Evolving Fluoroquinolone Resistance Among Coagulase-Negative Staphylococcus Isolates Causing Endophthalmitis

Endophthalmitis is a serious, sight-threatening condition resulting in substantial morbidity. With the widespread use of fluoroquinolone antibiotic eyedrops as a prophylactic agent, there is concern regarding increased frequency of fluoroquinolone resistance. We report the evolution of fluoroquinolone resistance among coagulase-negative Staphylococcus endophthalmitis isolates at the Bascom Palmer Eye Institute.

The study was approved by the Institutional Review Board of the University of Miami School of Medicine Medical Sciences Subcommittee for the Protection of Human Subjects. This was a retrospective, noncomparative, consecutive case series. We reviewed the microbiological and medical records of all patients with culture-proven endophthalmitis (positive cultures from the vitreous cavity) caused by coagulase-negative Staphylococcus at the Bascom Palmer Eye Institute between January 1, 1990, and July 1, 2011. Susceptibility testing of the intraocular isolates was performed using an automated system—the VITEK automatic microbial system (Biomérieux, Inc) or the E test (AB Biodisk NA, Inc and Remel Products). Frozen isolates were reconstituted as needed to evaluate sensitivities of earlier cases to newer-generation fluoroquinolones.

During the 21.5 years of the current study, 168 patients were identified as having culture-proven endophthalmitis caused by coagulase-negative Staphylococcus. The increasing resistance rates are shown in the Figure for 1990 to 1994 (n = 29), 1995 to 1999 (n = 23), 2000 to 2004 (n = 26), and 2005 to 2011 (n = 89). The respective resistances (in percentages) of the first 3 periods are the following: ciprofloxacin resistance, 10.3%, 17.4%, and 38.4%; levofloxacin resistance, 0%, 17.0%, and 38.4%; moxifloxacin resistance, 0%, 21.8%, and 26.9%; and gatifloxacin resistance, 0%, 21.8%, and 30.7%. The mean resistance rates for January 1, 2005, through July 1, 2011 (n = 89), were 60.5% for ciprofloxacin, 58.6% for levofloxacin, 57.8% for moxifloxacin, and 60.5% for gatifloxacin (Figure).

Despite the dual mechanisms of fluoroquinolones to avoid resistance to coagulase-negative Staphylococcus, the frequency of resistance to these organisms is increasing. Recent evidence shows that repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics, including fluoroquinolones, creates resistant strains.^1,2 It has further been shown that resistant strains of coagulase-negative Staphylococcus may be associated with greater ocular inflammation, greater virulence, and increased ocular infection rates compared with susceptible strains.^3,4

Fourth-generation fluoroquinolones are significantly more expensive than generic traditional antibiotic eyedrops such as gentamicin sulfate and polymyxin B sulfate/trimethoprim, which have been shown to cover endophthalmitis isolates at least as well.⁵ Additional recent reports demonstrate that the fourth-generation fluoroquinolones achieve subtherapeutic levels in the aqueous humor and vitreous against the most frequently identified staphylococcal endophthalmitis isolates.⁶ Given the frequent and increasing resistance, subtherapeutic penetration, and higher cost compared with other antibiotic eyedrops, the widespread perioperative and periprocedural use of fourth-generation fluoroquinolone antibiotic eyedrops should be reevaluated.

Correspondence: Dr Flynn, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St, Miami, FL 33136 (hflynn@med.miami.edu).