title: Urinary concentrations and urine ex-vivo effect of mecillinam and sulphamethizole.
abstract: Healthy adult volunteers received 1 g of sulphamethizole orally (n = 10) and later 400 mg of pivmecillinam (274 mg of mecillinam) (n = 9). All urine was collected in defined periods over 24 h, and the drug concentrations in urine were determined. For sulphamethizole, the maximum urine concentration for seven subjects was reached in 0-3 h, and for the remaining three in 3-6 h. For mecillinam, eight of the nine subjects attained a maximum urine concentration in 0-3 h, after which the concentration declined rapidly for six subjects in 3-6 h. Strains of Escherichia coli with different MICs for sulphamethizole and mecillinam were exposed to collected urine for 2.5 h and 5 h. The results indicated that a sensitive E. coli population should be suppressed by sulphamethizole in urine for two-thirds of the time (with 1 g twice-daily) and by mecillinam in urine throughout the 24-h period (with 400 mg three times a day). There was a slight but significant correlation between the ex-vivo effect (Delta log10 CFU/mL) and the log10 concentration/MIC ratio after exposure to sulphamethizole for 5 h (r2 = 0.27, p < 0.0001), and a significant correlation between the variables with mecillinam (r2 = 0.66, p < 0.0001).
authors.affiliation: Department of Microbiological R & D, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. mbp@ssi.dk
authors.forename: M B
authors.initials: MB
authors.lastname: Kerrn
authors.forename: N
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: F
authors.initials: F
authors.lastname: Espersen
mesh_terms: D000284:Administration, Oral; D000560:Amdinocillin / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D008875:Middle Aged; D013419:Sulfamethizole / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine*; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D013419:Sulfamethizole; D000560:Amdinocillin