title: Antibiotic use and the risk of carbapenem-resistant extended-spectrum-{beta}-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study.
abstract: OBJECTIVE
  To identify the roles of various antibiotics as risk factors for carbapenem-resistant extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) infection (ESBL-KP infection).
  
  
  METHODS
  Data were collected over 26 months in a tertiary care university hospital with established endemicity of carbapenem-resistant ESBL-KP (ESBL-CRKP). Using a case-case-control design, patients who presented an infection caused by carbapenem-susceptible ESBL-KP (ESBL-CSKP) and patients with ESBL-CRKP infection were compared with a common control group of hospitalized patients. Effects of treatment and duration of treatment with antibiotics were examined, adjusting for major non-antibiotic risk factors and controlling for confounding effects among the antibiotics via logistic regression models.
  
  
  RESULTS
  Ninety-six ESBL-CRKP cases, 55 ESBL-CSKP cases and 151 controls were analysed. Multivariate analysis, adjusting for major non-antibiotic risk factors, showed that the risk of ESBL-CRKP infection rose with increasing duration of prior treatment with β-lactam/β-lactamase inhibitor combinations [odds ratio (OR) 1.15 per day increase; P = 0.001] and revealed that increased duration of treatment with fluoroquinolones amplified the impact of exposure to carbapenems (and vice versa) on ESBL-CRKP infection risk (OR 1.02 for interaction term; P = 0.009). Duration of prior treatment with fluoroquinolones was also associated with increased risk of ESBL-CSKP infection (OR 1.07 per day increase; P = 0.028), while prior receipt of carbapenems presented a protective effect against ESBL-CSKP infection (OR 0.21; P = 0.003).
  
  
  CONCLUSIONS
  This study highlights the major role of treatment and duration of treatment with β-lactam/β-lactamase inhibitor combinations and combinations of carbapenems with fluoroquinolones. Clinicians should counterweight the potential benefits of administering these antibiotics against the increased risk of ESBL-CRKP infection.
authors: Laboratory of Infectious Diseases, University of Crete, Crete, Greece. ekritsot@otenet.gr
authors: Evangelos I
authors: EI
authors: Kritsotakis
authors: Constantinos
authors: C
authors: Tsioutis
authors: Maria
authors: M
authors: Roumbelaki
authors: Athanasia
authors: A
authors: Christidou
authors: Achilleas
authors: A
authors: Gikas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016022:Case-Control Studies; D004363:Drug Utilization / Q000706:statistics & numerical data*; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases