EyeWorld Asia-Pacific June 2019 Issue

EWAP JUNE 2019 37 FEATURE and more towards levofloxacin. In recent years, Singapore has had access to high-concentration 1.5% levofloxacin in a preserva- tive-free commercial preparation. With severe cases of keratitis, an hourly 1.5% levofloxacin solution combined with a cephalospo- rin can cover a broad range of gram-positive and gram-negative organisms at a high concentra- tion. Levofloxacin has a high safety profile with minimal toxicity. This safety profile is one reason levofloxacin is available commer- cially in a high concentration and why other antibiotics may not be available at such a high concen- tration. For countries without the commercially available 1.5% levofloxacin, Dr. Tan says the use of a fortified antibiotic is useful. The fortified antibiotic consists of compounding a higher concen- tration of an aminoglycoside or cefazolin, which can then be used aggressively every hour to try to increase the concentration of the drug once administered to rapidly kill the bacteria. As for Dr. Garg’s perspective on the use of fluoroquinolones, he believes that the newer class of fluoroquinolones should include four drugs: levofloxacin, besiflox- acin, gatifloxacin, and moxiflox- acin, with the latter two used in clinical practice for a sufficient length of time. Analyzing the data on those two drugs’ susceptibility, Dr. Garg sees an increasing level of resistance among gram-pos- itive organisms, especially the ciprofloxacin-resistant gram-pos- itive organisms. However, these data may not translate directly to levofloxacin and besifloxacin because these molecules are not on the market in some areas and may not be commonly used in practice. Because of these two factors, Dr. Garg expects that these drugs will have much better activity than gatifloxacin and moxifloxacin. In his own research, Dr. Garg found that enhancing corneal penetration can be ac- complished by modifying the for- mulation of these agents. Further, increasing the concentrations of levofloxacin and besifloxacin is likely to increase corneal concen- tration, resulting in more effective eradication of organisms. In Dr. Garg’s practice, he realized in 2005 that many organ- isms started to show resistance. He then switched from using first-generation fluoroquinolones to fourth-generation fluoroquino- lones in less severe cases. In more severe keratitis cases, a combination of cefazolin plus an aminoglycoside was used. Since then, Dr. Garg has moved to treating all bacterial infections with a combination drug therapy of cefazolin plus an aminoglyco- side or ciprofloxacin. The limiting factor for Dr. Garg is that cefazolin is not available as an ophthalmic preparation and aminoglycosides are lower in concentration, so both drugs must be formulated before dispensing to the patient. “We are trying to work with the in- dustry in order to identify ways to overcome the non-availability of these antibiotics,” Dr. Garg said. SPONSORED BY SANTEN PHARMACEUTICALS Figure 2A: Comparison of MIC values of first and fourth generation quinolones against clinical isolates in 2002. The values clearly show that the fourth generation quinolones had an excellent activity against ciprofloxacin resistant gram positive isolates. Source: Prashant Garg, MD Figure 2B: Activity of fourth generation quinolones against ciprofloxacin resistant isolates as determined in 2009. The figures clearly show marked reduction in susceptibility against ciprofloxacin resistant isolates, compared to 2002 data, when these molecules were introduced. Source: Prashant Garg, MD