TIME FOR A CHANGE? YES, BUT NOT TO CIPROFLOXACIN

Abstract

5 January 2006 Dear Editor, We read with interest the opinion of Coates1 about ear drops and tympanic membrane perforations. While we strongly agree that it is ‘time for a change’ away from topical aminoglycosides, we do not agree that the change should be to fluoroquinolones. Fluoroquinolones have established themselves as extremely valuable agents for the treatment of serious bacterial infections in humans, including those caused by bacteria resistant to other classes of drugs. Their value lies not only in these properties, but in our ability to use them orally and allow outpatient treatment for such infections, either as follow on from initial hospital treatment, or from the outset. Reflecting this perspective, the Pharmaceutical Benefits Scheme allows access to fluoroquinolones that is limited to ‘Authority required’ (except for ciprofloxacin and gonorrhoea which is a ‘Restricted benefit’). This is true for both oral and eye drop formulations, and for all fluoroquinolones. In addition, Australia has been one of the few countries to successfully prevent the introduction of fluoroquinolones into food animal production, thereby reducing resistance coming through the food chain to humans. Although arguments are sometimes made to the contrary, resistance can be selected with topical therapy despite locally high concentrations. If the opposite were true, then we would not be observing mupirocin resistance, because this agent is only used topically in ‘high concentration’. Unfortunately mupirocin resistance is now well documented, especially in areas of intensive use such as remote aboriginal communities – the same population where treatment of chronic suppurative otitis media (CSOM) is common.2 Of specific relevance to the use of ciprofloxacin ear drops, and counter to that stated by Coates, resistance has been selected during the treatment of CSOM. Jang and Park3 reported on failed ciprofloxacin therapy of CSOM in 88 patients. All patients were shown to have ciprofloxacin resistant Pseudomonas aeruginosa when recultured. Furthermore, topical use can provide the opportunity for local colonization with resistant organisms. Clinical trials of ciprofloxacin ear drops have not given rise to resistance selection in commensals in the short term. However, we cannot assume that it will not emerge in the long term, and indeed microbiological experience shows that eventually it does, with only rare exceptions. Evidence for resistance selection at sites distant to application of topical antibiotics has been demonstrated for tetracycline when used for acne4 and for he treatment of trachoma.5 We are therefore concerned that fluoroquinolones are now gaining currency as topical agents. While this can be justified for such sight-threatening conditions as bacterial keratitis, it is less than prudent to use them for minor conditions. Although CSOM is not a trivial infection, evidence has yet to emerge that topical antibiotics of any kind preserve hearing in the long term or prevent serious complications.6,7 Instead, the benefits are short-term and re-treatment is frequently required, leading to repeated antibiotic exposure and greater selection pressure for resistance. Hence, selecting for resistance with topical fluoroquinolone therapy for non-serious infections or for ‘prophylaxis’ puts the value of this class for truly serious infections under threat. To make our position clear, we are not strong supporters either of the use of topical aminoglycosides on resistance grounds. Aminoglycosides are also valuable antibiotics for serious infections. However, we know that neomycin, which is not used systemically, does not necessarily select for resistance to the standard systemic aminoglycosides such as gentamicin, and therefore not all topical aminoglycosides are alike. Unfortunately, using one fluoroquinolone topically will necessarily select for resistance to a range of valuable fluoroquinolones. The clinical problem addressed by Coates is a troublesome one, but rather than following his suggestions to lobby a wide range of groups to get ready access to ciprofloxacin ear drops, we believe that prescribers should urgently lobby the pharmaceutical industry to produce a safe and effective antimicrobial ear drop that does not have resistance implications for valuable reserve systemic antimicrobials. Australia has been very effective at controlling resistance to fluoroquinolones. We would like to keep it that way.