) pneumonias. On the other hand, cell mediated immune defects
(congenital and acquired) lead to increased infections with intracellular microbes
such as mycobacteria and herpesviruses as well as with microorganisms of very
low virulence, such as the fungus Pneumocystis jiroveci.
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Pneumonia is classified based on the etiologic agent or, if no pathogen can be

isolated (which occurs in about 50% of cases), by the clinical setting in which the
infection occurs. The latter considerably narrows the list of suspected pathogens,
providing a guide for empirical antimicrobial therapy. As Table 15.7 indicates,
pneumonia can arise in seven distinct clinical settings (“pneumonia syndromes”),
and the implicated pathogens are fairly specific to each category
PRIMARY DIAGNOSIS: COMMUNITY- ACQUIRED PNEUMONIA
ETIOLOGY
The list of potential

etiologic agents of CAP
includes bacteria, fungi,
viruses, and protozoa. Newer
viral pathogens include
metapneumo viruses, the
coronaviruses responsible for
severe acute respiratory
syndrome (SARS) and Middle
East respiratory syndrome
(MERS), and the recently
discovered coronavirus that
originated in Wuhan, China,
and is designated
SARS-CoV-2. First described in December 2019, SARS-CoV-2 and its associated
clinical disease, COVID-19, have reached pandemic proportions and are a cause
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of significant morbidity and mortality. The virus and the disease are discussed in
detail in Chap. 199.
Although most CAP cases are caused by relatively few pathogens, an

accurate determination of their prevalence is difficult because laboratory testing
methods are often insensitive and indirect (Table 126-1). Separation of potential
agents into “typical” bacterial pathogens and “atypical” organisms may be helpful.
The former group includes S. pneumoniae, Haemophilus influenzae, and, in
selected patients, S. aureus and gram-negative bacilli such as Klebsiella
pneumoniae and P. aeruginosa. The “atypical” organisms include Mycoplasma
pneumoniae, Chlamydia pneumoniae, and Legionella species as well as
respiratory viruses such as influenza virus, adenoviruses, human
metapneumovirus, respiratory syncytial virus, and coronaviruses.
With the increasing use of

pneumococcal vaccine, the incidence of
pneumococcal pneumonia is decreasing.
Cases due to M. pneumoniae and C.
pneumoniae, however, appear to be
increasing, especially among young adults.
Viruses are recognized as increasingly
important in pneumonia, and polymerase
chain reaction (PCR)–based testing indicates
their presence in the respiratory tract of
20–30% of healthy adults and in the same
percentage of pneumonia patients, including
those who are severely ill. The most
common are influenza, parainfluenza, and
respiratory syncytial viruses. Whether they
are true etiologic pathogens, co-pathogens,
or simply colonizers cannot always be
determined.
Atypical organisms cannot be cultured on standard media or seen on

Gram’s stain, but their frequency and importance have significant implications for
therapy. They are intrinsically resistant to all β-lactams and require treatment with
a macrolide, a fluoroquinolone, or a tetracycline. In the 10–15% of CAP cases that
are polymicrobial, the etiology usually includes a combination of typical and
atypical pathogens.
Earlier literature suggested that aspiration pneumonia was caused

primarily by anaerobes, with or without aerobic pathogens. A shift, however, has
been noted recently: if aspiration pneumonia is acquired in a community or
hospital setting, the likely pathogens are those usually associated with CAP or
HAP. Anaerobes may still play a role, especially in patients with poor dentition,
lung abscess, necrotizing pneumonia, or empyema.
S. aureus pneumonia is known to complicate influenza virus infection. However,

MRSA has been reported as a primary etiologic agent of CAP. Although cases
caused by MRSA are relatively uncommon, clinicians must be aware of its
potentially serious consequences, such as necrotizing pneumonia. Two factors
have led to this problem: the spread of MRSA from the hospital setting to the
community and the emergence of genetically distinct strains of MRSA in the
community. Community-associated MRSA (CA-MRSA) strains may infect healthy
individuals who have had no association with health care. Despite a careful
history, physical examination, and radiographic studies, the causative pathogen is
often difficult to predict with certainty, and in more than half of cases a specific
etiology is not determined. Nevertheless, epidemiologic and risk factors may
suggest certain pathogens (Table 126-2).
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Community-Acquired Bacterial Pneumonias

(Robbins & Cotran, 10e)
Community-acquired acute pneumonia refers to lung infection in

otherwise healthy individuals that is acquired from the normal environment (in
contrast to hospital-acquired pneumonia). It may be bacterial or viral. Clinical and
radiologic features are usually insensitive in differentiating between viral and
bacterial infections. One marker of inflammation, procalcitonin, an acute-phase
reactant produced primarily in the liver, is more significantly elevated in bacterial
than viral infections and has some predictive value, but is not specific, as it is also
markedly elevated in other severe inflammatory disorders, such as systemic
inflammatory response syndrome (SIRS) (Chapter 4).
Often, a bacterial infection follows an upper respiratory tract viral

infection. Bacterial invasion of the lung parenchyma causes the alveoli to be filled
with an inflammatory exudate, thus causing consolidation (“solidification”) of the
pulmonary tissue. Many variables, such as the specific etiologic agent, the host
reaction, and the extent of involvement, determine the precise form of pneumonia.
Predisposing conditions include extremes of age, chronic diseases (congestive
heart failure, COPD, and diabetes), congenital or acquired immune deficiencies,
and decreased or absent splenic function. The latter puts the patient at risk for
infection with encapsulated bacteria such as pneumococcus
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is the most common
cause of community-acquired acute pneumonia. Examination of Gram-stained
sputum is an important step in the diagnosis of acute pneumonia. The presence of
numerous neutrophils containing the typical gram-positive, lancet-shaped
diplococci supports the diagnosis of pneumococcal pneumonia, but it must be
remembered that S. pneumoniae is a part of the endogenous flora in 20% of
adults, and therefore false-positive results may be obtained. Isolation of
pneumococci from blood cultures is more specific but less sensitive (in the early
phase of illness, only 20% to 30% of patients have positive blood cultures).
Pneumococcal vaccines containing capsular polysaccharides from the common
serotypes are used in individuals at high risk for pneumococcal sepsis.
Haemophilus influenzae
Haemophilus influenzae is a pleomorphic, gram-negative organism that
occurs in encapsulated and nonencapsulated forms. There are six serotypes of
the encapsulated form (types a to f), of which type b is the most virulent.
Antibodies against the capsule protect the host from H. influenzae infection;
hence the capsular polysaccharide b is incorporated in the widely used vaccine
against H. influenzae. With routine use of H. influenzae vaccines, the incidence of
disease caused by the b serotype has declined significantly. By contrast,
infections with nonencapsulated forms, also called nontypeable forms, are
increasing. These are less virulent and tend to spread along the surface of the
upper respiratory tract, producing otitis media (infection of the middle ear),
sinusitis, and bronchopneumonia. Neonates and children with comorbidities such
as prematurity, malignancy, and immunodeficiency are at high risk for
development of invasive infection.
H. influenzae pneumonia, which may follow a viral respiratory infection, is

a pediatric emergency and has a high mortality rate. Descending
laryngotracheobronchitis results in airway obstruction as the smaller bronchi are
plugged by dense, fibrin-rich exudates containing neutrophils, similar to that seen
in pneumococcal pneumonias. Pulmonary consolidation is usually lobular and
patchy but may be confluent and involve the entire lung lobe. Before a vaccine
became widely available, H. influenzae was a common cause of suppurative
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meningitis in children up to 5 years of age. H. influenzae also causes an acute,

purulent conjunctivitis (pink eye) in children and, in predisposed older patients,
may cause septicemia, endocarditis, pyelonephritis, cholecystitis, and suppurative
arthritis. Finally, H. influenzae is the most common bacterial cause of acute
exacerbations of COPD.
Moraxella catarrhalis
Moraxella catarrhalis is recognized as a cause of bacterial pneumonia,
especially in the elderly. It is the second most common bacterial cause of acute
exacerbation of COPD. Along with S. pneumoniae and H. influenzae, M. catarrhalis
is one of the three most common causes of otitis media in children.
Staphylococcus aureus
Staphylococcus aureus is an important cause of secondary bacterial
pneumonia in children and healthy adults following viral respiratory illnesses (e.g.,
measles in children and influenza in both children and adults). Staphylococcal
pneumonia is associated with a high incidence of complications, such as lung
abscess and empyema. Intravenous drug users are at high risk for development of
staphylococcal pneumonia in association with endocarditis. It is also an important
cause of hospital-acquired pneumonia.
Klebsiella pneumoniae
Klebsiella pneumoniae is the most frequent cause of gramnegative
bacterial pneumonia. It commonly afflicts debilitated and malnourished people,
particularly chronic alcoholics. Thick, mucoid (often blood-tinged) sputum is
characteristic because the organism produces an abundant viscid capsular
polysaccharide, which the patient may have difficulty expectorating.
Pseudomonas aeruginosa
Although Pseudomonas aeruginosa most commonly causes
hospital-acquired infections, it is mentioned here because of its occurrence in
cystic fibrosis and immunocompromised patients. It is common in patients who are
neutropenic, and it has a propensity to invade blood vessels with consequent
extrapulmonary spread. Pseudomonas septicemia is a very fulminant disease.
Legionella pneumophila
Legionella pneumophila is the agent of legionnaires’ disease, the form of
pneumonia caused by this organism. It also causes Pontiac fever, a related
self-limited upper respiratory tract infection. This organism flourishes in artificial
aquatic environments, such as water-cooling towers and the tubing systems of
domestic (potable) water supplies. It is transmitted by either inhalation of
aerosolized organisms or aspiration of contaminated drinking water. Legionella
pneumonia is common in individuals with predisposing conditions such as cardiac,
renal, immunologic, or hematologic disease. Organ transplant recipients are
particularly susceptible. It can be quite severe, frequently requiring hospitalization,
and immunosuppressed patients have fatality rates of up to 50%. The diagnosis
can be made rapidly by detecting Legionella DNA in sputum using a polymerase
chain reaction (PCR)–based test or by identification of Legionella antigens in the
urine; culture remains the diagnostic gold standard, but takes 3 to 5 days.
Mycoplasma pneumoniae
Mycoplasma infections are particularly common among children and
young adults. They occur sporadically or as local epidemics in closed communities
(schools, military camps, and prisons).
MORPHOLOGY (Bacterial pneumonia)

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Bacterial pneumonia has two patterns of anatomic distribution: lobular

bronchopneumonia and lobar pneumonia (Fig. 15.32). Patchy consolidation of the
lung is the dominant characteristic of bronchopneumonia (Fig. 15.33), while
consolidation of a large portion of a lobe or of an entire lobe defines lobar
pneumonia (Fig. 15.34).
These anatomic categorizations may be difficult to apply in individual

cases because patterns overlap. The patchy involvement may become confluent,
producing lobar consolidation. Moreover, the same organisms may produce either
pattern depending on patient susceptibility. Most important from the clinical
standpoint are identification of the causative agent and determination of the
extent of disease.
In lobar pneumonia, four stages of the inflammatory response have

classically been described: congestion, red hepatization, gray hepatization, and
resolution. In the first stage of congestion, the lung is heavy, boggy, and red. It is
characterized by vascular engorgement, intra-alveolar edema fluid containing a
few neutrophils, and the presence of bacteria, which may be numerous. In the
next stage of red hepatization, there is massive confluent exudation, as
neutrophils, red cells, and fibrin fill the alveolar spaces (Fig. 15.35A).
On gross examination, the lobe is red, firm, and airless, with a liver-like
consistency, hence the name hepatization. The third stage of gray hepatization is
marked by progressive disintegration of red cells and the persistence of a
fibrinosuppurative exudate (Fig. 15.35B), resulting in a color change to
grayish-brown. In the final stage of resolution, the exudate within the alveolar
spaces is broken down by enzymatic digestion to produce granular, semifluid
debris that is resorbed, ingested by macrophages, expectorated, or organized by
fibroblasts growing into it (Fig. 15.35C). Pleural fibrinous reaction to the underlying
inflammation, often present in the early stages if the consolidation extends to the
lung surface (pleuritis), may similarly resolve. More often it undergoes
organization, leaving fibrous thickening or permanent adhesions.
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In lobar pneumonia, four stages of the inflammatory response have

classically been described: congestion, red hepatization, gray hepatization, and
resolution. In the first stage of congestion, the lung is heavy, boggy, and red. It is
characterized by vascular engorgement, intra-alveolar edema fluid containing a
few neutrophils, and the presence of
bacteria, which may be numerous. In the
next stage of red hepatization, there is
massive confluent exudation, as neutrophils,
red cells, and fibrin fill the alveolar spaces
(Fig. 15.35A). On gross examination, the lobe
is red, firm, and airless, with a liver-like
consistency, hence the name hepatization.
The third stage of gray hepatization is
marked by progressive disintegration of red
cells and the persistence of a
fibrinosuppurative exudate (Fig. 15.35B),
resulting in a color change to grayish-brown.
In the final stage of resolution, the exudate
within the alveolar spaces is broken down
by enzymatic digestion to produce granular,
semifluid debris that is resorbed, ingested
by macrophages, expectorated, or
organized by fibroblasts growing into it (Fig.
15.35C). Pleural fibrinous reaction to the
underlying inflammation, often present in
the early stages if the consolidation extends
to the lung surface (pleuritis), may similarly
resolve. More often it undergoes
organization, leaving fibrous thickening or
permanent adhesions.
Complications of pneumonia include:

1. Tissue destruction and necrosis,
causing abscess formation (particularly
common with pneumococcal or Klebsiella
infections).
2. Spread of infection.
Community-Acquired Viral Pneumonia

Common viral infections include influenza virus types A and B,
respiratory syncytial viruses, human metapneumovirus, adenovirus,
rhinoviruses, rubeola, and varicella viruses. Any of these agents can cause a
relatively mild upper respiratory tract infection, recognized as the common cold, or
a more severe lower respiratory tract infection. Factors that favor extension of the
infection to the lung include extremes of age, malnutrition, alcoholism, and
underlying debilitating illnesses.
Although the molecular details vary, all of the viruses that cause
pneumonia produce disease through similar general mechanisms. These viruses
have tropisms that allow them to attach to and enter respiratory lining cells. Viral
replication and gene expression leads to cytopathic changes, inducing cell death
and secondary inflammation. The resulting damage and impairment of local
pulmonary defenses, such as mucociliary clearance, may predispose to bacterial
superinfections, which are often more serious than the viral infection itself.
Influenza
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Influenza viruses of type A infect humans, pigs, horses, and birds and are
the major cause of pandemic and epidemic influenza infections. The influenza
genome encodes several proteins, but the most important from the vantage point
of viral virulence are the hemagglutinin and neuraminidase proteins.
Hemagglutinin has three major subtypes (H1, H2, H3), while neuraminidase has
two (N1, N2). Both proteins are embedded in a lipid bilayer, which constitutes the
influenza virus envelope. Hemagglutinin is particularly important, as it serves to
attach the virus to its cellular target via sialic acid residues on surface
polysaccharides. Following uptake of the virus into endosomal vesicles,
acidification of the endosome triggers a conformation change in hemagglutinin
that allows the viral envelope to fuse with the host cell membrane, releasing the
viral genomic RNAs into the cytoplasm of the cell. Neuraminidase in turn facilitates
the release of newly formed virions that are budding from infected cells by
cleaving sialic acid residues. Neutralizing host antibodies against viral
hemagglutinin and neuraminidase prevent and ameliorate, respectively, infection
with influenza virus
The viral genome is composed of eight single-stranded RNAs, each

encoding one or more proteins. The RNAs are packaged into helices by
nucleoproteins that determine the influenza virus type (A, B, or C). A single
subtype of influenza virus A predominates throughout the world at a given time.
Epidemics of influenza are caused by spontaneous mutations that alter antigenic
epitopes on the viral hemagglutinin and neuraminidase proteins. These antigenic
changes (antigenic drift) result in new viral strains that are sufficiently different to
elude, at least in part, anti-influenza antibodies produced in members of the
population in response to prior exposures to other flu strains. Usually, however,
these new strains bear sufficient resemblance to prior strains that some members
of the population are at least partially resistant to infection. By contrast,
pandemics, which are longer and more widespread than epidemics, occur when
both the hemagglutinin and the neuraminidase genes are replaced through
recombination with animal influenza viruses (antigenic shift). In this instance,
essentially all individuals are susceptible to the new influenza virus.
If the host lacks protective antibodies, the virus infects pneumocytes and
elicits several cytopathic changes. Shortly after entry into pneumocytes, the viral
infection inhibits sodium channels, producing electrolyte and water shifts that lead
to fluid accumulation in the alveolar lumen. This is followed by the death of the
infected cells through several mechanisms, including inhibition of host cell
messenger RNA translation and activation of caspases leading to apoptosis. The
death of epithelial cells exacerbates the fluid accumulation and releases “danger
signals” that activate resident macrophages. In addition, prior to their death,
infected epithelial cells release a variety of inflammatory mediators, including
several chemokines and cytokines, adding fuel to the inflammatory fire. In
addition, mediators released from epithelial cells and macrophages activate the
nearby pulmonary endothelium and serve as chemoattractants for neutrophils,
which migrate into the interstitium within the first day or two of infection. In some
cases viral infection may cause sufficient lung injury to produce ARDS, but more
often severe pulmonary disease stems from a superimposed bacterial pneumonia.
Of these, secondary pneumonias caused by S. aureus are particularly common
and often life-threatening.
Control of the infection relies on several host mechanisms. The presence

of viral products induces innate immune responses in infected cells, such as the
production of α- and β-interferon. These mediators upregulate the expression of
the MX1 gene, which encodes a guanosine triphosphatase that interferes with viral
gene transcription and viral replication. As with other viral infections, natural killer
cells and cytotoxic T cells can recognize and kill infected host cells, limiting viral
replication and viral spread to adjacent pneumocytes. The cellular immune
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response is eventually augmented by development of antibody responses to the

viral hemagglutinin and neuraminidase proteins.
Insight into future pandemics has come from studying past pandemics.
DNA analysis of viral genomes retrieved from the lungs of a soldier who died in
the great 1918 influenza pandemic that killed between 20 million and 40 million
people worldwide identified swine influenza sequences, consistent with this virus
having its origin in a “antigenic shift.” The first flu pandemic of this century, in
2009, was also caused by an antigenic shift involving a virus of swine origin. It
caused particularly severe infections in young adults, apparently because older
adults had antibodies against past influenza strains that conveyed at least partial
protection. Comorbidities such as diabetes, heart disease, lung disease, and
immunosuppression were also associated with a higher risk of severe infection.
What then might be the source of the next great pandemic? There is no
certainty, but one concern is centered on avian influenza, which normally infects
birds. One such strain, type H5N1, has spread throughout the world in wild and
domestic birds. Fortunately, the transmission of the current H5N1 avian virus is
inefficient. However, if H5N1 influenza recombines with an influenza that is highly
infectious for humans, a strain might result that is capable of sustained
human-to-human transmission (and thus of causing the next great pandemic).
Human Metapneumovirus
Human metapneumovirus, a paramyxovirus discovered in 2001, is found
worldwide and is associated with upper and lower respiratory tract infections.
Infections can occur in any age group but are most common in young children,
elderly adults, and immunocompromised patients. Some infections, such as
bronchiolitis and pneumonia, are severe; overall, metapneumovirus is responsible
for 5% to 10% of hospitalizations and 12% to 20% of outpatient visits of children
suffering from acute respiratory tract infections. Such infections are clinically
indistinguishable from those caused by human respiratory syncytial virus and are
often mistaken for influenza. The first human metapneumovirus infection occurs
during early childhood, but reinfections are common throughout life, especially in
older subjects. Diagnostic methods include PCR tests for viral RNA. Treatment
generally focuses on supportive measures. Although work is ongoing, a clinically
effective and safe vaccine has yet to be developed.
Human Coronaviruses
Coronaviruses are enveloped, positive-sense RNA viruses that infect
humans and several other vertebrate species. Weakly pathogenic coronaviruses
cause mild cold-like upper respiratory tract infections, while highly pathogenic
ones may cause severe, often fatal pneumonia. An example of a highly
pathogenic type is SARS-CoV-2, a strain that emerged in late 2019 in China that is
producing a still evolving pandemic as of early 2020 (discussed in Chapter 8).
Highly pathogenic coronaviruses like SARS-CoV-2 bind the ACE2 protein on the
surface of pulmonary alveolar epithelial cells, explaining the tropism of these
viruses for the lung. With highly pathogenic forms in susceptible hosts, typically
older individuals with comorbid conditions, the host immune response and locally
released cytokines often produce acute lung injury and ARDS.
MORPHOLOGY (Viral Pneumonia)
All viral infections produce similar morphologic changes. Upper

respiratory infections are marked by mucosal hyperemia and swelling, infiltration
of the submucosa by mononuclear cells (mainly lymphocytes and monocytes), and
overproduction of mucus secretions. The swollen mucosa and viscous exudate
may plug the nasal channels, sinuses, or the Eustachian tubes, leading to
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suppurative secondary bacterial infection. Virus-induced tonsillitis causing

hyperplasia of the lymphoid tissue within the Waldeyer ring is frequent in children.
In viral laryngotracheobronchitis and bronchiolitis there is vocal cord

swelling and abundant mucus production. Impairment of bronchociliary function
invites bacterial superinfection with more marked suppuration. Plugging of small
airways may give rise to focal lung atelectasis. With more severe bronchiolar
involvement, widespread plugging of secondary and terminal airways by cell
debris, fibrin, and inflammatory exudate may, if prolonged, lead to organization
and fibrosis, resulting in obliterative bronchiolitis and permanent lung damage.
Lung involvement may be quite patchy or may involve whole lobes

bilaterally or unilaterally. The affected areas are red-blue and congested. Pleuritis
or pleural effusions are infrequent. The histologic pattern depends on the severity
of the disease. Predominant is an interstitial inflammatory reaction involving the
walls of the alveoli. The alveolar septa are widened and edematous and usually
contain a mononuclear inflammatory infiltrate of lymphocytes, macrophages, and
occasionally plasma cells. In severe cases, neutrophils may also be present. The
alveoli may be free of exudate, but in many patients there is intra-alveolar
proteinaceous material and a cellular exudate. When complicated by ARDS, pink
hyaline membranes line the alveolar walls (see Fig. 15.4). Eradication of the
infection is followed by reconstitution of the normal lung architecture.
Superimposed bacterial infection modifies this picture by causing ulcerative

bronchitis, bronchiolitis, and bacterial pneumonia. Some viruses, such as herpes
simplex, varicella, and adenovirus, may be associated with necrosis of bronchial
and alveolar epithelium and acute inflammation. Characteristic viral cytopathic
changes are described in Chapter 8.
Health Care–Associated Pneumonia

Health care–associated pneumonia was recently described as a distinct
clinical entity associated with several risk factors. These are hospitalization of at
least 2 days within the recent past; presentation from a nursing home or long-term
care facility; attending a hospital or hemodialysis clinic; and recent intravenous
antibiotic therapy, chemotherapy, or wound care. The most common organisms
isolated are methicillin-resistant S. aureus and P. aeruginosa. These patients have
a higher mortality than those with community-acquired pneumonia.
Hospital-Acquired Pneumonia
Hospital-acquired pneumonias are defined as pulmonary infections
acquired in the course of a hospital stay. They are common in patients with severe
underlying disease, immunosuppression, prolonged antibiotic therapy, or invasive
access devices such as intravascular catheters. Patients on mechanical ventilation
are at particularly high risk. Superimposed on an underlying disease (that caused
hospitalization), hospital-acquired infections are serious and often life-threatening.
Gram-positive cocci (mainly S. aureus) and gram-negative rods
(Enterobacteriaceae and Pseudomonas species) are the most common isolates.
The same organisms predominate in ventilator-associated pneumonia, with gram
negative bacilli being somewhat more common in this setting.
Aspiration Pneumonia
Aspiration pneumonia occurs in markedly debilitated patients or those
who aspirate gastric contents either while unconscious (e.g., after a stroke) or
during repeated vomiting. These patients have abnormal gag and swallowing
reflexes that predispose to aspiration. The resultant pneumonia is partly chemical
due to the irritating effects of gastric acid and partly bacterial (from the oral flora).
Typically, more than one organism is recovered in culture, aerobes being more
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common than anaerobes. This type of pneumonia is often necrotizing, pursues a

fulminant clinical course, and is a frequent cause of death. In patients who survive,
lung abscess is a common complication.
Microaspiration, in contrast, occurs frequently in almost all people,

especially those with gastroesophageal reflux disease. It usually results in small,
poorly formed non-necrotizing granulomas with multinucleated foreign body giant
cell reactions. It is usually inconsequential, but may exacerbate other pre-existing
lung diseases such as asthma, interstitial fibrosis, and lung rejection.
CHRONIC PNEUMONIA
Chronic pneumonia is most often a localized lesion in the
immunocompetent patient, with or without regional lymph node involvement.
Typically the inflammatory reaction is granulomatous and is caused by bacteria
(e.g., Mycobacterium tuberculosis) or fungi (e.g., Histoplasma capsulatum).
Tuberculosis of the lung and other organs is described in Chapter 8. Chronic
pneumonias caused by fungi are discussed here.
Histoplasmosis
H. capsulatum infection is acquired by inhalation of dust particles from soil
contaminated with bird or bat droppings that contain small spores (microconidia),
the infectious form of the fungus. It is endemic along the Ohio and Mississippi
rivers and in the Caribbean. It is also found in Mexico, Central and South America,
parts of eastern and southern Europe, Africa, eastern Asia, and Australia. Like M.
tuberculosis, H. capsulatum is an intracellular pathogen that is found mainly in
phagocytes. The clinical presentations and morphologic lesions of histoplasmosis
bear a striking resemblance to those of tuberculosis, including (1) a self-limited and
often latent primary pulmonary involvement, which may result in coin lesions on
chest radiography; (2) chronic, progressive, secondary lung disease, which is
localized to the lung apices and causes cough, fever, and night sweats; (3) spread
to extrapulmonary sites, including mediastinum, adrenal glands, liver, or meninges;
and (4) widely disseminated disease in immunocompromised patients.
Histoplasmosis can occur in immunocompetent individuals but as per usual is
more severe in those with depressed cell mediated immunity.
The pathogenesis of histoplasmosis is incompletely understood. The

portal of entry is virtually always the lung. Macrophages ingest but cannot kill the
organism without T-cell help, and this allows the organism to multiply within
phagolysosomes and disseminate prior to the development of T-cell immunity,
which takes 1 to 2 weeks. In individuals with adequate cell-mediated immunity, the
infection is controlled by Th1 helper T cells that recognize fungal antigens and
subsequently secrete IFN-γ, which activates macrophages and enables them to kill
intracellular yeasts. In addition, Histoplasma induces macrophages to secrete TNF,
which recruits and stimulates other macrophages to kill Histoplasma
MORPHOLOGY
In the lungs of otherwise healthy adults, Histoplasma infections produce
granulomas, which usually become necrotic and may coalesce to produce areas
of consolidation. With spontaneous resolution or effective treatment, these lesions
undergo fibrosis and concentric calcification (tree-bark appearance) (Fig. 15.37A).
Histologic differentiation from tuberculosis, sarcoidosis, and coccidioidomycosis
requires identification of the 3- to 5-µm thin-walled yeast forms, which may persist
in tissues for years. In fulminant disseminated histoplasmosis, which occurs in
immunosuppressed individuals, granulomas do not form; instead, there are focal
accumulations of mononuclear phagocytes filled with fungal yeasts throughout the
body (Fig. 15.37B).
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The diagnosis of histoplasmosis may be established by serologic tests for

antibodies and fungal antigens, culture, or identification of the fungus in tissue
biopsies. The majority of cases resolve spontaneously. Progressive disease or
disease in immunocompromised patients is treated with antifungal agents.
Blastomycosis
Blastomyces dermatitidis is a soil-inhabiting dimorphic fungus. It causes
disease in the central and southeastern United States; infection also occurs in
Canada, Mexico, the Middle East, Africa, and India. There are three clinical forms:
pulmonary blastomycosis, disseminated blastomycosis, and a rare primary
cutaneous form that results from direct inoculation of organisms into the skin. The
pneumonia most often resolves spontaneously, but it may persist or progress to a
chronic lesion.
MORPHOLOGY
In the normal host, the lung lesions of blastomycosis are suppurative
granulomas. Macrophages have a limited ability to ingest and kill B. dermatitidis,
and the persistence of the yeast cells leads to the recruitment of neutrophils. In
tissue, B. dermatitidis is a round, 5- to 15-µm yeast cell that divides by
broad-based budding. It has a thick, double-contoured cell wall, and visible nuclei
(Fig. 15.38). Involvement of the skin and larynx is associated with marked epithelial
hyperplasia, which may be mistaken for squamous cell carcinoma.
Coccidioidomycosis
Almost everyone who inhales the spores of Coccidioides immitis
becomes infected and develops a delayed-type hypersensitivity reaction to the
fungus, but most remain asymptomatic. Indeed, more than 80% of people in
endemic areas of the southwestern and western United States and in Mexico have
a positive skin test reaction. One reason for the infectivity of C. immitis is that
infective arthroconidia, when ingested by alveolar macrophages, block fusion of
the phagosome and lysosome and so resist intracellular killing. Approximately 10%
of infected people develop lung lesions, and less than 1% of people develop
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disseminated C. immitis infection, which frequently involves the skin and

meninges. Certain ethnic groups (e.g., Filipinos and African Americans) and the
immunosuppressed are at high risk for disseminated disease.
MORPHOLOGY
Within macrophages or giant cells, C. immitis is present as thick walled,
nonbudding spherules 20 to 60 µm in diameter, often filled with small
endospores. A pyogenic reaction is superimposed when the spherules rupture to
release the endospores (Fig. 15.39). Rare progressive C. immitis disease involves
the lungs, meninges, skin, bones, adrenals, lymph nodes, spleen, or liver. At all
these sites, the inflammatory response may be purely granulomatous, pyogenic,
or mixed.
Pneumonia in the Immunocompromised Host

The appearance of a pulmonary infiltrate, with or without signs of infection
(e.g., fever), is one of the most common and serious complications in patients
whose immune defenses are suppressed by disease, immunosuppressive therapy
for organ or hematopoietic stem cell transplants, chemotherapy for tumors, or
irradiation. In addition to the usual pathogens, a wide variety of so-called
opportunistic infectious agents, many of which rarely cause infection in normal
hosts, can cause pneumonia, and often more than one agent is involved. Mortality
from these opportunistic infections is high. Table 15.8 lists some of the
opportunistic agents according to their prevalence and whether they cause local
or diffuse pulmonary infiltrates. The differential diagnosis of such infiltrates
includes drug reactions and involvement of the lung by tumor. The specific
infections are discussed in Chapter 8. Of these, the ones that commonly involve
the lung can be classified according to the etiologic agent: (1) bacteria (P.
aeruginosa, Mycobacterium species, L. pneumophila, and Listeria
monocytogenes), (2) viruses (cytomegalovirus [CMV] and herpesvirus), and (3)
fungi (P. jiroveci, Candida species, Aspergillus species, the Phycomycetes, and
Cryptococcus neoformans).
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Pulmonary Disease in Human Immunodeficiency Virus Infection

Pulmonary disease accounts for 30% to 40% of hospitalizations in
HIV-infected individuals. Although the use of potent antiretroviral agents and
effective chemoprophylaxis has markedly altered the incidence and outcome of
pulmonary disease in HIV-infected persons, the plethora of infectious agents and
other pulmonary lesions make diagnosis and treatment a distinct challenge. Some
of the individual microbial agents afflicting HIV-infected individuals have already
been discussed; this section focuses only on the general principles of
HIV-associated pulmonary disease
● Despite the emphasis on opportunistic infections, it must be remembered
that bacterial lower respiratory tract infections caused by the “usual”
pathogens are among the most serious pulmonary disorders in HIV
infection. The implicated organisms include S. pneumoniae, S. aureus, H.
influenzae, and gram-negative rods. Bacterial pneumonias in HIVinfected
persons are more common, more severe, and more often associated with
bacteremia than in those without HIV infection
● Not all pulmonary infiltrates in HIV-infected individuals are infectious in
etiology. A host of noninfectious diseases, including Kaposi sarcoma
(Chapters 6 and 11), nonHodgkin lymphoma (Chapter 13), and lung cancer,
occur with increased frequency and must be excluded.
● The CD4+ T-cell count determines the risk of infection with specific
organisms. As a rule of thumb, bacterial and tubercular infections are
more likely at higher CD4+ counts (>200 cells/mm3 ). Pneumocystis
pneumonia usually strikes at CD4+ counts less than 200 cells/mm3 , while
CMV, fungal, and Mycobacterium avium-intracellulare complex infections
are uncommon until the disease is very advanced (CD4+ counts less than
50 cells/mm3 ).
Finally, pulmonary disease in HIV-infected persons may result from more

than one cause, and even common pathogens may present with atypical
manifestations. Therefore the diagnostic work-up of these patients may be more
extensive (and expensive) than would be necessary in an immunocompetent
individual.
EPIDEMIOLOGY
More than 5 million CAP cases occur annually in the United States. Along
with influenza, CAP is the eighth leading cause of death in this country. CAP
causes more than 55,000 deaths annually and results in more than 1.2 million
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hospitalizations; ~70% of patients are treated as outpatients and 30% as

inpatients. The mortality rate among outpatients is usually <5% but ranges from
~12% to 40% among hospitalized patients, with the exact rate depending on
whether treatment takes place in or outside the intensive care unit (ICU). In the
United States, CAP is the leading cause of death from infection among patients
>65 years of age. Moreover, 18% of hospitalized CAP patients are readmitted
within 1 month of discharge. The overall yearly CAP cost is estimated at $17 billion.
The overall incidence among adults is ~16–23 cases per 1000 persons per year,
with the highest rates at the extremes of age.
The risk factors for CAP in general and for pneumococcal pneumonia in
particular have implications for treatment. They include alcoholism, asthma,
immunosuppression, institutionalization, and age >70 years. In the elderly,
decreased cough and gag reflexes and reduced antibody and Toll-like receptor
responses increase the likelihood of pneumonia. Risk factors for pneumococcal
pneumonia include dementia, seizure disorders, heart failure, cerebrovascular
disease, alcoholism, tobacco smoking, chronic obstructive pulmonary disease
(COPD), and HIV infection. CA-MRSA pneumonia is more likely in patients with
skin colonization or infection with CA-MRSA and after viral infection.
Enterobacteriaceae tend to infect patients who have recently been hospitalized or
given antibiotics or who have comorbidities such as alcoholism, heart failure, or
renal failure. P. aeruginosa is a particular problem in patients with severe structural
lung disease (e.g., bronchiectasis, cystic fibrosis, or severe COPD). Risk factors for
Legionella infection include diabetes, hematologic malignancy, cancer, severe
renal disease, HIV infection, smoking, male gender, and a recent hotel stay or trip
on a cruise ship.
CLINICAL FINDINGS
The clinical presentation of pneumonia can vary from indolent to fulminant

and from mild to fatal in severity. Manifestations of worsening severity include
both constitutional findings and those limited to the lung and associated
structures. The patient is frequently febrile and/ or tachycardic and may
experience chills and/or sweats. Cough may be nonproductive or productive of
mucoid, purulent, or blood-tinged sputum. Gross hemoptysis is suggestive of
necrotizing pneumonia (e.g., that due to CA-MRSA). Depending on severity, the
patient may be able to speak in full sentences or may be short of breath. With
pleural involvement, the patient may experience pleuritic chest pain. Up to 20% of
patients may have gastrointestinal symptoms such as nausea, vomiting, or
diarrhea. Other symptoms may include fatigue, headache, myalgias, and
arthralgias. Findings on physical examination vary with the degree of pulmonary
consolidation and the presence or absence of a significant pleural effusion. An
increased respiratory rate and use of accessory muscles of respiration are
common. Palpation may reveal increased or decreased tactile fremitus, and the
percussion note can vary from dull to flat, reflecting underlying consolidated lung
and pleural fluid, respectively. Crackles, bronchial breath sounds, and possibly a
pleural friction rub may be heard. The clinical presentation may be less obvious in
the elderly, who may initially display new-onset or worsening confusion but few
other manifestations. Severely ill patients may have septic shock and evidence of
organ failure. In cases of CAP, symptoms can range from almost nonexistent to
severe, and chest radiographic findings are often in gravity-dependent parts of the
lung.
Clinical Features of Community-Acquired Bacterial Pneumonias

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The major symptoms of community-acquired acute bacterial pneumonia

are abrupt onset of high fever, shaking chills, and cough producing mucopurulent
sputum and occasionally hemoptysis. When pleuritis is present it is accompanied
by pleuritic pain and pleural friction rub. The whole lobe is radiopaque in lobar
pneumonia, whereas there are focal opacities in bronchopneumonia. The clinical
picture is markedly modified by the administration of effective antibiotics.
Appropriately treated patients may become afebrile with few clinical signs 48 to
72 hours after the initiation of antibiotics. The identification of the organism and
the determination of its antibiotic sensitivity are the keystones of therapy. Fewer
than 10% of patients with pneumonia severe enough to merit hospitalization now
succumb, and in most instances death results from a complication, such as
empyema, meningitis, endocarditis, or pericarditis, or is attributable to some
predisposing influence, such as debility or chronic alcoholism.
Clinical Features of Community-Acquired Viral Pneumonias

The clinical course of viral pneumonia is extremely varied. Many cases

masquerade as severe upper respiratory tract infections or as chest colds. Even
individuals with well developed atypical pneumonia have few localizing symptoms.
Cough may be absent, and the major manifestations may consist only of fever,
headache, and myalgia. The edema and exudation often cause
ventilation-perfusion mismatch leading to hypoxemia and thus evoke symptoms
out of proportion to the scant physical findings.
Viral pneumonias are usually mild and resolve spontaneously without any
lasting sequelae. However, interstitial viral pneumonias may assume epidemic
proportions, and in such instances even a low rate of complications can lead to
significant morbidity and mortality, as is typically true of influenza epidemics.
PROGNOSIS
The prognosis depends on the patient’s age, comorbidities, and site of

treatment (inpatient or outpatient). Young patients without comorbidity do well and
usually recover fully after ~2 weeks. Older patients and those with comorbid
conditions may take several weeks longer to recover fully. The overall mortality
rate for the outpatient group is <5%. For patients requiring hospitalization, overall
mortality ranges from 12% to 40%, depending on the category of patient and the
processes of care, particularly the timely administration of appropriate antibiotics.
DIAGNOSIS
When confronted with possible CAP, the physician must ask two
questions: is this pneumonia, and, if so, what is the likely pathogen? The former
question is answered by clinical and radiographic methods, whereas the latter
requires laboratory techniques.
Clinical Diagnosis
The differential diagnosis includes infectious and noninfectious entities,
including acute bronchitis, exacerbations of chronic bronchitis, heart failure, and
pulmonary embolism. The importance of a careful history cannot be
overemphasized. The diagnosis of CAP requires a compatible history, such as
cough, sputum production, fever and dyspnea, and a new infiltrate on chest
radiography. Unfortunately, the sensitivity and specificity of findings on physical
examination are only 58% and 67%, respectively. Chest radiography is often
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necessary to differentiate CAP from other conditions. Radiographic findings may

suggest increased severity (e.g., cavitation or multilobar involvement).
Occasionally, radiographic results suggest an etiologic diagnosis, such as
pneumatoceles in S. aureus infection or an upper-lobe cavitating lesion in
tuberculosis. CT may be of value in suspected loculated effusion or cavitary cases
or in postobstructive pneumonia caused by a tumor or foreign body. For
outpatients, clinical and radiologic assessments are usually all that is required
before treatment is started since most laboratory results are not available soon
enough to influence initial management. In certain cases, the availability of rapid
point-of-care outpatient tests can be important; for example, rapid diagnosis of
influenza infection can prompt specific anti-influenza treatment and secondary
prevention measures.
Etiologic Diagnosis
The etiology of pneumonia usually cannot be determined solely on the
basis of clinical or radiographic presentation. Data from more than 17,000
emergency department CAP cases showed an etiologic determination in only
7.6%. Except for CAP patients admitted to the ICU, no data exist to show that
treatment directed at a specific pathogen is statistically superior to empirical
therapy. The benefit of establishing a microbial etiology may be questioned,
particularly in light of the cost of diagnostic testing. However, a number of reasons
exist for attempting an etiologic diagnosis. Identification of a specific or
unexpected pathogen allows narrowing of the initial empiric regimen, with a
consequent decrease in antibiotic selection pressure and in the risk of resistance.
Pathogens with important public safety implications, such as Mycobacterium
tuberculosis and influenza virus, may be found. Finally, without susceptibility data,
trends in resistance cannot be followed accurately, and appropriate empirical
therapeutic regimens are harder to devise.
GRAM’S STAIN AND CULTURE OF SPUTUM.

The main purpose of the sputum Gram’s stain is to ensure suitability of a specimen
for culture. (To be suitable, a sputum sample must have >25 neutrophils and <10
squamous epithelial cells per low-power field.) However, staining may also identify
certain pathogens (e.g., S. pneumoniae, S. aureus, and gram-negative bacteria).
The sensitivity and specificity of the sputum Gram’s stain and culture are highly
variable. Even in cases of proven bacteremic pneumococcal pneumonia, the yield
of positive cultures from sputum is ≤50%.
Many patients, particularly elderly individuals, may be unable to produce an

appropriate sputum sample. Others may be taking antibiotics that interfere with
culture results. Inability to produce sputum can be caused by dehydration, whose
correction may result in increased sputum production and a more obvious infiltrate
on chest radiography. For patients admitted to the ICU and intubated, a
deep-suction aspirate or bronchoalveolar lavage sample has a high yield on
culture when sent to the laboratory as soon as possible. Since pathogens in
severe and mild CAP may differ (Table 126-1), the greatest benefit of staining and
culturing respiratory secretions is to alert the physician to unexpected and/or
resistant pathogens and to permit appropriate modification of therapy. Other
stains and cultures (e.g., for M. tuberculosis or fungi) may be useful as well. The
sputum Gram’s stain and culture are recommended only for hospitalized CAP
patients, particularly those with severe cases or those with risks of MRSA or P.
aeruginosa infection.
BLOOD CULTURES
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The yield from blood cultures, even when samples are collected before antibiotic
therapy, is disappointingly low. Only 5–14% of cultures from hospitalized CAP
patients are positive, and the most common pathogen is S. pneumoniae. Since
recommended empirical regimens all provide pneumococcal coverage, a blood
culture positive for this pathogen has little, if any, effect on clinical outcome.
However, susceptibility data may allow narrowing of antibiotic therapy in
appropriate cases. Because of the low yield and the lack of significant impact on
outcome, blood cultures are not considered de rigueur for all hospitalized CAP
patients. Certain high-risk patients should have blood cultured, including those
with neutropenia secondary to pneumonia, asplenia, complement deficiencies,
chronic liver disease, or severe CAP and those at risk of MRSA or P. aeruginosa
infection.
URINARY ANTIGEN TESTS

Two commercially available tests detect pneumococcal and Legionella antigen in
urine. The Legionella pneumophila test detects only serogroup 1, which accounts
for most community- acquired cases of Legionnaires’ disease in the United States.
The sensitivity and specificity of this antigen test are 70% and 99%, respectively.
The pneumococcal urine antigen test also is quite sensitive and specific (70% and
>90%, respectively). Although false-positive results can be obtained for
pneumococcus-colonized children, the test is generally reliable. Both tests can
detect antigen even after the initiation of appropriate antibiotic therapy. Testing of
urine for pneumococcal antigen can be reserved for severe cases; Legionella
antigen can be sought in severe cases and in situations where relevant
epidemiologic factors are present.
POLYMERASE CHAIN REACTION

PCR tests amplify a microorganism’s DNA or RNA, and multiplex PCR panels test
for a number of viral and bacterial pathogens. These tests dramatically improve
response times, but the contamination of respiratory specimens by upper-airway
flora may make semi quantitative or quantitative assays necessary for best results.
PCR of nasopharyngeal swabs has become the standard for diagnosis of
respiratory viral infection. PCR can also detect the nucleic acid of Legionella
species, M. pneumoniae, C. pneumoniae, and mycobacteria. The
cost-effectiveness of PCR testing, however, has not been definitively established.
SEROLOGY
A fourfold rise in specific IgM antibody titer between acute- and
convalescent-phase serum samples is generally considered diagnostic of infection
with a particular pathogen. Until recently, serologic tests were used to help
identify atypical pathogens as well as selected unusual organisms such as
Coxiella burnetii. However, these tests have fallen out of favor because of the time
required to obtain a final result for the convalescent-phase sample and the
difficulty of interpretation.
BIOMARKERS
Two of the most commonly used markers are C-reactive protein (CRP) and
procalcitonin (PCT). Levels of these acute-phase reactants increase in the
presence of an inflammatory response, particularly to bacterial pathogens.
Nevertheless, PCT is insufficiently accurate for use in the diagnosis of bacterial
CAP, and initial serum PCT levels should not be used as a basis for withholding
initial antibiotic treatment. CRP is considered even less sensitive than PCT for
detecting bacterial pathogens. Thus these tests should not be used alone but, in
conjunction with findings from the history, physical examination, radiography, and
laboratory tests, may facilitate antibiotic stewardship and appropriate
management of seriously ill CAP patients.
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TREATMENT/MANAGEMENT
SITE OF CARE.
The decision to hospitalize a patient with CAP has considerable
implications. The cost of inpatient management exceeds that of outpatient
treatment by a factor of 20, and hospitalization accounts for most CAP-related
expenditures. However, late admission to the ICU is associated with increased
mortality rates. The choice can be difficult: some patients can be managed at
home, while others require hospitalization. Tools that objectively assess the risk of
adverse outcomes, including severe illness and death, can help to minimize
unnecessary hospital admissions. The two most frequently used rules are the
Pneumonia Severity Index (PSI), a prognostic model that identifies patients at low
risk of dying, and the CURB-65 criteria, which yield a severity-of-illness score. To
determine the PSI, points are given for 20 variables, including age, coexisting
illness, and abnormal physical and laboratory findings. On the basis of the score,
patients are assigned to one of five classes with these mortality rates: class 1, 0.1%;
class 2, 0.6%; class 3, 2.8%; class 4, 8.2%; and class 5, 29.2%. Use of the PSI
results in lower admission rates for class 1 and class 2 patients. Class 3 patients
could ideally be admitted to an observation unit pending further decisions.
The CURB-65 criteria include five variables: confusion (C); urea >7
mmol/L (U); respiratory rate ≥30/min (R); blood pressure— systolic ≤90 mmHg or
diastolic ≤60 mmHg (B); and an age of ≥65 years. Patients with a score of 0 (a
30-day mortality rate of 1.5%) can be treated as outpatients. With a score of 1 or 2,
the patient should be hospitalized unless the score is entirely or in part
attributable to an age of ≥65 years; in such cases, hospitalization may not be
necessary. Among patients with scores of ≥3, mortality rates are 22% overall;
these patients may require ICU admission. The PSI has greater efficacy than
CURB-65 but is more difficult to calculate.
If a patient is unable to maintain oral intake, if compliance is thought to be

an issue when assessed on the basis of mental condition or living situation (e.g.,
cognitive impairment or homelessness), or if the patient’s O2 saturation on room
air is <92%, hospitalization is necessary. If these considerations do not apply,
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clinical judgment in conjunction with a prediction rule should be used to

determine the site of care.
Neither PSI nor CURB-65 is accurate in determining the need for ICU
admission. Patients with septic shock requiring vasopressors or with acute
respiratory failure requiring intubation and mechanical ventilation should be
admitted directly to an ICU (Table 126-3), and those with three of the nine minor
criteria listed in the latter table should be admitted to an ICU or a high-level
monitoring unit. Mortality rates are higher among less ill patients who were
admitted to a medical floor but then deteriorated than among equally ill patients
initially monitored in the ICU.
ANTIBIOTIC RESISTANCE
Antimicrobial resistance is a significant problem that threatens to diminish
our therapeutic armamentarium. Antibiotic misuse results in increased antibiotic
selection pressure that can affect resistance locally and globally by clonal
dissemination. For CAP, the main resistance issues currently involve S.
pneumoniae and CA-MRSA.
S. pneumoniae.
In general, pneumococcal resistance to β-lactams is acquired by (1) direct
DNA incorporation and remodeling of penicillin-binding proteins through contact
with closely related oral commensal bacteria (e.g., viridans group streptococci), (2)
the process of natural transformation, or (3) mutation of certain genes.
The S. pneumoniae minimal inhibitory concentration (MIC) breakpoint

cutoffs for penicillin in pneumonia are ≤2 μg/mL for susceptible, >2–4 μg/mL for
intermediate, and ≥8 μg/mL for resistant. A change in susceptibility thresholds
dramatically decreased the proportion of pneumococcal isolates considered non
susceptible. For meningitis, MIC thresholds remain at the former lower levels.
Fortunately, resistance to penicillin appeared to plateau even before the change
in MIC thresholds. Of isolates in the United States, <20% are resistant to penicillins
and <1% to cephalosporins. Risk factors for penicillin-resistant pneumococcal
infection include recent antimicrobial therapy, an age of <2 or >65 years,
attendance at a day-care center, recent hospitalization, and HIV infection.
In contrast to penicillin resistance, macrolide resistance is increasing in S.

pneumoniae through several mechanisms. Target-site modification caused by
ribosomal methylation in 23S rRNA encoded by the ermB gene results in
high-level resistance (MIC, ≥64 μg/mL) to macrolides, lincosamides, and
streptogramin B–type antibiotics. The efflux mechanism encoded by the mef gene
(M phenotype) is usually associated with low-level resistance (MIC, 1–32 μg/mL).
These two mechanisms account for ~40% and ~60%, respectively, of resistant
pneumococcal isolates in the United States. High-level resistance to macrolides is
more common in Europe, whereas lower-level resistance predominates in North
America. The prevalence of macrolide-resistant S. pneumoniae exceeds 25% in
some countries; in Canada the prevalence is ~22%, and in the United States it
exceeds 30%. Much of this resistance is high level, and failures of treatment may
result in such cases. In these situations, a macrolide should not be used as
empirical monotherapy. Estimates of the prevalence of doxycycline resistance in
the United States are generally <20%.
The rate of pneumococcal resistance to fluoroquinolones (e.g.,

ciprofloxacin, moxifloxacin, and levofloxacin) is usually <2%. Changes can occur in
one or both target sites (topoisomerases II and IV); these changes are attributable
to mutations in the gyrA and parC genes, respectively. In addition, an efflux pump
may play a role in pneumococcal resistance to fluoroquinolones.
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Isolates resistant to drugs from three or more antimicrobial classes with

different mechanisms of action are considered MDR strains. The propensity for an
association of pneumococcal resistance to penicillin with reduced susceptibility to
other drugs, such as macrolides, tetracyclines, and
trimethoprim-sulfamethoxazole, is of concern. In the United States, 58.9% of
penicillin-resistant pneumococcal blood isolates are also resistant to macrolides.
The most important risk factor for antibiotic-resistant pneumococcal

infection is use of a specific antibiotic within the previous 3 months. A history of
prior antibiotic treatment is a critical factor in avoiding the use of an inappropriate
antibiotic.
CA-MRSA
CAP due to MRSA may be caused by the classic hospital-acquired strains
or by genotypically and phenotypically distinct community-acquired strains. Most
infections with the former have been acquired either directly or indirectly during
contact with the healthcare environment. However, in some hospitals, CA-MRSA
strains are displacing the classic hospital-acquired strains; this change suggests
that the newer community-acquired strains may be more robust.
Methicillin resistance in S. aureus is determined by the mecA gene, which

encodes for resistance to all β-lactam drugs. At least five staphylococcal
chromosomal cassette mec (SCCmec) types have been described. The typical
hospital-acquired strain usually has a type II or III SCCmec element, whereas
CA-MRSA has type IV. CA-MRSA isolates tend to be less resistant than the older
hospital-acquired strains and are often susceptible to
trimethoprim-sulfamethoxazole, clindamycin, and tetracycline in addition to
vancomycin and linezolid. However, the most important distinction is that
CA-MRSA strains also carry genes for superantigens such as enterotoxins B and C
and Panton-Valentine leukocidin; the latter is a membrane-tropic toxin that can
create cytolytic pores in neutrophils, monocytes, and macrophages.
M. pneumoniae
Macrolide-resistant M. pneumoniae has been reported in a number of
countries, including Germany (3%), Japan (30%), China (95%), and France and the
United States (5–13%). Mycoplasma resistance to macrolides is increasing as a
result of binding-site mutation in domain V of 23S rRNA.
Gram-Negative Bacilli
A detailed discussion of resistance among gram-negative bacilli is beyond
the scope of this chapter (see Chap. 161). Fluoroquinolone resistance among
community isolates of Escherichia coli is increasing. Enterobacter species are
typically resistant to cephalosporins, and the drugs of choice for use against these
organisms are usually fluoroquinolones or carbapenems. Similarly, when infections
due to bacteria producing extended-spectrum β-lactamases (ESBLs) are
documented or suspected, a carbapenem should be considered.
INITIAL ANTIBIOTIC MANAGEMENT

ment, initial therapy is usually empirical and designed to cover the likeliest
pathogens. In all cases, treatment should be initiated as expeditiously as possible.
New CAP treatment guidelines in the United States have been presented in a joint
statement from the American Thoracic Society (ATS) and the Infectious Diseases
Society of America (IDSA). These guidelines consider the likely pathogens, risk of
antimicrobial resistance, severity of illness, site of care, and risk of infection with
specific bacteria such as MRSA and P. aeruginosa (Fig. 126-1, Tables 126-4 and
126-5). In the figure and the tables, the antibiotics are not listed in order of
preference.
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The approach to treatment of aspiration pneumonia is based upon a

number of factors, including site of acquisition (community vs hospital), normal or
abnormal chest radiograph, and additional variables such as illness severity, state
of dentition, and risk of infection with an MDR pathogen. Routine coverage of
anaerobes is unnecessary unless dentition is poor or there is a lung abscess or
necrotizing pneumonia. Our approach to the treatment of CAP (Tables 126-4 and
126-5) is very similar to that proposed in the new CAP guidelines with the
exceptions listed below.
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OUTPATIENT
The exceptions to the CAP guidelines that we follow in treating patients
are
● We usually initiate coverage that includes atypical organisms as
well as S. pneumoniae.
● Generally, we do not consider the risk of infection with P. aerug
inosa or MRSA particularly significant in outpatients.
● Prior antibiotic use should include both oral and parenteral
agents.
Patients are stratified into two groups: those without comorbidity or risk
factors for antibiotic resistance and those with comorbidities (e.g., chronic heart,
lung, liver, or kidney disease; diabetes; alcoholism; malignancy; or asplenia) with
or without risk factors for resistance (Table 126-4). As a general rule, if patients
have been treated with a drug from a particular class of antibiotics within the
previous 3 months, drugs from a different class should be used to minimize
resistance issues.
For those without comorbidity or resistance risk factors, amoxicillin alone

or doxycycline is recommended in the recent guidelines. Monotherapy with
amoxicillin is based on evidence of its efficacy in the treatment of hospitalized
CAP patients. This recommendation is a change from that in the 2007 IDSA/ATS
CAP guidelines. As a rule, however, we usually tend to initiate treatment that
includes coverage for S. pneumoniae as well as the atypical pathogens (Table
126-4).
Monotherapy with a macrolide is recommended in the new guidelines

only if there are contraindications to amoxicillin or doxycycline and there is
documented low risk of macrolide resistance (<25%). Otherwise, the treatment of
outpatients is quite similar to the regimens recommended in the 2007 IDSA/ATS
guidelines.
INPATIENTS
Our exceptions to the recommendations in the CAP guidelines are:
● As a general rule, when initiating treatment for infection with P.
aeruginosa, we use double coverage.
● The presence of all three risk factors is not required for drug
resistance (recent hospitalization, recent oral or IV antibiotic
treatment, ± local validation)
The main considerations for determining initial empirical treatment of

hospitalized CAP patients are clinical severity and risk factors for infection with
drug-resistant pathogens such as MRSA or P. aeruginosa. Hospitalization alone is
not now considered a significant risk factor for these pathogens. Hospitals should
collect local data on MRSA and P. aeruginosa with regard to prevalence, risk
factors for infection, and antibiotic susceptibilities. Patients can be categorized as
having nonsevere or severe CAP (Table 126-3), and those in each of these
categories may or may not have risk factors for MRSA or P. aeruginosa (Fig. 126-1).
In the scenarios involving these variables in hospitalized CAP patients, empirical
treatment for either of these pathogens should be added to standard therapy
unless a patient’s illness is considered nonsevere and the risk factors are recent
hospitalization and antibiotic treatment ± local validation data (Fig. 126-1).
Depending upon the patient, we may begin treatment in this situation and then
de-escalate it if appropriate. In such cases, cultures should be performed but
treatment is usually withheld unless the culture results or the rapid nasal PCR
results for MRSA are positive.
Nonsevere, No Risk Factors
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For patients with nonsevere infection and no risk factors, treatment

should consist of either a combination of a β-lactam and a macrolide or
monotherapy with a respiratory fluoroquinolone (Table 126-5). In the event of
contraindications to macrolides and fluoroquinolones, a β-lactam together with
doxycycline may be used. Treatment with a combination of a β-lactam and a
macrolide or a fluoroquinolone alone results in lower mortality than monotherapy
with a β-lactam.
Severe, No Risk Factors

Patients with severe infection but no risk factors should receive
combination therapy with either a β-lactam and a macrolide or a β-lactam and a
respiratory fluoroquinolone (Table 126-5).
Nonsevere and Severe, with Risk Factors

To date, there are no prediction rules reliably identifying patients who
should be started empirically on treatment for MRSA or P. aeruginosa. Current risk
factors for infection with these pathogens are hierarchical. Prior isolation of these
organisms, especially from the respiratory tract within the previous year, is a more
robust risk factor than recent hospitalization and exposure to parenteral
antibiotics. For P. aeruginosa, underlying lung disease (e.g., bronchiectasis or very
severe COPD) also is an important risk factor. If MRSA or P. aeruginosa has been
isolated previously, appropriate empirical therapy should be started in both severe
and nonsevere cases (Table 126-5). We prefer linezolid over vancomycin as
first-line treatment for MRSA because of its inhibition of bacterial exotoxin and its
better lung penetration. If the organism is not isolated from respiratory secretions
or blood and/or the nasal or bronchoalveolar lavage PCR test for MRSA is
negative and the patient is improving at 48 h, treatment may be de-escalated to a
standard regimen.
If, on the other hand, the risk factors are recent hospitalization and
antibiotic use within the previous 3 months, appropriate samples should be
obtained for culture, and, in severe cases, extended-spectrum treatment for MRSA
or P. aeruginosa should be initiated. Depending upon the severity of infection,
local data on P. aeruginosa resistance, and antibiotic use within the previous 90
days, single- or double-drug coverage should be used.
If two antipseudomonal agents are started, the drugs should not be from
the same class. Whenever possible, assessment for possible de-escalation of
therapy is urged. If the patient’s illness is not severe, empirical extended treatment
should be withheld until culture results are available.
Regardless of the site of care, CAP patients testing positive for influenza
should be given anti-influenza treatment (e.g., oseltamivir) as well as appropriate
antibacterial therapy. Physicians should be vigilant about possible superinfection
with MRSA.
Although hospitalized patients have traditionally received initial therapy

by the IV route, some drugs, particularly the fluoroquinolones, are very well
absorbed and may be given orally from the outset to select patients. For those
initially treated with IV agents, a switch to oral treatment is appropriate when the
patient can ingest and absorb the drugs, is hemodynamically stable, and is
showing clinical improvement. A 5-day course of treatment is usually sufficient for
uncomplicated CAP, but longer treatment may be required for patients who have
not stabilized clinically and for those with bacteremia, metastatic infection, or
infection with a more virulent pathogen such as P. aeruginosa or MRSA.
Adjunctive Measures
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In addition to appropriate antimicrobial therapy, certain adjunctive measures

should be used. Adequate hydration, oxygen therapy for hypoxemia, vasopressor
treatment, and assisted ventilation when necessary are critical to successful
treatment. Routine use of glucocorticoids is not recommended for CAP except in
patients with refractory septic shock.
Failure to Improve
Patients slow to respond to therapy should be reevaluated at about day 3
(sooner if their condition is worsening), with several scenarios considered. A
number of noninfectious conditions mimic pneumonia, including pulmonary
edema, pulmonary embolism, lung carcinoma, radiation and hypersensitivity
pneumonitis, and connective tissue disease involving the lungs. If the patient truly
has CAP and empirical treatment is aimed at the correct pathogen, lack of
response may be explained in a number of ways. The pathogen may be resistant
to the drug selected, or a sequestered focus (e.g., lung abscess or empyema) may
prevent antibiotic access to the pathogen. The patient may be getting the wrong
drug or the correct drug at the wrong dose or frequency of administration.
Another possibility is that CAP has been diagnosed correctly but an unexpected
pathogen (e.g., CA-MRSA, M. tuberculosis, or a fungus) is the cause. Nosocomial
superinfections—both pulmonary and extrapulmonary—are other possible
explanations for a hospitalized patient’s failure to improve. In all cases of delayed
response or worsening condition, the patient must be carefully reassessed and
appropriate studies initiated, possibly including CT or bronchoscopy.
Complications
Complications of severe CAP include respiratory failure, shock and
multiorgan failure, and exacerbation of comorbid illnesses. Three particularly
noteworthy conditions are metastatic infection, lung abscess, and complicated
pleural effusion. Metastatic infection (e.g., brain abscess or endocarditis) is
unusual and requires a high degree of suspicion and a detailed workup for proper
treatment. Lung abscess may occur in association with aspiration pneumonia or
with infection caused by pathogens such as CA-MRSA, P. aeruginosa, or (rarely) S.
pneumoniae. A significant pleural effusion should be tapped for both diagnostic
and therapeutic purposes. If the fluid has a pH <7.2, a glucose level of <2.2
mmol/L, and a lactate dehydrogenase concentration of >1000 U/L or if bacteria are
seen or cultured, drainage is needed.
Follow Up
Fever and leukocytosis usually resolve within 2–4 days in otherwise
healthy patients with CAP, but physical findings may persist longer. Chest
radiographic abnormalities are slowest to resolve (4–12 weeks), with the speed of
clearance depending on the patient’s age and underlying lung disease. Patients
may be discharged from the hospital once their clinical condition, including any
comorbidity, is stable. The site of residence after discharge (nursing home, home
with family, home alone) is an important consideration, particularly for elderly
patients. For a hospitalized patient, we generally recommend a follow-up
radiograph ~4–6 weeks later. If relapse or recurrence is documented, particularly
in the same lung segment, the possibility of an underlying neoplasm must be
considered. For individuals managed as outpatients, routine follow-up chest
radiography is not necessary if they are nonsmokers, if they are otherwise well,
and if their symptoms are resolved within 5–7 days.
PREVENTION
The main preventive measure is vaccination (Chap. 123).
Recommendations of the Advisory Committee on Immunization Practices should
be followed for influenza and pneumococcal vaccines. A pneumococcal
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polysaccharide vaccine (PPSV23) and a protein conjugate pneumococcal vaccine

(PCV13) are available in the United States (Chap. 146). The former contains
capsular material from 23 pneumococcal serotypes; in the latter, capsular
polysaccharide from 13 of the most common pneumococcal pathogens affecting
children is linked to an immunogenic protein. PCV13 produces T-cell–dependent
antigens, resulting in long-term immunologic memory.
Administration of this vaccine to children has led to a decrease in the

prevalence of antimicrobial-resistant pneumococci and in the incidence of
invasive pneumococcal disease among both children and adults. However,
vaccination can result in the replacement of vaccine with nonvaccine serotypes,
as seen with serotypes 19A and 35B following introduction of the original 7-valent
conjugate vaccine. PCV13 is also recommended for the elderly and for younger
immunocompromised patients. Because of an increased risk of pneumococcal
infection, even among patients without obstructive lung disease, smokers should
be strongly encouraged to quit. The influenza vaccine is available in an inactivated
or recombinant form. During an influenza outbreak, unprotected patients at risk
from complications should be vaccinated immediately and given
chemoprophylaxis with either oseltamivir or zanamivir for 2 weeks—i.e., until
vaccine-induced antibody levels are sufficiently high.
RISK STRATIFICATION FOR COMMUNITY ACQUIRED PNEUMONIA

Source: 2020-Community-Acquired-Pneumonia-Clinical-Practice-Guidelines
EMPIRIC TREATMENT RECOMMENDATIONS FOR MANAGEMENT OF

CAP
Source: 2020-Community-Acquired-Pneumonia-Clinical-Practice-Guidelines
Patients with low risk CAP without Amoxicillin 1 gram, three times daily
comorbidities: (Strong recommendation, low quality of
evidence
OR
Clarithromycin 500mg, twice daily
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OR
Azithromycin 500 mg once daily (Strong
recommendation, low quality of
evidence)
Patients with low risk CAP with stable Beta-lactam

comorbidities: Co-amoxiclav (amoxicillin/clavulanate
500mg/125mg three times daily OR
Amoxicillin/Clavulanate 875mg/125mg
twice daily)
OR
Cefuroxime 500mg, twice daily (Strong
recommendation, moderate quality of
evidence)
PLUS OR MINUS (+/-)
Macrolide
Clarithromycin 500mg, twice daily
OR
Azithromycin 500 mg once daily (Strong
recommendation, low quality of
evidence)
OR
Doxycycline 100mg, twice daily
(Conditional recommendation, low
quality of evidence)
Patients with moderate risk CAP Non-pseudomonal Beta-lactam antibiotic

without MDRO infection: Ampicillin-sulbactam 1.5-3g every 6h
OR
Cefotaxime 1-2g every 8h
OR
Ceftriaxone 1-2g daily PLUS Macrolide
Azithromycin 500 mg daily
OR
Clarithromycin 500 mg twice daily
(Strong recommendation, moderate
quality of evidence)
Patients with high risk CAP without FIRST LINE THERAPY

MDRO infection: Non-pseudomonal Beta-lactam antibiotic
Ampicillin-sulbactam 1.5-3g IV every 6h
OR
Cefotaxime 1-2g IV every 8h OR
Ceftriaxone 1-2g IV daily
PLUS
Macrolide Azithromycin 500mg PO/IV
daily
OR
Erythromycin 500mg PO every 6h
OR
Clarithromycin 500 mg PO twice daily
(Strong recommendation, low quality of
evidence)
ALTERNATIVE THERAPY
Non-pseudomonal Beta-lactam antibiotic
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PLUS
Respiratory fluoroquinolone*
Levofloxacin 750 mg PO/IV daily
OR
Moxifloxacin 400 mg PO/IV daily
(Conditional recommendation, low
quality of evidence) *given as 1 hr IV
infusion
Risk for Methicillin Resistant Non-pseudomonal Beta-lactam antibiotic

Staphylococcus aureus (MRSA) PLUS
Macrolide OR Respiratory
● Prior colonization or infection fluoroquinolone*
with MRSA within 1 year PLUS
● Intravenous antibiotic therapy Vancomycin 15mg/kg IV every 12h^
within 90 days OR
Linezolid 600mg IV every 12h^
OR
Clindamycin 600mg IV every 8h^
Risk for ESBL REPLACE Non-pseudomonal

● Prior colonization or infection Beta-lactam antibiotic with:
with ESBL-producing organisms
within 1 year Ertapenem 1g IV every 24h
OR
Meropenem 1g IV every 8h (if Ertapenem
is not available)
PLUS
Macrolide
OR
respiratory fluoroquinolone*
Risk for Pseudomonas aeruginosa REPLACE Non-pseudomonal

● Prior colonization or infection Beta-lactam antibiotic with:
with P. aeruginosa within 1 year
● Severe bronchopulmonary Piperacillin-Tazobactam 4.5g IV every 6h
disease (severe COPD, OR
bronchiectasis, prior Cefepime 2g IV every 8h
tracheostomy) OR
Ceftazidime 2g IV every 8h
OR
Aztreonam 2g IV every 8h
OR
Meropenem 1g IV every 8h (especially if
with ESBL risk)
PLUS
Macrolide or respiratory
fluoroquinolone
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DIFFERENTIAL DIAGNOSIS 1: PLEURAL EFFUSION

The pleural space lies between the lung and the chest wall and
normally contains a very thin layer of fluid, which serves as a coupling system.
A pleural effusion is present when there is an excess quantity of fluid in the
pleural space.
ETIOLOGY
Pleural fluid accumulates when pleural fluid formation exceeds pleural

fluid absorption. Normally, fluid enters the pleural space from the capillaries in the
parietal pleura and is removed via the lymphatics in the parietal pleura. Fluid also
can enter the pleural space from the interstitial spaces of the lung via the visceral
pleura or from the peritoneal cavity via small holes in the diaphragm. The
lymphatics have the capacity to absorb 20 times more fluid than is formed
normally. Accordingly, a pleural effusion may develop when there is excess pleural
fluid formation (from the interstitial spaces of the lung, the parietal pleura, or the
peritoneal cavity) or when there is decreased fluid removal by the lymphatics.
DIAGNOSTIC APPROACH
Patients suspected of having a pleural effusion should undergo chest

imaging to diagnose its extent. Chest ultrasound has replaced the lateral
decubitus x-ray in the evaluation of suspected pleural effusions and as a guide to
thoracentesis. When a patient is found to have a pleural effusion, an effort should
be made to determine the cause (Figure 294-1). The first step is to determine
whether the effusion is a transudate or an exudate. A transudative pleural effusion
occurs when systemic factors that influence the formation and absorption of
pleural fluid are altered. The leading causes of transudative pleural effusions in
the United States are left ventricular failure and cirrhosis. An exudative pleural
effusion occurs when local factors that influence the formation and absorption of
pleural fluid are altered. The leading causes of exudative pleural effusions are
bacterial pneumonia, malignancy, viral infection, and pulmonary embolism. The
primary reason for making this differentiation is that additional diagnostic
procedures are indicated with exudative effusions to define the cause of the local
disease.
Transudative and exudative pleural effusions are distinguished by

measuring the lactate dehydrogenase (LDH) and protein levels in the pleural fluid.
Exudative pleural effusions meet at least one of the following criteria, whereas
transudative pleural effusions meet none:
1. Pleural fluid protein/serum protein >0.5

2. Pleural fluid LDH/serum LDH >0.6
3. Pleural fluid LDH more than two-thirds the normal upper limit for serum
These criteria misidentify ~25% of transudates and exudates. If one or

more of the exudative criteria are met and the patient is clinically thought to have
a condition producing a transudative effusion, the difference between the protein
levels in the serum and the pleural fluid should be measured. If this gradient is >31
g/L (3.1 g/dL), the exudative categorization by these criteria can be ignored
because almost all such patients have a transudative pleural effusion. If a patient
has an exudative pleural effusion, the following tests on the pleural fluid should be
obtained: description of the appearance of the fluid, glucose level, differential cell
count, microbiologic studies, and cytology.
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PATHOGENESIS
Source: Robbins and Cotran Pathologic Basis of Disease, 10th edition, Chapter
13 Lung
Pleural effusion is a common manifestation of both primary and secondary

pleural diseases, which may be inflammatory or noninflammatory. Normally, no
more than 15 mL of serous, relatively acellular, clear fluid lubricates the pleural
surface. Accumulation of pleural fluid occurs in the following settings:
● Increased hydrostatic pressure, as in congestive heart failure

● Increased vascular permeability, as in pneumonia
● Decreased osmotic pressure, as in nephrotic syndrome
● Increased intrapleural negative pressure, as in atelectasis
● Decreased lymphatic drainage, as in mediastinal carcinomatosis
Inflammatory Pleural Effusions

Serous, serofibrinous, and fibrinous pleuritis all have an inflammatory basis,
differing only in the intensity and duration of the process. The most common
causes of pleuritis are disorders associated with inflammation of the underlying
lung, such as tuberculosis, pneumonia, lung infarction, lung abscess, and
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bronchiectasis. Rheumatoid arthritis, systemic lupus erythematosus, uremia,

diffuse systemic infections, and metastatic involvement of the pleura can also
cause serous or serofibrinous pleuritis. Radiotherapy for tumors in the lung or
mediastinum often causes a serofibrinous pleuritis. In most of these disorders, the
pleural reaction is minimal, and the fluid exudate is resorbed with either resolution
or organization of the fibrinous component.
However, large amounts of fluid sometimes accumulate and compress the

lung, causing respiratory distress. A purulent pleural exudate (empyema) usually
results from bacterial or mycotic seeding of the pleural space. Most commonly,
this seeding occurs by contiguous spread of organisms from intrapulmonary
infection, but occasionally it occurs through lymphatic or hematogenous
dissemination from a more distant source. Rarely, infections below the diaphragm,
such as the subdiaphragmatic or liver abscess, may extend by continuity through
the diaphragm into the pleural spaces, more often on the right side. Empyema is
characterized by loculated, yellow-green, creamy pus composed of masses of
neutrophils admixed with other leukocytes. Although empyema may accumulate in
large volumes (up to 500 to 1000 mL), usually the volume is small, and the pus
becomes walled off by fibrosis. Empyema may resolve, but more often the
exudate organizes into dense, tough fibrous adhesions that frequently obliterate
the pleural space or envelop the lungs; either can seriously restrict pulmonary
expansion.
Hemorrhagic pleuritis manifested by sanguineous inflammatory exudates

is infrequent and is most often associated with hemorrhagic diatheses, rickettsial
infections, and neoplastic involvement of the pleural cavity. The sanguineous
exudate must be differentiated from hemothorax (discussed later). When
hemorrhagic pleuritis is encountered, a careful search should be made for the
presence of tumor cells.
Non-Inflammatory Pleural Effusions
Noninflammatory collections of serous fluid within the pleural cavities are

called hydrothorax. The fluid is clear and straw colored. Hydrothorax may be
unilateral or bilateral, depending on the underlying cause. The most common
cause of hydrothorax is heart failure, and for this reason it is usually accompanied
by pulmonary congestion and edema. Hydrothorax may also be seen in any other
systemic disease associated with generalized edema, such as patients with renal
failure or cirrhosis of the liver.
The escape of blood into the pleural cavity is known as hemothorax. It is

most commonly a complication of trauma or less commonly surgery, but can also
accompany rupture of an aortic aneurysm, a setting in which it is almost invariably
fatal. Chylothorax is an accumulation of milky fluid, usually of lymphatic origin, in
the pleural cavity. Chyle is milky white because it contains finely emulsified fats.
Chylothorax is most often caused by thoracic duct trauma or by obstruction of a
major lymphatic duct, usually by a malignancy. Such cancers most commonly arise
within the thoracic cavity and invade the lymphatics locally, but occasionally more
distant cancers metastasize via the lymphatics and grow within the right lymphatic
or thoracic duct, producing obstruction.
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CLINICAL MANIFESTATIONS AND MANAGEMENT
Effusion Due to Heart Failure

The most common cause of pleural effusion is left ventricular failure. The
effusion occurs because the increased amounts of fluid in the lung interstitial
spaces exit in part across the visceral pleura; this overwhelms the capacity of the
lymphatics in the parietal pleura to remove fluid. In patients with heart failure, a
diagnostic thoracentesis should be performed if the effusions are not bilateral and
comparable in size, if the patient is febrile, or if the patient has pleuritic chest pain
to verify that the patient has a transudative effusion. Otherwise, the patient’s heart
failure is treated. If the effusion persists despite therapy, a diagnostic
thoracentesis should be performed. A pleural fluid N-terminal pro-brain natriuretic
peptide (NT-proBNP) >1500 pg/mL is virtually diagnostic that the effusion is
secondary to congestive heart failure.
Hepatic Hydrothorax
Pleural effusions occur in ~5% of patients with cirrhosis and ascites. The
predominant mechanism is the direct movement of peritoneal fluid through small
openings in the diaphragm into the pleural space. The effusion is usually
right-sided and frequently is large enough to produce severe dyspnea.
Parapneumonic Effusion
Parapneumonic effusions are associated with bacterial pneumonia, lung
abscess, or bronchiectasis and are probably the most common cause of exudative
pleural effusion in the United States. Empyema refers to a grossly purulent
effusion. Patients with aerobic bacterial pneumonia and pleural effusion present
with an acute febrile illness consisting of chest pain, sputum production, and
leukocytosis. Patients with anaerobic infections present with a subacute illness
with weight loss, a brisk leukocytosis, mild anemia, and a history of some factor
that predisposes them to aspiration. The possibility of a parapneumonic effusion
should be considered whenever a patient with bacterial pneumonia is initially
evaluated. The presence of free pleural fluid can be demonstrated with a lateral
decubitus radiograph, computed tomography (CT) of the chest, or ultrasound. If
the free fluid separates the lung from the chest wall by >10 mm, a therapeutic
thoracentesis should be performed. Factors indicating the likely need for a
procedure more invasive than a thoracentesis (in increasing order of importance)
include the following:
1. Loculated pleural fluid
2. Pleural fluid pH <7.20
3. Pleural fluid glucose <3.3mmol/L (<60mg/dL)
4. Positive Gram stain or culture of the pleural fluid
5. Presence of gross pus in the pleural space
If the fluid recurs after the initial therapeutic thoracentesis and if any of
these characteristics is present, a repeat thoracentesis should be performed. If the
fluid cannot be completely removed with the therapeutic thoracentesis,
consideration should be given to inserting a chest tube and instilling the
combination of a fibrinolytic agent (e.g., tissue plasminogen activator, 10 mg) and
deoxyribonuclease (5 mg) or performing a thoracoscopy with the breakdown of
adhesions. Decortication should be considered when these measures are
ineffective.
Effusion Secondary to Malignancy

Malignant pleural effusions secondary to metastatic disease are the
second most common type of exudative pleural effusion. The three tumors that
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cause ~75% of all malignant pleural effusions are lung carcinoma, breast
carcinoma, and lymphoma. Most patients complain of dyspnea, which is frequently
out of proportion to the size of the effusion. The pleural fluid is an exudate, and its
glucose level may be reduced if the tumor burden in the pleural space is high. The
diagnosis usually is made via cytology of the pleural fluid. If the initial cytologic
examination is negative, thoracoscopy is the best next procedure if malignancy is
strongly suspected.
At the time of thoracoscopy, a procedure such as pleural abrasion should

be performed to effect a pleurodesis. An alternative to thoracoscopy is CT- or
ultrasound-guided needle biopsy of pleural thickening or nodules. Patients with a
malignant pleural effusion are treated symptomatically for the most part, since the
presence of the effusion indicates disseminated disease and most malignancies
associated with pleural effusion are not curable with chemotherapy. The only
symptom that can be attributed to the effusion itself is dyspnea. If the patient’s
lifestyle is compromised by dyspnea and if the dyspnea is relieved with a
therapeutic thoracentesis, one of the following procedures should be considered:
1. Insertion of a small indwelling catheter or

2. Tube thoracostomy with the installation of a sclerosing agent such as
doxycycline (500 mg).
Mesothelioma
Malignant mesotheliomas are primary tumors that arise from the
mesothelial cells that line the pleural cavities; most are related to asbestos
exposure. Patients with mesothelioma present with chest pain and shortness of
breath. The chest radiograph reveals a pleural effusion, generalized pleural
thickening, and a shrunken hemithorax. The diagnosis is usually established with
image-guided needle biopsy or thoracoscopy.
Effusion Secondary to Pulmonary Embolization

The diagnosis most commonly overlooked in the differential diagnosis of
a patient with an undiagnosed pleural effusion is pulmonary embolism. Dyspnea is
the most common symptom. The pleural fluid is almost always an exudate. The
diagnosis is established by spiral CT scan or pulmonary arteriography (Chap. 273).
Treatment of a patient with a pleural effusion secondary to pulmonary embolism is
the same as it is for any patient with pulmonary emboli. If the pleural effusion
increases in size after anticoagulation, the patient probably has recurrent emboli
or another complication, such as a hemothorax or a pleural infection.
Tuberculosis Pleuritis
In many parts of the world, the most common cause of an exudative
pleural effusion is tuberculosis (TB), but tuberculous effusions are relatively
uncommon in the United States. Tuberculous pleural effusions usually are
associated with primary TB and are thought to be due primarily to a
hypersensitivity reaction to tuberculous protein in the pleural space. Patients with
tuberculous pleuritis present with fever, weight loss, dyspnea, and/or pleuritic
chest pain.
The pleural fluid is an exudate with predominantly small lymphocytes. The

diagnosis is established by demonstrating high levels of TB markers in the pleural
fluid (adenosine deaminase >40 IU/L or interferon γ >140 pg/mL). Alternatively, the
diagnosis can be established by culture of the pleural fluid, needle biopsy of the
pleura, or thoracoscopy. The recommended treatments of pleural and pulmonary
TB are identical.
Effusion Secondary to Viral Infection
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Viral infections are probably responsible for a sizable percentage of

undiagnosed exudative pleural effusions. In many series, no diagnosis is
established for ~20% of exudative effusions, and these effusions resolve
spontaneously with no long-term residual. The importance of these effusions is
that one should not be too aggressive in trying to establish a diagnosis for the
undiagnosed effusion, particularly if the patient is improving clinically.
Chylothorax
A chylothorax occurs when the thoracic duct is disrupted and chyle
accumulates in the pleural space. The most common cause of chylothorax is
trauma (most frequently thoracic surgery), but it also may result from tumors in the
mediastinum. Patients with chylothorax present with dyspnea, and a large pleural
effusion is present on the chest radiograph. Thoracentesis reveals milky fluid, and
biochemical analysis reveals a triglyceride level that exceeds 1.2 mmol/L (110
mg/dL). Patients with chylothorax and no obvious trauma should have a
lymphangiogram and a mediastinal CT scan to assess the mediastinum for lymph
nodes.
The treatment of choice for most chylothoraxes is insertion of a chest tube

plus the administration of octreotide. If these modalities fail, percutaneous
transabdominal thoracic duct blockage effectively controls most chylothoraces. An
alternative treatment is ligation of the thoracic duct. Patients with chylothoraxes
should not undergo prolonged tube thoracostomy with chest tube drainage
because this will lead to malnutrition and immunologic incompetence.
Hemothorax
When a diagnostic thoracentesis reveals bloody pleural fluid, a hematocrit
should be obtained on the pleural fluid. If the hematocrit is more than one-half of
that in the peripheral blood, the patient is considered to have a hemothorax. Most
hemothoraxes are the result of trauma; other causes include rupture of a blood
vessel or tumor. Most patients with hemothorax should be treated with tube
thoracostomy, which allows continuous quantification of bleeding. If the bleeding
emanates from a laceration of the pleura, apposition of the two pleural surfaces is
likely to stop the bleeding. If the pleural hemorrhage exceeds 200 mL/h,
consideration should be given to angiographic coil embolization, thoracoscopy or
thoracotomy.
Miscellaneous Causes of Pleural Effusion

There are many other causes of pleural effusion (Table 294-1). Key
features of some of these conditions are as follows: If the pleural fluid amylase
level is elevated, the diagnosis of esophageal rupture or pancreatic disease is
likely. If the patient is febrile, has predominantly polymorphonuclear cells in the
pleural fluid, and has no pulmonary parenchymal abnormalities, an intraabdominal
abscess should be considered. The diagnosis of an asbestos pleural effusion is
one of exclusions. Benign ovarian tumors can produce ascites and a pleural
effusion (Meigs’ syndrome), as can the ovarian hyperstimulation syndrome.
Several drugs can cause pleural effusion; the associated fluid is usually
eosinophilic. Pleural effusions commonly occur after coronary artery bypass
surgery.
Effusions occurring within the first weeks are typically left-sided and
bloody, with large numbers of eosinophils, and respond to one or two therapeutic
thoracenteses. Effusions occurring after the first few weeks are typically left-sided
and clear yellow, with predominantly small lymphocytes, and tend to recur. Other
medical manipulations that induce pleural effusions include abdominal surgery;
radiation therapy; liver, lung, or heart transplantation; and the intravascular
insertion of central lines.
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DIFFERENTIAL DIAGNOSIS 2: LUNG ABSCESS

Source: Harrison’s Principles of Internal Medicine 21st edition, Chapter 127 Lung Abscess
Lung abscess represents necrosis and cavitation of the lung following

microbial infection. Lung abscesses can be single or multiple but usually are
marked by a single dominant cavity >2 cm in diameter.
Source: Robbins and Cotran Pathologic Basis of Disease, 10th edition, Chapter 13 Lung
The term pulmonary abscess describes a local suppurative process that

produces necrosis of lung tissue. Oropharyngeal surgical or dental procedures,
sinobronchial infections, and bronchiectasis play important roles in their
development
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ETIOLOGY
The low prevalence of lung abscesses makes them difficult to study in

randomized controlled trials. Although the incidence of lung abscesses has
decreased in the antibiotic era, they are still a source of significant morbidity and
mortality.
Lung abscesses are usually characterized as either primary (~80% of

cases) or secondary. Primary lung abscesses usually arise from aspiration, are
often caused principally by anaerobic bacteria, and occur in the absence of an
underlying pulmonary or systemic condition. Secondary lung abscesses arise in
the setting of an underlying condition, such as a post obstructive process (e.g., a
bronchial foreign body or tumor) or a systemic process (e.g., HIV infection or
another immunocompromising condition). Lung abscesses can also be
characterized as acute (<4–6 weeks in duration) or chronic (~40% of cases).
EPIDEMIOLOGY
The majority of the existing epidemiologic information involves primary

lung abscesses. In general, middle-aged men are more commonly affected than
middle-aged women. The major risk factor for primary lung abscesses is
aspiration. Patients at particular risk for aspiration, such as those with altered
mental status, alcoholism, drug overdose, seizures, bulbar dysfunction, prior
cerebrovascular or cardiovascular events, or neuromuscular disease, are most
commonly affected. In addition, patients with esophageal dysmotility or
esophageal lesions (strictures or tumors) and those with gastric distention and/or
gastroesophageal reflux, especially those who spend substantial time in the
recumbent position, are at risk for aspiration.
It is widely thought that colonization of the gingival crevices by anaerobic

bacteria or microaerophilic streptococci (especially in patients with gingivitis and
periodontal disease), combined with a risk of aspiration, is important in the
development of lung abscesses. In fact, many physicians consider it extremely
rare for lung abscesses to develop in the absence of teeth as a nidus for bacterial
colonization.
The importance of these risk factors in the development of lung

abscesses is highlighted by a significant reduction in abscess incidence in the late
1940s that coincided with a change in oral surgical technique: beginning at that
time, these operations were no longer performed with the patient in the seated
position without a cuffed endotracheal tube, and the frequency of perioperative
aspiration events was thus decreased. In addition, the introduction of penicillin
around the same time significantly reduced the incidence of and mortality rate
from lung abscess.
PATHOGENESIS
PRIMARY LUNG ABSCESS

The development of primary lung abscesses is thought to originate when
chiefly anaerobic bacteria (as well as microaerophilic streptococci) in the gingival
crevices are aspirated into the lung parenchyma in a susceptible host (Table 127-1).
Patients who develop primary lung abscesses usually carry an overwhelming
burden of aspirated material or are unable to clear the bacterial load. Pneumonitis
develops initially (exacerbated in part by tissue damage caused by gastric acid);
then, over a period of 7–14 days, the anaerobic bacteria produce parenchymal
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necrosis and cavitation whose extent depends on host-pathogen interaction (Fig.

127-1). Anaerobes are thought to produce more extensive tissue necrosis in
polymicrobial infections in which virulence factors of the various bacteria can act
synergistically to cause more significant tissue destruction.
SECONDARY LUNG ABSCESS

The pathogenesis of secondary abscesses depends on the predisposing
factor. For example, in cases of bronchial obstruction from malignancy or a foreign
body, the obstructing lesion prevents clearance of oropharyngeal secretions,
leading to abscess development. With underlying systemic conditions
(e.gimmunosuppression after bone marrow or solid organ transplantation),
impaired host defense mechanisms lead to increased susceptibility to the
development of lung abscesses caused by a broad range of pathogens, including
opportunistic organisms (Table 127-1).
Lung abscesses also arise from septic emboli, either in tricuspid valve
endocarditis (often involving Staphylococcus aureus) or in Lemierre’s syndrome, in
which an infection begins in the pharynx (classically involving Fusobacterium
necrophorum) and then spreads to the neck and the carotid sheath (which
contains the jugular vein) to cause septic thrombophlebitis.
Source: Robbins and Cotran Pathologic Basis of Disease, 10th edition
Although under appropriate circumstances any pathogen can produce an

abscess, the commonly isolated organisms include aerobic and anaerobic
streptococci, S. aureus, and a host of gram-negative organisms. Mixed infections
often occur because of the important causal role played by inhalation of foreign
material. Anaerobic organisms normally found in the oral cavity, including
members of the Bacteroides, Fusobacterium, and Peptococcus species, are the
exclusive isolates in about 60% of cases.
The causative organisms are introduced by the following mechanisms:

● Aspiration of infective material (the most frequent cause). This is
particularly common in acute alcoholism, coma, anesthesia, sinusitis,
gingivodental sepsis, and debilitation in which the cough reflexes are
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depressed. Aspiration first causes pneumonia which progresses to tissue

necrosis and formation of lung abscess.
● Antecedent primary lung infection. Post Pneumonic abscess formations
are usually associated with S. aureus, K. pneumoniae, and type 3
pneumococcus. Posttransplant or otherwise immunosuppressed
individuals are at special risk.
● Septic embolism. Infected emboli from thrombophlebitis in any portion of
the systemic venous circulation or from the vegetations of infective
bacterial endocarditis on the right side of the heart are trapped in the
lung.
● Neoplasia. Secondary infection is particularly common in the
bronchopulmonary segment obstructed by a primary or secondary
malignancy (postobstructive pneumonia).
● Miscellaneous. Direct traumatic penetrations of the lungs; spread of
infections from a neighboring organ, such as suppuration in the
esophagus, spine, subphrenic space, or pleural cavity; and hematogenous
seeding of the lung by pyogenic organisms all may lead to lung abscess
formation.
When all these causes are excluded, there are still cases in which no discernible
basis for the abscess formation can be identified. These are referred to as primary
cryptogenic lung abscesses.
MORPHOLOGY
(Pathology and Microbiology)
Primary Lung Abscesses

The dependent segments (posterior upper lobes and superior lower
lobes) are the most common locations of primary lung abscesses, given the
predisposition of aspirated materials to be deposited in these areas. Generally, the
right lung is affected more commonly than the left because the right mainstem
bronchus is less angulated.
Primary lung abscesses often are polymicrobial, primarily including

anaerobic organisms as well as microaerophilic streptococci (Table 127-1). The
retrieval and culture of anaerobes can be complicated by the contamination of
samples with microbes from the oral cavity, the need for expeditious transport of
the cultures to the laboratory, the need for early plating with special culture
techniques, the prolonged time required for culture growth, and the need for
collection of specimens prior to administration of antibiotics. When attention is
paid to these factors, rates of recovery of specific isolates are reportedly as high
as 78%.
Because it is not clear that knowing the identity of the causative

anaerobic isolate alters the response to treatment of a primary lung abscess,
practice has shifted away from the use of specialized techniques to obtain
material for culture, such as transtracheal aspiration and bronchoalveolar lavage
with protected brush specimens that allow recovery of culture material while
avoiding contamination from the oral cavity. When no pathogen is isolated from a
primary lung abscess (which occurs as often as 40% of the time), the abscess is
termed a nonspecific lung abscess, and the presence of anaerobes is often
presumed. A putrid lung abscess refers to cases with foul-smelling breath, sputum,
or empyema; these manifestations are essentially diagnostic of an anaerobic lung
abscess.
Secondary Lung Abscesses
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The location of secondary abscesses may vary with the underlying cause.
The microbiology of secondary lung abscesses can encompass a broad bacterial
spectrum, with infection by Pseudomonas aeruginosa and other gram-negative
rods the most common. In addition, a broad array of pathogens can be identified
in patients from certain endemic areas and in specific clinical scenarios (e.g., a
significant incidence of fungal infections among immunosuppressed patients
following bone marrow or solid organ transplantation). Because
immunocompromised hosts and patients without the classic presentation of a
primary lung abscess can be infected with a wide array of unusual organisms
(Table 127-1), it is of special importance to obtain culture material in order to target
therapy.
Abscesses vary in diameter from a few millimeters to large cavities of 5 to
6 cm (Fig. 15.36). They may affect any part of the lung and may be single or
multiple. Pulmonary abscesses due to aspiration are more common on the right
(because of the more vertical right main bronchus) and are most often single.
Abscesses that develop in the course of pneumonia or bronchiectasis are usually
multiple, basal, and diffusely scattered. Septic emboli and pyemic abscesses are
multiple and may affect any region of the lungs.
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The cardinal histologic change in all abscesses is suppurative destruction

of the lung parenchyma within the central area of cavitation. The abscess cavity
may be filled with suppurative debris or, if there is communication with an air
passage, may be partially drained to create an air-containing cavity. Superimposed
saprophytic infections are prone to develop within the necrotic debris. Continued
infection leads to large, poorly demarcated, fetid, green-black, multilocular cavities
designated gangrene of the lung. In chronic cases considerable fibroblastic
proliferation produces a fibrous wall.
CLINICAL FINDINGS
Clinical manifestations initially may be similar to those of pneumonia, with

fevers, cough, sputum production, and chest pain; a more chronic and indolent
presentation that includes night sweats, fatigue, and anemia is often observed
with anaerobic lung abscesses. A subset of patients with putrid lung abscesses
may report discolored phlegm and foul-tasting or foul-smelling sputum. Patients
with lung abscesses due to non-anaerobic organisms, such as S. aureus, may
present with a more fulminant course characterized by high fevers and rapid
progression.
Findings on physical examination may include fevers, poor dentition,

and/or gingival disease as well as amphoric and/or cavernous breath sounds on
lung auscultation. Additional findings may include digital clubbing and the
absence of a gag reflex.
The manifestations of pulmonary abscesses are much like those of

bronchiectasis and characteristically include cough, fever, and copious amounts of
foul-smelling purulent or sanguineous sputum. Fever, chest pain, and weight loss
are common. Clubbing of the fingers and toes may appear. The diagnosis can be
only suspected from the clinical findings and must be confirmed radiologically.
Whenever an abscess is discovered in older individuals, it is important to rule out
an underlying carcinoma, which is present in 10% to 15% of cases.
The course of abscesses is variable. With antimicrobial therapy, most

resolve, leaving behind a scar. Complications include extension of the infection
into the pleural cavity, hemorrhage, the development of brain abscesses or
meningitis from septic emboli, and (rarely) secondary amyloidosis (type AA).
DIFFERENTIAL DIAGNOSIS
55 of 59
The differential diagnosis of lung abscesses is broad and includes other

noninfectious processes that result in cavitary lung lesions, including lung
infarction, malignancy, sequestration, cryptogenic organizing pneumonia,
sarcoidosis, vasculitides and autoimmune diseases (e.g., granulomatosis with
polyangiitis), lung cysts or bullae containing fluid, and septic emboli (e.g., from
tricuspid valve endocarditis). Other less common entities can include pulmonary
manifestations of diseases that usually present at locations other than the chest
(e.g., inflammatory bowel disease, pyoderma gangrenosum).
DIAGNOSIS
Lung abscesses are documented by chest imaging. Although a chest

radiograph usually detects a thick- walled cavity with an air-fluid level, CT permits
better definition and may provide earlier evidence of cavitation. CT may also yield
additional information regarding a possible underlying cause of lung abscess,
such as malignancy, and may help distinguish a peripheral lung abscess from a
pleural infection. This distinction has important implications for treatment because
a pleural space infection, such as an empyema, may require urgent drainage.
As described earlier (see “Pathology and Microbiology,” above), more

invasive diagnostics (such as transtracheal aspiration) were traditionally
undertaken for primary lung abscesses, whereas empirical therapy that includes
drugs targeting anaerobic organisms currently is used more often. While sputum
can be collected noninvasively for Gram’s stain and culture, which may yield a
pathogen, the infection is likely to be polymicrobial, and culture results may not
reflect the presence of anaerobic organisms. As stated above, many physicians
consider putrid-smelling sputum to be virtually diagnostic of an anaerobic
infection.
When a secondary lung abscess is present or empirical therapy fails to

elicit a response, sputum and blood cultures are advised in addition to serologic
studies for opportunistic pathogens (e.g., viruses and fungi causing infections in
immunocompromised hosts). Additional diagnostics, such as bronchoscopy with
bronchoalveolar lavage or protected brush specimen collection and CT-guided
percutaneous needle aspiration, can be undertaken. Risks posed by these more
invasive diagnostics include spillage of abscess contents into the other lung (with
bronchoscopy) and pneumothorax and bronchopleural fistula development (with
CT-guided needle aspiration). However, early diagnostics in secondary abscesses,
especially in immunocompromised hosts, are particularly important, because the
patients involved may be especially fragile, at risk for infection with a broad array
of pathogens, and therefore less likely than other patients to respond to empirical
therapy.
TREATMENT/MANAGEMENT
The availability of antibiotics in the 1940s and 1950s established therapy

with this drug class as the primary approach to the treatment of lung abscess.
Previously, surgery had been relied upon much more frequently. For many
decades, penicillin was the antibiotic of choice for primary lung abscesses in light
of its anaerobic coverage; however, because oral anaerobes can produce
β-lactamases, clindamycin has proved superior to penicillin in clinical trials. For
primary lung abscesses, the recommended regimens are (1) clindamycin (600 mg
IV three times daily; then, with the disappearance of fever and clinical
improvement, 300 mg PO four times daily) or (2) an IV-administered 921
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β-lactam/β-lactamase combination, followed—once the patient’s condition is

stable—by orally administered amoxicillin- clavulanate. This therapy should be
continued until imaging demonstrates that the lung abscess has cleared or
regressed to a small scar. Treatment duration may range from 3–4 weeks to as
long as 14 weeks. One small study suggested that moxifloxacin (400 mg/d PO) is
as effective and well tolerated as ampicillin-sulbactam. Notably, metronidazole is
not effective as a single agent: it covers anaerobic organisms but not the
microaerophilic streptococci that are often components of the mixed flora of
primary lung abscesses.
In secondary lung abscesses, antibiotic coverage should be directed at

the identified pathogen, and a prolonged course (until resolution of the abscess is
documented) is often required. Treatment regimens and courses vary widely,
depending on the immune state of the host and the identified pathogen. Other
interventions may be necessary as well, such as relief of an obstructing lesion or
treatment directed at the underlying condition predisposing the patient to lung
abscess. Similarly, if the condition of patients with presumed primary lung abscess
fails to improve, additional studies to rule out an underlying predisposing cause
for a secondary lung abscess are indicated.
Although it can take as long as 7 days for patients receiving appropriate

therapy to defervesce, as many as 10–20% of patients may not respond at all, with
continued fevers and progression of the abscess cavity on imaging. An abscess
>6–8 cm in diameter is less likely to respond to antibiotic therapy without
additional interventions. Options for patients who do not respond to antibiotics
and whose additional diagnostic studies fail to identify an additional pathogen that
can be treated include surgical resection and percutaneous drainage of the
abscess, especially when the patient is a poor surgical candidate. Timing of
surgical intervention can be challenging; the goal is to balance the
morbidity/mortality risk of a procedure with the need for definitively clearing the
abscess in the setting of persistent infection that is not responsive to nonsurgical
approaches. Possible complications of percutaneous drainage include bacterial
contamination of the pleural space as well as pneumothorax and hemothorax.
COMPLICATIONS
Larger cavity size on presentation may correlate with the development of

persistent cystic changes (pneumatoceles) or bronchiectasis. Additional possible
complications include recurrence of abscesses despite appropriate therapy,
extension to the pleural space with development of empyema, life-threatening
hemoptysis, and massive aspiration of lung abscess contents.
PROGNOSIS AND PREVENTION

Reported mortality rates for primary abscesses have been as low as 2%,
while rates for secondary abscesses are generally higher—as high as 75% in some
case series. Other poor prognostic factors include an age of >60, the presence of
aerobic bacteria, sepsis at presentation, symptom duration of >8 weeks, and
abscess size of >6 cm. Mitigation of underlying risk factors may be the best
approach to prevention of lung abscesses, with attention directed toward airway
protection, oral hygiene, and minimized sedation with elevation of the head of the
bed for patients at risk for aspiration. Prophylaxis against certain pathogens in
at-risk patients (e.g., recipients of bone marrow or solid organ transplants or
patients whose immune systems are significantly compromised by HIV infection)
may be undertaken.
57 of 59
APPROACH TO THE PATIENT

For patients with a lung abscess and a low likelihood of malignancy (e.g.,
smokers <45 years old) and with risk factors for aspiration, it is reasonable to
administer empirical treatment and then to pursue further evaluation if therapy
does not elicit a response. However, some clinicians may opt for up-front cultures,
even in primary lung abscesses. In patients with risk factors for malignancy or
other underlying conditions (especially immunocompromised hosts) or with an
atypical presentation, earlier diagnostics should be considered, such as
bronchoscopy with biopsy or CT-guided needle aspiration. Bronchoscopy should
be performed early in patients whose history, symptoms, or imaging findings are
consistent with possible bronchial obstruction. In patients from areas endemic for
tuberculosis or patients with other risk factors for tuberculosis (e.g., underlying HIV
infection), induced sputum samples should be examined early in the workup to
rule out this disease.
CASE RESOLUTION
Nico was admitted as a case of Community Acquired Pneumonia with

para-pneumonic effusion, right. Though COVID cases have dropped significantly
in the city, he was still considered as COVID suspect.
The NPS for SARSCOV2 RTPCR however turned out negative. CBC and
Chest XR obtained on admission show:
CBC:
● WBC of 20,000
● Hgb of 13g/dL
● Hct of 39%
● Platelet of 360,000/uL
● Neutrophils of 80%
● Lymphocytes of 18%.
CXR result: Right lower lobe consolidation with parapneumonic effusion
● Sonographic studies of the chest reveal free flowing fluid on the right
with an estimated volume of about 500cc.
● Diagnostic thoracentesis confirmed presence of parapneumonic
effusion. Blood culture and sputum culture did not yield any growth
after 5 days of incubation.
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● Nico received treatment for moderate risk pneumonia (Ceftriaxone IV

and Azithromycin PO).
● Gradual improvement of his condition led to eventual discontinuation
of the IV medication and shift to oral form. He was discharged and
improved on the 7th hospital day; his IV medication was shifted to oral
and continued at home.
● On follow up 2 weeks later, his repeat X-ray showed clearing of
infiltrates and resolution of pleural effusion on the right. His attending
physician referred Nico to a dentist to improve his dentition and to a
smoking and alcohol cessation clinic to address his alcoholism and
chronic cigarette smoking issues.
GRID
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Module 4.

1. Harrison’s Principles of Internal Medicine, 21st ed, Chapter 126

PHYSICAL EXAMINATION OF THE CHEST AND LUNGS

Examination of the Posterior Chest

rib cage as it expands and contracts. This movement is

The technique of percussion can be practiced on any surface. As you

changes in the percussion note due to your technique rather than

Now, estimate the extent of diaphragmatic excursion by determining the

the chest wall? Are breath sounds diminished, or are there

Breath Sounds (Lung Sounds). Learn to identify breath sounds by their

Examination of the Anterior Chest

Percuss for liver dullness and gastric tympany.

DIFFERENTIATE RALES FROM OTHER ADVENTITIOUS SOUNDS

TRANSMITTED VOICE SOUNDS.

DIFFERENTIATE THE CAUSES OF DECREASED BREATH SOUNDS

CAUSES OF CHEST PAIN RELATED TO RESPIRATORY DISORDERS

PROBLEM PROCESS LOCATION QUALITY SEVERITY

Tracheobronchitis Inflammation of Upper sternal or Burning Mild-to-moderate

Pleural pain Inflammation of Chest wall Sharp, knifelike Often severe

Table 8-8: Physical Findings in Selected Chest Disorders

Pneumonia is an infection of the pulmonary parenchyma. Despite

Pneumonia caused by macroaspiration of oropharyngeal or gastric

Pneumonia is the result of the proliferation of microbial pathogens at the

Recent use of culture-independent techniques of microbial identification

The constitution of the lung microbiota is determined by three factors:

A possible model for pneumonia is as follows. An inflammatory event

Classic pneumonia evolves through a series of stages. The initial stage is

Source: Robbins and Cotran Pathologic Basis of Disease, 10th edition

Pulmonary antimicrobial defense mechanisms are described in Chapter 8.

Defects in innate immunity (including neutrophil and complement defects) and

Defects in innate immunity (including neutrophil and complement defects) and

Pneumonia is classified based on the etiologic agent or, if no pathogen can be

PRIMARY DIAGNOSIS: COMMUNITY- ACQUIRED PNEUMONIA

The list of potential

Although most CAP cases are caused by relatively few pathogens, an

With the increasing use of

Atypical organisms cannot be cultured on standard media or seen on

Earlier literature suggested that aspiration pneumonia was caused

S. aureus pneumonia is known to complicate influenza virus infection. However,

Community-Acquired Bacterial Pneumonias

Community-acquired acute pneumonia refers to lung infection in

Often, a bacterial infection follows an upper respiratory tract viral

H. influenzae pneumonia, which may follow a viral respiratory infection, is

meningitis in children up to 5 years of age. H. influenzae also causes an acute,

MORPHOLOGY (Bacterial pneumonia)

Bacterial pneumonia has two patterns of anatomic distribution: lobular

These anatomic categorizations may be difficult to apply in individual

In lobar pneumonia, four stages of the inflammatory response have

In lobar pneumonia, four stages of the inflammatory response have

Complications of pneumonia include:

Community-Acquired Viral Pneumonia

The viral genome is composed of eight single-stranded RNAs, each

Control of the infection relies on several host mechanisms. The presence

response is eventually augmented by development of antibody responses to the

MORPHOLOGY (Viral Pneumonia)

(Robbins & Cotran, 10e)

All viral infections produce similar morphologic changes. Upper

suppurative secondary bacterial infection. Virus-induced tonsillitis causing

In viral laryngotracheobronchitis and bronchiolitis there is vocal cord

Lung involvement may be quite patchy or may involve whole lobes