|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 2019 Oct 18];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
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3]