A 10-year study of cultures obtained between 1994 and 2003 from patients with bacterial conjunctivitis found a threefold increase in resistance to ciprofloxacin for gram-positive pathogens (11.7% to 35.6%).60 Two studies of resistance among S. aureus isolates identified increases from 8% of isolates in 1990-1995 to 20.7% in 1996-2001 for ciprofloxacin, and from 11% in 1990 to 28% in 1998 for both ciprofloxacin and ofloxacin.66,67
The balanced binding of the newer fluoroquinolones to DNA gyrase and topoisomerase IV has delayed the development of resistance to these agents. However, resistance is being reported: 18.9% and 15.9% of methicillin-sensitive S. aureus isolates were resistant to gatifloxacin and moxifloxacin, respectively, in the Ocular TRUST surveillance study.53
An in vitro study of coagulase-negative staphylococci isolates from patients with clinical endophthalmitis found that resistance to gatifloxacin increased from 0% in 1990-1994 to 22% in 1995-1999 and to 31% in 2000-2004. At least 65% of ciprofloxacin-resistant coagulase-negative Staphylococcus isolates were resistant to gatifloxacin and moxifloxacin.68
The continuing increase in the presence of MRSA and methicillin-resistant S. epidermidis (MRSE) has become especially worrisome because fluoroquinolone resistance often occurs concurrently with methicillin resistance. The percentage of isolates with MRSA bacteria recovered from patients with bacterial conjunctivitis in one study increased from 4.4% in 1994-1995 to 42.9% in 2002-2003.60
Another U.S. study of MRSA isolates obtained from ocular infections, which were primarily conjunctivitis, reported resistance rates of 68% for moxifloxacin, 71% for gatifloxacin, and 94% for ciprofloxacin and ofloxacin.69 Resistance by MRSE endophthalmitis isolates to fluoroquinolones has been less than that of MRSA, but a rate of 33% for moxifloxacin and gatifloxacin is still relatively high.70
Besifloxacin was not included in the surveillance studies because it was not available until after those studies were concluded. However, MRSA bacteria accounted for 14% of S. aureus isolates obtained in three clinical studies that evaluated the efficacy and safety of besifloxacin for the treatment of bacterial conjunctivitis. Sixty-five percent of the MRSA isolates were resistant to ciprofloxacin, and all ciprofloxacin-resistant isolates were resistant to levofloxacin, ofloxacin, gatifloxacin, and moxifloxacin.71
In the same analysis, MRSE constituted 46% of S. epidermidis isolates, including 47% that were resistant to ciprofloxacin and other comparator fluoroquinolones. In contrast, besifloxacin demonstrated potent in vitro activity against ciprofloxacin-resistant MRSA and MRSE.71,72 Besifloxacin is the first fluoroquinolone developed solely for topical ophthalmic use. The absence of a systemic counterpart reduces the contribution to resistance development from previous systemic use.
Choosing effective therapy
Bacterial conjunctivitis is a self-limited disease, but treatment with an ophthalmic antibiotic can reduce the time to resolution of symptoms and prevent potentially vision-threatening complications. To treat bacterial conjunctivitis effectively, select a medication with broad-spectrum activity against ocular pathogens, rapid bactericidal activity, high concentrations in the eye, a long residence time, and safety and tolerability for patients. It is also important to consider how an antibiotic’s formulation will affect its efficacy and tolerability.
Choosing an appropriate treatment has become more difficult because increased bacterial resistance has compromised the effectiveness of many options. Such older ophthalmic medications as the aminoglycosides, polymyxin B combinations, and macrolides have become especially susceptible to bacterial resistance.
Fluoroquinolones remain the best choice for the treatment of bacterial conjunctivitis, but the older fluoroquinolones have experienced increasing resistance by the bacteria that most often cause bacterial conjunctivitis. Further, fluoroquinolone-resistant MRSA bacteria have exhibited high rates of resistance to most of the newer fluoroquinolones. In vitro studies have shown that besifloxacin is active against fluoroquinolone-resistant MRSA, although further studies are needed to confirm these results.
Ms. Spering is a nurse practitioner with Brndjar Medical Associates in Emmaus, Pa. Editorial assistance in the development of this manuscript was provided by Churchill Communications and funded by Bausch + Lomb. The author has no relationship to disclose relating to the content of this article.
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