title: Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.
abstract: BACKGROUND
  Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD).
  
  
  METHODS
  We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers.
  
  
  RESULTS
  Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses.
  
  
  CONCLUSIONS
  Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.
authors: Mount Sinai Hospital, Toronto, Canada University Hospital Zurich and University of Zurich, Switzerland.
authors: Stefan P
authors: SP
authors: Kuster
authors: Mount Sinai Hospital, Toronto, Canada University of Toronto.
authors: Wallis
authors: W
authors: Rudnick
authors: Mount Sinai Hospital, Toronto, Canada.
authors: Altynay
authors: A
authors: Shigayeva
authors: Mount Sinai Hospital, Toronto, Canada.
authors: Karen
authors: K
authors: Green
authors: University of Toronto William Osler Health System, Etobicoke General Site.
authors: Mahin
authors: M
authors: Baqi
authors: University of Toronto University Health Network.
authors: Wayne L
authors: WL
authors: Gold
authors: The Scarborough Hospital.
authors: Reena
authors: R
authors: Lovinsky
authors: University of Toronto St Michael's Hospital.
authors: Matthew P
authors: MP
authors: Muller
authors: University of Toronto Toronto East General Hospital, Toronto.
authors: Jeff E
authors: JE
authors: Powis
authors: University of Toronto Halton Healthcare, Oakville.
authors: Neil
authors: N
authors: Rau
authors: University of Toronto Sunnybrook Health Sciences Centre, Toronto, Canada.
authors: Andrew E
authors: AE
authors: Simor
authors: University of Toronto University Health Network.
authors: Sharon L
authors: SL
authors: Walmsley
authors: Mount Sinai Hospital, Toronto, Canada University of Toronto University Health Network.
authors: Donald E
authors: DE
authors: Low
authors: Mount Sinai Hospital, Toronto, Canada University of Toronto.
authors: Allison
authors: A
authors: McGeer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D015995:Prevalence; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents
keywords: S. pneumoniae; antibiotic use; fluoroquinolone; resistance