Response to correspondence from Lichtenstein and Granet Re: Fluoroquinolones compared to 1% azithromycin in DuraSite® for bacterial conjunctivitis

In a recent issue of Clinical Ophthalmology, Friedlaender and Protzko (2007) review the development and effi cacy of 1% azithromycin in DuraSite ® (AzaSite™, Inspire Pharmaceuticals , Inc., Durham, NC) for the treatment of bacterial conjunctivitis. The authors conclude that 1% azithromycin in DuraSite offers a simplifi ed dosing regimen with sustained bactericidal levels that decrease resistance development. While 1% azithromycin in DuraSite is a new formulation of azithromycin that allows topical ocular use, azithromycin and DuraSite have been around for many years. Evidence demonstrates a greater potential for emerging resistance with azithromycin, an older drug, especially when formulated in a vehicle that prolongs low levels of antibiotic exposure over time. Azithromycin is derived from the parent class of macrolides, known to be bac-teriostatic. The ability of azithromycin to achieve high intracellular concentrations compared with other macrolides is credited for its bactericidal activity. However, in clinical practice, given the high level of Gram-positive resistance patterns, azithromycin demonstrates time-dependent, bacteriostatic kill against most bacteria within its clinical spectrum. DuraSite technology allows azithromycin to stay in contact with the ocular surface longer than conventional aqueous eye drops; a potential concern for resistance that led to a US Food and Drug Administration (FDA) warning on their package insert regarding missing doses: " Skipping doses or not completing the full course of therapy may … increase the likelihood that bacteria will develop resistance and will not be treatable by AzaSite (azithromycin ophthalmic solution) or other antibiotic drugs in the future. " (Azasite 2007). In contrast, potent, rapid-killing, broad-spectrum topical anti-infectives are less likely to promote resistance and do not carry such an FDA warning. Among these agents are the ophthalmic fourth-generation fl uoroquinolones (FQs) that demonstrate concentration-dependent bactericidal kill and are not reliant on time as suggested by the authors. The authors state that changing trends in the activity of newer-generation FQs demonstrate increased resistance among common bacterial conjunctivitis pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus infl uenzae. However, within the article, all 3 cited references (Goldstein et al 1999; Venezia et al 2001; Ambrose et al 2004) document resistance patterns in older-generation FQs instead of newer fourth-generation agents such as moxifl oxacin 0.5% and gatifl oxacin 0.3%. The distinction is critical. The development of resistance to older FQs develops through a single-step topoisomerase mutation (topoisomerase II or topoisomerase IV). However, resistance to newer FQs requires 2 spontaneous mutations at both topoisomerase …