Korean J Lab Med.  2008 Dec;28(6):401-412. 10.3343/kjlm.2008.28.6.401.

Extended-spectrum beta-Lactamases: Implications for the Clinical Laboratory and Therapy

• Harada S
• Ishii Y
• Yamaguchi

• KMID: 1781573
• DOI: http://doi.org/10.3343/kjlm.2008.28.6.401

Abstract

Production of extended-spectrum beta-lactamase (ESBL) is one of the most important resistance mechanisms that hamper the antimicrobial treatment of infections caused by Enterobacteriaceae. ESBLs are classified into several groups according to their amino-acid sequence homology. While TEM and SHV enzymes were the most common ESBLs in the 1990s, CTX-M enzymes have spread rapidly among Enterobacteriaceae in the past decade. In addition, some epidemiological studies showed that organisms producing CTX-M enzymes had become increasingly prevalent in the community setting in certain areas in the world. Several novel enzymes with hydrolyzing activity against oxyimino-cephalosporins, albeit with additional enzymatic characteristics different from those of original TEM and SHV ESBLs (e.g., inhibitor-resistance), have been discovered and pose a problem on the definition of ESBLs. Although several methods to detect the production of ESBL are available in clinical laboratories, existence of other factors contributing resistance against beta-lactams, e.g., inducible production of Amp-C beta-lactamase by some species of Enterobacteriaceae, or inhibitor-resistance in some ESBLs may hinder the detection of ESBLs with these methods. Carbapenems are stable against hydrolyzing activity of ESBLs and are regarded as the drug of choice for the treatment of infections caused by ESBL-producing Enterobacteriaceae. Although several other antimicrobial agents, such as fluoroquinolones and cephamycins, may have some role in the treatment of mild infections due to those organisms, clinical data that warrant the use of antimicrobial agents other than carbapenems in the treatment of serious infections due to those organisms are scarce for now.

Keyword

Beta-lactamase

MeSH Terms

Anti-Bacterial Agents/*pharmacology/therapeutic use
Carbapenems/pharmacology/therapeutic use
Disk Diffusion Antimicrobial Tests
Enterobacteriaceae/drug effects/*enzymology/genetics
Enterobacteriaceae Infections/*drug therapy/microbiology
Fluoroquinolones/pharmacology/therapeutic use
Humans
Microbial Sensitivity Tests/methods
beta-Lactamases/*biosynthesis/metabolism
beta-Lactams/*pharmacology/therapeutic use

Figure

• 

  Fig. 1. Positive CLSI recommended method for ESBL producing strains. The inhibition zone around the CTX/CVA disk is apparently larger than that around the CTX disk, indicating ESBL production. Comparable result is obtained with CAZ disk and CAZ/CVA disk. Note that the inhibition zone diameter around the CAZ disk is within the susceptible range (≥18 mm). Adherence to the protocol and the use of both CTX and CAZ disks are crucial for the highly sensitive detection of ESBL production.

• 

  Fig. 2. Positive Etest ESBL test. MICs are CT>16 mg/L, CTL 0.064 mg/L, TZ >32 μg/mL, and TZL 0.25 μg/mL. ESBL production is suggested by a ≥3 two-fold reduction of MIC value in the presence of clavulanate. In addition, ‘phantom zone’ is observed below the CT gradient (arrrow).

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