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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Stability in the presence of widespread beta-lactamases. A prerequisite for the antibacterial activity of beta-lactam drugs.

Bacterial resistance to the beta-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 beta-lactamases. While the number of characterised beta-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 beta-lactamases are usually dominant in nosocomial pathogens where oral antibiotic therapy is seldom used. Therefore, the threat posed by beta-lactamases must be considered in general practice. Several effective strategies have been implemented in order to overcome beta-lactamase-mediated resistance, e.g. use of non-beta-lactam drugs or beta-lactamase inhibitors. Another option has been the development of new beta-lactam compounds that possess a high intrinsic stability against the hydrolytic action of common beta-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 beta-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, alpha-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.[1]


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