title: Efficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii.
abstract: The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.
authors.affiliation: Laboratory of Experimental Infection, Infectious Disease Service. Microbiology Department, Hospital de Bellvitge, University of Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. amontero@bell.ub.es
authors.forename: A
authors.initials: A
authors.lastname: Montero
authors.forename: J
authors.initials: J
authors.lastname: Ariza
authors.forename: X
authors.initials: X
authors.lastname: Corbella
authors.forename: A
authors.initials: A
authors.lastname: Doménech
authors.forename: C
authors.initials: C
authors.lastname: Cabellos
authors.forename: J
authors.initials: J
authors.lastname: Ayats
authors.forename: F
authors.initials: F
authors.lastname: Tubau
authors.forename: C
authors.initials: C
authors.lastname: Ardanuy
authors.forename: F
authors.initials: F
authors.lastname: Gudiol
mesh_terms: D000150:Acinetobacter / Q000187:drug effects*; D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003091:Colistin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D005260:Female; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012293:Rifampin; D003091:Colistin