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[Cefuroxime stability to beta-lactamases: clinical implications]
1Dipartimento di Scienze e Tecnologie Biomediche; Facolta di Medicina e Chirurgia dell'Universita dell'Aquila. Direzione Medica, Glaxo Wellcome Italia, Verona.
Abstract:
Bacteria continuously evolve their resistance mechanisms to antibiotics, either in community or in the hospital setting. Production of beta-lactamases is one of the oldest way to overcome antimicrobial agents activity, since it was first described in 1944 immediately after the penicillin discovery. Beta-lactamases are enzymes hydrolysing the beta-lactam nucleus of beta-lactam antibiotics by using two strategies: a nucleophilic attack of a serine residue or activating a water molecule via a Zn++. Cefuroxime is a injectable cephalosporin which can be also orally administered as a pro-drug named cefuroxime axetil. Cefuroxime has been classified as a second generation cephalosporin, even though the strict subgrouping of cephalosporins into classes is critically discussed by the Authors. Cefuroxime was the first beta-lactam with a higher stability to beta-lactamase hydrolysis due to its methoxy-imino side chain in position 7 of the cephem nucleus. Many of the clinically significant bacterial species producing beta-lactamases such as Haemophilus, Moraxella, Staphylococci and most Enterobacteriaceae then remain susceptible to cefuroxime. The more evoluted enzymes such as carbapenemases, extended-spectrum beta-lactamases or over-expressed cephalosporinases hydrolyse nearly all the beta-lactams antibiotics including cefuroxime. The available literature on the bacterial susceptibility to cefuroxime in Italy and use of cefuroxime in clinical settings where beta-lactamase producing bacteria could be involved has been analysed in the review. In conclusion, cefuroxime still represents a valid therapeutic option even in presence of most of the beta-lactamase producing bacteria.