Effects of ß‐Lactamase‐Mediated Antimicrobial Resistance: The Role of ß‐Lactamase Inhibitors

Abstract

Production of ß‐lactamase is the most common mechanism of bacterial resistance to ß‐lactam antibiotics. Virtually all bacteria have the capability of synthesizing the enzyme. Microorganisms may already possess the native genetic information necessary for ß‐lactamase production (i.e., chromosomal), or may acquire the capacity by transfer of DNA from another organism (i.e., plasmid‐mediated). The level of ß‐lactamase production may be stable and noninducible (constitutive enzyme production), or may be stimulated on exposure to selected ß‐lactam antibiotics (inducible enzyme production). Inhibitors such as clavulanic acid and sulbactam prevent antibiotic degradation by the ß‐lactamases of many clinically significant pathogens. Therefore, currently available ß‐lactam‐ß‐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.