Commentary
Extended-spectrum β-lactamases: A challenge for clinical microbiologists and infection control specialists

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Since first reported in Europe in the early 1980s, extended-spectrum β-lactamases (ESBLs) have spread worldwide. When producing these broad-spectrum plasmid-encoded enzymes, organisms become highly effective at inactivating penicillins, most cephalosporins, and aztreonam. Mainly produced by Klebsiella spp, ESBLs have been isolated worldwide in different species, most of them belonging to the Enterobacteriaceae. ESBL-producing bacteria can appear as in vitro susceptible to β-lactams by conventional laboratory methods, making the laboratory diagnosis problematic. Once detected, all β-lactams except carbapenem and β-lactamase inhibitor compounds should be reported as resistant. In addition, organisms harboring ESBLs are frequently resistant to other antibiotic classes, such as fluoroquinolones and aminoglycosides. Because of the very limited remaining alternatives for treatment and ESBLs significant prevalence worldwide, infection control remains the best way to deal with this bacterial resistance mechanism.

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Background

Since the early 1980s, third-generation cephalosporins have become an important tool in the treatment of severe infections. Unfortunately, clavulanic acid-inhibited extended-spectrum β-lactamases (ESBLs), a heterogeneous group of plasmid- and integron-encoded enzymes responsible for resistance against almost all penicillins, cephalosporins (except cephamycins), and other monobactams,1 have been developed by a great number of bacterial species. Because the above-mentioned drugs were often found

Bacterial species and ESBL types

As mentioned above, TEM and SHV enzyme types are the most common ESBLs mostly found in Klebsiella pneumoniae and Escherichia coli. A total of more than one hundred different enzymes are included in both families together. Recently, these and other types of ESBLs have also been detected in Klebsiella oxytoca, Proteus mirabilis, nontyphoid Salmonella species, other members of the Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp.11, 12

In general, there is a considerable geographic

Prevalence of ESBLs

According to a survey by the National Committee for Clinical Laboratory Standards (NCCLS), the prevalence of ESBLs is probably underestimated.23 Estimates of ESBL-producing isolates among Enterobacteriaceae range from a national average of 3% in the United States21 to much higher numbers in Europe, where the prevalence of ESBL production among isolates of Enterobacteriaceae varies greatly from country to country. In The Netherlands, a survey of 11 hospital laboratories showed that <1% of E coli

Risk factors for acquirement

Several case-control studies have evaluated the risk factors for colonization or infection with ESBL-producing organisms in the hospitalized patient. Reported risk factors include presence of intravascular catheters, emergency intraabdominal surgery, gastrostomy or jejunostomy tube, gastrointestinal colonization, length of hospital or intensive care unit stay, prior antibiotics (including third-generation cephalosporins), prior nursing home stay, severity of illness, presence of a urinary

Clinical significance

Although it is widely accepted that in vitro susceptibility of ESBL-producing organisms to broad-spectrum cephalosporins does not necessarily predict success of treatment, this fact was barely demonstrated in well-designed trials. However, numerous case reports and field experience could lead to such a conclusion: Mortality rates varying from 42% to 100% have been reported when patients infected by ESBL-producing organisms were treated with cephalosporins. A multicountry study conducted by

Detection and reporting

Detection of organisms producing these enzymes can be difficult because the presence of ESBLs in a bacterial cell does not always produce a resistance phenotype when one is using the traditional minimal inhibitory concentration (MIC) and disk diffusion interpretative criteria published by the National Committee for Clinical Laboratory Standards (NCCLS). The fact that ESBL strains cannot be detected by the routine antimicrobial susceptibility testing (AST) used in most laboratories facilitate

Antibiotic therapy

ESBL-producing bacteria often show cross-resistance with other groups of antibiotics, such as fluoroquinolones. In 2 different studies, 18% of ESBL-producing isolates were also ciprofloxacin resistant.39, 40 The close relationship between ESBL production and quinolone resistance is particularly worrisome because the first reported instance of plasmid-mediated ciprofloxacin resistance has been in an isolate of K pneumoniae also possessing an ESBL. However, this phenomenon is still very rare.41

Conclusions

Bacterial resistance to antimicrobial treatment is emerging as one of the major public health threats at the beginning of the 21st Century. The widespread use and, in some cases, misuse of antimicrobials in all health care settings over the past several decades has been cited as a contributing factor in the development of drug resistance in virtually all bacterial species.

The emergence of resistance in bacterial strains that had been consistently susceptible to standard antimicrobial therapy is

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