|Year : 1999 | Volume
| Issue : 2 | Page : 101-109
Trends in antibiotic resistance of corneal pathogens: Part II. An analysis of leading bacterial keratitis isolates
Savitri Sharma1, Derek Y Kunimoto2, Nagaraja T Rao1, Prashant Garg1, Gullapalli N Rao1
1 Jhaveri Microbiology Centre and Cornea Service, L.V. Prasad Eye Institute, Hyderabad, India
2 Harvard Medical School, Boston, USA
Dept. of Microbiology, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad - 500 034
Source of Support: None, Conflict of Interest: None
Purpose: To analyse leading bacterial keratitis pathogens for in-vitro susceptiblity to commonly used ocular antibiotics and to determine trends in antibiotic susceptibility for these pathogens. Methods: A retrospective review of microbiology records from 1991-1997 at the LV Prasad Eye Institute, Hyderabad, India identified the five leading bacterial keratitis pathogens.. Antibiotic susceptibility of corneal isolates was determined for various ocular antibiotics using the Kirby-Bauer disc-diffusion method. Results: Linear regression analyses were performed. Statistically significant trends included a 3.56% increase per year in the percentage of Staphylococcus epidermidis isolates susceptible to chloramphenicol (p = 0.032) [-6.61 - -0.51, 95% CI]; a 9.93% decrease per year in the percentage of Corynebacterium species isolates susceptible to ciprofloxacin (p = 0.050) [0 -19.86, 95% CI]; a 0.69% increase per year in the percentage of Staphylococcus aureus isolates susceptible to gentamicin (p = 0.012) [-11.35 - -2.49, 95% CI]; and a 5.53% increase per year in the percentage of Staphylococcus aureus isolates susceptible to norfloxacin (p = 0.040) [-10.66 - -0.40, 95% CI]. A trend of borderline significance included a 3.77% decrease per year in the percentage of Pseudomonas aeruginosa isolates susceptible to ciprofloxacin (p=0.064) [-0.34 - 7.89]. Conclusion: This study provides information on the trends in antibiotic susceptibility for the leading bacterial keratitis pathogens. It is hoped that this study will provide a rational approach for initial therapy, taking into account changing trends in antibiotic susceptibility
Keywords: Infectious keratitis, bacteria, antibiotic sensitivity, antibiotic resistance, treatment
|How to cite this article:|
Sharma S, Kunimoto DY, Rao NT, Garg P, Rao GN. Trends in antibiotic resistance of corneal pathogens: Part II. An analysis of leading bacterial keratitis isolates. Indian J Ophthalmol 1999;47:101-9
|How to cite this URL:|
Sharma S, Kunimoto DY, Rao NT, Garg P, Rao GN. Trends in antibiotic resistance of corneal pathogens: Part II. An analysis of leading bacterial keratitis isolates. Indian J Ophthalmol [serial online] 1999 [cited 2020 Jul 9];47:101-9. Available from: http://www.ijo.in/text.asp?1999/47/2/101/22781
The steps in successful management of bacterial keratitis include clinical diagnosis, laboratory identification of the corneal pathogen with susceptibility studies, initiation of antibiotic therapy, modification of initial antibiotic therapy, and termination of therapy. This study will focus on the second and third steps, laboratory studies and initiation of antibiotic therapy. The leading corneal pathogens of bacterial keratitis include the Micrococcaceae (Staphylococcus species and Micrococcus species), Streptococcus species, Pseudomonas species, Corynebacterium species, and the Enterobacteriaceae (Citrobacter species, Enterobacter species, Klebsiella species, Proteus species, and Serratia species). However, recent series on bacterial keratitis from different regions of the world report varying prevalence of these leading pathogens, suggesting that familiarity with the local microbial flora will aid in the identification of corneal pathogens and the selection of initial antibiotic therapy. Furthermore, while the awareness of occurrence rates of local pathogens is important in the treatment of bacterial keratitis, it is equally important to note the trends of antibiotic susceptibility in these pathogens.
In this communication, the authors present bacterial keratitis culture and in-vitro sensitivity results from the LV Prasad Eye Institute, Hyderabad, India. Part 1 of this series is addressed mainly to community-based ophthalmologists who do not have access to extensive microbiology facilities, and discusses the in-vitro effectiveness of commonly used ocular antibiotics describing their coverage of bacterial species, in the hope that this information will aid decision-making during the empiric initial treatment. Part II of this series is addressed to ophthalmologists who have access to microbiology facilities, and describes the trends in antibiotic resistance among the leading keratitis etiopathogens. This could ensure a rational approach to initial therapy that can take into account changing trends in antibiotic susceptibility.
| Materials and Methods|| |
A retrospective review of microbiology records at the LV Prasad Eye Institute identified 1,633 bacterial isolates from 1,353 patients of culture-proven bacterial keratitis seen between March 1, 1991 and June 30, 1997.
Standard techniques, described in Part-I of this series, were used for the microbiological processing of corneal scrapings and determination of antibiotic susceptibility. Susceptibility was graded as either resistant (R), intermediate sensitivity (I), or sensitive (S).
The 5 leading bacterial pathogens were analysed by linear regression to determine whether there was any trend of increased or decreased susceptibility to commonly used ocular antibiotics over time [Table - 1]-[Table - 2], [Figure - 1]-[Figure - 5].
| Results|| |
A complete picture of 1633 bacterial pathogens isolated from corneal scrapings is presented in [Table - 1]. Gram-positive cocci accounted for 1,129 (69.1%) of all bacterial isolates, gram-positive bacilli for 309 (18.9%), gram-negative cocci for 22 (1.3%), gram-negative bacilli for 151 (9.2%), and acid-fast or partially acid-fast organisms for 22 (1.3%) of all isolates. The 5 leading pathogens, Staphylococcus epidermidis (680/1633; 41.6%), Corynebacterium species (204/1633; 12.5), Streptococcus pneumoniae (155/1,633;9.5%), Staphylococcus aureus (129/1633;7.9%), and Pseudomonas aeruginosa (101/1,633;6.2%) were examined for yearly incidence and susceptibility to various ocular antibiotics [Table - 2]. These 5 pathogens accounted for 1,269 (77.8%) of the 1,633 corneal isolates.
Linear regression analyses to examine antibiotic susceptibility trends of the 5 leading pathogens shown in [Table - 3]. Statistically significant trends included a 3.56% increase per year in the percentage of Staphylococcus epidermidis isolates susceptible chloramphenicol (p = 0.032) [-6.61 - -0.51, 95% CI]; a 9.93% increase per year in the percentage of Corynebacterium species isolates resistant to ciprofloxacin (p = 0.050) [0 - 19.86, 95% CI]; a 0.69% increase per in the percentage of Staphylococcus aureus isolates susceptible to gentamicin (p = 0.012) [-11.35 - -2.49,95% CI]; and a 5.53% increase per year in the percentage of Staphylococcus aureus isolates susceptible to norfloxacin (p = 0.040) [-10.66 - -0.40, 95% CI]. A trend of borderline significance included a 3.77% increase per year in the percentage of Pseudomonas aeruginosa isolates resistant to ciprofloxacin (p= 0.064) [-0.34 - 7.89].
Susceptibility profiles of the 5 leading bacterial pathogens to selected ocular antibiotics are illustrated in [Figure - 1]-[Figure - 5].
| Discussion|| |
There has been growing concern in the recent literature regarding increased resistance of ocular pathogens to commonly used topical antibiotics. Results from the present study support this and indicate that there are significant trends of changing antibiotic resistance in the 5 leading corneal pathogens, which account for 1,269 (77.8%) of 1,633 isolates.
Pseudomonas aeruginosa is a virulent corneal pathogen associated with the rapid, liquefactive necrosis of the cornea. Results from this series indicate that Pseudomonas aeruginosa is most susceptible to gentamicin, ciprofloxacin, and norfloxacin [Figure - 5]. However, there have been increasing reports in the literature of Pseudomonas resistance to both fluoroquinolones and aminoglycosides., Early studies hailed fluoroquinolones as broad-spectrum drugs which are also effective against Pseudomonas species. However, a recent series which examined systemic isolates of Pseudomonas revealed a significant increase in ciprofloxacin resistance (p = 0.0001), and the results of this series provide the evidence to suggest that there may be increasing resistance to ciprofloxacin among ocular isolates of Pseudomonas species (p = 0.064) [-0.34 - 7.89, 95% CI]. Thus, the initial therapy of suspected Pseudomonas keratitis with ciprofloxacin may not be advisable.
Regarding Corynebacterium species, there have been several reports of increased resistance to various antibiotics including chloramphenicol, ciprofloxacin, norfloxacin, and kanamycin in systemic and ocular isolates of Corynebacterium species., Of note, results from this series indicate that Corynebacterium species exhibit an increasing resistance to ciprofloxacin (p = 0.050) [0 - 19.86, 95% CI], consistent with a recent report showing increased resistance to norfloxacin in ocular isolates of Corynebacterium species. These results suggest that the empiric treatment of Corynebacterium species with fluoroquinolones should be considered with caution. Recent studies have reported best coverage for Corynebacterium species by beta-lactam antibiotics or vancomycin,, a finding consistent with the results from this series which suggest that Corynebacterium species is most susceptible to cefazolin [Figure - 2].
Staphylococcus aureus is a common cause of suppurative keratitis, and there have been recent reports of resistance to various antibiotics including tobramycin, gentamicin, cefazolin, and ciprofloxacin in systemic and ocular isolates of S. aureus., Of note, a linear trend of increased susceptibility to both gentamicin (p = 0.012) and norfloxacin (p = 0.040) was identified among S. aureus isolates in this series. As per Medline search this is the first known report of statistically significant increased susceptibility to gentamicin and norfloxacin in corneal isolates of S. aureus. The use of combination antibiotic therapy probably contributes to this observation. The results from this series also suggest that S. aureus is most susceptible to cefazolin [Figure - 4], despite reports of increased cefazolin-resistance in systemic isolates of S. aureus. A report of Mader et al also suggests treatment of ocular S. aureus infection with a cephalosporin such as cefazolin.
There have been recent reports of Staphylococcus epidermidis resistance to various antibiotics including tobramycin, gentamicin, ciprofloxacin, and kanamycin in systemic and ocular isolates of this organism.,,,,, The results from this study indicate a linear trend of increased susceptibility to chloramphenicol (p=0.032). To the best of our knowledge, this is the first known report of statistically significant increased susceptibility to chloramphenicol in corneal isolates of S. epidermidis. However, bacteriostatic effect, antagonistic activity in combination with aminoglycosides, and risk of bone marrow depression caution against increased use of this antibiotic. The results from this study also suggest that S. epidermidis is most susceptible to cefazolin [Figure - 1], consistent with another report, and thus initial empiric treatment of S. epidermidis with a cephalosporin would not be unreasonable.
Lastly, regarding Streptococcus pneumoniae, there have been recent reports of resistance to various antibiotics including fluoroquinolones, gentamicin, and chloramphenicol in systemic and ocular isolates of S. pneumoniae., There are no significant trends of changing antibiotic susceptibility noted for S. pneumoniae in this series. The results suggest that S. pneumoniae is most susceptible to cefazolin [Figure - 3], and despite increasing reports of cephalosporin-resistance among systemic S. pneumoniae isolates,, this trend has not been reported among ocular isolates of this organism.
It must be noted that the conventional criteria of resistance may not directly apply to corneal pathogens since the ocular antibiotic levels achievable by topical administration may be considerably higher than the "resistance breakpoint" defined by serum levels which have been evaluated safe for parenteral therapy. Indeed, there have been many reports of pathogens with in-vitro resistance to an antibiotic which have been successfully treated in vivo by that antibiotic.,,
To the best of the authors' knowledge, this is the first report of statistically significant linear trends in antibiotic susceptibility of corneal pathogens. It is hoped that once a pathogen is identified by microbiologic procedures, this information will aid the clinician in formulating a rational approach to antibiotic treatment of bacterial keratitis.
| Acknowledgement|| |
This study was supported by a grant from Hyderabad Eye Research Foundation
| References|| |
Jones DB. Decision-making in the management of microbial keratitis. Ophthalmology
Burd EM, Ogawa GSH, Hyndiuk RA. Bacterial keratitis and conjunctivitis. In: Smolin G, Thoft RA, editors. The Cornea. Scientific Foundations and Clinical Practice.
3rd ed. Boston: Little, Brown, & Co; 1994. p 115-67.
Asbell P, Stenson S. Ulcerative keratitis: Survey of 30 years' laboratory experience. Arch Ophthalmol
Liesegang TJ, Forster RK. Spectrum of microbial keratitis in South Florida. Am J Ophthalmol
Ormerod LD, Hertzmark E, Gomez DS, Stabiner RG, Schanzlin DJ, Smith RE. Epidemiology of microbial keratitis in Southern California. A multivariate analysis. Ophthalmology
McClellan KA, Bernard BJ, Billson FA. Microbial investigations in keratitis at the Sydney Eye Hospital. Aust NZ J Ophthalmol
Ormerod LD. Causation and management of microbial keratitis in subtropical Africa. Ophthalmology
Neumann M, Sjostrand J. Central microbial keratitis in a Swedish city population. A three-year prospective study in Gothenburg. Acta Ophthalmol Copenh
Wahl JC, Katz HR, Abrams DA. Infectious keratitis in Baltimore. Ann Ophthalmol
Gonawardena SA, Ranasinghe KP, Arseculratne SN, Seimon CR, Ajello L. Survey of mycotic and bacterial keratitis in Sri Lanka. Mycopathologia
Williams G, McClellan K, Billson F. Suppurative keratitis in rural Bangladesh:the value of gram stain in planning management. Int Ophthalmol
Sharma S, Kunimoto DY, Garg P, Rao GN. Trends in antibiotic resistance of corneal pathogens: Part I. An analysis of commonly used ocular antibiotics. Indian J Ophthalmol
Jones DB, Liesegang TJ, Robinson NM. Laboratory Diagnosis of Ocular Infections.
Washington DC: Cumitech 13, American Society for Microbiology; 1981.
Knauf HP, Silvany R, Southern PM, Risser RC, Wilson SE, et al. Susceptibility of corneal and conjunctival pathogens to Ciprofloxacin. Cornea
Bower KS, Kowalski MS, Gordon YJ. Fluoroquinolones in the treatment of bacterial keratitis. Am J Ophthalmol
Snyder ME, Katz HR. Ciprofloxacin-resistant bacterial keratitis. Am J Ophthalmol
Maffett M, O'Day DM. Ciprofloxacin-resistant bacterial keratitis [letter]. Am J Ophthalmol
Koguchi M, Suzuki Y, Tanaka S, Fukayama S, Ishihara R, Deguchi K, et al. Antimicrobial activities of norfloxacin against clinical isolates from ocular infections. Jpn J Antibiot
Mathers WD, Lemp MA. Corneal rim cultures. Cornea
Ooishi M, Miyao M. Antibiotic sensitivity of recent clinical isolates from patients with ocular infections. Ophthalmologica
Lindquist TD, Weber K, Spika J, Facklam R. Gentamicin-resistant streptococcal endophthalmitis after keratoplasty. Cornea
Gopinathan U, Agrawal V, Sharma S, Rao GN. Donor corneoscleral rim contamination by gentamicin-resistant organisms. Indian J Ophthalmol
Brown SF, Bloomfield SE, Tam WI. The cornea destroying enzyme of Pseudomonas aeruginosa. Invest Ophthalmol
Hobden JA, Reidy JJ, O'Callaghan RJ, Insler MS, Hill JM. Ciprofloxacin iontophoresis for aminoglycoside-resistant pseudomonal keratitis. Invest Ophthalmol Vis Sci
Hobden JA, Reidy JJ, O'Callaghan RJ, Insler MS, Hill JM. Quinolones in collagen shields to treat aminoglycoside-resistant pseudomonal keratitis. Invest Ophthalmol Vis Sci
Leibowitz, HM. Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis. Am J Ophthalmol
Hyundiuk RA, Eiferman RA, Caldwell DR, Rosenwasser GO, Santos CI, Katz HR, et al. Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ophthalmol
O'Brien TP, Maguire MG, Fink NE, Alfonso E, M Donnell P. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Arch Ophthalmol
Neu HC. Microbiologic aspects of fluoroquinolones. Am J Ophthalmol
Vajpayee RB, Gupta SK, Angra SK, Munjal A. Topical norfloxacin therapy in Pseudomonas
corneal ulceration. Cornea
Murphy PG, Ferguson WP. Corynebacterium jeikeium (Group JK) resistance to ciprofloxacin emerging during therapy [letter]. J Antimicrob Chemother
Tauch A, Kassing F, Kalinowski J, Puhler A. The erythromycin resistance gene of the Corynebacterium xerosis
R-plasmid pTP10 also carrying chloramphenicol, kanamycin, and tetracycline resistances is capable of transposition in Corynebacterium glutatnicum. Plasmid
Roberts MC, Leonard RB, Briselden A, Schoenknecht FD, Coyle MB. Characterization of antibiotic-resistant Corynebacterium striatum strains. J Antimicrob Chemother
Ahmed K, Kawakami K, Watanabe K, Mitsushima H, Nagatake T, Matsumoto K. Corynebacterium pseudodiphtheriticum:
A respiratory tract pathogen. Clin Infect Dis
Williams DY, Selepak ST, Gill VJ. Identification of clinical isolates of nondiphtherial Corynebacterium
species and their antibiotic susceptibility patterns. Diagn Microbiol Infect Dis
Matsuo K, Uete T. Evaluation of in-vitro
antimicrobial activity of ccefazolin alone and in combination with cefmetazole or flomexef using agar dilution method and disk diffusion method. Jpn J Antibiot
Torres Garcia M, Tejodor Junco MT, Gonzalez Martin M, Gonzalez Lama Z. Selection of subpopulations resistant to amikacin and netilmicin of gentamicin-resistant clinical strains of Staphylococcus aureus
and Staphylococcus epidermidis. Zentralbl Bakteriol
Mader TH, Maher KL, Stulting RD. Gentamicin resistance in Staphylococcal corneal ulcers. Cornea
Callegan MC, Hill JM, Insler MS, Hobden JA, O'Callaghan RJ. Methiciliin-resistant Staphylococcus aureus
keratitis in the rabbit: Therapy with ciprofloxacin, vancomycin and cefazolin. Curr Eye Res
Utili R, Tripodi MF, Rosaria P, Andreana A, Locateli A, Rambaldi A, et al. Different susceptibility of coagulase-positive and coagulase-negative staphylococci to ciprofloxacin. New Microbiol
Hwang DG, Nakamura T, Trousdale MD, Smith TM. Combination antibiotic supplementation of corneal storage medium. Am J Ophthalmol
Burnie JP, Loudon KW. Ciprofloxacin-resistant Staphylococcus epidermidis and hands [letter]. Lancet
Schwarz S, Gregory PD, Werckenthin C, Curnockc S, Dyke KG. A novel plasmid from Staphylococcus epidermidis specifying resistance to kanamycin, neomycin and tetracycline. J Med Microbiol
Perichon B, Tankovic J, Courvalin P. Characterization of a mutation in the parE gene that confers fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother
Renneberg J, Niemann LL, Gutschik E. Antimicrobial susceptibility of 278 streptococcal blood isolates to seven antimicrobial agents. J Antimicrob Chemother
Gratten M, Nimmo G, Carlisle J, Shoonneveldt J, Seneviratue E, Kelly R, et al. Emergence of further serotypes of multiple drug-resistant Streptococcus pneumonia
in Queensland. Commun Dis Intell
Wise R, Brenwald N, Gill M, Fraise M. Streptococcus pneumoniae
resistance to fluoroquinolones [letter]. Lancet
Skull SA, Leach AJ, Currie BJ. Streptococcus pneumoniae
carriage and penicillin/ceftriaxone resistance in hospitalized children in Darwin. Aust NZ J Med
Schutze GE, Lewno MJ, Mason EO Jr. Use of ceftizoxime screening for the detection of cephalosporin-resistant pneumococci. Diagn Microbiol Infect Dis
Ormerod LD, Heseltine PNR, Alfonso E, Becker MI, Kenyon KR, Baerveldt G, et al. Gentamicin-resistant pseudomonal infection: Rationale for a redefinition of ophthalmic antimicrobial sensitivities. Cornea
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3]