Efficacy, cost favor use of older antibiotics for topical endophthalmitis prophylaxis

June 1, 2008

Significant controversy surrounds selection of antibiotics for endophthalmitis prophylaxis. Richard K. Forster, MD, explains why he believes fourth-generation fluoroquinolones should not replace older antibiotics.

Key Points

Miami-Older topical antibiotics, such as gentamicin and polymyxin B-trimethoprim, remain viable choices for prophylaxis of postoperative endophthalmitis, said Richard K. Forster, MD.

Dr. Forster's statement was based on his analysis of the issues, considering the objectives for using topical antibiotic prophylaxis, the etiology of these infections, current data on in vitro antibiotic susceptibility, and medication cost.

"My opinion may be at odds with others'. However, it considers that gentamicin and polymyxin B-trimethoprim are much more effective than the newer fourth-generation fluoroquinolones against the organisms causing about 80% of cases of infectious endophthalmitis, namely coagulase-negative staphylococci and methicillin-sensitive and methicillin-resistant Staphylococcus aureus, and are less expensive as well," Dr. Forster explained. He is the Richard K. Forster Chair in Corneal and External Ocular Diseases, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami.

Next, Dr. Forster identified the most common causes of postoperative endophthalmitis by considering data from the 1993 report of the Endophthalmitis Vitrectomy Study (EVS) and from a second study in press from Bascom Palmer that reports on a series of eyes with endophthalmitis postcataract surgery. The EVS included more than 200 culture-proven cases of endophthalmitis, and the contemporary series included 70 eyes that had undergone phacoemulsification through a clear corneal incision. In the two reports, coagulase-negative staphylococci accounted for approximately 70% of the clinical isolates and S. aureus represented about 10%.

"In our recent data, the S. aureus isolates were about equally divided between methicillin-resistant and methicillin-sensitive strains," Dr. Forster said.

Streptococcus spp. accounted for another 10% of the endophthalmitis pathogens, and other miscellaneous organisms, including gram-negative bacteria, comprised the rest of the clinical isolates.

Resistant strains risk

In considering the risk of selecting out resistant strains, Dr. Forster referred to a recent paper from Deramo et al. reporting on 42 patients with acute onset endophthalmitis developing within 6 weeks of cataract surgery. In that series, almost three-fourths of patients had been treated perioperatively with one of the fourth-generation fluoroquinolones, moxifloxacin 0.5% (Vigamox, Alcon Laboratories) or gatifloxacin 0.3% (Zymar, Allergan), and more than half (57%) were using one of those medications at the time of endophthalmitis diagnosis. Coagulase-negative staphylococci was the most frequently isolated pathogen.

"In this series, the fourth-generation fluoroquinolones certainly did not prevent endophthalmitis, and that is consistent with a dramatic rise we have noted in the resistance of coagulase-negative staphylococci to these antibiotics over the past 15 years," Dr. Forster said.

He presented data from the Ocular Microbiology Laboratory, Bascom Palmer Eye Institute, to show the changing susceptibility patterns. Between 1990 and 1994, 97% of coagulase-negative staphylococci isolates were sensitive to gatifloxacin or moxifloxacin; the MIC90 values for those antibiotics were 0.19 µg/ml and 0.12 µg/ml, respectively. In contrast, for the period from 2000 to 2005, only 65.4% of coagulase-negative staphylococci isolates were sensitive to the fourth-generation fluoroquinolones. The MIC90 values for both gatifloxacin and moxifloxacin had risen to =32 µg/ml.

Susceptibility testing of 30 or more randomly selected coagulase-negative staphylococci isolates from the more recent period showed 97% were sensitive to gentamicin, 66% were sensitive to trimethoprim, 50% were sensitive to gatifloxacin, and 53% were sensitive to moxifloxacin, Dr. Forster said.

In addition, a review of the susceptibility data for S. aureus isolates showed that the older and newer antibiotics maintain potent activity against methicillin-sensitive strains. Much greater disparity exists, however, with methicillin-resistant S. aureus, for which gentamicin had efficacy against 81% of isolates and 74% were sensitive to trimethoprim, whereas gatifloxacin and moxifloxacin were effective against only 32% and 45% of isolates, respectively.

Considering other endophthalmitis pathogens, all four antibiotics were highly effective against the most common gram-negative isolates, although only the fourth-generation fluoroquinolones provide good coverage against the relevant streptococcal pathogens.

"However, Streptococcus spp. comprise only about 10% of all endophthalmitis isolates," Dr. Forster said.

Calculated efficacy

He collated the information on the prevalence of the various pathogens and the antimicrobial susceptibility data to calculate the percentage of endophthalmitis cases in which the organism would be expected to be sensitive to a chosen antibiotic. The analysis showed that gentamicin would offer the highest efficacy, because it would be expected to be effective against 87% of potential endophthalmitis pathogens. Calculated efficacies for polymyxin B-trimethoprim, moxifloxacin, and gatifloxacin were 66%, 62%, and 58%, respectively.

"Gentamicin sulfate, available as a generic, is also the least expensive of these agents. Based on the average wholesale price listed in Red Book: Pharmacy's Fundamental Reference, 2007 Edition, a bottle of gentamicin sulfate costs $9.50, while generic polymyxin B-trimethoprim lists for $17.42, and the wholesale cost for both the branded fourth-generation fluoroquinolones exceeds $60," he said.