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Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae

Despite the relevance of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) infections there are a scarce number of studies to evaluate in vivo the efficacy of combinations therapies. The bactericidal activity of colistin, rifampin, and its combination was studied (time–kill curves) against four...

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Autores principales: Pachón-Ibáñez, María E., Labrador-Herrera, Gema, Cebrero-Cangueiro, Tania, Díaz, Caridad, Smani, Younes, del Palacio, José P., Rodríguez-Baño, Jesús, Pascual, Alvaro, Pachón, Jerónimo, Conejo, M. Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962653/
https://www.ncbi.nlm.nih.gov/pubmed/29867823
http://dx.doi.org/10.3389/fmicb.2018.00912
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author Pachón-Ibáñez, María E.
Labrador-Herrera, Gema
Cebrero-Cangueiro, Tania
Díaz, Caridad
Smani, Younes
del Palacio, José P.
Rodríguez-Baño, Jesús
Pascual, Alvaro
Pachón, Jerónimo
Conejo, M. Carmen
author_facet Pachón-Ibáñez, María E.
Labrador-Herrera, Gema
Cebrero-Cangueiro, Tania
Díaz, Caridad
Smani, Younes
del Palacio, José P.
Rodríguez-Baño, Jesús
Pascual, Alvaro
Pachón, Jerónimo
Conejo, M. Carmen
author_sort Pachón-Ibáñez, María E.
collection PubMed
description Despite the relevance of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) infections there are a scarce number of studies to evaluate in vivo the efficacy of combinations therapies. The bactericidal activity of colistin, rifampin, and its combination was studied (time–kill curves) against four clonally unrelated clinical isolates of CP-Kp, producing VIM-1, VIM-1 plus DHA-1(acquired AmpC β-lactamase), OXA-48 plus CTX-M-15 (extended spectrum β-lactamase) and KPC-3, respectively, with colistin MICs of 0.5, 64, 0.5, and 32 mg/L, respectively. The efficacies of antimicrobials in monotherapy and in combination were tested in a murine peritoneal sepsis model, against all the CP-Kp. Their efficacies were tested in the pneumonia model against the OXA-48 plus CTX-M-15 producers. The development of colistin-resistance was analyzed for the colistin-susceptible strains in vitro and in vivo. In vitro, colistin plus rifampin was synergistic against all the strains at 24 h. In vivo, compared to the controls, rifampin alone reduced tissue bacterial concentrations against VIM-1 and OXA-48 plus CTX-M-15 strains; CMS plus rifampin reduced tissue bacterial concentrations of these two CP-Kp and of the KPC-3 strain. Rifampin and the combination increased the survival against the KPC-3 strain; in the pneumonia model, the combination also improved the survival. No resistant mutants appeared with the combination. In conclusion, CMS plus rifampin had a low and heterogeneous efficacy in the treatment of severe peritoneal sepsis model due to CP-Kp producing different carbapenemases, increasing survival only against the KPC-3 strain. The combination showed efficacy in the less severe pneumonia model. The combination prevented in vitro and in vivo the development of colistin resistant mutants.
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spelling pubmed-59626532018-06-04 Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae Pachón-Ibáñez, María E. Labrador-Herrera, Gema Cebrero-Cangueiro, Tania Díaz, Caridad Smani, Younes del Palacio, José P. Rodríguez-Baño, Jesús Pascual, Alvaro Pachón, Jerónimo Conejo, M. Carmen Front Microbiol Microbiology Despite the relevance of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) infections there are a scarce number of studies to evaluate in vivo the efficacy of combinations therapies. The bactericidal activity of colistin, rifampin, and its combination was studied (time–kill curves) against four clonally unrelated clinical isolates of CP-Kp, producing VIM-1, VIM-1 plus DHA-1(acquired AmpC β-lactamase), OXA-48 plus CTX-M-15 (extended spectrum β-lactamase) and KPC-3, respectively, with colistin MICs of 0.5, 64, 0.5, and 32 mg/L, respectively. The efficacies of antimicrobials in monotherapy and in combination were tested in a murine peritoneal sepsis model, against all the CP-Kp. Their efficacies were tested in the pneumonia model against the OXA-48 plus CTX-M-15 producers. The development of colistin-resistance was analyzed for the colistin-susceptible strains in vitro and in vivo. In vitro, colistin plus rifampin was synergistic against all the strains at 24 h. In vivo, compared to the controls, rifampin alone reduced tissue bacterial concentrations against VIM-1 and OXA-48 plus CTX-M-15 strains; CMS plus rifampin reduced tissue bacterial concentrations of these two CP-Kp and of the KPC-3 strain. Rifampin and the combination increased the survival against the KPC-3 strain; in the pneumonia model, the combination also improved the survival. No resistant mutants appeared with the combination. In conclusion, CMS plus rifampin had a low and heterogeneous efficacy in the treatment of severe peritoneal sepsis model due to CP-Kp producing different carbapenemases, increasing survival only against the KPC-3 strain. The combination showed efficacy in the less severe pneumonia model. The combination prevented in vitro and in vivo the development of colistin resistant mutants. Frontiers Media S.A. 2018-05-15 /pmc/articles/PMC5962653/ /pubmed/29867823 http://dx.doi.org/10.3389/fmicb.2018.00912 Text en Copyright © 2018 Pachón-Ibáñez, Labrador-Herrera, Cebrero-Cangueiro, Díaz, Smani, del Palacio, Rodríguez-Baño, Pascual, Pachón and Conejo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Pachón-Ibáñez, María E.
Labrador-Herrera, Gema
Cebrero-Cangueiro, Tania
Díaz, Caridad
Smani, Younes
del Palacio, José P.
Rodríguez-Baño, Jesús
Pascual, Alvaro
Pachón, Jerónimo
Conejo, M. Carmen
Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title_full Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title_fullStr Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title_full_unstemmed Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title_short Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae
title_sort efficacy of colistin and its combination with rifampin in vitro and in experimental models of infection caused by carbapenemase-producing clinical isolates of klebsiella pneumoniae
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962653/
https://www.ncbi.nlm.nih.gov/pubmed/29867823
http://dx.doi.org/10.3389/fmicb.2018.00912
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