Emerging ciprofloxacin-resistant Pseudomonas aeruginosa

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Complications of laser-assisted in situ keratomileusis may occur in each step of the procedure, including the use of the microkeratome, excimer laser, or postoperative management. Severe complications have been reported such as corneal perforation caused by inappropriate assembly of the microkeratome,1 displacement of the corneal flap,2 and melting of the corneal flap because of progressive epithelial ingrowth.3 This patient had irregular corneal thickness, and accidental perforation of the corneal stromal bed resulted from the inexperience of the surgeon. It is speculated that the anterior lens capsule was ruptured by inappropriate suturing of the stromal bed to seal the perforation site. Surgeons performing laser-assisted in situ keratomileusis should be aware of potentially devastating complications. REFERENCES

1. Moner JIB, Granados JIB. Intrastromal keratomileusis: complications associated with the microkeratome. In: Buratto L, Brint SF, editors. LASIK principles and techniques. Thorofare, New Jersey: Slack, 1998:365–369. 2. Hoffman CJ, Rapuano CJ, Cohen EJ, Laibson PR. Displacement of corneal lenticule after automated lamellar keratoplasty. Am J Ophthalmol 1994;118:109 –111. 3. Castillo A, Diaz-Valle D, Gutierrez AR, Toledano N, Romero F. Peripheral melt of flap after laser in situ keratomileusis. J Refract Surg 1998;14:61– 63.

Emerging Ciprofloxacin-Resistant Pseudomonas aeruginosa Nauman A. Chaudhry, MD, Harry W. Flynn, Jr, MD, Timothy G. Murray, MD, Homayoun Tabandeh, MD, Mozart O. Mello, Jr, MD, and Darlene Miller, MS, MPH PURPOSE:

To report a clinical series of ciprofloxacinresistant ocular isolates of Pseudomonas aeruginosa from a tertiary care ophthalmic center. METHODS: Review of in vitro sensitivities of all ocular isolates of P. aeruginosa between July 1991 and September 1998. In vitro resistance was defined as a minimum inhibitory concentration of 4 or more ␮g per ml. RESULTS: Nine of 423 ocular isolates of P. aeruginosa showed in vitro resistance to ciprofloxacin. From 1991 to 1994, 0.44% (1/227) of ocular isolates were resistant to Accepted for publication May 22, 1999. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Ft Lauderdale, Florida, 1999. Reprint requests to Timothy G. Murray, MD, Bascom Palmer Eye Institute, 900 NW 17th St, University of Miami School of Medicine, Miami, FL 33136; fax: (305) 326-6417.

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ciprofloxacin, whereas from 1995 to 1998, 4.1% (8/ 196) of ocular isolates showed in vitro resistance (P ⴝ .014). CONCLUSIONS: Ciprofloxacin-resistant P. aeruginosa has been identified in recent clinical ocular specimens. Ciprofloxacin resistance among ocular isolates of P. aeruginosa is a local and worldwide concern. (Am J Ophthalmol 1999;128:509 –510. © 1999 by Elsevier Science Inc. All rights reserved.)



ophthalmic practice.1 It is a broad-spectrum fluoroquinolone with coverage against most gram-positive and gram-negative organisms, including Pseudomonas aeruginosa. The emergence of ciprofloxacin-resistant ocular isolates is a growing concern.2–5 This study was conducted to examine the susceptibility of ocular isolates of P. aeruginosa to ciprofloxacin. In the microbiology department of the Bascom Palmer Eye Institute, a review of in vitro sensitivities of all ocular isolates of P. aeruginosa between January 1991 and December 1998 was performed. In vitro resistance was defined as a minimum inhibitory concentration (MIC) of 4 or more ␮g per ml. The sensitivities were tested with the automated Vitek test system (bioMerieux Vitek Inc, Missouri) and confirmed with the conventional disk diffusion method and the “E” test (AB Biodisk, Remel, Lenexa, Kansas). During the 8-year study period, a total of 499 ocular isolates of P. aeruginosa were identified; 76 isolates were excluded because of multiple cultures from the same patients. Of the 423 ocular isolates included in this study, nine showed in vitro resistance to ciprofloxacin. The source of ocular specimens included cornea (4), conjunctiva (2), orbital tissue (2), and lacrimal sac (1). All isolates were sensitive to gentamicin (Table 1). The isolates were not tested for other fluoroquinolones because resistance to ciprofloxacin implies resistance to all other clinically available fluoroquinolones, including ofloxacin, norfloxacin, lomefloxacin, and enoxacin.6 To study the trend in susceptibility of ciprofloxacin to ocular P. aeruginosa, we studied the susceptibility pattern between 1991 to 1994 and 1995 to 1998 (Figure 1). During the 1991 to 1994 interval, 227 ocular isolates were tested, and only one (0.44%) showed in vitro resistance to ciprofloxacin. Between 1995 and 1998, 196 isolates were studied and eight (4.1%) were resistant to ciprofloxacin. The change in susceptibility was statistically significant (P ⫽ .014; Fisher exact test). Reported ciprofloxacin-resistant ocular isolates include coagulase-negative Staphylococcus, Staphylococcus aureus, Streptococcus viridans, Corynbacterium pseudodiphtheriticum, Xanthomonas maltophila, and Mycobacterium chelonae.1–5 The possible mechanisms for acquired resistance include a decrease in the susceptibility of DNA gyrase to the



TABLE 1. In Vitro Antibiotic Sensitivities of Ocular Isolates of Pseudomonas aeruginosa*


1 (Orbit)†

2 (Cornea)

3 (Cornea)

4 (Conjunctiva)

5 (Cornea)

6 (Lacrimal sac)

7 (Scleral buckle)

8 (Cornea)

9 (Orbit)

Amikacin Aztreonam Ceftazidime Ciprofloxacin Chloremphenicol Gentamicin Imipenem Piperacillin Tobramycin Ticarcillin

S — S R — S — — S —

S S S R — S I S S —

S S — R — S S S S —

S S S R — I — S S S

S S S R — S S S S —

S — S R — S S — S —


S — — R — S S — S —

S — — R — S — S — —

I ⫽ intermediate sensitivity; R ⫽ resistant; S ⫽ sensitive; — ⫽ not tested. *Sensitivities were determined by the Kirby-Bauer disk diffusion. † Source of specimen.

current series). Since then, eight additional cases have been identified and are included in the current series. Two cases (Cases 7 and 8) failed to respond clinically to topical ciprofloxacin. The remaining seven cases were not treated with fluoroquinolones during the clinical course. It is important to mention that in vitro resistance to a given antibiotic does not mean that the ocular infection will not improve with topical antibiotic therapy.4 The in vitro susceptibilities are based on MIC values for serum concentration of antibiotics and do not always equate with the in vivo susceptibilities. When antibiotics are given topically, much higher concentrations may be obtained, and host factors also play a critical role. However, in this series, clinical failure of treatment correlated with the in vitro results for both patients treated with topical ciprofloxacin. The current series and the report by Kuminoto and associates5 remind us of the worldwide emerging resistance against this class of antibiotics. If the present trend continues, clinicians may encounter more frequent ciprofloxacin resistance among common ocular isolates.

FIGURE 1. Susceptibility to ciprofloxacin of ocular P. aeruginosa. Percent susceptible for 1991 to 1994 compared with 1995 to 1998.

drug-mediated inhibition, a decrease in the amount of drug accumulation within the bacteria, or both.2 Knauf and associates4 showed a statistically significant increase in ciprofloxacin-resistant nonocular isolates (including P. aeruginosa) from 1988 to 1993. All these systemic isolates are also common ocular pathogens. Recently, Kuminoto and associates5 reported in vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin at a major eye hospital in India. Of the 1,558 corneal isolates, 478 (30.7%) were not sensitive to ciprofloxacin. The resistant isolates included gram-positive and gram-negative organisms, as well as actinomycetes and related organisms. Eight (8.4%) of 95 corneal isolates of P. aeruginosa were resistant. Between 1992 and 1997, there was a trend of significantly increasing ciprofloxacin insensitivity in bacteria. We previously reported a case of scleral buckle infection from ciprofloxacin-resistant P. aeruginosa2 (Case 7 in the 510



1. Wilhelmus KR, Hyndiuk RA, Caldwell DR, et al. 0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. Arch Ophthalmol 1993;111:1210 –1218. 2. Chaudhry NA, Tabandeh H, Rosenfeld PJ, Smith D, Davis J. Scleral buckle infection with ciprofloxacin-resistant Pseudomonas aeruginosa. Arch Ophthalmol 1998;116:1251. 3. Snyder ME, Katz HR. Ciprofloxacin-resistant bacterial keratitis. Am J Ophthalmol 1992;114:336 –338. 4. Knauf HP, Silvany R, Southern PM, Risser RC, Wilson SE. Susceptibility of corneal and conjunctival pathogens to ciprofloxacin. Cornea 1996;15:66 –71. 5. Kunimoto DY, Sharma S, Garg P, Rao GN. In vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin: emerging resistance. Ophthalmology 1999;106:80 – 85. 6. Lorian V. Antibiotics in laboratory medicine, ed 4. Baltimore: Williams & Wilkins, 1996:478. OF



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