Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii : the significance of co-administration of rifampicin

• Published in: International journal of antimicrobial agents 2007-01, Vol.29 (1), p.51-55
• Main Authors: Pantopoulou, Alkistis, Giamarellos-Bourboulis, Evangelos J, Raftogannis, Maria, Tsaganos, Thomas, Dontas, Ismini, Koutoukas, Pantelis, Baziaka, Fotini, Giamarellou, Helen, Perrea, Despina
• Format: Article
• Language: English
• Subjects: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Acinetobacter Infections - mortality; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Blood - drug effects; Blood - microbiology; Colistin; Colistin - administration & dosage; Colistin - blood; Colistin - therapeutic use; Cyclophosphamide - administration & dosage; Cyclophosphamide - pharmacology; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Infectious Disease; Injections, Intramuscular; Injections, Intravenous; Liver - drug effects; Liver - microbiology; Lung - drug effects; Lung - microbiology; Male; Medical sciences; Multidrug resistance; Pharmacology. Drug treatments; Rats; Rats, Wistar; Rifampicin; Rifampin - administration & dosage; Rifampin - blood; Rifampin - therapeutic use; Spleen - drug effects; Spleen - microbiology; Survival Analysis; Survival Rate; Treatment Outcome
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2006.09.009

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; 5 mg/kg of rifampicin was administered intravenously and 3 mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4 h 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.