title: Relationship between the distribution of cefepime minimum inhibitory concentrations and detection of extended-spectrum β-lactamase production among clinically important Enterobacteriaceae isolates obtained from patients in intensive care units in Taiwan: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2007.
abstract: BACKGROUND
  The data on susceptibility of important cephalosporins against four Enterobacteriaceae members producing potential extended-spectrum β-lactamase (ESBL) collected from Taiwanese intensive care units are lacking.
  
  
  METHODS
  Minimum inhibitory concentrations (MICs) of cefotaxime, ceftazidime, and cefepime were determined using agar dilution method, against Escherichia coli (n = 344), Klebsiella pneumoniae (n = 359), Enterobacter cloacae (n = 103), and Proteus mirabilis (n = 78). Susceptibilities of these isolates to three cephalosporins were assessed according to MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013. The double-disk synergy test using disks containing cefepime (30 μg) with or without clavulanate (10 μg) was applied to confirm production of ESBL for isolates with cephalosporin MIC ≥ 2 μg/mL.
  
  
  RESULTS
  A total of 175 isolates were verified as ESBL producers. The rates of cefepime susceptibility among the ESBL-producing isolates, according to CLSI (EUCAST) criteria, were 56.7% (22.4%) for E. coli, 61.3% (12.0%) for K. pneumoniae, 57.9% (31.6%) for E. cloacae, and 71.4% (7.1%) for P. mirabilis. Using different cefepime MIC breakpoints (MICs ≥ 16 μg/mL recommended by CLSI criteria and ≥ 2 μg/mL by EUCAST criteria) to define nonsusceptibility, we found that both criteria were poorer at predicting ESBL producers among K. pneumoniae and E. cloacae than among the other two species. In addition, we also found that the cefepime MIC level of 1.0 μg/mL best distinguished non-ESBL- from ESBL-producing K. pneumoniae and E. cloacae.
  
  
  CONCLUSIONS
  To detect ESBLs, CLSI should revise the cefepime MIC breakpoint against Enterobacteriaceae.
authors: Department of Emergency Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Shio-Shin
authors: SS
authors: Jean
authors: Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Wen-Sen
authors: WS
authors: Lee
authors: Department of Pulmonary, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Kuan-Jen
authors: KJ
authors: Bai
authors: Department of Emergency Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Carlos
authors: C
authors: Lam
authors: Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Chin-Wang
authors: CW
authors: Hsu
authors: Department of Internal Medicine, Pathology, and Laboratory Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors: Kwok-Woon
authors: KW
authors: Yu
authors: Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors: Chun-Hsing
authors: CH
authors: Liao
authors: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center (NDMC), Taipei, Taiwan.
authors: Feng-Yi
authors: FY
authors: Chang
authors: Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan.
authors: Wen-Chien
authors: WC
authors: Ko
authors: School of Medical Technology, National Cheng-Kung University College of Medicine, Tainan, Taiwan.
authors: Jiunn-Jong
authors: JJ
authors: Wu
authors: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Yen-Hsu
authors: YH
authors: Chen
authors: Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Yao-Shen
authors: YS
authors: Chen
authors: Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung Medical College, Kaohsiung, Taiwan.
authors: Jien-Wei
authors: JW
authors: Liu
authors: Department of Laboratory Medicine and Internal Medicine, Chung Shan Medical and Dental University, Taichung, Taiwan.
authors: Min-Chi
authors: MC
authors: Lu
authors: Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Cheng-Yi
authors: CY
authors: Liu
authors: Department of Emergency Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Ray-Jade
authors: RJ
authors: Chen
authors: Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: hsporen@ntu.edu.tw.
authors: Po-Ren
authors: PR
authors: Hsueh
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000077723:Cefepime; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology*; D062665:Epidemiological Monitoring; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D013624:Taiwan; D001618:beta-Lactamases / Q000145:classification / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime; D001618:beta-Lactamases; D002439:Cefotaxime
keywords: Cefepime; Clinical and Laboratory Standards Institute; Enterobacteriaceae; Extended-spectrum β-lactamase; Surveillance for Monitoring Antimicrobial Resistance in Taiwan