title: Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii: the significance of co-administration of rifampicin.
abstract: The effect of colistin on bacterial eradication and survival was tested in experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh infection model was applied in 86 neutropenic Wistar rats. Six rats were used for the induction of neutropenia and for the selection of the dose regimen of colistin; the remainder was equally divided into four groups: A, controls; B, rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after bacterial challenge; 5mg/kg of rifampicin was administered intravenously and 3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4h after therapy; blood and tissue samples were sampled. Median survival of animals of groups A, B, C and D was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100, 100, 100 and 70%, respectively (P=0.018 between groups). Statistically significant decreases of bacteria were found in blood, liver, lung and spleen of group B compared with A; in lung of group C compared with A; and in blood and liver of group D compared with A. Colistin was effective in prolonging survival in an experimental thigh infection by multidrug-resistant A. baumannii in neutropenic rats. Its activity was enhanced after co-administration with rifampicin. These results mandate the application of colistin in the event of infections by multidrug-resistant pathogens and the need for its co-administration with rifampicin.
authors.affiliation: Department of Experimental Surgery and Surgical Research, University of Athens, Medical School, Athens 115 27, Greece.
authors.forename: Alkistis
authors.initials: A
authors.lastname: Pantopoulou
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Maria
authors.initials: M
authors.lastname: Raftogannis
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Ismini
authors.initials: I
authors.lastname: Dontas
authors.forename: Pantelis
authors.initials: P
authors.lastname: Koutoukas
authors.forename: Fotini
authors.initials: F
authors.lastname: Baziaka
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D040981:Acinetobacter baumannii; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D001769:Blood / Q000187:drug effects / Q000382:microbiology; D003091:Colistin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003520:Cyclophosphamide; D012293:Rifampin; D003091:Colistin