Extended-spectrum beta-lactamases (ESBLs) are enzymes that inactivate and confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. They are found exclusively in gram-negative organisms, primarily Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. Many different varieties of ESBL exist. They differ in their activity against particular beta-lactam substrates and in their geographical distribution. Most ESBLs do not break down cephamycins or carbapenems and are susceptible to beta-lactamase inhibitors.
Laboratory detection of an ESBL in an organism is based on resistance to particular cephalosporins and the ability of a beta-lactamase inhibitor to block this resistance. However, the heterogeneity of the ESBL varieties can make identification difficult. Thus, the Clinical and Laboratory Standards Institute has adjusted susceptibility breakpoint recommendations for gram-negative bacilli. As a result, many organisms that previously would have been categorized as susceptible using the former breakpoints may now be considered intermediate or resistant. This often precludes the need to identify the ESBL in order to make treatment decisions.
ESBL-producing gram-negative bacilli have been reported worldwide. They are most often isolated from hospitalized patients but are an increasing cause of community-acquired infections. Risk factors for infection include prior administration of an antibiotic, presence of urinary or vascular catheters, and longer hospital or ICU stays.
The best therapeutic option for severe infections caused by ESBL-producing organisms is a carbapenem (imipenem, meropenem, doripenem, and ertapenem). We use meropenem or imipenem for most ESBL infections. Ertapenem is an acceptable option in the absence of resistance or severe sepsis and can be particularly useful in the outpatient setting.
Cefepime may be effective against ESBL-producing organisms that test susceptible if administered in high doses (ie, 2 g every eight hours). Use of other cephalosporins and piperacillin-tazobactam has been associated with treatment failures. Ceftolozane-tazobactam and ceftazidime-avibactam combinations appear promising, but further clinical data are needed to establish their efficacy relative to carbapenems. There is little clinical evidence for cephamycin use, which has been associated with development of resistance. Resistance to aminoglycosides and fluoroquinolones is also common in these organisms.
Infections with ESBL-producing organisms are associated with higher mortality rates, longer hospital stays, greater hospital expenses, and reduced rates of clinical and microbiologic response compared with similar infections with gram-negative bacteria that do not produce ESBL.
The spread of ESBL-producing organisms within institutions can be slowed by the use of barrier protection and restriction of later generation cephalosporins．
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β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisa... - PubMed - NCBI
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