title: Trimethoprim in vitro antibacterial activity is not increased by adding sulfamethoxazole for pediatric Escherichia coli urinary tract infection.
abstract: OBJECTIVE
  The combination of trimethoprim/sulfamethoxazole is often used to treat uncomplicated urinary tract infections in children. The rationale for combining trimethoprim and sulfamethoxazole is that they may act synergistically to increase antibacterial activity. However, approximately 3% of patients show allergic reactions to sulfamethoxazole, of which some are serious (liver failure and Stevens-Johnson syndrome). We determined whether adding sulfamethoxazole is necessary to increase in vitro antibacterial activity for pediatric urinary tract infection compared to that of trimethoprim alone.
  
  
  METHODS
  We prospectively identified 1,298 children with urinary tract infection (greater than 100,000 cfu/ml Escherichia coli) from a total of 4 American regions. In vitro susceptibility of bacterial isolates to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole was determined using disk diffusion. Ampicillin susceptibility was tested at 2 sites. At 1 site all uropathogens from consecutive urinary isolates were evaluated.
  
  
  RESULTS
  E. coli susceptibility to trimethoprim was 70%, comparable to the 70% of trimethoprim/sulfamethoxazole (p = 0.9) and higher than the 56.9% of sulfamethoxazole (p <0.05). This susceptibility pattern was without regional differences. At 2 sites susceptibility to trimethoprim was significantly higher than to ampicillin. At 1 site the susceptibility of other uropathogens to trimethoprim and trimethoprim/sulfamethoxazole was similar to that of E. coli.
  
  
  CONCLUSIONS
  In children with urinary tract infection in vitro susceptibility to trimethoprim was comparable to that to trimethoprim/sulfamethoxazole and significantly higher than to sulfamethoxazole. This finding was similar at all sites. Adding sulfamethoxazole appears unnecessary and may represent a risk to patients. Trimethoprim can be used as an alternative to trimethoprim/sulfamethoxazole based on in vitro antibacterial susceptibility. Routine trimethoprim/sulfamethoxazole use for urinary tract infection should be carefully reevaluated.
authors.affiliation: Departments of Urology, Children's Hospital, Boston, Massachusetts, USA. Hiep.Nguyen@childrens.harvard.edu
authors.forename: Hiep T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hurwitz
authors.forename: W Robert
authors.initials: WR
authors.lastname: Defoor
authors.forename: Eugene
authors.initials: E
authors.lastname: Minevich
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: McAdam
authors.forename: Joel E
authors.initials: JE
authors.lastname: Mortensen
authors.forename: Susan M
authors.initials: SM
authors.lastname: Novak-Weekley
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Minnillo
authors.forename: Jack S
authors.initials: JS
authors.lastname: Elder
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use; D000704:Analysis of Variance; D000892:Anti-Infective Agents, Urinary / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D013420:Sulfamethoxazole / Q000627:therapeutic use*; D016896:Treatment Outcome; D014295:Trimethoprim / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014481:United States; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000892:Anti-Infective Agents, Urinary; D004338:Drug Combinations; D000667:Ampicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole