Drug interactions during therapy with three major groups of antimicrobial agents

This review focuses on drug-drug interactions with three major groups of antimicrobial agents: macrolides (including azalides and ketolides), quinolones, which are widely used for the treatment of bacterial infections, and azoles, which are used for antifungal therapy. Macrolides and the ketolide telithromycin are potent inhibitors of CYP3A4 and thus interfere with the pharmacokinetics of many other drugs that are metabolised by this enzyme. In contrast, although closely related, azithromycin is not a cytochrome inhibitor. All quinolones form complexes with di- and trivalent cations and, therefore, the absorption of quinolones can be dramatically reduced when given concomitantly with mineral antacids, zinc or iron preparations. Ciprofloxacin exhibits an inhibitory potential for the cytochrome isoenzyme 1A2, resulting in an inhibition of theophylline metabolism. Other quinolones, such as levofloxacin or moxifloxacin, do not interfere with theophylline metabolism. The systemic azoles, such as ketoconazole, itraconazole, fluconazole and voriconazole, are inhibitors of CYP isoenzymes, such as CYP3A4, CYP2C9 and CYP2C19, to varying degrees. In addition, some are substrates of the MDR-1 gene product, P-glycoprotein. These features are the basis for most of the interactions occurring during azole therapy (e.g., in severely ill patients in the hospital who are treated with multiple drugs).