Pseudomonas Keratitis

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 by Augustine Hong, MD on August 3, 2022.


Disease Entity

Disease

Pseudomonas aeruginosa is a gram-negative rod. It is an opportunistic human pathogen, known to cause a variety of infectious diseases. In the eye, P. aeruginosa is a common cause of bacterial keratitis, particularly in contact lens wearers. It is known to be particularly virulent, with pseudomonas keratitis being more difficult to treat and have worse prognosis than other forms of bacterial keratitis. P. aeruginosa secretes proteases that can cause liquefactive necrosis of the cornea, leading to rapid corneal weakening and perforation.

Epidemiology

Pseudomonas is the leading cause of gram-negative bacterial keratitis, and one of the most common causes of bacterial keratitis overall. In one meta-analysis, prevalence of P. aeruginosa isolates in bacterial keratitis ranged from 6.8 to 55%[1].

It is widely known that pseudomonas keratitis is strongly associated with contact lens wear. In one study, incidence of pseudomonas keratitis was 2.76 cases per 10000 individuals per year, but rose to 13.04 cases per 10000 individuals when only considering contact lens wearers[2]. In the same study, 55% of cases of pseudomonas keratitis were associated with contact lens wear.

Extended contact lens use allows adhesion of P. aeruginosa to contact lens surfaces and subsequently the cornea. P. aeruginosa possesses specific virulence factors, including pili, glycocalyx, and exotoxins, which allow adherence and invasion into the cornea[3].

Pseudomonas keratitis in non-contact lens wearers tends to occur more commonly in the elderly and also causes significant morbidity. Worse initial visual acuity, older age, and size and extent of stromal involvment appear to be associated with worse outcomes in non-contact lens wearers.[4]

Diagnosis and treatment

All cases of suspected pseudomonas keratitis should be scraped and cultured. Empiric broad spectrum antibiotics should be initiated for infectious keratitis. Treatment regimens for pseudomonas keratitis are variable and include monotherapy or combination therapy with a topical fluoroquinolones, aminoglycosides, cephalosporins, , carbapenems and chloramphenicol [5][6][7] . A report by O'Brien et al in 1995 demonstrated that ofloxacin monotherapy was not inferior and had fewer side effects compared to combined tobramycin-cefazolin[8]. However, disease severity, regional microbial resistance rates, and pseudomonas strain type are important considerations [9][10]. Cytotoxic strains of Pseudomonas often confer resistance to fluoroquinolones [11]. Invasive strains of Pseudomonas may be less responsive to tobramycin initially[12]. Combination therapy is often utilized to take advantage of potential additive or synergistic effects of medication, especially in treatment-refractory cases[6].

While progression to endophthalmitis is rare, Pseudomonas is commonly cited as the causative pathogen of microbial keratitis leading to endophthalmitis leading to evisceration or enucleation. [13][14][15][16]

Steroid use in conjunction with antibiotics is controversial in the setting of pseudomonas keratitis as well as microbial keratitis as a whole. On subgroup analysis on patients from the steroids for corneal ulcers trial (SCUT), showed that pseudomonas ulcers had no overall benefit with the addition of corticosteroids[17]. However, the same study showed that the invasive subtype of P. aeruginosa may demonstrate a small improvement in visual acuity with steroids versus placebo.

References

  1. Teweldemedhin M, Gebreyesus H, Atsbaha AH, Asgedom SW, Saravanan M. Bacterial profile of ocular infections: a systematic review. BMC Ophthalmol. 2017;17(1):212. Published 2017 Nov 25.
  2. Jeng BH, Gritz DC.Epidemiology of ulcerative keratitis in northern California. Arch Ophthalmol. 2010 Aug;128(8):1022-8.    
  3. Dart JKG , Seal DV. Pathogenesis and Therapy of Pseudomonas aeruglnosa Keratitis. Eye (1988) 2, Suppl S46-S55
  4. Enzor R, Bowers EMR, Perzia B, Perera C, Palazzolo L, Mammen A, Dhaliwal DK, Kowalski RP, Jhanji V. Comparison of Clinical Features and Treatment Outcomes of Pseudomonas aeruginosa Keratitis in Contact Lens and Non-Contact Lens Wearers. Am J Ophthalmol. 2021 Jul;227:1-11. doi: 10.1016/j.ajo.2021.02.024. Epub 2021 Feb 28. PMID: 33657419.
  5. Willcox MD. Review of resistance of ocular isolates of Pseudomonas aeruginosa and staphylococci from keratitis to ciprofloxacin, gentamicin and cephalosporins. Clin Exp Optom. 2011 Mar;94(2):161-8. doi: 10.1111/j.1444-0938.2010.00536.x. Epub 2010 Nov 17. PMID: 21083760.
  6. 6.0 6.1 Bozkurt E, Muhafiz E, Kepenek HS, Bozlak ÇEB, Koç Saltan S, Bingol SA. A New Treatment Experience in Pseudomonas Keratitis: Topical Meropenem and Cefepime. Eye Contact Lens. 2021 Apr 1;47(4):174-179. doi: 10.1097/ICL.0000000000000745. PMID: 33196501.
  7. Bourkiza R, Kaye S, Bunce C, Shankar J, Neal T, Tuft S. Initial treatment of Pseudomonas aeruginosa contact lens-associated keratitis with topical chloramphenicol, and effect on outcome. Br J Ophthalmol. 2013 Apr;97(4):429-32. doi: 10.1136/bjophthalmol-2012-302251. Epub 2013 Jan 23. PMID: 23343655.
  8. O'Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study Research Group. P Arch Ophthalmol. 1995 Oct; 113(10):1257-65.
  9. Soleimani M, Tabatabaei SA, Masoumi A, Mirshahi R, Ghahvechian H, Tayebi F, Momenaei B, Mahdizad Z, Mohammadi SS. Infectious keratitis: trends in microbiological and antibiotic sensitivity patterns. Eye (Lond). 2021 Nov;35(11):3110-3115. doi: 10.1038/s41433-020-01378-w. Epub 2021 Jan 19. PMID: 33469134; PMCID: PMC8526825.
  10. Subedi D, Vijay AK, Willcox M. Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: an ocular perspective. Clin Exp Optom. 2018 Mar;101(2):162-171. doi: 10.1111/cxo.12621. Epub 2017 Oct 18. PMID: 29044738
  11. Subedi D, Vijay AK, Kohli GS, Rice SA, Willcox M. Association between possession of ExoU and antibiotic resistance in Pseudomonas aeruginosa. PLoS One. 2018 Sep 28;13(9):e0204936. doi: 10.1371/journal.pone.0204936. PMID: 30265709; PMCID: PMC6161911.
  12. Lee EJ, Truong TN, Mendoza MN, Fleiszig SM. A comparison of invasive and cytotoxic Pseudomonas aeruginosa strain-induced corneal disease responses to therapeutics. Curr Eye Res. 2003 Nov;27(5):289-99. doi: 10.1076/ceyr.27.5.289.17220. PMID: 14562165.
  13. Dhirachaikulpanich D, Soraprajum K, Boonsopon S, Pinitpuwadol W, Lourthai P, Punyayingyong N, Tesavibul N, Choopong P. Epidemiology of keratitis/scleritis-related endophthalmitis in a university hospital in Thailand. Sci Rep. 2021 May 27;11(1):11217. doi: 10.1038/s41598-021-90815-1. PMID: 34045630; PMCID: PMC8160326.
  14. Tóth G, Pluzsik MT, Sándor GL, Németh O, Lukáts O, Nagy ZZ, Szentmáry N. Clinical Review of Microbial Corneal Ulcers Resulting in Enucleation and Evisceration in a Tertiary Eye Care Center in Hungary. J Ophthalmol. 2020 May 18;2020:8283131. doi: 10.1155/2020/8283131. PMID: 32509342; PMCID: PMC7254073.
  15. Stevenson LJ, Dawkins RCH, Sheorey H, McGuinness MB, Hurley AH, Allen PJ. Gram-negative endophthalmitis: A prospective study examining the microbiology, clinical associations and visual outcomes following infection. Clin Exp Ophthalmol. 2020 Aug;48(6):813-820. doi: 10.1111/ceo.13768. Epub 2020 May 11. PMID: 32348002.
  16. Dave TV, Dave VP, Sharma S, Karolia R, Joseph J, Pathengay A, Pappuru RR, Das T. Infectious endophthalmitis leading to evisceration: spectrum of bacterial and fungal pathogens and antibacterial susceptibility profile. J Ophthalmic Inflamm Infect. 2019 May 16;9(1):9. doi: 10.1186/s12348-019-0174-y. PMID: 31098742; PMCID: PMC6522574.
  17. Borkar DS, Fleiszig SM, Leong C, et al. Association between cytotoxic and invasive Pseudomonas aeruginosa and clinical outcomes in bacterial keratitis. JAMA Ophthalmol. 2013;131(2):147–153.
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