title: The importance of addressing multidrug resistance and not assuming single-drug resistance in case-control studies.
abstract: BACKGROUND
  Case-control studies analyzing antibiotic exposure as a risk factor for antimicrobial resistance usually assume single-drug resistance in the bacteria under study, even though resistance to multiple antimicrobials may be present. Since antibiotic selection pressures differ depending on the susceptibility profile of the antimicrobial-resistant bacteria, an accurate assessment of whether exposure to an individual antimicrobial is a risk factor for the emergence of resistance should distinguish between single-drug-resistant and multidrug-resistant bacteria.
  
  
  OBJECTIVE
  To determine whether the exposures to individual antibiotics that were identified as independent risk factors in case-control studies differed depending on whether single-drug-resistant or multidrug-resistant bacteria were evaluated.
  
  
  METHODS
  Two retrospective case-control studies were performed with data on patients harboring Pseudomonas aeruginosa strains resistant only to ciprofloxacin (CRPA) and patients harboring P. aeruginosa strains resistant to ciprofloxacin and other antibiotics (multidrug-resistant P. aeruginosa [MDR-PA]). These 2 groups were compared with patients not harboring P. aeruginosa.
  
  
  METHODS
  Two tertiary care hospitals.
  
  
  RESULTS
  A total of 41 patients harboring CRPA and 151 patients harboring MDR-PA were identified and matched to 192 control subjects. By conditional logistic regression, independent risk factors associated with presence of CRPA were nonambulatory status (OR, 5.6 [95% confidence interval {CI}, 1.4-23]; P=.02) and prior ciprofloxacin exposure (OR, 5.0 [95% CI, 1.2-21]; P=.03). Independent risk factors for presence of MDR-PA were a Charlson score greater than 2 (OR, 3.3 [95% CI 1.8-6.0]; P<.001) and exposure to quinolones (OR, 2.8 [95% CI, 1.2-5.0]; P=.001), third- and fourth-generation cephalosporins (OR, 3.5 [95% CI, 1.7-7.1]; P<.001), imipenem (OR, 3.8 [95% CI, 1.2-12.1]; P=.02), and/or aminoglycosides (OR, 2.3 [95% CI, 1.04-5.1]; P=.04).
  
  
  CONCLUSIONS
  There were substantial differences in exposure to individual antimicrobials between patients harboring CRPA and patients harboring MDR-PA. Future case-control studies addressing risk factors for single-drug-resistant bacteria should consider the complete susceptibility profile of the bacteria under investigation.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. edagata@bidmc.harvard.edu
authors.forename: Erika M C
authors.initials: EM
authors.lastname: D'Agata
authors.forename: Maria Adriana
authors.initials: MA
authors.lastname: Cataldo
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Evelina
authors.initials: E
authors.lastname: Tacconelli
mesh_terms: D016022:Case-Control Studies; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012189:Retrospective Studies; D012307:Risk Factors