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Synergistic Interaction of the Triple Combination of Amphotericin B, Ciprofloxacin, and Polymorphonuclear Neutrophils against Aspergillus fumigatus

  1. Author:
    Stergiopoulou, T.
    Meletiadis, J.
    Sein, T.
    Papaioannidou, P.
    Walsh, T. J.
    Roilides, E.

  2. Author Address

    [Stergiopoulou, T; Roilides, E] Aristotle Univ Thessaloniki, Sch Med, Dept Pediat 3, Hippokrat Hosp, GR-54642 Thessaloniki, Greece. [Stergiopoulou, T; Meletiadis, J; Walsh, TJ; Roilides, E] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Meletiadis, J] Univ Athens, Sch Med, Lab Clin Microbiol, Attiko Univ Hosp, GR-11527 Athens, Greece. [Sein, T] SAIC Frederick Inc, Ft Detrick, MD 21702 USA. [Papaioannidou, P] Aristotle Univ Thessaloniki, Sch Med, Dept Pharmacol, Fac Med, GR-54642 Thessaloniki, Greece. [Walsh, TJ] Cornell Univ, Weill Cornell Med Coll, Transplantat Oncol Infect Dis Program, Div Infect Dis, New York, NY 10021 USA.;Roilides, E (reprint author), Aristotle Univ Thessaloniki, Sch Med, Dept Pediat 3, Hippokrat Hosp, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece;roilides@med.auth.gr
    1. Year: 2011
    2. Date: Dec
  2. Journal: Antimicrobial Agents and Chemotherapy
    1. 55
    2. 12
    3. Pages: 5923-5929
  4. Type of Article: Article
  5. ISSN: 0066-4804
  1. Abstract:

    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 mu g/ml of AMB, 0.1 to 50 mu g/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 mu g/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 mu g/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 mu g/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.

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External Sources

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  2. DOI: 10.1128/aac.00548-11
  3. View record in Web of Science®
  4. WOS: 000296920600067

Library Notes

  1. Fiscal Year: FY2011-2012
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