The threat of resistance to the new oral cephalosporins.
Phenotypic resistance to beta-lactam antibiotics is mainly due to the prevalence of beta-lactamases. The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated. The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections. Two principal mechanisms, however, may cause resistance to these new compounds: the overproduction of chromosomally encoded beta-lactamases with predominating cephalosporinase activity, and the recently observed extended-spectrum beta-lactamases. The overproduction of chromosomally mediated beta-lactamases has been observed only in some species (Enterobacter cloacae, Citrobacter freundii, Serratia spp.) which cause mainly nosocomial infections and are therefore of minor importance in outpatients. The extended-spectrum beta-lactamases TEM-3 to TEM-12 and SHV-2 to SHV-7 have been observed in various countries, they derived from the original enzymes by point mutations and occurred in intensive-care units. These enzymes may cause resistance to 3rd-generation cephalosporins including the recently developed orally active compounds. Moderate resistance to cefetamet is observed only in strains producing either the TEM-3 or the TEM-4 enzyme, whereas the prevalence of the other enzymes is of no consequence for the activity of cefetamet. Consequently, cefetamet will not exhibit a marked selection pressure favoring the spread of extended-spectrum beta-lactamase-producing strains.
Cullmann
W
W
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D001424:Bacterial Infections / Q000382:microbiology*; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology; D010403:Penicillin Resistance; D012141:Respiratory Tract Infections / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000382:microbiology*; D001618:beta-Lactamases / Q000096:biosynthesis*
D002511:Cephalosporins; D001618:beta-Lactamases