Treatment options for extended-spectrum β-lactamase-producers

Abstract

A review of antibiotic options for the treatment of infections caused by extended-spectrum β-lactamase-producing isolates is presented. The use of the third-generation cephalosporin, cefotaxime, for infections caused by isolates producing ceftazidimase-type extended-spectrum β-lactamases is controversial, despite in vitro susceptibility to the antibiotic in many instances. The fourth-generation cephalosporin, cefipime, although active against most extended-spectrum β-lactamases, is reported to show a marked inoculum effect. The cephamycins, such as cefoxitin, are generally effective against Enterobacteriaceae producing TEM- and SHV-derived extended-spectrum β-lactamases, but Klebsiella pneumoniae strains are prone to cephamycin resistance as a result of porin loss. The use of β-lactamase inhibitor combinations is variable. Sulbactam is less effective than clavulanate for the inhibition of SHV-derived extended-spectrum β-lactamases and a marked inoculum effect has been noted, while the efficacy of tazobactam against SHV-derived extended-spectrum β-lactamase producers is controversial. Furthermore, extended-spectrum β-lactamases are often encoded by multi-resistant plasmids carrying genes conferring resistance to aminoglycosides, chloramphenicol, sulfonamides, trimethoprim and other antimicrobials, severely limiting even alternative therapies. Extensive susceptibility testing before the institution of antibiotic therapy is thus vital.