Synergistic interaction of the triple combination of amphotericin B, ciprofloxacin, and polymorphonuclear neutrophils against Aspergillus fumigatus.pdf
[en] Aspergillus is damaged by polymorphonuclear neutrophils (PMNs) by means of nonoxidative and oxidative mechanisms, which may be affected by antifungal and antibacterial agents that patients with invasive pulmonary aspergillosis often receive. The pharmacodynamic interactions among deoxycholate amphotericin B (AMB), ciprofloxacin (CIP), and human PMNs against Aspergillus fumigatus growth are unknown. We therefore studied the interactions between 0.032 to 2.0 mug/ml of AMB, 0.1 to 50 mug/ml of CIP at a fixed AMB/CIP ratio of 1:3.125, and PMNs from six donors at an effector-to-target (E:T) ratio of 400:1 against a clinical A. fumigatus isolate using an XTT metabolic assay and the Bliss independence pharmacodynamic-interaction model. CIP exhibited no antifungal activity alone or in combination with PMNs. Synergy was found between AMB and PMNs, with interaction indices (II) of 0.06 to 0.21; the highest interaction of 21% +/- 3.6% was observed at 0.22 +/- 0.09 mug/ml of AMB. The AMB and CIP (AMB+CIP) combination was synergistic (II = 0.39) at low AMB concentrations and antagonistic (II = 1.39) at high AMB concentrations, with a maximal synergistic interaction of 16% +/- 3.7% observed at 0.16 +/- 0.08 mug/ml of AMB. The triple combination AMB+CIP+PMNs was synergistic, with interaction indices of 0.05 to 0.20, and a maximal synergistic interaction of 24% +/- 4% was observed at 0.20 +/- 0.07 mug/ml of AMB. The increased percentage of Bliss synergy of the triple combination AMB+CIP+PMNs (24% +/- 4%) was the product of those of the constituent double combinations AMB+PMNs (21% +/- 3.6%) and AMB+CIP (16% +/- 3.7%). Thus, the antifungal activity of AMB, at clinically relevant concentrations, was enhanced in combination with PMNs and CIP against A. fumigatus growth in a concentration-dependent manner.
STERGIOPOULOU, Theodouli ; 3rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, Thessaloniki, Greece and Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Meletiadis, Joseph; Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland and Laboratory of Clinical Microbiology, Attiko University Hospital, University of Athens School of Medicine, Athens, Greece
Sein, Tin; SAIC-Frederick, Inc., P. O. Box B Frederick, Maryland 21702
Papaioannidou, Paraskevi; Department of Pharmacology, Medical Faculty, Aristotle University, School of Medicine, Thessaloniki, Greece
Walsh, Thomas J.; Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland and Transplantation-Oncology Infectious Diseases Program Division of Infectious Diseases, Weill Cornell Medical College of Cornell University, New York, New York
Roilides, Emmanuel; 3rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, Thessaloniki, Greece and Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Language :
English
Title :
Synergistic interaction of the triple combination of amphotericin B, ciprofloxacin, and polymorphonuclear neutrophils against Aspergillus fumigatus.
Publication date :
December 2011
Journal title :
Antimicrobial Agents and Chemotherapy
ISSN :
0066-4804
eISSN :
1098-6596
Publisher :
American Society for Microbiology, Washington, United States - District of Columbia
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