title: Laboratory identification, risk factors, and clinical outcomes of patients with bacteremia due to Escherichia coli and Klebsiella pneumoniae producing extended-spectrum and AmpC type β-lactamases.
abstract: BACKGROUND
  Extended-spectrum β-lactamase (ESBL)-producing bacteria coexpressing AmpC type β-lactamase (ACBL) are associated with the laboratory issue of false susceptibility to third-generation cephalosporins. This study was to evaluate laboratory tests and clinical significance of bacteremic isolates of Escherichia coli and Klebsiella pneumoniae with both ESBL and ACBL [dual-type lactamases (DTL)].
  
  
  METHODS
  From 2006 to 2009, 78 E coli and 12 pneumoniae bacteremic isolates with reduced susceptibility to cefotaxime (CTX) or ceftazidime (CAZ) were identified and relevant patients' data were collected for analysis. Phenotypic and genotypic characterizations of these selected isolates were determined by inhibitor-based assays and polymerase chain reaction-based genetic analyses, respectively.
  
  
  RESULTS
  Among the 90 isolates, 47 had DTL production. There was an increasing annual prevalence from 29% in 2006 to 56% in 2009 (p=0.02). Phenotypic assays had a sensitivity and specificity of 57% (43/76) and 93% (13/14) for ESBL detection and 95% (58/61) and 34% (10/29) for ACBL, respectively. Among the DTL-producing isolates, phenotypic assays yielded a higher false negative rate of ESBL detection than that of ACBL detection (70% versus 6%), while all false negative ESBL results were associated with ESBL genes other than bla(CTx-M). The majority of the DTL-producing isolates were in the category of resistance to CTX (47/47, 100%) and CAZ (44/47, 94%) by the Clinical and Laboratory Standards Institute (CLSI) 2010 interpretive criteria, of which many were considered intermediate or fully susceptible to CTX (25/47, 53%) and CAZ (15/47, 32%) by the previous ones (CLSI-2009). The DTL-producing isolates exhibited a lower susceptibility rate to fluoroquinolones, aztreonam, and β-lactam/lactamase inhibitors than those with either ESBL or ACBL alone. The use of indwelling catheters or nasogastric tubes was associated with bacteremia due to the DTL isolates, but the mortality rates were not different among those due to isolates with ESBL, ACBL, or both. By multivariate analysis, Pittsburg bacteremia score and Charlson comorbidity index were the significant predictors for all-cause mortalities.
  
  
  CONCLUSIONS
  Bacteremic episodes due to DTL-producing E coli and K pneumoniae became increasingly prevalent and were often associated with coresistance to antibiotics other than β-lactams, but they were not associated with a worse prognosis than those due to ESBL- or ACBL-producing bacteria.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Cathay General Hospital, Taipei City, Taiwan.
authors.forename: Kochung
authors.initials: K
authors.lastname: Tsui
authors.forename: Swee-Siang
authors.initials: SS
authors.lastname: Wong
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Lin
authors.forename: Chim-Ren
authors.initials: CR
authors.lastname: Tsai
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Chen
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Huang
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002439:Cefotaxime / Q000494:pharmacology / Q000627:therapeutic use; D002442:Ceftazidime / Q000494:pharmacology / Q000627:therapeutic use; D016009:Chi-Square Distribution; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D012680:Sensitivity and Specificity; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D002439:Cefotaxime