In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum
Author(s) -
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
Publication year - 2015
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01480-15
Subject(s) - minocycline , tigecycline , azithromycin , clarithromycin , in vivo , checkerboard , antimicrobial , microbiology and biotechnology , broth microdilution , antibiotics , pharmacology , antibacterial agent , biology , minimum inhibitory concentration
The present study investigated thein vitro and thein vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline againstPythium 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 againstP. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted inin vitro synergistic interactions (>60%). Antagonism was not observed. Thein 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.
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