Effects of beta-lactamase-mediated antimicrobial resistance: the role of beta-lactamase inhibitors.
Production of beta-lactamase is the most common mechanism of bacterial resistance to beta-lactam antibiotics. Virtually all bacteria have the capability of synthesizing the enzyme. Microorganisms may already possess the native genetic information necessary for beta-lactamase production (i.e., chromosomal), or may acquire the capacity by transfer of DNA from another organism (i.e., plasmid-mediated). The level of beta-lactamase production may be stable and noninducible (constitutive enzyme production), or may be stimulated on exposure to selected beta-lactam antibiotics (inducible enzyme production). Inhibitors such as clavulanic acid and sulbactam prevent antibiotic degradation by the beta-lactamases of many clinically significant pathogens. Therefore, currently available beta-lactam-beta-lactamase-inhibitor combinations exhibit broad spectra of in vitro activity. Ticarcillin-clavulanate possesses clinically significant activity against many bacteria, including streptococci, Staphylococcus aureus, Bacteroides fragilis, and numerous Enterobacteriaceae. Amoxicillin-clavulanate and ampicillin-sulbactam demonstrate clinically significant activity against streptococci (including enterococci), S. aureus, B. fragilis, and some Enterobacteriaceae. Ticarcillin-clavulanate is indicated for treatment of serious infections, including septicemia. Amoxicillin-clavulanate is useful in the treatment of upper respiratory, urinary tract, and skin and soft tissue infections. Ampicillin-sulbactam may be used for treatment of intraabdominal, gynecologic, urinary tract, and skin and soft tissue infections.
Maddux
M S
MS
Department of Pharmacy Practice, College of Pharmacy, University of Illinois, Chicago.
D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001421:Bacteria, Anaerobic / Q000201:enzymology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000145:classification / Q000494:pharmacology; D002875:Chromosomes / Q000201:enzymology; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000201:enzymology; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000145:classification / Q000494:pharmacology; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D010957:Plasmids; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000145:classification
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004338:Drug Combinations; D046915:Penicillin-Binding Proteins; D065093:beta-Lactamase Inhibitors; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases