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In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

2015; American Society for Microbiology; Volume: 60; Issue: 1 Linguagem: Inglês

10.1128/aac.01480-15

1098-6596

Francielli Pantella Kunz de Jesus, Érico Silva Loreto, Laerte Ferreiro, Sydney Hartz Alves, David Driemeier, Suyene Oltramari de Souza, Raqueli Teresinha França, Sônia T.A. Lopes, Maiara B. Pilotto, Aline Ludwig, María Isabel de Azevedo, Tatiana Corrêa Ribeiro, Juliana S. M. Tondolo, Jânio Morais Santúrio,

Veterinary Oncology Research

The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.