title: In vitro activity of antibiotic combinations against multidrug-resistant strains of Acinetobacter baumannii and the effects of their antibiotic resistance determinants.
abstract: Various combinations of antibiotics are reported to show synergy in treating nosocomial infections with multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii). Here, we studied hospital-acquired outbreak strains of MDR A. baumannii to evaluate optimal combinations of antibiotics. One hundred and twenty-one strains were grouped into one major and one minor clonal group based on repetitive PCR amplification. Twenty representative strains were tested for antibiotic synergy using Etest(®). Five strains were further analyzed by analytical isoelectric focusing and PCR to identify β-lactamase genes or other antibiotic resistance determinants. Our investigation showed that the outbreak strains of MDR A. baumannii belonged to two dominant clones. A combination of colistin and doxycycline showed the best result, being additive or synergistic against 70% of tested strains. Antibiotic additivity was observed more frequently than synergy. Strains possessing the same clonality did not necessarily demonstrate the same response to antibiotic combinations in vitro. We conclude that the effect of antibiotic combinations on our outbreak strains of MDR A. baumannii seemed strain-specific. The bacterial response to antibiotic combinations is probably a result of complex interactions between multiple concomitant antibiotic resistance determinants in each strain.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. yoko.miyasaki@cshs.org
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyasaki
authors.forename: Margie A
authors.initials: MA
authors.lastname: Morgan
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Chan
authors.forename: W Stephen
authors.initials: WS
authors.lastname: Nichols
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Hujer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: A Rekha
authors.initials: AR
authors.lastname: Murthy
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D003428:Cross Infection / Q000382:microbiology; D004347:Drug Interactions; D024901:Drug Resistance, Multiple, Bacterial; D005838:Genotype; D006801:Humans; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D001618:beta-Lactamases / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases