title: Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains.
abstract: The objective of this work was to evaluate the efficacy of rifampin, and its combinations with imipenem or sulbactam, in an experimental pneumonia model caused by two panresistant Acinetobacter baumannii strains (HUVR99 and HUVR113). Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) (μg/ml) of the strains were rifampin 128/>128 for both strains, imipenem 128/>256 and 256/>256 for HUVR99 and HUVR113, respectively, and sulbactam >256/>256 for both strains. In time-kill studies, at MICs, rifampin was bactericidal for both strains and sulbactam against the HUVR99 strain. Rifampin plus imipenem or sulbactam, at the MIC or mice C (max), were synergistic. In vivo, against HUVR99 and HUVR113, rifampin (73% and 40%) and its combinations improved the survival with respect to the control group (20% and 0%, p < 0.05), respectively. Rifampin (87% and 46%) and its combinations improved the sterilization of blood cultures with respect to the control groups (0%, p < 0.05). In regard to the bacterial clearance from lungs, rifampin (2.57 ± 2.47 and 5.35 ± 3.03 log(10) cfu/g) and its combinations with imipenem or sulbactam diminished the bacterial lung concentration with respect to the control group (10.89 ± 3.00 and 11.86 ± 0.49, p < 0.05) with both strains. In conclusion, rifampin alone or associated to imipenem or sulbactam were effective for the treatment of murine pneumonia caused by selected panresistant A. baumannii strains.
authors.affiliation: Infectious Diseases Services, Institute of Biomedicine of Sevilla (IBIS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Sevilla, Spain. meniapi@hotmail.com
authors.forename: M E
authors.initials: ME
authors.lastname: Pachón-Ibáñez
authors.forename: F
authors.initials: F
authors.lastname: Docobo-Pérez
authors.forename: M E
authors.initials: ME
authors.lastname: Jiménez-Mejias
authors.forename: J
authors.initials: J
authors.lastname: Ibáñez-Martínez
authors.forename: A
authors.initials: A
authors.lastname: García-Curiel
authors.forename: C
authors.initials: C
authors.lastname: Pichardo
authors.forename: J
authors.initials: J
authors.lastname: Pachón
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015378:Imipenem / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D012293:Rifampin / Q000008:administration & dosage* / Q000494:pharmacology; D012376:Rodent Diseases / Q000188:drug therapy; D013407:Sulbactam / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D013407:Sulbactam; D012293:Rifampin