title: [Mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii and the application of a combination of drugs in vitro].
abstract: OBJECTIVE
  To investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.
  
  
  METHODS
  A total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.
  
  
  RESULTS
  The resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).
  
  
  CONCLUSIONS
  Production of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.
authors.affiliation: Institute of Burns, Wuhan City Hospital No.3 & Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Chaoli
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Institute of Burns, Wuhan City Hospital No.3 & Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Burns, Wuhan City Hospital No.3 & Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Burns, Wuhan City Hospital No.3 & Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Institute of Burns, Wuhan City Hospital No.3 & Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004364:Pharmaceutical Preparations; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D013407:Sulbactam / Q000494:pharmacology; D013845:Thienamycins / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D004364:Pharmaceutical Preparations; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; C035444:sultamicillin; D000667:Ampicillin; D000077723:Cefepime; D010397:Penicillanic Acid; D000077731:Meropenem; D013407:Sulbactam; D010878:Piperacillin