engleski

Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad and extended-spectrum beta-lactamases

Bacteria harbouring extended-spectrum beta-lactamases (ESBLs) derived by mutation from TEM-1, TEM-2 or SHV-1 beta-lactamases have been described worldwide. The in vitro activities of these enzymes against beta-lactam antibiotics including oral cephalosporins have been previously studied. The aim of this investigation was to assess the bactericidal activity of oral beta-lactam antibiotics available in Croatia (amoxycillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten) in biological fluids against isogenic Escherichia coli strains producing broad (TEM-1, TEM-2 and SHV-1) and extended-spectrum beta-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12) in ex vivo model. Bactericidal activity of oral beta-lactams in plasma and urine was tested in time-kill experiments and by determination of bactericidal titres in 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 maintained throughout the whole dosing interval only with ceftibuten against strains producing broad and some extended-spectrum beta-lactamases (SHV-2 and SHV-3). According to the results of this study, none of the oral beta-lactam antibiotics should be recommended for the therapy of the systemic infections caused by beta-lactamase-positive E. coli due to their low titres in plasma as expected. Only ceftibuten or oral beta-lactams could be considered for the therapy of urinary tract infections caused by E. coli with all plasmid-mediated beta-lactam resistance, except SHV-4, SHV-5 or SHV-12 beta-lactamase. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring beta-lactamases (TEM-1, TEM-2 and SHV-1) and a shorter dosing interval is needed.

beta-lactam antibiotics; Escherichia coli; extended-spectrum beta-lactamases

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