title: In vitro activity of doripenem in combination with various antimicrobials against multidrug-resistant Acinetobacter baumannii: possible options for the treatment of complicated infection.
abstract: OBJECTIVE
  The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay.
  
  
  RESULTS
  Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods.
  
  
  CONCLUSIONS
  This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.
authors: 1 Laboratory of Microbiology and Virology, Alessandro Manzoni Hospital , Lecco, Italy .
authors: Luigi
authors: L
authors: Principe
authors: Alessandro
authors: A
authors: Capone
authors: Antonio
authors: A
authors: Mazzarelli
authors: Silvia
authors: S
authors: D'Arezzo
authors: Eugenio
authors: E
authors: Bordi
authors: Antonino
authors: A
authors: Di Caro
authors: Nicola
authors: N
authors: Petrosillo
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D000583:Amikacin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use*; D003091:Colistin / Q000627:therapeutic use; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D063128:Tertiary Health Care; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000078304:Tigecycline; D000583:Amikacin; D000077726:Doripenem; D008911:Minocycline; D003091:Colistin