title: In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum.
abstract: 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.
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Francielli P K
authors.initials: FP
authors.lastname: Jesus
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Érico S
authors.initials: ÉS
authors.lastname: Loreto
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Laerte
authors.initials: L
authors.lastname: Ferreiro
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Sydney H
authors.identifier: http://orcid.org/0000-0001-5740-387X
authors.initials: SH
authors.lastname: Alves
authors.affiliation: Setor de Patologia Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Driemeier
authors.affiliation: Setor de Patologia Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Suyene O
authors.initials: SO
authors.lastname: Souza
authors.affiliation: Clinica Médica e Cirúrgica de Pequenos Animais-Patologia Clínica Veterinária, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Raqueli T
authors.initials: RT
authors.lastname: França
authors.affiliation: Clinica Médica e Cirúrgica de Pequenos Animais-Patologia Clínica Veterinária, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Sonia T A
authors.initials: ST
authors.lastname: Lopes
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Maiara B
authors.initials: MB
authors.lastname: Pilotto
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Ludwig
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Azevedo
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Ribeiro
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Juliana S M
authors.initials: JS
authors.lastname: Tondolo
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil janio.santurio@gmail.com.
authors.forename: Janio M
authors.initials: JM
authors.lastname: Santurio
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015999:Multivariate Analysis; D058968:Pythiosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011775:Pythium / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D000078304:Tigecycline
chemical_list: D000935:Antifungal Agents; D000078304:Tigecycline; D017963:Azithromycin; D008911:Minocycline; D017291:Clarithromycin