Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus

Abstract

Objectives: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Ciprofloxacin, a carboxyfluoroquinolone, was previously observed to demonstrate the pharmacodynamic interactions with antifungal agents by altering their growth inhibitory activity against Candida albicans and Aspergillus fumigatus. However, little is known about the interaction between other extended-spectrum fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents against C. albicans and A. fumigatus.

Methods: Using a microdilution chequerboard technique, we employed isobolographic analysis adapted to incorporate a non-active agent in order to analyse the potential in vitro interaction between ciprofloxacin, levofloxacin or moxifloxacin and the following representative antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin.

Results: Synergistic interactions [interaction indices (Iis) 0.69-0.83, P < 0.05] were observed between amphotericin B (0.07-0.31 mg/L) and either ciprofloxacin (0.19-7.65 mg/L) or levofloxacin (0.41-32.88 mg/L) against C. albicans and A. fumigatus. Synergy (Iis 0.56-0.87, P < 0.05) also was found between voriconazole (0.09-0.14 mg/L) and ciprofloxacin (0.22-11.41 mg/L) as well as between caspofungin (8.94-22.07 mg/L) and levofloxacin (0.14-5.17 mg/L) against A. fumigatus. Some antagonistic (Iis 1.16-1.29, P < 0.05) interactions were observed between fluoroquinolones and fluconazole against C. albicans. In general, ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin and levofloxacin against both C. albicans and A. fumigatus.

Conclusions: The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections.

Figure 1

Box-whisker plots of the Iis for the combination between ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MXF) and (i) amphotericin B, (ii) fluconazole or (iii) caspofungin against three C. albicans isolates. The symbols * and † indicate statistically significant synergistic and antagonistic interactions, respectively, using Wilcoxon's rank test. The brackets at the top of the plots join the combinations for which statistically significant comparative results (P < 0.05) were observed using the Kruskal–Wallis test.

Figure 2

Box-whisker plots of the Iis for the combination between ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MXF) and (i) amphotericin B, (ii) voriconazole or (iii) caspofungin against three A. fumigatus isolates. The symbol * indicates statistically significant deviation of Iis from 1 using Wilcoxon's rank test. The brackets at the top of the plots join the combinations for which statistically significant comparative results (P < 0.05) were observed using the Kruskal–Wallis test.