title: Serum and urinary cefpodoxime levels and time killing curves performed in the urine of children presenting urinary tract infections.
abstract: Since resistance to several oral antimicrobials useful for the treatment of pediatric urinary tract infections (UTI) is overwhelming in Argentina, an in vitro investigation was performed testing 400 isolates obtained from urines of children suffering UTI's, 200 collected in 1990 and 200 in 1991. Their susceptibility against oral antimicrobials marketed in Argentina and appropriate for the treatment of UTI was determined by the agar dilution methods. An increase of the resistance to aminopenicillin combined with beta-lactamase inhibitors and to fluoroquinolones was observed comparing the two periods. Cefpodoxime (CPD), cefixime and fluoroquinolones except norfloxacin were the sole oral antimicrobials showing in vitro activity at the 90 per cent level. Unfortunately fluoroquinolones are not yet approved for pediatric use. Consequently we realized an in vitro and in vivo pharmacokinetic study in order to determine CPD activity against E. coli isolated in UTI cases. Five children (6-10 y) showing E. coli UTI infections received 10 mg/kg/d CPD in a single oral daily dose and were treated up to 10 days, 3 had lower UTI and 2 upper UTI. All patients were clinical and bacteriologically cured. Cultures obtained up to 4 weeks after treatment were negative. CPD serum levels at 2 hours after the first dose of treatment showed a median of 2.7 mg/l (2.3-3.4 range). Bactericidal serum titers at the same time against the patients own strain and an E. coli TEM-1 hyperproducer strain (MIC 4,096 mg/l for ampicillin and 0.5 mg/l for CPD) showed a median value of 1/8 against patients strains and 1/2 against the THP strain.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Infectious Diseases Dept. Universidad Católica, Buenos Aires, Argentina.
authors.forename: J M
authors.initials: JM
authors.lastname: Casellas
authors.forename: G
authors.initials: G
authors.lastname: Tome
authors.forename: R
authors.initials: R
authors.lastname: Exeni
authors.forename: I
authors.initials: I
authors.lastname: Grimoldi
authors.forename: M
authors.initials: M
authors.lastname: Goldberg
authors.forename: A E
authors.initials: AE
authors.lastname: Farinati
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000892:Anti-Infective Agents, Urinary / Q000627:therapeutic use; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use / Q000652:urine; D002648:Child; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007709:Klebsiella / Q000187:drug effects / Q000302:isolation & purification; D008297:Male; D011513:Proteus mirabilis / Q000187:drug effects / Q000302:isolation & purification; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D000097623:Cefpodoxime
chemical_list: D000900:Anti-Bacterial Agents; D000892:Anti-Infective Agents, Urinary; D015296:Ceftizoxime; D000097623:Cefpodoxime