Extended-spectrum beta-lactamase-producing organisms

Abstract

Extended-spectrum beta-lactamases (ESBLs), which hydrolyse extended-spectrum cephalosporins and are inhibited by clavulanic acid, are spreading among Enterobacteriaceae. The CTX-M enzymes are replacing SHV and TEM enzymes as the prevalent type of ESBLs, principally in community-acquired infections caused by Escherichia coli. Associated infectious syndromes include mainly urinary tract infections, and secondly bloodstream and intra-abdominal infections, and may be serious enough to warrant hospitalisation. Affected patients commonly have various underlying risk factors. This is also observed in hospital-acquired infections. The rates of ESBL-expression among nosocomial Enterobacteriaceae isolates, particularly Klebsiella pneumoniae, have risen substantially in several countries. The hospital epidemiology of these infections is often complex; multiple clonal strains causing focal outbreaks may co-exist with sporadic ones. Relevant infection-control measures should focus on reducing patient-to-patient transmission via the inanimate environment, hospital personnel, and medical equipment. Wise use of antibiotics is also essential. The available therapeutic options for the treatment of ESBL-associated infections are limited by drug resistance conferred by the ESBLs, along with frequently observed co-resistance to various antibiotic classes, including cephamycins, fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole. Relevant clinical data regarding the effectiveness of different regimens for ESBL-associated infections are limited. Although certain cephalosporins may appear active in vitro, associated clinical outcomes are often suboptimal. beta-Lactam/beta-lactamase inhibitor combinations may be of value, but the supporting evidence is weak. Carbapenems are regarded as the agents of choice, and may be more effective than fluoroquinolones for serious infections. Tigecycline and polymyxins have substantial antimicrobial activity against ESBL-producing Enterobacteriaceae, and, along with fosfomycin, merit further evaluation.