Reviews

Ageing and infection

Gaëtan Gavazzi and Karl-Heinz Krause

Average life expectancy throughout developed countries

has rapidly increased during the latter half of the 20th
century and geriatric infectious diseases have become an
increasingly important issue. Infections in the elderly are not
only more frequent and more severe, but they also have
distinct features with respect to clinical presentation,
laboratory results, microbial epidemiology, treatment, and
infection control. Reasons for increased susceptibility
include epidemiological elements, immunosenescence, and
malnutrition, as well as a large number of age-associated
physiological and anatomical alterations. Moreover, ageing
may be the cause of infection but infection can also be the
cause of ageing. Mechanisms may include enhanced
inflammation, pathogen-dependent tissue destruction, or
accelerated cellular ageing through increased turnover. In
most instances, treatment of infection leads to a
satisfactory outcome in the elderly. However, in palliative
care situations and in patients with terminal dementia, the
decision whether or not to treat an infectious disease is
becoming a difficult ethical issue.

Lancet Infect Dis 2002; 2: 659–66

Figure 1. Sir William Osler, 1849–1919. Pneumonia, friend or foe of the old?
See Reflection & Reaction page 655
In the 3rd edition of his textbook, Principles and Practice of Medicine,4
Osler raised the possibility that pneumonia might be the old man’s friend.
Over the past century, human life expectancy has increased However, infections do not always lead to a benign end of life and, in 1919,
dramatically in developed countries. In Switzerland in 1900, Osler himself died after protracted pneumonia.
the percentages of the old (65–79 years) and very old (>80
years) were 2% and less than 0·5%, respectively. These Particularities of infections in the elderly
figures are now 11·4% and 4%, and estimates suggest that Prevalence of infections in the elderly
they will rise to 15% and 9% by 2060 (http://www.statistik. Certain infections are more prevalent in the elderly than in
admin.ch/stat_ch/ber01/eufr01.htm). Providing care for this younger adults. This increased prevalence ranges from three-
ageing population presents a major challenge for 21st fold for community-acquired pneumonia to 20-fold for
century medicine. By comparison with the younger urinary-tract infection.5–11 The most commonly encountered
population, many diseases in the elderly are more frequent infections are due to pyogenic bacteria, in particular urinary-
and more severe. This is certainly true for infectious diseases, tract infection, pneumonia, diverticulitis, endocarditis,
which are common in the elderly and associated with poor bacteraemia, and skin and soft tissue infection (especially
outcome.1 Pneumonia, influenza, and complications of diabetic foot infection).1 The frequency of nosocomial
bacteraemia are among the ten major causes of death in the bacterial infections is strongly increased with age, not simply
elderly.1 Thus, analysis of the specificities of infection in the because of an increased hospitalisation rate, but because of an
elderly is an important issue in modern medicine that increased risk of infection per day of hospitalisation.12 This is
should be jointly addressed by geriatricians and infectious also true for infections that occur in elderly patients
disease specialists.2,3 institutionalised in nursing home settings.13 Due to the
In this article we address four aspects of the association frequent use of prosthetic devices in the elderly population,
between ageing and infection. First, we provide an overview of foreign body infection is also, and will continue to be, an
epidemiological, clinical, and therapeutic particularities of increasingly common problem in geriatric medicine.14
infections in the elderly. Second, we discuss the causes Meningitis is rare in the very old and pneumococcal
underlying the changed pattern of infection in the elderly
GG and K-HK are both at the Department of Geriatrics, Geneva
from macroscopic anatomical changes to immunosenescence. University Hospitals, Geneva, Switzerland.
Third, we analyse the extent to which infections may
Correspondence: Professor Karl-Heinz Krause, Biology of Ageing
contribute to the ageing process and, finally, we discuss the Laboratory, 2 Chemin du Petit Bel-Air, 1225 Geneva, Switzerland.
ethical aspects of treatment or non-treatment of infection in Tel +41 22 3055451; fax +41 22 3055455;
the very old and in the dying (figure 1). email Karl-Heinz.Krause@medecine.unige.ch

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 Review Ageing and infection

meningitis is the most common cause. The risk of listeria with non-infectious diseases,28,30 which makes infectious
meningitis, although a rare disease, is increased in the elderly,5 disease more difficult to identify.
while meniningococcal and Haemophilus influenza meningitis Fever of unknown origin (FUO) is an important topic for
is virtually non-existent.5 the infectious diseases specialist. FUO is not especially
Of clinical importance, but infrequent, are several other frequent in the geriatric setting, but it has its specificities. A
bacterial infections, especially tuberculosis, which indicates cause of FUO is almost invariably found in the elderly (95% of
the decrease in immune function,15 and pneumonia due to cases) compared with only about two-thirds of the cases in
Legionella pneumoniae and Chlamydia pneumoniae (while younger adults.31 The distribution of the major causes of FUO
mycoplasma infection is virtually non-existent in the very in the elderly is as follows: infections (especially tuberculosis)
old).7,8,16 Viral infections are rare by comparison with the about 30%, inflammatory multisystem diseases (especially
younger population, with the notable exception of influenza, temporal arteritis) about 30%, and neoplasms about 20%.29,31
herpes zoster reactivation (shingles),17,18 and viral Thus, FUO in the elderly warrants careful investigation and
gastroenteritis.13 has a high diagnostic yield.

Microbiology of infection in the elderly Biological analysis

The type of microorganism encountered during a specific type As seen with younger patients, the triad of leucocytosis,
of infection is different in the elderly.1,8,9,19 The changes in neutrophilia, and left shift strongly suggests bacterial infection
microbiology may be related to age itself and/or to co- if present, although these indicators lack sensitivity.32,33
morbidities.1,8,9,11,19,20 Importantly, there is not only a switch in Procalcitonin, a relatively specific marker of severe sepsis has
the types of microorganisms encountered during infection, not yet been assessed in the elderly population.34 Serum C-
but, generally, there is a greater diversity of pathogens in the reactive protein (CRP) is a sensitive marker of infection, but
elderly compared with younger adults.1,8,9,11,19 In the elderly, the unfortunately lacks specificity,35,36 particularly in the elderly
type of pathogen likely to cause disease also depends on the population.37,38 However, given the absence of a reliable febrile
setting of acquisition of infection—eg, in the community, in a response, CRP measurements are extremely useful in the
long-term care setting, or in an acute-care hospital.1,8,9,13,20 geriatric setting: a normal CRP concentration allows exclusion
Published data concerning the microbial epidemiology of of a severe bacterial infection with a high probability; and a
specific infections as well as the antibiotic sensitivities are rapid increase in CRP is highly suggestive of bacterial
useful;1,8,9,21 however, local data should be obtained for best infection. Nevertheless, further studies and improved
patient management.1,8,9,21 biological markers for the diagnosis of infections in the elderly
Apart from the altered epidemiology of microorganisms, are needed.
there are also practical difficulties in achieving
microbiological diagnosis. In many instances it is very difficult Diagnostic procedures
or even impossible to obtain high quality specimens for A given diagnostic procedure may not have the same yield in
microbiological diagnosis2,22 for reasons that include patient the elderly. A good example for this is transthoracic
collaboration, incontinence, increased difficulty of procedure echocardiography. Its sensitivity is 75% in the younger adult,
because of anatomical alterations—eg, lumbar puncture—or but drops to 45% in the elderly due to interference from
the potentially increased risk of invasive procedures. In our echogenic calcifications.39 Only by doing additional
experience, bronchoscopy is well tolerated and should be transoesophageal echocardiography may one reach a good
considered in therapy-resistant pneumonia, or in pneumonia diagnostic sensitivity (90%) in the elderly.39 Unfortunately, for
with atypical presentation.23,24 Clearly, empirical antimicrobial many other diagnostic procedures such analysis has not yet
therapy has to be initiated very often, either because of been done and more studies addressing this question are
delayed diagnosis or the impossibility of the diagnostic absolutely necessary.
procedure. Therapy should be based on a competent clinical
diagnosis and, preferably, a good knowledge of the local Treatment of infection in the elderly
microbial epidemiology. Pharmokinetics
From a pharmacological point of view, a range of age-related
Clinical presentation of infections in the elderly modifications in drug metabolism have been shown, but few
The clinical presentation of common infectious diseases in seem to change the efficacy of the treatment.40 Renal failure is
very old patients differs markedly from presentation in a very common modification in elderly patients and leads to
younger patients.25–28 Instead of a typical constellation of an increased risk of adverse effects and drug interaction rather
several symptoms as seen in the younger adult, infections in than to lowered treatment efficiency.1,40
the elderly tend to have fewer symptoms. Fever is clearly one
of the cardinal signs of infection in the younger adult, but is Mode of administration
absent or blunted in 20–30% of well-documented severe Intravenous treatments pose many problems in the geriatric
infections in the elderly.29 The most common signs of setting. Problems of finding veins suited for intravenous lines
infection in the elderly are very non-specific manifestations are notorious and catheter infections are frequent. Most
such as falls, delirium, anorexia, or generalised weakness.25–28 It importantly, however, intravenous lines are poorly tolerated
should be noted, however, that exactly the same clinical and often forcibly removed by patients with delirium and/or
presentations are also commonly seen in a geriatric context dementia (which may be present in up to 50% of the patient

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 Ageing and infection
Review

Table 1. Frequently observed antibiotic side-effects in the

geriatric setting
Drug or drug class Adverse drug reaction Commentary
␤ lactamines Anaphylaxis40,54 Cross-reactions (penicillin
and cephalosporin) are
more frequent
Imipenem Seizure55 Impact of impaired renal
function
Cefepime Encephalopathy56 Impact of impaired renal
function
Carboxypenicillin Cardiac insufficiency40 Elderly patients with
congestive heart failure
because of high sodium
load
Thrimethoprim Bone marrow Impact of impaired renal
suppression40,54 function
Sulfamethoxazole Dyscrasia48 Drug interaction
(warfarine)
Figure 2. Chest radiograph: community-acquired pneumonia of the lingula Aminosides/ Nephrotoxicity, Impact of drug interaction
in an 89-year-old woman without significant comorbidities. Pneumonia is a vancomycin ototoxicity40,54 and impaired renal
leading cause of morbidity and mortality in the elderly even without function
comorbidities.8
Rifampicin/ Hepatitis57 Drug interaction
population who have been admitted to a general geriatric isoniazide
hospital).41,42 Intramuscular or subcutaneous application of Quinolone Seizure, tendinitis, Contradictory data about
antibiotics may be a solution in some selected cases and for delirium, sleep the prevalence, CNS side
disorders58 effects more common in
some antibiotics; however, in most cases oral treatment can be the elderly
the best solution (either immediately or after a short period of
Macrolides Gastrointestinal More frequent in the
intravenous treatment). Absorption of oral antibiotics in the intolerance58 elderly
very old patient is remarkably efficient and there are no
pharmacokinetic reasons that argue against this type of prosthesis: older adults rarely support the two-stage exchange
treatment.40 Compliance, however, remains a challenge.43 In arthroplasty, which is optimum in younger adults, and the
view of the very frequent polypharmacy in the elderly, assessment of novel treatment approaches is crucial.59 This
compliance may drop to 50% for oral therapy.44 In the idea is not only true for surgical interventions, but might also
hospital and long-term care settings, this problem can be become more important with respect to choice of antibiotics.
easily overcome by directly observed therapy (DOT). DOT
may also be used in the home treatment of certain patients.45 Outcome of infections
Most common infections have a poorer outcome in the
Adverse effects elderly than in the young adult,1 although this does not
Adverse drug reactions are more frequent and more severe in necessarily mean that antimicrobial therapy is less efficient in
the elderly population40,46,47 with antibiotics being an the elderly population. Several factors probably contribute to
important cause.48 Unfortunately, very few elderly patients are these higher morbidity and mortality rates: (1) late diagnosis
enrolled in clinical trials and few clinical trials are designed and initiation of therapy because of decreased symptoms and
specifically for this population. Thus, few prospective data are atypical presentation;60–62 (2) less aggressive diagnostis and
available and it is still unclear whether age itself is a risk factor treatment in the context of terminal disease or dementia; (3)
or whether confounding factors such as polypharmacy and increased frequency of comorbidities; and (4) poor tolerance
comorbidities have an important role.40,46,47 Antibiotics of intravenous treatments. Indeed, based on multivariate
commonly cause gastrointestinal side-effects including nausea analysis, several studies suggest that comorbidities, and
and antibiotic-associated diarrhoea.48,49 The latter is more functional and nutritional status, rather than age by itself, are
frequently noted in the geriatric context50 with an incidence relevant risk factors for failure of antibiotic treatment.11,20,63,64
ranging between 2% and 25%51 depending on the antibiotic
used. Importantly, most adverse reactions of antibiotics are Infection control and vaccination
increased in the presence of renal failure or because of drug In view of the high number of vulnerable patients needing a
interaction.40,52,53 Table 1 shows the more frequently reported high level of care, the risk of nosocomial transmission of
side-effects compared with a younger population. infection in geriatric hospitals and in long-term care settings is
particularly high.22,65 These infections, particularly pneumonia,
Different treatment strategies urinary-tract infections, and soft tissue infections are
In many cases, different treatment strategies for a given type of associated with a high rate of morbidity and mortality.1,13,22,66,67
infection are possible. And certain optimum treatment Thus, infection control plays a relevant part in the geriatric
strategies in the younger adult may not be suited for the setting. In many institutions infection control is not managed
elderly. One example in this context is the infected hip by the clinical infectious-disease specialist, but rather by a

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 Review Ageing and infection

40 Table 2. Changes in the immune system associated with

35·4 ageing32,75
35
Elements of Modifications
30 Women the immune system
Men Innate immunity
25
Percentage

Granulocytes (PMN) Normal neutrophilia during acute infection;

20 possibly some decrease in phagocytosis and killing
20
16 Monocytes/ Possibly some alterations in the secretion of
15 macrophages/ cytokines
cytokines
10 Natural killer cells Some decrease in function and in responses to
5 5·7
cytokines stimulation (but compensated by numeric
5
1 0·1 increase)
0·1
0 Specific immunity
18–45 45–64 >65 >65 T lymphocytes Involution of thymus, impaired T cell proliferation,
Community Institution decreased Th1 response, increased Th2 response
Figure 3. Cumulative data of prevalence of symptomless bacteriuria B lymphocytes Decreased generation of specific antibodies
according to age and, for patients >64 years old, according to lifestyle (primary and secondary response), increased
(community or institution).98 generation of autoantibodies

specialised infection-control team. However, interventions in to cells of innate immunity (granulocytes, and
the geriatric setting require specific knowledge and insight. monocytes/macrophages; natural killer cells might even be
Infection-control measures have to be adapted to the type of slightly increased in the elderly) as well as for cells of
institution (hospital, unskilled setting, nursing home, long- adaptative immunity (B lymphocytes and T lymphocytes).
term care), patient population, and the work-load of the However, there seem to be functional alterations in at least in
health-care workers.13,22 For example, isolation, the classic some of these cells. Table 2 summarises the reported effects of
infection-control measure, is a major cause of delirium in the ageing on individual elements of the immune system.
hospitalised elderly68 and can also lead to a rapid loss of At present, few data are available concerning the
residual competence in demented patients.41 Similarly, when correlation of the above mentioned elements of
giving practical recommendations, infection-control experts immunosenescence with a clinically detectable increased risk
have to take into account the gross work overload for nurses of infection in the elderly. Based on available results, two quite
in many geriatric institutions.13,22 different scenarios can be envisaged.
Primary prevention is also based on vaccination. The First, immunosenescence is the composite effect of a
elderly should receive an annual influenza vaccination.8,69 gradual decline of virtually every part of the host defence
Pneumococcal vaccine should be given once before the age of system. This would imply a multitude of mechanisms leading
70, and a second time 10 years later.70,71 However, especially in to immunosenescence and the involvement of many different
the sick and institutionalised elderly, vaccinations are less cells from the immune system. Thus, immunosenescence
effective.69 Thus, additional preventive measures are needed; would be a logical consequence of the “damage theory of
as an example, influenza vaccination of health-care workers ageing”.32,75
has been shown to efficiently save lives of hospitalised elderly Second, immunosenescence is a decline in a limited
people.72 number of specific elements of the host defence system. This
scenario would suggest that there are one, or a few,
Increased sensitivity to infection identifiable mechanisms that account significantly for the
Immunosenescence development of immunosenescence. It has been postulated
The term immunosenescence usually refers to the notion that that telomere shortening in rapidly dividing cells of the
there is an age-related dysfunction of the immune system immune system is a key mechanism of immunosenescence
which leads to enhanced risk of infection. The number of and telomerase-based therapies have been proposed.77
studies in this area is large and, unfortunately, the results are The difference between the two mechanisms is crucial.
often contradictory. However, there is no doubt that a The latter is certainly the more exciting since it implies that
decreased immune function in the elderly does exist. Two targeted therapies could be developed and infection rates in
examples, both with respect to antibody production and to T the elderly could be ultimately diminished. By contrast, if the
cell proliferative responses, are reactivation of tuberculosis in former were true, the likelihood of developing specific
the elderly population15 and the decreased effectiveness of therapies would be very low.
influenza vaccination in the elderly.73,74
In this section we will give a very brief overview of Malnutrition
mechanisms involved in immunosenescence. Details and Malnutrition seems to be a—if not the—major cause of
more extensive information on the subject are published decreased immune function worldwide.78 Whereas in the
elsewhere.32,75,76 There seems to be at least one consensus in the developing world this affects primarily children, in
field of immunosenescence: that there is no decrease in the industrialised nation, the problem is essentially geriatric.
number of immune cells with ageing. This is true with respect Indeed, 10–25% of community-dwelling elderly present

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 Ageing and infection
Review

closure during swallowing. A high

acidity in the stomach protects not
only the small bowel from pathogens,
but also decreases the risk of lung
colonisation through reflux. Here we
discuss the age-related decline of non-
immune host defence mechanisms for
selected organ systems.

Lung
Pneumonia is one of the most frequent
infections in the elderly with a higher
morbidity and mortality rate compared
Figure 4. Chronic atrophic gastritis (A) with metaplasia (B) in an 87-year-old woman. The prevalence with the younger population (figure 2).
of Helicobacter pylori is 40–70% in the elderly population and in one-third is associated with
100
Apart from a decrease in immune
chronic atrophic gastritis. This leads to a decrease in gastric acidity and then to increased
101

infectious burden in the stomach.

function, the following mechanisms
are likely to contribute to the
nutritional deficits, and this figure may be as high as 50% for pneumonia risk of the elderly: blunting of protective reflexes
elderly patients who are admitted for hospitalisation.79–82 in the airway, seen most obviously after stroke, but also a part
Malnutrition in the elderly may be represented as a global of normal ageing;94 decrease in mucociliary clearance;95 loss of
calorific deficiency, protein deficiency, and/or micronutrient local immunity (decreased T cell subsets and
(vitamins and trace minerals) deficiency. For more details see immunoglobulin in respiratory secretions;96 and loss of acid
specialised reviews.83–86 Not only is malnutrition a major risk production by the stomach.94
factor for infection, but because of an increase in metabolic
demand and its duration, infection is also an important cause Urinary tract
of malnutrition.83,87,88 This factor is especially relevant in a Urinary tract infections (UTI) are the most common
geriatric context where patients generally do not have infections in the elderly population. Urine is usually sterile in
nutritional reserve. Such a two-way association between younger adults but, with ageing, a substantial proportion of
nutrition and infection creates a vicious circle whereby the elderly have a so-called “symptomless bacteriuria”.
malnutrition is the cause of infection and infection leads to Depending on the setting (community, long-term care), the
further malnutrition, which in turn enhances the probability prevalence is between 15–30% in men and 25–50% in
of a more severe course of infection or the acquisition of women (figure 3).67,76 This age-dependent increase in
additional infectious events.82,83,89 symptomless bacteruria is paralleled by an increase in
Decreased immune function as a cause of malnutrition symptomatic UTI. Factors contributing to this bacterial
should not be confused with immunosenescence. First, it is a colonisation and infection of the urinary tract of the elderly
different event that is not age-related. Second, and most include mechanical changes (reduction in bladder capacity,
importantly, as opposed to immunosenescence, malnutrition uninhibited contractions, decreased urinary flow rate, and
is a potentially treatable cause of immune dysfunction. post-void residual urine), urothelial change (enhanced
Clinical recognition of malnutrition in the elderly cannot be bacterial adherence), prostatic hypertrophy in men,67,76 and
simply assessed by raw body weight. By contrast, a mini- hormonal changes (lack of oestrogen in postmenopausal
nutritional assessment associated with biological markers women).97 Attempts to prevent progression from
(serum albumin) and a lean body mass (quickly and symptomless bacteriuria towards symptomatic UTI have
inexpensively determined by bioelectric impedance) is very been disappointing and, accordingly, symptomless
useful.90–92 Once detected, malnutrition, especially in the bacteriuria in the elderly should not be treated, even if
context of infection, should be rapidly treated, possibly with accompanied by leucocyturia.9,67
the help of a nutritional expert team.93
Gastrointestinal tract
Anatomic and physiological modifications Gastroenteritis and colitis are also more frequent in the
predisposing to infections elderly. Age-dependent factors contributing to this increased
Although generally efficient defences against infection are risk of bacterial gastrointestinal infection include decreased
associated with the immune system, many other elements gastric acidity (gastric atrophy, proton pump inhibitors,
have an important role. Epithelia from skin, bladder, the surgery), decreased intestinal motility, modifications of
bronchial, and the digestive system form a physical barrier resident intestinal flora and intestinal mucus,76,99 as well as
and thereby play a key part in preventing bacteria from increased use of antibiotics in this population. Figure 4
invading the human body.76 Efficient removal of bacteria illustrates one of the above-mentioned modifications
from quasi-sterile body compartments is crucial for associated with age and chronic infection. Antibiotics and
prevention of infection—eg, mucociliary clearance, rapid proton pump inhibitors are potentially avoidable risk factors
urine flow. Valve-like mechanisms participate in the for bacterial gastrointestinal infections in the elderly and their
exclusion of bacteria from these compartments—eg, larynx prescription should therefore be limited to the absolute

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 Review Ageing and infection

Search strategy and selection criteria disease: macrophages in the vascular wall phagocytose
Data for this review were identified by a Medline search of damaged LDL cholesterol and thereby initiate an
articles published in English or French since 1981 in the field of inflammatory cascade. If inflammation has a key role in
geriatric and infectious diseases. Inclusion in the reference list atherosclerosis, chronic infection might influence the disease.
depended on relevant original approaches for each major Moreover, several chronic infections have been
section of the review, particularities of infection in the elderly, epidemiologically associated with an increased risk for
mechanisms of susceptibility to infection, infection as cause of atherosclerosis, such as Chlamydia pneumoniae, Helicobacter
ageing, and ethical aspects. The two main search terms used pylori, cytomegalovirus, herpes simplex virus (HSV), and
were “elderly population” and “infection”; a subset of criteria
chronic periodontitis.106–108 Most studies have reported an at
was cross-used with these and included “epidemiology”,
“microbiology”, “immunosenescence”, “malnutrition”, “nosoco-
least two-fold increase in individuals at risk for
mial”, “long-term care”, “vaccination”, “infection control”, atherosclerosis with cytomegalovirus, C pneumoniae, or
“illness presentation”, “outcome”, “adverse drug reaction”, chronic periodontitis, while available data concerning HSV
“antibiotic”, “atherosclerosis”, “dementia”, “inflammation”, and H pylori are less convincing.105,106,108,109 Recent data suggest
“C reactive protein”, “leucocytosis”, “procalcitonin”, “ethic”, that the infectious burden might be more important than the
“ethic and antibiotic”. presence of one particular pathogen.110,111 Of interest is also
the observation that the consumption of various types of
minimum necessary. antibiotics has been shown to be epidemiologically associated
Finally, many age-associated comorbidities increase the with a decreased cardiovascular mortality.105 Taken together,
sensitivity to infection (diabetes, inflammatory rheumatisms, these results suggest that chronic infection contributes to
chronic obstructive pulmonary diseases, stroke, etc).1,19 atherogenesis through generalised inflammation, rather than
However, comorbidities alone do not account for the through pathogen-specific mechanisms.
increased prevalence and severity of infections in the elderly.
Dementia
Infection as a cause of ageing The risk for developing dementia and, more specifically,
Ageing is not only a major risk factor for infection, but Alzheimer’s disease has been associated with HSV1, C
infection may also contribute to the ageing process. We pneumoniae, and possibly also cytomegalovirus
suggest three possible models to explain this hypothesis. First, infection.112–114 Although it is most likely that these pathogens
in the simplest model, direct tissue destruction by a pathogen are not causative organisms in this type of disease, their
may participate in the ageing process. Second, there is possible role as aggravating cofactors in patients with a
possibly a trade-off between the capacity of our host defence susceptible genetic background115 should be taken seriously.
system to kill microorganisms and the damage it causes to
surrounding host tissue.102 Thus, the beneficial effects of Others
inflammation devoted to the neutralisation of H pylori is clearly involved in the development of atrophic
dangerous/harmful agents early in life and in adulthood gastritis.101 Bacterial and viral lung infection/colonisation
become detrimental late in life due to an accumulation of stimulates an inflammatory response that causes local
damage to host tissues. Indeed, a chronic low-grade proteolytic injury and participates in the progression of
inflammation can be seen even in healthy elderly.75 Another obstructive lung disease such as emphysema.116,117 Accelerated
possibility is the contribution of latent or chronic infection to immunosenescence as evidenced by precocious shortening of
the ageing process. Latent infection might periodically be telomeres is also reported in AIDS patients.118
reactivated, leading to immune-mediated killing of the
productively infected cells. In tissues with a low proliferative Ethical aspects
index (eg, the brain), this might lead to significant loss of cells Is pneumonia the old man’s friend, as Sir William Osler
over the course of a lifetime. Microorganisms that are able to suggested in 1899 in his third edition of the Principles and
cause chronic infection usually find ways to avoid immune practice of medicine?4 In other words, is the treatment of
response, but through their manipulation of cell and tissue infectious diseases in the geriatric setting an unnecessary
function, such microorganisms might contribute to ageing. prolongation of suffering? This question leads to the essence
of palliative care and is therefore closely associated with,
Epidemiological evidence for contribution of although not specific to, geriatrics. Indeed, a large part of our
microorganisms to ageing and age-related diseases population over 75 years, does not suffer from a terminal
Atherosclerosis disease and does not have other reasons (unbearable pain,
Atherosclerosis is a universal form of vascular ageing seen in etc) that would justify the withholding of a relatively benign
both human beings and animals.103 However, while every intervention such as an antibiotic treatment. Notably, even
individual will eventually develop atherosclerosis, the severity severe infections in the elderly, such as pneumonia, do not
of the disease and the age of onset of clinical symptoms varies always have a fatal outcome, while they invariably lead to
tremendously. Thus there are modifying factors, which might substantial suffering.
be genetic—eg, apoE4104—or biochemical—eg, LDL In our opinion, the age of the patient alone should under
cholesterol.105 Recent progress in the understanding of no circumstances be a determining factor for the withholding
atherosclerosis has clearly shown that it is an inflammatory of antibiotic therapy. So, on what criteria should we base our

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 Ageing and infection
Review

decision to give or to withhold antibiotic therapy? A recent can we use antibiotics with a minimum of induction of
review has summarised the issue.119 Decision should be based resistance?
on four major ethical principles: autonomy, beneficence,
non-maleficence, and justice.119 Autonomy should be a first Conclusions
consideration. A patient who does not have a terminal Infections may participate in ageing throughout life and
disease, but who refuses antibiotic treatment, should be taken certainly participate towards the end of life. Infectious disease
as seriously as a patient with a terminal disease who considers specialists will be increasingly confronted in the next few
that gaining 2 weeks of life is an aim worth fighting for. decades with the problems and issues of a fast-growing elderly
Unfortunately, for some patients, no autonomous decision is population. The specialty is broad and there is an urgent need
possible given the high prevalence of dementia in the elderly to undertake research to elucidate the subtle mechanisms that
(roughly 30% of the population over 85 years old).8,119 In this lead to the increased susceptibility of infection. Clinical
case, it may be a useful strategy to involve family members or research is also needed in diagnostic procedures, treatments,
possibly close friends in the decision to gain an enhanced prevention, and infection control. Funding agencies should
insight into the patient’s probable preferences. Advance recognise the need to finance such research, which would
directives may be helpful tools in this decision-making and allow us to establish the best strategies to address these issues.
should be discussed with the patient at an appropriate time, Moreover, we recommend that geriatric fellowship training
even though their implementation is still difficult.120 The programmes2,3 should have a curriculum that includes
patient, however, also needs the expert advice of the infectious diseases and immunology, and that infectious
physician to make his or her decision. And here the principles disease fellowship programmes should include the biology of
of beneficence and non-maleficence become important. The ageing and the unique aspects of infections in the elderly.
physician has to provide the patient with an equilibrated and Finally, we suggest senior geriatricians and infectious disease
simple-to-understand information about the potential specialists remain up-to-date with these issues through
benefits, but also the disadvantages (side-effects, intravenous continuing medical education courses.2
line, etc) and limitations (probability of cure, relative
contribution to the overall outcome) of the antibiotic Acknowledgements
treatment. Only with this information to hand can the We thank Nathalie Salles, Geriatric Department, University Hospitals of
Geneva, for kindly providing the gastric histology material reproduced
patient profit from his autonomy. Justice is the most abstract in figure 4. The photograph of Sir William Osler is reproduced courtesy
of these principles. Indeed, the right of the individual to of the Alan Mason Chesney Medical Archives of the Johns Hopkins
Medical Institutions. This work was supported by a grant from the Swiss
receive the best treatment has to be weighed against the rights National Science Foundation and the Louis Jeantet Foundation.
of the others. For example, in terms of costs, how can we
most reasonably invest the limited amount of money Conflict of interest
available for health care? Or in terms of collective risk, how We have no conflict of interest connected with this review.

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