title: Synergy of imipenem/colistin methanesulfonate combinations against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii.
abstract: BACKGROUND
  The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates.
  
  
  METHODS
  Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction.
  
  
  RESULTS
  A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively.
  
  
  CONCLUSIONS
  The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: hsleu@adm.cgmh.org.tw.
authors.forename: Hsieh-Shong
authors.initials: HS
authors.lastname: Leu
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Jung-Jr
authors.initials: JJ
authors.lastname: Ye
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ming-Hsun
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Su
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ching-Tai
authors.initials: CT
authors.lastname: Huang
mesh_terms: D000046:Academic Medical Centers; D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D016521:Electrophoresis, Gel, Pulsed-Field; D005838:Genotype; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D015378:Imipenem; D003091:Colistin
keywords: Colistin; Imipenem; Multidrug-resistant Acinetobacter baumannii