In vitro antibacterial activity of azole antifungals against carbapenemresistant Enterobacteriaceae

Abstract

Introduction: The frequency of serious bacterial infections has increased due to the high prevalence of HIV, contributing to the increasing rates of multi-drug organisms which include carbapenem-resistant Enterobacteriaceae (CRE). This has resulted in higher use of immunosuppressive and cytotoxic drugs to treat serious bacterial infections and optimal treatment for infections caused by CRE remains unknown. The benefits of azole antifungals and its derivatives have become very topical due to their diverse spectrum of pharmacological properties, but its efficacy has not been tested in the South African context. The aim of this study was to determine the antibacterial effects of azole antifungals against CRE.
Method: Different concentrations of azole antifungals (ketoconazole, metronidazole and fluconazole) were used to prepare sensitivity discs and four pathogenic strains of CRE (K. pneumoniae, E. coli, S. marcesens and C. freundii). These were obtained from Lancet Laboratory in Durban and were used to determine the antibacterial activity of the selected azole antifungals, using: Disc Diffusion, Modified Agar Diffusion and Minimum Inhibition Concentration (MIC) method, as described by Bauer et al 1966.
Results: Antimicrobial Susceptibility Testing revealed that azoles have no inhibition activity against CRE test organisms and biochemical tests also demonstrated that azoles have no adverse effects on the CRE organisms.
Conclusion: Although the results obtained in this study indicated no activity of azoles against CRE, clinical studies are still necessary for the modification of the azole substituents and synthesis of azole derived drugs to confirm and optimise the antibacterial efficacy of these compounds.