title: Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia.
abstract: Acinetobacter baumannii is a common cause of nosocomial pneumonia and other nosocomial infections. Multiresistant A. baumannii has also a high prevalence, which can make effective treatment difficult. We designed a new model of A. baumannii experimental pneumonia using C57BL/6 immunocompetent mice. This model was used to compare the efficacy of imipenem, doxycycline and amikacin in monotherapy, and the combination of imipenem plus amikacin and doxycycline plus amikacin. Doxycycline plus amikacin were synergic in vitro after 24 h incubation, whereas imipenem plus amikacin showed no in vitro synergy. The number of sterile lungs and the lung clearance of A. baumannii were greater in the group treated with imipenem than in those treated with amikacin or doxycycline in monotherapy (P < 0.05). The combination of imipenem plus amikacin and doxycycline plus amikacin was no more effective than imipenem alone in the clearance of organisms from lungs (2.42 +/- 1.46 cfu/g versus 2.7 +/- 1.5 cfu/g versus 1.23 +/- 1.02 cfu/g). These results suggest that the addition of amikacin does not improve the results obtained by imipenem monotherapy. Doxycycline plus amikacin is an alternative to imipenem in the therapy of A. baumannii pneumonia.
authors.affiliation: Service of Infectious Diseases and Service of Microbiology, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Seville, Spain. rodher@cica.es
authors.forename: M J
authors.initials: MJ
authors.lastname: Rodríguez-Hernández
authors.forename: J
authors.initials: J
authors.lastname: Pachón
authors.forename: C
authors.initials: C
authors.lastname: Pichardo
authors.forename: L
authors.initials: L
authors.lastname: Cuberos
authors.forename: J
authors.initials: J
authors.lastname: Ibáñez-Martínez
authors.forename: A
authors.initials: A
authors.lastname: García-Curiel
authors.forename: F J
authors.initials: FJ
authors.lastname: Caballero
authors.forename: I
authors.initials: I
authors.lastname: Moreno
authors.forename: M E
authors.initials: ME
authors.lastname: Jiménez-Mejías
mesh_terms: D000150:Acinetobacter; D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D000583:Amikacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004318:Doxycycline / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015378:Imipenem / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis; D013845:Thienamycins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D015378:Imipenem; D000583:Amikacin; D004318:Doxycycline