Effects of beta-lactamase-mediated antimicrobial resistance: the role of beta-lactamase inhibitors.

Abstract

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.