Effect of Ciprofloxacin and Ofloxacin on Bacterial Flora

The article about the effect of topical ciprofloxacin and ofloxacin on the reduction of bacterial flora concludes that only ciprofloxacin 0.3% effectively reduces conjunctival flora over the first 2 hours after application.1 This conclusion is based on the results of 20 patients per treatment arm in an unmasked, nonrandomized study supported in part by an unrestricted grant from Alcon. The results suggest that ofloxacin has little effect on reducing bacterial flora over at least the first 2 hours after application. At the 60 minute time point, however, the control arm had a greater reduction in colony counts (53.3%) than the ofloxacin arm (41.8%). The variability in the control arm colony counts calls into question the reliability of the culturing technique used in the study. The study also ignores the results of a much larger study reported by Rhee et al.2 that more accurately reflects the preoperative condition. They randomized 200 surgical patients to treatment with ciprofloxacin or ofloxacin and cultured at similar time points. The results in the ciprofloxacin group were very similar to the results reported in this study. The ofloxacin results, however, were essentially identical to the ciprofloxacin results, leading to the conclusion that there was no statistical difference in the rate of conjunctival sterilization between ciprofloxacin and ofloxacin used in the 2 hours prior to surgery. Snyder-Perlmutter and coauthors proceed to discuss the relative advantages of the fluoroquinolones, particularly ciprofloxacin, with regard to inhibitory quotients, kill curves, and tear-film levels. In each instance, they claim ciprofloxacin has a clear advantage. Yet, with regard to kill curves, they refer to a study limited to 2 strains of Pseudomonas. They do not discuss the study by Callegan and coauthors3 that compared kill curves of ciprofloxacin and ofloxacin against many different ocular pathogens. While the difference in the kill rate across all pathogens did not achieve statistical significance, there was a clear trend toward ofloxacin killing more quickly even against Pseudomonas. To quote the conclusion, “…tofloxacin achieved killing of the majority of ocular pathogens tested at rates equivalent to or faster than that of ciprofloxacin.”. The measurement of tear-film levels can also be questioned because of the inability to distinguish solubilized drug from crystallized drug. Ciprofloxacin precipitates more readily than ofloxacin due to its low pH of solubility, 4.5, compared to that of ofloxacin, 6.4. While the drug may remain chemically active in its crystallized form, it is not bioavailable. For the drug to be bioavailable, it must be in a solubilized form capable of penetrating to the nucleus of the bacteria to bind to the DNA-gyrase. Furthermore, the low-solubility pH ensures that very little of the ciprofloxacin will resolubilize and become bioavailable once it has crystallized. Hence, the tear level does not reflect the amount of drug that is bioavailable on the ocular surface. This same difficulty coupled with the wide variability of MIC levels prevents the determination of clinically relevant information from inhibitory quotients. The authors state that “ofloxacin appears to penetrate ocular tissues slightly better.” Donnenfeld et al.4 show that ofloxacin reaches the aqueous at levels 5-fold greater than ciprofloxacin, indicating more than “slightly better” penetration. Finally, caution must be exercised when reaching clinical conclusions based on the data of small unmasked nonrandomized studies supported by the company selling the product under study. The discussion in this study should have addressed the issues their results raise in relation to other published studies. John R Wittpenn MD aStony Brook, New York, USA