title: Stability in the presence of widespread beta-lactamases. A prerequisite for the antibacterial activity of beta-lactam drugs.
abstract: 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.
authors.affiliation: Institute of Microbiology, University of Genoa Medical School, Italy.
authors.forename: G C
authors.initials: GC
authors.lastname: Schito
authors.forename: A
authors.initials: A
authors.lastname: Pesce
authors.forename: E A
authors.initials: EA
authors.lastname: Debbia
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D006801:Humans; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D015296:Ceftizoxime; D001618:beta-Lactamases; C047445:cefetamet pivoxyl