Download bacterial keratitis

ASCRS ♦ ASOA Symposium & Congress
Technicians & Nurses Program
April 17-21, 2015 – San Diego, California
BACTERIAL KERATITIS
It is estimated that 30,000 cases of microbial keratitis (including bacteria,
fungus, and acanthamœba) occur annually in the United States.1 Bacterial
keratitis rarely occurs in the normal eye because of the human cornea's natural
resistance to infection. However, predisposing factors including contact lens
wear; trauma; corneal surgery; ocular surface disease including tear deficiencies
and corneal abnormalities; systemic diseases,2 and immunosuppression may
alter the defense mechanisms of the ocular surface and permit bacteria to invade
the cornea (see Risk Factors).
The most common pathogenic organisms identified in bacterial keratitis include
gram-negative rods (Pseudomonas species), Staphylococci and Streptococci.
Studies differ regarding the epidemiology of bacterial keratitis. A review of 30
years of cultures for suspected infectious keratitis in Miami showed that grampositive isolates remained relatively stable and gram-negative isolates declined.3
A review of 5 years of bacterial isolates from cases of bacterial keratitis in
Pittsburgh showed gram-positive isolates decreasing while gram-negative
isolates remained relatively stable.4 A review of 15 years of bacterial isolates
from cases of keratitis in London showed that the Pseudomonas species
increased in proportion to organisms identified, but there was no overall
increase in the proportion of gram-negative isolates.5 In bacterial keratitis
associated with the use of cosmetic contact lenses, Pseudomonas is the most
commonly identified etiologic agent, accounting for up to two-thirds of cases.6-9
A review from Florida found that Serratia marcescens was as commonly
isolated as Pseudomonas aeruginosa in contact lens-associated keratitis.10
Pseudomonas is also a common pathogen in bacterial keratitis that occurs in
hospitalized infants and in adults who are respirator dependent.11
RISK FACTORS
Exogenous Factors

Use of contact lenses, especially on an extended-wear basis.2,6-9,12-17 (High
prevalence of inadequate contact lens disinfection, contact lens storage-case
contamination, and contaminated contact lens solutions among contact lens
users have been reported. However, bacterial keratitis has occurred in patients
with apparently good compliance with contact lens care regimens.18)

Trauma, including chemical and thermal injuries, foreign bodies, and local
irradiation

Previous ocular and eyelid surgery

Loose sutures19

Previous corneal surgery, including refractive surgery and penetrating
keratoplasty

Medication related and medicamentosa (e.g., contaminated ocular medications,
topical nonsteroidal anti-inflammatory drugs, anesthetics, steroids,
antimicrobials, preservatives, glaucoma medications)

Immunosuppression (topical and systemic)

Factitious disease, including anesthetic abuse
Ocular Surface Disease

Misdirection of eyelashes

Abnormalities of eyelid anatomy and function (including exposure)

Tear film deficiencies

Adjacent infection: conjunctivitis including gonococcal, blepharitis, canaliculitis,
dacryocystitis
Corneal Epithelial Abnormalities

Neurotrophic keratopathy (neuropathy of cranial nerve V, herpes keratitis)

Disorders predisposing to recurrent erosion of cornea

Viral keratitis (herpes simplex or zoster keratitis)

Corneal epithelial edema, especially bullous keratopathy
Systemic Conditions

Diabetes mellitus

Debilitating illness, especially malnourishment and/or respirator dependence

Collagen vascular disease

Substance abuse

Dermatological/mucous membrane disorders (e.g., Stevens-Johnson syndrome,
ocular cicatricial pemphigoid)

Immunocompromised status

Atopic dermatitis/blepharoconjunctivitis

Gonococcal infection with conjunctivitis

Vitamin A deficiency
NATURAL HISTORY
While some forms of bacterial keratitis may not result in corneal scarring and
visual loss, most are associated with corneal scarring or tissue alteration and the
risk of subsequent loss of vision. Untreated bacterial keratitis may result in
corneal perforation, with the potential for development of endophthalmitis and
loss of the eye. Because this process of destruction can take place rapidly (within
24 hours when the infection is caused by a virulent organism), optimal
management requires rapid recognition and timely institution of therapy.
Bacterial keratitis can occur in any part of the cornea, but infections involving
the central cornea are of paramount importance. Scarring in this location has
the potential to cause significant visual loss, even if the infecting organism is
successfully eradicated. While some bacteria (e.g., gonococcus) can invade an
intact corneal epithelium, most bacterial keratitis develops at the site of an
abnormality or defect in the corneal surface.
The rate of disease progression is dependent on the virulence of the infecting
organism and on host factors. For example, highly virulent organisms such as
Pseudomonas or gonococcus cause rapid tissue destruction, while other
organisms such as nontuberculous mycobacteria and viridans-type
Streptococcus are usually associated with a more indolent course. Some bacteria,
which are considered to be normal conjunctival flora (e.g., Corynebacteria), may
become opportunistic pathogens in the compromised eye.
DIAGNOSIS
History
Obtaining a detailed history is important in evaluating patients with bacterial
keratitis. Pertinent information includes the following:

Ocular symptoms (e.g., degree of pain, redness, discharge, blurred vision,
photophobia, duration of symptoms, circumstances surrounding the onset of
symptoms)

Review of prior ocular history, including risk factors such as contact lens
wear,13,20 swimming or using a hot tub while wearing contact lenses, herpes
simplex virus keratitis, herpes zoster virus keratitis, previous bacterial keratitis,
previous ocular surgery including refractive surgery, trauma, and dry eye

Review of other medical problems

Current ocular medications and medications recently used

Medication allergies
Diagnostic Tests
Cultures and Smears
The majority of community-acquired cases of bacterial keratitis resolve with
empiric therapy and are managed without smears or cultures.25,26 Smears and
cultures are indicated, however, in cases with a corneal infiltrate that is large
and extends to the middle to deep stroma, that are chronic in nature or
unresponsive to broad spectrum antibiotic therapy, or that have clinical features
suggestive of fungal, amœbic, or mycobacterial keratitis.27 Smears and cultures
are often helpful in eyes with an unusual history, e.g., trauma with vegetable
matter or using a hot tub while wearing contact lenses. The hypopyon that
occurs in eyes with bacterial keratitis is usually sterile, and aqueous or vitreous
taps should not be performed unless there is a high suspicion of microbial
endophthalmitis, such as following an intraocular surgery. Prior to initiating
antimicrobial therapy, cultures are indicated in sight-threatening or severe
keratitis of suspected microbial origin.
A culture is a means of identifying the causative organism(s) and the only means
of determining sensitivity to antibiotics. Cultures are helpful to guide
modification of therapy in patients with a poor clinical response to treatment
and to decrease toxicity by eliminating unnecessary drugs. In eyes treated
empirically without first obtaining cultures in which the clinical response is
poor, obtaining cultures then may be helpful, although a delay in pathogen
recovery may occur.28,29 If the cultures are negative, the ophthalmologist may
consider stopping antibiotic treatment for 12 to 24 hours and then reculturing.
Microbial pathogens may be categorized by examining stained smears of
corneal scrapings;25 this may increase yield of identification of pathogen,
especially if the patient is on antibacterial therapy. Polymerase chain reaction
(PCR) and immunodiagnostic techniques may be useful30 but are not currently
widely available.
Corneal material is obtained by instilling a topical anesthetic agent and using a
heat-sterilized platinum (Kimura) spatula, blade, or other similar sterile
instrument to obtain scrapings of material from the advancing borders of the
infected area of the cornea. A thiol or thioglycollate broth-moistened
dacron/calcium alginate or sterile cotton swab may also be used to obtain
material. This is most easily performed with slit-lamp magnification.
Corneal scrapings for culture should be inoculated directly onto appropriate
culture media in order to maximize culture yield.31 If this is not feasible,
specimens should be placed in transport media.32 In either case, cultures should
be immediately incubated or taken promptly to the laboratory. Cultures of
contact lenses, lens case, and solution may be useful in situations where
acanthamœba is suspected or corneal cultures are negative. The material for
smear is applied to clean glass microscope slides in an even, thin layer.
TREATMENT
Initial
Topical antibiotic eye drops are capable of achieving high tissue levels and are
the preferred method of treatment in most cases. Ocular ointments may be
useful at bedtime in less severe cases and also may be useful for adjunctive
therapy.
Subconjunctival antibiotics may be helpful where there is imminent scleral
spread or perforation or in cases where adherence to the treatment regimen is
questionable. Systemic therapy may be useful in cases of scleral or intraocular
extension of infection or systemic infection such as gonorrhea. Collagen shields
or soft contact lenses soaked in antibiotics are sometimes used and may enhance
drug delivery. They may also be useful in cases where there is an anticipated
delay in initiating appropriate therapy, but these modalities have not been fully
evaluated in terms of the potential risk for inducing drug toxicity.36-38 In
addition, collagen shields and soft contact lenses can become displaced or lost,
leading to unrecognized interruption of drug delivery. In selected cases, the
choice of initial treatment may be guided by the results obtained from smears
that are diagnostic.
Topical broad-spectrum antibiotics are used initially in the empiric treatment of
bacterial keratitis. For severe keratitis (e.g., deep stromal involvement or a
defect larger than 2 mm with extensive suppuration), a loading dose every 5 to
15 minutes for the first hour, followed by applications every 15 minutes to 1
hour around the clock, is recommended. For less severe keratitis, a regimen
with less frequent dosing is appropriate. Cycloplegic agents may be used to
decrease synechia formation and to decrease pain in more severe cases of
bacterial keratitis and are indicated when significant anterior chamber
inflammation is present.
Single-drug therapy using a fluoroquinolone (e.g., ciprofloxacin, ofloxacin) has
been shown to be as effective as combination therapy utilizing antibiotics that
are fortified by increasing their concentration over commercially available
topical antibiotics.39-41 Some pathogens (e.g., Streptococci, anaerobes) reportedly
have variable susceptibility to fluoroquinolones,42-47 and the prevalence of
resistance to the fluoroquinolones appears to be increasing.4,10,43,48 Gatifloxacin
and moxifloxacin (fourth-generation fluoroquinolones) have been reported to
have better coverage of gram-positive pathogens than earlier generation
fluoroquinolones in head-to-head in vitro studies.49 The fourth-generation
fluoroquinolones are not yet FDA-approved for the treatment of bacterial
keratitis. Although there have been some concerns of increased perforation
when utilizing fluoroquinolones in the management of severe bacterial keratitis
compared to traditional fortified topical antibiotics (cefazolin and
tobramycin),50,51 these reports are retrospective, not randomized, and will need
confirmation in future studies.
Combination fortified-antibiotic therapy is an alternative to consider for severe
infection and for eyes unresponsive to treatment.50,52 Treatment with more than
one agent may be necessary for non-tuberculous mycobacteria; infection with
this pathogen has been reported in association with LASIK.53
Systemic antibiotics are rarely needed, but may be considered in severe cases
where the infectious process has extended to adjacent tissues (e.g., the sclera) or
when there is impending or frank perforation of the cornea. Systemic therapy is
necessary in cases of gonococcal keratitis.54
Therapy for Complicated Cases
Additional treatment is necessary in cases where the integrity of the eye is
compromised, such as an extremely thin corneal surface, or impending or frank
perforation, or where there is progressive or unresponsive disease or
endophthalmitis. Application of tissue adhesive, lamellar keratoplasty, and
penetrating keratoplasty are among the treatment options.
REFERENCES
1.
Pepose JS, Wilhelmus KR. Divergent approaches to the management of corneal ulcers. Am
J Ophthalmol 1992;114:630-2.
2.
Wilhelmus KR. Review of clinical experience with microbial keratitis associated with
contact lenses. Clao J 1987;13:211-4.
3.
Forster RK. Conrad Berens Lecture. The management of infectious keratitis as we
approach the 21st century. Clao J 1998;24:175-80.
4.
Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial
keratitis: a 5-year review. Ophthalmology 1999;106:1313-8.
5.
Tuft SJ, Matheson M. In vitro antibiotic resistance in bacterial keratitis in London. Br J
Ophthalmol 2000;84:687-91.
6.
Galentine PG, Cohen EJ, Laibson PR, et al. Corneal ulcers associated with contact lens
wear. Arch Ophthalmol 1984;102:891-4.
7.
Alfonso E, Mandelbaum S, Fox MJ, Forster RK. Ulcerative keratitis associated with
contact lens wear. Am J Ophthalmol 1986;101:429-33.
8.
Donnenfeld ED, Cohen EJ, Arentsen JJ, et al. Changing trends in contact lens associated
corneal ulcers: an overview of 116 cases. CLAO J 1986;12:145-9.
9.
Cohen EJ, Laibson PR, Arentsen JJ, Clemons CS. Corneal ulcers associated with cosmetic
extended wear soft contact lenses. Ophthalmology 1987;94:109-14.
10. Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in south Florida
and emerging resistance to fluoroquinolones. Ophthalmology 2000;107:1497-502.
11. Burns RP, Rhodes DH, Jr. Pseudomonas eye infection as a cause of death in premature
infants. Arch Ophthalmol 1961;65:517-25.
12. Poggio EC, Glynn RJ, Schein OD, et al. The incidence of ulcerative keratitis among users
of daily-wear and extended-wear soft contact lenses. N Engl J Med 1989;321:779-83.
13. Dart JK. Predisposing factors in microbial keratitis: the significance of contact lens wear.
Br J Ophthalmol 1988;72:926-30.
14. Schein OD, Glynn RJ, Poggio EC, et al. The relative risk of ulcerative keratitis among
users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial
Keratitis Study Group. N Engl J Med 1989;321:773-8.
15. Matthews TD, Frazer DG, Minassian DC, et al. Risks of keratitis and patterns of use with
disposable contact lenses. Arch Ophthalmol 1992;110:1559-62.
16. Buehler PO, Schein OD, Stamler JF, et al. The increased risk of ulcerative keratitis among
disposable soft contact lens users. Arch Ophthalmol 1992;110:1555-8.
17. Schein OD, Buehler PO, Stamler JF, et al. The impact of overnight wear on the risk of
contact lens-associated ulcerative keratitis. Arch Ophthalmol 1994;112:186-90.
18. Najjar DM, Aktan SG, Rapuano CJ, et al. Contact lens-related corneal ulcers in compliant
patients. Am J Ophthalmol 2004;137:170-2.
19. Siganos CS, Solomon A, Frucht-Pery J. Microbial findings in suture erosion after
penetrating keratoplasty. Ophthalmology 1997;104:513-6.
20. Schein OD, Poggio EC. Ulcerative keratitis in contact lens wearers. Incidence and risk
factors. Cornea 1990;9 Suppl 1:S55-8; discussion S62-3.
21. American Academy of Ophthalmology. Policy Statement: Protective Eyewear for Young
Athletes, 2003; (Joint statement with the American Academy of Pediatrics and the
American Academy of Ophthalmology). Available at:
www.aao.org/member/policy/index.cfm.
22. American Academy of Ophthalmology. Comprehensive Adult Medical Eye Evaluation,
Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology, 2005.
Available at: www.aao.org/ppp.
23. American Academy of Ophthalmology. Pediatric Eye Evaluations, Preferred Practice
Pattern. San Francisco: American Academy of Ophthalmology, 2002. Available at:
www.aao.org/ppp.
24. Stein RM, Clinch TE, Cohen EJ, et al. Infected vs sterile corneal infiltrates in contact lens
wearers. Am J Ophthalmol 1988;105:632-6.
25. McLeod SD, Kolahdouz-Isfahani A, Rostamian K, et al. The role of smears, cultures, and
antibiotic sensitivity testing in the management of suspected infectious keratitis.
Ophthalmology 1996;103:23-8.
26. Rodman RC, Spisak S, Sugar A, et al. The utility of culturing corneal ulcers in a tertiary
referral center versus a general ophthalmology clinic. Ophthalmology 1997;104:1897-901.
27. Wilhelmus K, Liesegang TJ, Osato MS, Jones DB. Laboratory diagnosis of ocular
infections. Washington DC: American Society for Microbiology, 1994; Cumitech Series
#13A.
28. McDonnell PJ, Nobe J, Gauderman WJ, et al. Community care of corneal ulcers. Am J
Ophthalmol 1992;114:531-8.
29. Marangon FB, Miller D, Alfonso EC. Impact of prior therapy on the recovery and
frequency of corneal pathogens. Cornea 2004;23:158-64.
30. Rudolph T, Welinder-Olsson C, Lind-Brandberg L, Stenevi U. 16S rDNA PCR analysis of
infectious keratitis: a case series. Acta Ophthalmol Scand 2004;82:463-7.
31. Waxman E, Chechelnitsky M, Mannis MJ, Schwab IR. Single culture media in infectious
keratitis. Cornea 1999;18:257-61.
32. Kaye SB, Rao PG, Smith G, et al. Simplifying collection of corneal specimens in cases of
suspected bacterial keratitis. J Clin Microbiol 2003;41:3192-7.
33. Newton C, Moore MB, Kaufman HE. Corneal biopsy in chronic keratitis. Arch Ophthalmol
1987;105:577-8.
34. Alexandrakis G, Haimovici R, Miller D, Alfonso EC. Corneal biopsy in the management of
progressive microbial keratitis. Am J Ophthalmol 2000;129:571-6.
35. Hwang DG. Lamellar flap corneal biopsy. Ophthalmic Surg 1993;24:512-5.
36. Phinney RB, Schwartz SD, Lee DA, Mondino BJ. Collagen-shield delivery of gentamicin
and vancomycin. Arch Ophthalmol 1988;106:1599-604.
37. Mondino BJ. Collagen shields. Am J Ophthalmol 1991;112:587-90.
38. Lee BL, Matoba AY, Osato MS, Robinson NM. The solubility of antibiotic and
corticosteroid combinations. Am J Ophthalmol 1992;114:212-5.
39. Hyndiuk RA, Eiferman RA, Caldwell DR, et al. Comparison of ciprofloxacin ophthalmic
solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers.
Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology 1996;103:1854-62;
discussion 62-3.
40. Ofloxacin monotherapy for the primary treatment of microbial keratitis: a double-masked,
randomized, controlled trial with conventional dual therapy. The Ofloxacin Study Group.
Ophthalmology 1997;104:1902-9.
41. O'Brien TP, Maguire MG, Fink NE, et al. Efficacy of ofloxacin vs cefazolin and
tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study
Research Group. Arch Ophthalmol 1995;113:1257-65.
42. Cokingtin CD, Hyndiuk RA. Insights from experimental data on ciprofloxacin in the
treatment of bacterial keratitis and ocular infections. Am J Ophthalmol 1991;112:25S-8S.
43. Knauf HP, Silvany R, Southern PM, Jr., et al. Susceptibility of corneal and conjunctival
pathogens to ciprofloxacin. Cornea 1996;15:66-71.
44. Cutarelli PE, Lass JH, Lazarus HM, et al. Topical fluoroquinolones: antimicrobial activity
and in vitro corneal epithelial toxicity. Curr Eye Res 1991;10:557-63.
45. Osato MS, Jensen HG, Trousdale MD, et al. The comparative in vitro activity of ofloxacin
and selected ophthalmic antimicrobial agents against ocular bacterial isolates. Am J
Ophthalmol 1989;108:380-6.
46. Wilhelmus KR, Abshire RL, Schlech BA. Influence of fluoroquinolone susceptibility on
the therapeutic response of fluoroquinolone-treated bacterial keratitis. Arch Ophthalmol
2003;121:1229-33.
47. Khokhar S, Sindhu N, Mirdha BR. Comparison of topical 0.3% ofloxacin to fortified
tobramycin-cefazolin in the therapy of bacterial keratitis. Infection 2000;28:149-52.
48. Garg P, Sharma S, Rao GN. Ciprofloxacin-resistant Pseudomonas keratitis. Ophthalmology
1999;106:1319-23.
49. Kowalski RP, Dhaliwal DK, Karenchak LM, et al. Gatifloxacin and moxifloxacin: an in
vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial
keratitis isolates. Am J Ophthalmol 2003;136:500-5.
50. Gangopadhyay N, Daniell M, Weih L, Taylor HR. Fluoroquinolone and fortified antibiotics
for treating bacterial corneal ulcers. Br J Ophthalmol 2000;84:378-84.
51. Mallari PL, McCarty DJ, Daniell M, Taylor H. Increased incidence of corneal perforation
after topical fluoroquinolone treatment for microbial keratitis. Am J Ophthalmol
2001;131:131-3.
52. Bower KS, Kowalski RP, Gordon YJ. Fluoroquinolones in the treatment of bacterial
keratitis. Am J Ophthalmol 1996;121:712-5.
53. John T, Velotta E. Nontuberculous (atypical) mycobacterial keratitis after LASIK: current
status and clinical implications. Cornea 2005;24:245-55.
54. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and
Prevention. MMWR Recomm Rep 2002;51:1-78.
55. American Academy of Ophthalmology. Basic Clinical and Science Course, 2005-2006;
Section 8, External Disease and Cornea, pg 172.
56. Wilhelmus KR. Indecision about corticosteroids for bacterial keratitis: an evidence-based
update. Ophthalmology 2002;109:835-42; quiz 43.
57. Leibowitz HM, Kupferman A. Topically administered corticosteroids: effect on antibiotictreated bacterial keratitis. Arch Ophthalmol 1980;98:1287-90.
58. Larkin DF, Kilvington S, Easty DL. Contamination of contact lens storage cases by
Acanthamoeba and bacteria. Br J Ophthalmol 1990;74:133-5.
59. Stern GA. Contact lens associated bacterial keratitis: past, present, and future. CLAO J
1998;24:52-6.
60. American Academy of Ophthalmology. Vision Rehabilitation for Adults, Preferred
Practice Pattern. San Francisco: American Academy of Ophthalmology, 2001. Available
at: www.aao.org/ppp.