CLINICAL DECISION MAKING

IN MICROBIAL KERATITIS

Gregory M. Schultz, O.D.,F.A.A.O.

Eye Center of Virginia
Williamsburg and Gloucester Virginia
:
GOALS OF THIS COURSE:
QUESTIONS WE WILL ANSWER

• Do I have an “infectious” corneal ulcer?

• How do I determine if this infiltrate/ulcer is “sterile”
vs. infection?
• Do I have to culture?
• How do I maximize my yield if I culture?
• How aggressive must I be with my treatment?
• When do I modify my treatment plan?
QUESTIONS WE WILL ANSWER:

• The Standard of Care : What is my liability here?

• Is a fourth generation Fluoroquinolone enough?
• What is the recommended dosing regimen?
• Do I keep my patient up through the night?
• Should I use drops, ointments or both?
• When or should I employ a steroid?
GOALS OF THIS COURSE

• When would I use fortified antibiotics?

• If I treat with commercially available AB, do
I use a 2nd, 3rd, or a fourth generation
fluoroqinolone
• What about besifloxacin, is it the best?
• New treatments of bacterial keratitis
 INFECTIOUS KERATITIS
• Infectious keratitis is a potentially blinding eye disease
• 30,000 cases each year
• Bacterial ,fungal, Acanthamoeba (Pepose,JS et al AJO 1992)

• If Appropriate antimicrobial treatment is delayed only 50% of

eyes gain reasonably good visual recovery

• * AAO Preferred Practice Patterns for bacterial keratitis

PREDISPOSING FACTORS:
BACTERIAL KERATITIS
• Contact lens wear/ EW, homemade soln. /use of tap water
• DW 1 case / 2,500 per year
• EW 1 case / 150-300 / year
• Ocular surface disease ( MGD, DES)
• Previous HSK
• Corneal anesthesia
• Exposure/ lagophthalmus
• Bullous Keratopathy
• trauma
PREDISPOSING FACTORS:
BACTERIAL KERATITIS
• Immuno-compromised host
• Debilitating illness ( DM, Cancer/chemo)
• Recent ocular surgery
• LASIK / LASEK, PK, PRK
• Dry eye/ OSID
• Lid deformities/ trichiasis, entropion/ectropion
• Chronic use of topical steroids
• Contact lens wear and or abuse
Virtually anything
that will put a chink
in the armor !
HOWEVER THERE ARE A FEW BUGS THAT
CAN PENETRATE AN INTACT CORNEAL
EPITHELIUM

Neisseria species
Cornybacterium diphtheriae
Haemophilus species, Aegyptius
Listeria species
SYSTEMIC CONDITIONS THAT PREDISPOSE TO
BACTERIAL KERATITIS

• Diabetes
• Vitamin A deficiency
• Collagen vascular diseases
• Gonococcal infection with conjunctivitis
 INFECTIOUS KERATITIS

The hallmark of Corneal infection is

Corneal Leukocytic infiltration!
BACTERIAL KERATITIS:
SIGNS/ SYMPTOMS
• Focal white opacity in the
stroma
• Mild to severe ocular pain • (infiltrative lesion)
• Photophobia • Stromal edema
• Decreased vision • Corneal ectasia
• Tearing with discharge • Liquifactive necrosis
• Mild to severe • Mild to severe hypopyon,
A/C reaction
conjunctival inflammation
• Lid edema
PSEUDOMONAS INFECTION
DIFFERENTIATING INFECTIOUS FROM STERILE
KERATITIS
Characteristic Infectious “Sterile”
Pain Significant Little to none
Onset Acute onset/ More indolent course
24 hours or <
Location Central / para-central Peripheral/mid-periph
Injection Significant: Trace to 1+
grade 3-4+
Discharge excessive Minimal to none
Visual Acuity Typically reduced Often unaffected
A/C reaction 2-4+ trace
 THE RULE OF 2
• A corneal ulcer is less likely to be infectious when:

• It is < 2 mm in diameter
• There is < 2+ cells in the anterior chamber
• The lesion is > 2mm from the visual axis
DISTRIBUTION OF CAUSATIVE ORGANISMS
IN MONOMICROBIAL KERATITIS
LEVY SB ET AL CORNEA. 1997; 16:383-386 H. INFLUENZA, MORAXELLA

Organism Percent of
Gram+/-
infections
Staphylococcus 47%
epidermidis +
Pseudomonas Aeruginosa 21%

-
Staphylococcus aureus 13.2%
+
Serratia 5.3%

-
Streptococcus 5.3%
pneumonia** +
BACTERIAL FLORA IN THE NORMAL EYE
• Staph epidermidis 75-90 %
• Diptheroida 20-33%
• Staphylococcus aureus 20-25%
• Hemophilus influenza. 3% or >
• Streptococcus pneumoniae 1-3 %
• Gram negative rods 1%
• Psuedomonas 0-5%
GRAM (+) COCCI
(EYE PATHOGENS)
• Staphylococcus Aureus/ epidermidis
• Micrococcus Species
• Streptococcus pneumonia
• Streptococcus pyogenese
• Streptococcus viridans
GRAM (+) BACILLI (EYE PATHOGENS)

• Cornybacterium
• Propionibacterium Acnes ( P. Acnes)
• Clostidium
• Listeria
GRAM (-) COCCI (EYE PATHOGENS)

• Neisseria gonorrhoeae
• Moraxella
• Proteus
• Serratia Marcesens
GRAM (-) BACILLI (EYE PATHOGENS)

• Pseudomonas aeruginosa
• H. influenza
• Moraxella lacunata
• Proteus
• Serratia Marcescens
PSEUDOMONAS AERUGINOSA

• Ubiquitous gram (-) rod

• Most virulent corneal pathogen
• Can not penetrate an intact corneal epithelium
• Can perforate a cornea in 24 hours
 THESE BACTERIA CAUSE
RAPID TISSUE DESTRUCTION
Pseudomonas
Streptococcus pneumoniae
gonococcus
RESULTS OF BACTERIAL KERATITIS

• Corneal scarring
• Visual morbidity
• Corneal perforation
• Endophthalmitis
RETROSPECTIVE CASE SERIES
WILL’S EYE HOSPITAL ( MAH-SADORRA JH ET AL CORNEA 2005)

• In 1996-1999, 12% of all cases were related to

CL wear
• In 1999-2002, 30% of all cases were related to
CL use
• 43 % of CL related infections related to daily
wear, frequent replacement soft CL’s
BACTERIA , FUNGI, PROTOZOA AND VIRUSES
CAN ALL INFECT THE CORNEA

How do we know what

we are dealing with?
 DIFFERENTIAL DIAGNOSIS
• Must differentiate from:
• Herpetic ulcers
• Hypoesthesia, geographic lesions, dendritic lesions
• Disciform lesions of stroma / ring immune infiltrate
• Fungal ulcers
• Characteristic “feathery” appearance
• Poor response to antibiotic therapy
• History of vegetative trauma
 HSK
Geographic ulcer Dendritic ulcer
EPITHELIAL WITH STROMAL DISEASE
FUNGAL KERATITIS
DIAGNOSIS
• Clinical suspicion, corneal scraping, superficial
keratectomy
• Diagnostic stains: Gram stain, Giemsa stain, PAS,
acridine orange, calcofluor white

• Culture media: Sabouraud’s dextrose agar, blood agar

• Confocal microscopy
MOST COMMON FUNGAL KERATITIS
• Aspergillus, filamentous fungi
• Fusarium, filamentous fungi,
• Yeast ( candida albicans)
• There are 40 different genera that cause keratomycoses
• Nation wide about 300 cases per year

• Treatment:
• Natamycin 5% (Natacyn)
• Amphotericin B 0.15%
TREATMENT OF FUNGAL KERATITIS
• Topical : natamycin 5 % suspension
• Q1h for 24-48 hrs
• Amphotericin-B 0.1-0.5%
• Q 15-20 minutes for 24-48 hours
• Miconazole 1%- very toxic
• Q1h

• Oral therapy
• Ketoconazole (Nizoral) or Fluconizole ( Diflucan) 100-200
mg /day
FUNGAL KERATITIS
FUNGAL KERATITIS
 DIFFERENTIAL DIAGNOSIS

• Endophthalmitis does not follow bacterial keratitis

without corneal perforation
• Unlike fungal keratitis

• Therefore A/C and vitreous taps are not necessary

when perforation is absent in bacterial keratitis!
 ACANTHAMOEBA KERATITIS: COURSE

• Pain, photophobia, and tearing that is out of proportion

with the clinical picture
• Often starts as non-specific keratitis
• Epithelial micro-erosions, micro-cystic edema and
perineural infiltrates in radial pattern
• Proceeding to a classic ring infiltrate
ACANTHAMOEBA KERATITIS:
PROTOZOAN

• A ubiquitous protozoan feeds on other microbes not human

tissue
• Seven species infect the eye
• Explains indolent course
• Has the ability to encyst when food supply is low
• Most have a history of CL wear with bad hygiene habits
• Unsanitary water conditions; lakes pools hot-tubs
• 10% are not CL wearers
ACANTHAMOEBA KERATITIS
ENCYSTED ORGANISM : ACANTHAMOEBA
ACANTHAMOEBA KERATITIS:
TREATMENT
• Brolene 0.1%
• Polyhexamethylene Biguanide (PHMB) 0.2%
• DESTROYS cysts and trophozoites

• Alternate therapies include ;

• Neomycin
• Clotrimazole
• Chlorhexidine
• Baquacil
TREATMENT OF ACANTHAMOEBA
USE ONE FROM THE BIOCIDE/CATIONIC
ANTISEPTIC GROUP PLUS ONE OR MORE OF THE
FOLLOWING

Polyhexamethylene biguanide
(PHMB, Baquasil, Cosmocil)
chlorhexidine digluconate
TREATMENT OF ACANTHAMOEBA

• Antibiotic / Aminoglycoside
• Paromomycin ( Humatin)/ neomycin
• Antifungal
• Clotrimazole,ketoconazole, itraconazole, miconazole
,fluconazole ( Diflucan)
• Anti-parasitic
• Propamidine isethionate (Brolene)
 DIFFERENTIAL DIAGNOSIS
• Non-infectious stromal inflammation may be associated with CL
wear (EWCL)
• Systemic diseases such as collagen vascular disorders
( RA, SLE)
• Vasculitic disorders – polyarteritis nodosa
• Wegener’s granulomatosis
• Sarcoid
• Severe rosacea
• Atopy/ limbal vernal
CORNEAL PERFORATIONS
CORNEAL CULTURING AND
SCRAPINGS
A must in severe bacterial keratitis!
INDICATIONS FOR CORNEAL CULTURING
CORNEAL SCRAPING IS A MUST IN SEVERE/SERIOUS
INFECTIOUS KERATITIS

• Central location
• Large lesions (>2mm)
• Painful lesions
• Post-op corneal infections
• Suspected fungal infection
 WHEN YOU NEED TO CULTURE

• Depth of infiltrate middle to deep stroma

• Simultaneous presence of significant A/C
reaction, fibrin or hypopyon
• Poor vision
• Presence of corneal abscess
• Unresponsive to broad spectrum therapy!
 HOW TO CULTURE
AND OBTAIN RELIABLE RESULTS

MAXIMIZING YOUR YIELD

CULTURING: WHAT IS OUR GOAL

• The culture guided approach to managing

bacterial keratitis involves taking a sample of
corneal tissue ( by scraping) and performing
microbiological tests to determine the type of
bacterial organisms and their sensitivities
• Avoiding contamination and false positives!
WHAT YOU WILL NEED: SUPPLIES

• Kimura Spatula
• Heat sterilization method
• Culture media
• Blood agar
• Chocolate agar
• Thioglycolate broth
• Sabaraud’s dextrose agar
• Access to calcofluor white
 STANDARD CULTURE MEDIA
Culture media Growth of Isolates

Blood agar Aerobic and facultative anaerobic bacteria

P. aeruginosa, S. aureus, S.epidermidis,
S.pneumonia
Chocolate Agar H. influenza, N. Gonorrhea,
bartonella species

Thioglycolate broth Aerobic and facultative anaerobic bacteria

Sabaraud's dextrose agar Fungi

SUPPLEMENTAL CULTURE MEDIA
Culture media Growth of Isolates

Anaerobic Blood agar P. Acnes, streptococcus

Lowenstein-Jensen Mycobacterium species

Middlebrook agar Mycobacterium species

Thayer- Martin Agar Pathogenic Neisseria

WHAT YOU WILL NEED: SUPPLIES

• Sterile cotton swabs

• Glass microscopic slides for gram staining
and smears
CULTURING SUPPLIES
KIMURA SPATULA
HOW TO CULTURE: TECHNIQUE
• Instill topical anesthetic! ( better if preservative free )
• This helps with patient cooperation
• Yield may improve if PF anesthetics are used
• Culturing only the purulent material often yields
inadequate sample
• Grab stroma!
• Inoculate directly onto culture media
• Consider the CL case, the CL and solutions!
HOW TO CULTURE: TECHNIQUE
• Consider culturing when ulcer presents with features
that are suggestive of fungal, amoebic or mycobacterial
keratitis
• Culture when the history is suspicious
• Trauma
• Vegetative injury
• CL hx. In lakes, pools, or hot tubs
• Post LASIK
SPECIALIZED CULTURES
• Fungal
• Acanthamoeba
• Moraxella
• Proteus
CULTURING TECHNIQUES
CULTURING TECHNIQUES
DIAGNOSTIC STAINS
Diagnostic stain Organisms Visualized
Best for bacteria, can visualize fungi and
Gram Stain Acanthamoeba

Giemsa Stain Bacteria, fungi, chlamydia,

Acanthamoeba

Mycobacterium, nocardia
Acid fast
Bacteria ,fungi, Acanthamoeba
Acridine Orange
fungi, Acanthamoeba
Calcofluor White
GRAM STAIN PROCEDURE
STAINING PROPERTIES OF BACTERIA
INVITRO VIEW
TREATMENT OF BACTERIAL KERATITIS

Review of Standard of Care

And New Treatment Alternatives
GOALS OF THERAPY
• Preserve the globe
• Minimize stromal scar formation
• Minimize inducement of irregular astigmatism
• Vision rehabilitation
• PTK
• CL’s or PK
• Collagen cross linking
 “MOST CASES OF COMMUNITY ACQUIRED
BACTERIAL KERATITIS RESPOND TO
EMPIRICAL TREATMENT WITH BROAD
SPECTRUM ANTIBIOTICS”

Preferred Practice Guidelines on bacterial keratitis, AAO

KEYS TO SUCCESSFUL THERAPY

• RAPID RECOGNITION
• TIMELY INSTITUTION OF THERAPY
• APPROPRIATE FOLLOW-UP
 MEDICAL TREATMENT
• Broad spectrum topical antibiotics
• Fluoroquinolones
• 2nd generation….. Ciloxan, Ocuflox
• 3rd generation……Quixin
• 4th generation………Vigamox, Zymar, Besivance
• Fortified Antibiotics: When to use them
• Judicious Use of Corticosteroids
PROCEDURAL TREATMENT
• Cultures and smears
• Cultures and sensitivities
• Gram/ geimsa staining
• Deeper tissue corneal biopsy
• TISSUE GLUE
• Collagen cross linking
• PDT
• PTK
• PKP
BROAD SPECTRUM ANTIBIOTICS ARE THE
MAINSTAY OF TREATMENT

PREFERRED TREATMENT IN
NON-SEVERE CASES
BROAD SPECTRUM ANTIBIOTICS
THE FLUOROQUINOLONES

2nd generation: ciprofloxacin, ofloxacin

3rd generation: levofloxacin

4th generation: moxifloxacin, gatifloxacin,

besifloxacin
THE FLUOROQUINOLONES:
SOME INTERESTING POINTS

• Some clinical trials have shown 4 th generation

Fluoroquinolones to be as effective/potent as combined
fortified antibiotics against the common pathogens that
cause bacterial keratitis
• The Ofloxacin Study Group, Ophthalmology 1997
• There are still concerns with resistance (2 nd and 3rd gen)
• No difference in clinical efficacy or overall time to cure
TOPICAL FLUOROQUINOLONES:
CLINICAL INDICATIONS
Drug / concentration Indications Rec. treatment
duration
Ciprofloxacin 0.3% Conjunctivitis 7days
Corneal ulcers 14 days
Ofloxacin 0.3% Conjunctivitis 7 days
Corneal ulcers 9 days

3rd gen

Levofloxacin 0.5% Bacterial conjunctivitis 7days

Corneal ulcers
4th gen

Moxifloxacin 0.5% Bacterial conjunctivitis 7days TID

Gatifloxacin 0.3% Bacterial conjunctivitis Days 1-2 q2h

Days 3-7 QID
THE MECHANISM OF ACTION OF
FLUOROQUINOLONES

• Fluoroquinolones inhibit bacterial DNA gyrase (topoisomerase II),

topoisomerase IV OR BOTH.
• These are the key enzymes in bacterial DNA replication and
transcription
• 2nd generation FQ inhibit DNA gyrase
• 3rd generation FQ inhibits DNA gyrase
• 4th generation FQ inhibit both enzymes
• Inhibition of these enzymes will result in bacterial cell death
THE FLUOROQUINOLONES: MOA

• Topoisomerase IV is the main target for most gram + organisms

• DNA gyrase ( topoisomerase II) is the main target for most gram
negatives
• 4th Generation FQ inhibit both
• Gatifloxacin, Moxifloxacin, besifloxacin
• 2nd generation FQ inhibit / target DNA gyrase ( topoisomerase II)
• Ciprofloxacin, ofloxacin
TOPICAL 4TH GENERATION FQ ARE GOOD
ALTERNATIVES TO COMBINATION
FORTIFIEDS
THE 4TH GEN FLUOROQUINOLONES

• Highly soluble with excellent tissue penetration

• BAK free……..self preserved! (Vigamox)
• Formulated at near neutral (6.8) pH = comfort
• Less likely to select for resistance
4TH GENERATION FLUOROQUINOLONES

• Several controlled studies have shown both gatifloxacin

and moxifloxacin performed at least as well as standard
therapy with fortified cefazolin and tobramycin
• Both 4th gen fluoroquinolones are not approved for
treatment of bacterial keratitis by the FDA
• Any use in this regard is “off label”
• So what is the standard of care?
THE 4TH GEN FLUOROQUINOLONES

• The 4th generation FQ’s are more effective against

Gram + organisms while maintaining adequate
coverage against Gram (-)
• One FQ resistant organism is atypical mycobacterium
4TH GEN FLUOROQUINOLONES:
STUDIES SUPPORTING USE

• Parmar et al compared gatifloxacin 0.3% to ciprofloxacin 0.3%

in treatment of bacterial keratitis ( ulcers > 2mm).
• Looked at the susceptibility to bacterial isolates
• Dosing q1h for bacterial ulcers
• Found susceptibility to gram +
• was 96% to gatifloxacin, 60% to ciprofloxacin
• Found susceptibility to gram –
• Was 93% to gatifloxacin
• Was 86% to ciprofloxacin
4TH GEN FLUOROQUINOLONES:
STUDIES SUPPORTING USE
• Shah et al looked at bacterial corneal ulcers >2mm and
randomized their treatment to:
• Moxifloxacin 0.5%, q1h for 48-72 hours
• Gatifloxacin 0.3% q1h for 48-72 hours
• Fortified AB ( 5% Cefazolin, 1.3% Tobramycin) or
(10.4% Cefazolin with 5.2% Tobramycin) both q1h
• Cure rates for Fortifieds was 90%
• Cure rates Gatifloxacin/moxifloxacin group was 95%
 MIC 90’S
• MIC 90 for Gram +’s is lower for 4th generation FQ than 2nd or 3 rd
• Especially for FQ resistant staph aureus
• MIC 90 for Gram –’s is better with the 2 nd generation than 4 th gen. FQ

• Of the 4th generation FQ

• Moxifloxacin has a lower MIC 90 for most gram +
• Gatifloxacin has a lower MIC 90 for most gram –

• One interesting fact is ciprofloxacin (2 nd gen.) had lower MIC

90’s than both the 4 th generation FQ against gram –’s
( esp pseudomonas species)
 TOPICAL FLUOROQUINOLONES

• Current treatment of choice in non-severe bacterial

keratitis
• Treatment is broken down into 2 critical phases each with a
clear endpoint for clinical review and decision making
• Sterilization Phase
• Clinical signs may not indicate when sterilization has
occurred after starting intensive therapy
• Sterilization often precedes both epithelialization and
resolution of inflammatory signs
• Healing phase
DOSING OF THE FLUOROQUINOLONES IN
SUSPECTED BACTERIAL KERATITIS

• Dosing needs to be aggressive early on in treatment

• Q 5-15 min to start for several hours
• Q 30 min through the first day
• Q 1-2 hours through the night
• Checking for improvement daily or every other day
DOSING IN LESS SEVERE KERATITIS

• Q2h, q3h with loading dose hs

• Cycloplegics for pain and synechia prevention.
SEVERE BACTERIAL KERATITIS
SEVERE BACTERIAL KERATITIS
FOLLOW-UP PROTOCOL

• Frequent initially every day until clinical improvement

is seen
• Frequency of re-evaluation
• depends on extent of disease
• Then follow-up appointments can be spaced according
to level of improvement and practitioner comfort level
NIGHT TIME THERAPY: DO I HAVE TO HAVE
MY PATIENT GET UP DURING THE NIGHT?

• Depends on severity of disease

• If the patient has a central ulcer with reduced VA ---YES!
• Any features consistent with severe keratitis—Yes!
• If the lesion is mid-peripheral and less ominous consider
• Ointment HS (as cover hs)
• Loading Dose HS
• Avoid using ointments in patients with severe keratitis!
FEATURES OF SEVERE
INFECTIOUS KERATITIS
• Significant pain
• Dense central infiltrates
• Large Ulcers
• Hypopyon/ fibrin in AC
• Suppurative lesions/ liquifactive necrosis
• The stroma turns to soup!
• Unresponsive to initial therapy with 4 th gen FQ
FEATURES OF SEVERE
INFECTIOUS KERATITIS
• Infection extending into sclera
• May require injected sub-conjunctival AB
• Heavy mucous discharge
• Impending perforation
• Gonococcal keratitis
• Requires systemic therapy
• Oral Azithromycin or Doxycycline 100 mg BID X 7 days
FEATURES SUGGESTIVE OF POSITIVE
RESPONSE TO TREATMENT

• Decreased pain
• Decreased discharge
• Lessened eyelid edema
• Decreased density of stromal infiltrate
• Reduced stromal edema
FEATURES SUGGESTIVE OF POSITIVE
RESPONSE TO TREATMENT

• Consolidation and sharper demarcation of

stromal infiltrates perimeter
• Reduced A/C reaction, fibrin, hypopyon
• Re-epithelialization, reduced epithelial defect
• Measure it !!!
POSITIVE RESPONSE TO TREATMENT: SERRATIA
 MODIFICATION OF THERAPY:
• Efficacy of treatment judged on clinical response to empirical
treatment
• If condition improving therapy need not be adjusted on basis of
lab results
• Dual AB therapy may not be necessary
• Modify the treatment plan if the eye shows a lack of response /
improvement after 48-72 hours
• Culture results may have an impact on the modification of
therapy
• Especially when the response has been poor
WHAT ABOUT RESISTANCE: CAN IT HAPPEN?

2 concomitant mutations are necessary for the development of

resistance to the 4 th generation fluoroquinolones
 EMERGING CHALLENGES:
BACTERIAL RESISTANCE TO FQ

• Already widespread resistance to 3 rd generation FQ

• Studies have shown increasing resistance to 2 nd generation FQ
• Prashant et al Ophthalmology July 1999
• Studied cultured proven pseudomonas keratitis
• 1991 6.2% were ciprofloxacin resistant
• 1998 23% were ciprofloxacin resistant
THE MECHANISMS
RESISTANCE TO FQ

• Mutation of target enzymes

• Formation of gyrase protecting proteins
• Reduction in cell permeability
• Increases in drug efflux
• Despite all this still a relatively low incidence of
resistance to 4th gen FQ
RESISTANCE TO THERAPY
NEW KIDS ON THE BLOCK: THE LATEST PLAYERS

• Zymaxid 0.5% , gatifloxacin, Zymar 0.3%

• Moxeza 0.5%, moxifloxacin with xanthan gum vehicle
• Prolongs contact time with the ocular tissues
• Increases tissue penetration
• Besivance 0.6% , besifloxacin ophthalmic suspension
formulated with Durasite vehicle
• Good broad spectrum FQ
• Should have increased contact time and better tissue penetration
as a result of Durasite
• No FDA labeling for bacterial keratitis, only bacterial conjunctivitis
• Novel fluoroquinolone without a systemic counterpart
BESIVANCE : BESIFLOXACIN
• Only dual halogenated fluoroquinolone AB
• Effective treatment in studies for :
• MRSA (previous FQ have shown to be poorly effective)
• MRSE
• Pseudomonas aeruginosa (FDA approval) on its labeling
• Potent balanced inhibition
• DNA gyrase inhibition- hits gram -’s
• Topoisomerase IV inhibition – hits gram +’s
• bactercidal drug
• Uses the same Durasite muco-adhesive vehicle as Azasite
MODIFYING THERAPY IN SEVERE DISEASE
MODIFICATION OF AB THERAPY:
SEVERE DISEASE

• Every 5-15 minutes in the 1st few hours

• Every 15 minutes to 1 hour around the clock
• Patient sets alarm to get up during night!
• Cycloplegia
• pain from cilliary spasms
• reduce posterior synechia
WHAT IF THINGS ARE GOING BADLY ………?

CONSIDER FORTIFIED ANTIBIOTICS!

FOR SEVERE INFECTION OF EYES UNRESPONSIVE TO
TREATMENT WITH SINGLE AGENTS
 COMPOUNDING FORTIFIED ANTIBIOTICS
Drug Effective Concentration
against
Cefazolin • Gram + 50mg/ml

Vancomycin • Gram + 15mg/ml

25mg/ml
50mg/ml

Tobramycin • Gram - 14mg/ml

Gentamycin • Gram - 14mg/ml

 FORTIFIED ANTIBIOTICS
THE LONGSTANDING STANDARD OF CARE

• Probably the best choice in the eyes of the law

• Have withstood the test of time
TREATMENT PEARLS:
SEVERE BACTERIAL KERATITIS

• Bandage CL’s and Collagen shields are risky in treatment of

severe bacterial keratitis
• They can become dislodged interrupting AB therapy
• May actually impair AB penetration into the ulcer bed
• Subconjunctival AB therapy in cases of scleral extension,
systemic infection
• Steer away from ointments at night, the drops are more potent
and these interfere with penetration of fortifieds or 4th FQ
• Instead dose through the night!
•
TREATMENT ROLE OF STEROIDS

When to pull the trigger !

CORTICOSTEROID USE
FOR INFECTIOUS KERATITIS

• Many believe steroids have a place in treatment of bacterial

keratitis
• Judicious use of steroids can reduce ocular morbidity
• Suppresses inflammation and subsequent scarring leading to
better visual outcomes
• Ideally should not be used until culture results return or positive
response to therapy
CORTICOSTEROID USE
FOR INFECTIOUS KERATITIS

• In order to have success with steroid therapy

• Use the minimal amount of steroid required to control
inflammation
• Optimal timing: AB response, C/S results, not fungal
• Careful dose regulation
• use adequate and appropriate concomitant AB
• Close follow up, monitor IOP
IN TREATMENT OF SEVERE BACTERIAL
KERATITIS INVOLVING THE VISUAL AXIS

General Rule of Thumb

After 2-3 days of steady improvement with
topical AB’s safe to introduce a steroid
 DISADVANTAGES WITH STEROID TREATMENT

• Recurrence of infection
• Local immunosuppression
• Inhibition of collagen synthesis predisposing to corneal melts
• No conclusive evidence that steroids alter the clinical outcome in
bacterial keratitis
• Closer follow-up is necessary
• Optimal timing and dose regulation
TREATMENT IN COMPLICATED CASES

Perforations, progressive unresponsive

disease, Endophthalmitis
ADJUVANT THERAPY
• Collagenase inhibitors
• EDTA, Tetracyclines, Doxycycline
• Steroids?
• NSAIDS
• Tissue adhesives
• Debridement/ biopsy
• Bandage lenses/ collagen shields
• Therapeutic / tectonic PK
COLLAGEN CROSS-LINKING: NEW TREATMENT
• Collagen cross-linking (CXL) is a technique that uses
riboflavin (B2) and Ultraviolet-A irradiation to cause a
strengthening effect in corneal tissue which enhances
its rigidity. The interactive effect of riboflavin with UV-A
irradiation strengthens formation of chemical bonds
between collagen fibrils in the corneal stroma and helps
in increasing resistance against enzymatic digestion
COLLAGEN CROSS-LINKING

• Collagen cross-linking may be considered

in treatment-resistant infectious keratitis or
as an adjunct to antibiotics therapy
COLLAGEN CROSS-LINKING
• Three patients with Acanthamoeba keratitis were
successfully treated with a topical application of
0.1% riboflavin solution and 30 minutes of UV
irradiation focused on the corneal ulcer. [2]
TREATMENT IN COMPLICATED CASES
Perforation Tissue glue
THERAPY IN COMPLICATED CASES
• Thin Corneas
• Impending perforation
• Tissue adhesives
• PK
• Lamellar PK
• Endophthalmitis
 THANKS FOR
YOUR ATTENTION
• Gregory M. Schultz, O.D.,F.A.A.O.
• Eye Center of Virginia
• Williamsburg VA
• Email: gschultz31@cox.net