title: Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad- and extended-spectrum beta-lactamases.
abstract: Bacteria harbouring extended-spectrum beta-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 beta-lactamases, have been described world-wide. The in vitro activities of these enzymes against beta-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral beta-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum beta-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral beta-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller-Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 beta-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 beta-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered.
authors.affiliation: Department of Microbiology, A. Stampar School of Public Health, Medical School, University of Zagreb, Croatia. branka.bedenic@zg.htnet.hr
authors.forename: Branka
authors.initials: B
authors.lastname: Bedenic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Vranes
authors.forename: Sandra
authors.initials: S
authors.lastname: Suto
authors.forename: Zivojin
authors.initials: Z
authors.lastname: Zagar
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D005260:Female; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015610:Serum Bactericidal Test; D014556:Urine / Q000382:microbiology; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000097:blood / Q000494:pharmacology* / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases