Stability in the Presence of Widespread β-Lactamases: A Prerequisite for the Antibacterial Activity of β-Lactam Drugs

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Abstract

Summary

Bacterial resistance to the β-lactam drugs is extremely widespread, as a result of extensive drug use. Loss of susceptibility is primarily attributable to hydrolysis by inactivating enzymes, namely the β-lactamases. While the number of characterised β-lactamases may exceed 100, only a few are a problem in the treatment of community-acquired infections (TEM-1, TEM-2, SHV-1, BRO-1). Chromosomally mediated and extended-spectrum β-lactamases are usually dominant in nosocomial pathogens where oral antibiotic therapy is seldom used.

Therefore, the threat posed by β-lactamases must be considered in general practice. Several effective strategies have been implemented in order to overcome β-lactamase-mediated resistance, e.g. use of non-β-lactam drugs or β-lactamase inhibitors. Another option has been the development of new β-lactam compounds that possess a high intrinsic stability against the hydrolytic action of common β-lactamases. Among these compounds, the oral third generation cephalosporins represent an important breakthrough.

Cefetamet pivoxil, a new oral third generation cephalosporin, is characterised by excellent antimicrobial potency against Enterobacteriaceae, and Moraxella (Branhamella) catarrhalis and Haemophilus influenzae, irrespective of their ability to produce β-lactamases. The Gram-positive respiratory pathogens, Streptococcus pyogenes and penicillin-susceptible S. pneumoniae, are also satisfactorily covered. The activity of cefetamet has recently been corroborated in a survey conducted in Italy involving 4191 isolates. However, cefetamet shows no activity against enterococci, staphylococci, Listeria, α-streptococci, Pseudomonas, Acinetobacter and anaerobes.

Given this antibacterial profile, cefetamet pivoxil may provide a useful alternative to other oral antibacterial agents in the empirical therapy of acute community-acquired respiratory and urinary tract infections. From the results of the Italian survey, cefetamet emerged as the only agent among those considered (which included cefuroxime, cefaclor, cefalexin, cefadroxil, ampicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, doxycycline, erythromycin and clindamycin) that might be selected as the drug of choice in the empirical therapy of outpatient infections.

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