M-2125. Triple Combination of Amphotericin B (AB), Cyclosporine (CS) and Ciprofloxacin (CIP) Against Candida albicans (CA) and Aspergillus fumigatus (AF)
Session: Poster Session: Antifungal Drugs
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: Immunocompromised patients may receive immunosuppressants (e.g. cyclosporine) simultaneously with antibacterial (e.g. ciprofloxacin) and antifungal agents. Cyclosporine exhibits antifungal activity against CA and AF; whereas, ciprofloxacin interacts with amphotericin B. Little is known about the interaction of these three drugs together. We therefore analyzed the combination of all 3 agents against 3 isolates of CA and AF by checkerboard microdilution.
Methods: Twofold serial dilutions of AB (0.015-0.5 mg/l), CS (0.095-3 mg/l) and CIP (4.25-68 mg/l) were combined with drug-free controls in RPMI 1640 (pH 7.0 with MOPS) and inoculated with 103/ml CA or 104/ml AF conidia at 37oC for 48 h. The minimal inhibitory concentration (MIC) was calculated for each drug alone and in combination as the lowest drug concentration showing no visible growth. Interactions were analyzed with the fractional inhibitory concentration (FIC) index calculated as MICABcomb/MICABalone + MICCScomb/MICCSalone + MICCIPcomb/MICCIPalone, where MICcomb and MICalone are the MICs of AB, CS and CIP alone and in combination, respectively. Significant (p<0.05) synergy or antagonism was concluded when mean FIC ± 95% confidence interval was lower or higher than 1, respectively. When 95% confidence interval included 1, additivity was concluded.
Results: MICs of AB, CS and CIP were 0.125-0.25 mg/l, >3 mg/l and >68 mg/l, respectively, for all CA and AF isolates. The FIC index of the triple combination was 0.13 for CA isolates and 0.37-0.51 for AF isolates observed at 0.03-0.25 mg/l of AB, 0.095-1.5 mg/l of CS in the absence of CIP. At 17 -68 mg/l of CIP, FIC indices were increased to 0.78-0.79.
Conclusion: AB interacts with CS synergistically against CA and AF. This synergy is reduced when CIP is combined.
Paraskevi Papaioannidou1, Emmanuel Roilides, PhD2, Ioannis Tsiouris1, Joseph Meletiadis, PhD3, Cathy Cotten4, Theodouli Stergiopoulou, MD3, Thomas Walsh, MD, FIDSA5, Tin Sein, MD6 and  T. Stergiopoulou, None., (1)Aristotle Univ., (2)Hippokration Hospital, Thessaloniki, Greece, (3)NCI, Bethesda, MD, (4)NIH, (5)National Cancer Institute, Bethesda, MD, (6)NCI, Bethesda MD, Bethesda, MD

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