title: Antimicrobial susceptibilities of Proteus mirabilis: a longitudinal nationwide study from the Taiwan surveillance of antimicrobial resistance (TSAR) program.
abstract: BACKGROUND
  Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) β-lactam breakpoints on susceptibility rates and on detecting extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues.
  
  
  METHODS
  Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC β-lactamases gene detection by PCR. Univariate and multivariate analyses were performed.
  
  
  RESULTS
  Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P < 0.01). The revised CLSI breakpoints had significant impact on susceptibility to cefazolin (2009 vs. current breakpoints, 71.9% vs. 0.9%) and imipenem (99.8% vs. 55.1%) (P < 0.001 for both). However, using the 2014 cefazolin breakpoints for urinary tract infections, 81.2% of the urine isolates were susceptible. Susceptibilities of isolates from different specimen types were mostly similar but outpatient isolates were more susceptible than inpatient isolates. The overall prevalence of ESBL- and AmpC- producers was 8.2% and 4.7%, respectively, but AmpC carriage increased significantly over the years (from 0 to 7.0%, P < 0.001). ESBL and AmpC β-lactamase-producers were more likely to be found in elderly and ICU patients. The predominant ESBL and AmpC β-lactamase genes were CTX-M- and CMY- types, respectively.
  
  
  CONCLUSIONS
  A significant decrease in susceptibility to 3rd-generation cephalosporins and ciprofloxacin occurred in P. mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC β-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these β-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.
authors.forename: Jann-Tay
authors.initials: JT
authors.lastname: Wang
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Chen
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Shiau
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Wang
authors.forename: Jui-Fen
authors.initials: JF
authors.lastname: Lai
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Huang
authors.forename: Mei-Chen
authors.initials: MC
authors.lastname: Tan
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, No, 35 Keyan Road, Zhunan 35053, Taiwan. lauderdale@nhri.org.tw.
authors.forename: Tsai-Ling Yang
authors.initials: TL
authors.lastname: Lauderdale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011159:Population Surveillance; D011512:Proteus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D011513:Proteus mirabilis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013624:Taiwan / Q000453:epidemiology; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D001398:Aztreonam; D002439:Cefotaxime