title: Antimicrobial Combinations against Pan-Resistant Acinetobacter baumannii Isolates with Different Resistance Mechanisms.
abstract: The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible) with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP) analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii.
authors.affiliation: Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil.|Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.
authors.forename: Gleice Cristina
authors.initials: GC
authors.lastname: Leite
authors.affiliation: Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil.|Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Maura Salaroli
authors.initials: MS
authors.lastname: Oliveira
authors.affiliation: Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil.|Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.|Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Lauro Vieira
authors.initials: LV
authors.lastname: Perdigão-Neto
authors.affiliation: Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.
authors.forename: Cristiana Kamia Dias
authors.initials: CK
authors.lastname: Rocha
authors.affiliation: Department of Infection Control, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Guimarães
authors.affiliation: Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Rizek
authors.affiliation: Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil.|Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.|Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Anna Sara
authors.initials: AS
authors.lastname: Levin
authors.affiliation: Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil.|Laboratory of Medical Investigation 54 (LIM-54), São Paulo, Brazil.|Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Silvia Figueiredo
authors.initials: SF
authors.lastname: Costa
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents