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Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy.
Fedrigo, Nayara Helisandra; Shinohara, Danielle Rosani; Mazucheli, Josmar; Nishiyama, Sheila Alexandra Belini; Carrara-Marroni, Floristher Elaine; Martins, Frederico Severino; Zhu, Peijuan; Yu, Mingming; Sy, Sherwin Kenneth B; Tognim, Maria Cristina Bronharo.
Afiliación
  • Fedrigo NH; Laboratório de Microbiologia, Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790, Maringá, Paraná, CEP 87020-900, Brazil.
  • Shinohara DR; Laboratório de Microbiologia, Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790, Maringá, Paraná, CEP 87020-900, Brazil.
  • Mazucheli J; Department of Statistics, State University of Maringá, Maringá, Paraná, Brazil.
  • Nishiyama SAB; Laboratório de Microbiologia, Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790, Maringá, Paraná, CEP 87020-900, Brazil.
  • Carrara-Marroni FE; Department of Pathology, Clinical and Toxicological Analysis, University Hospital, State University of Londrina, Londrina, Paraná, Brazil.
  • Martins FS; esqLABS GmbH, Hambierich 34, 26683, Saterland, Germany.
  • Zhu P; Alexion Pharmaceuticals, Boston, MA, USA.
  • Yu M; School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, China.
  • Sy SKB; Department of Statistics, State University of Maringá, Maringá, Paraná, Brazil.
  • Tognim MCB; Laboratório de Microbiologia, Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790, Maringá, Paraná, CEP 87020-900, Brazil. mcbtognim@uem.br.
Sci Rep ; 11(1): 11339, 2021 05 31.
Article en En | MEDLINE | ID: mdl-34059725
The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimixina B / Infecciones por Acinetobacter / Farmacorresistencia Bacteriana / Acinetobacter baumannii / Antibacterianos Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimixina B / Infecciones por Acinetobacter / Farmacorresistencia Bacteriana / Acinetobacter baumannii / Antibacterianos Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido