Perspectives of beta-lactamases inhibitors in therapy of infections caused by Escherichia coli or Klebsiella with plasmidic resistance to third generation cephalosporins.
New plasmidic beta-lactamases inactivating so far stable cephalosporins, aztreonam and cephamycins restrict the use of these antibiotics in therapy of infections, e.g., by Escherichia coli and Klebsiella. Thus, combinations of beta-lactamase inhibitors and beta-lactam antibiotics were investigated in vitro with regard to their therapeutic perspectives. Minimal inhibitory concentrations and the kinetics of killing in a pharmacodynamic model were determined. Extended broad spectrum beta-lactamases (EBS-beta-lactamases) representative both for the TEM- and SHV-type were included. None of the available fixed combinations of penicillins and beta-lactamase inhibitors appears useful for therapy of infections caused by producers of EBS-beta-lactamases. In contrast, combinations of piperacillin and tazobactam or sulbactam plus cephalosporins (cefoperazone, cefotaxime, ceftazidime) or aztreonam are highly active (both by their MICs and bactericidal activity) against TEM-type EBS-beta-lactamases, but less promising for the SHV-type EBS-beta-lactamases, and plasmidic cephamycinase. Of the beta-lactams available, the monobactam carumonam and the carbapenems (imipenem, meropenem) remain safe in infections caused by E. coli and Klebsiella EBSBase producers.
Bauernfeind
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Max von Pettenkofer-Institut, Munich, FR Germany.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy; D007709:Klebsiella / Q000187:drug effects*; D007710:Klebsiella Infections / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology*; D010957:Plasmids; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; D065093:beta-Lactamase Inhibitors