title: Efficacy of trimethoprim/sulfamethoxazole in experimental Escherichia coli bacteremia and meningitis.
abstract: We evaluated the activity of trimethoprim/sulfamethoxazole (TMP/SMZ) against a K1 Escherichia coli strain. Minimal inhibitory and bactericidal concentrations were 0.06/1.14 and 0.25/4.75 micrograms/ml, respectively. In vivo studies using an infant rat model of bacteremia and meningitis revealed that TMP/SMZ penetrated well into the cerebrospinal fluid (CSF) and that 37% of serum levels were achieved. The efficacy of TMP/SMZ was compared with that of ampicillin, chloramphenicol, cefotaxime and lamoxactam. Bacterial clearance from blood and CSF was significantly greater with TMP/SMZ than with ampicillin or chloramphenicol and mortality was significantly less than with chloramphenicol (p less than 0.01). However, 3 of 21 (14%) and 2 of 8 animals (25%) still had positive blood and CSF cultures after 3 days of treatment with TMP/SMZ. None of the survivors in the cefotaxime and lamoxactam groups were bacteremic after 1 day of therapy. Furthermore, 5 of 13 animals (38%) treated with TMP/SMZ developed meningitis during therapy, in contrast with none in the cefotaxime and lamoxactam groups. These findings indicate that although the activity of TMP/SMZ is bactericidal in vitro and in vivo against E. coli, TMP/SMZ may not provide optimal therapy for gram-negative bacillary meningitis in this model.
mesh_terms: D000818:Animals; D003114:Colony-Forming Units Assay; D004338:Drug Combinations / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000188:drug therapy*; D008581:Meningitis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013420:Sulfamethoxazole / Q000627:therapeutic use*; D014295:Trimethoprim / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
chemical_list: D004338:Drug Combinations; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole