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Breakpoints for intravenously used cephalosporins in Enterobacteriaceae--EUCAST and CLSI breakpoints
1Department of Clinical Microbiology, Central Hospital, Växjö, Sweden. gunnar.kahlmeter@ltkronoberg.se
Abstract:
It has long been acknowledged that the cephalosporin breakpoints used in most European countries and the USA fail to detect many or most extended spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and that all ESBLs are clinically significant. Therefore, microbiological laboratories have undertaken not only regular cephalosporin susceptibility tests based on breakpoints, but also special tests to detect all ESBLs. An increasing accumulation of clinical data implies that the clinical success of third generation cephalosporin therapy is related more to the minimum inhibitory concentration (MIC) than to the presence or absence of an ESBL. However, the breakpoints must be lower than those previously recommended by many breakpoint committees. In Europe, this adjustment has been achieved by EUCAST (European Committee on Antimicrobial Susceptibility Testing) through the ongoing process of harmonising European breakpoints. In the USA, the CLSI recently voted to adopt similar guidelines but are waiting to implement these while revising other beta-lactam breakpoints. As Enterobacteriaceae are becoming increasingly resistant, a less 'diehard' interpretation of the relationship among MICs, ESBLs and clinical outcome may provide therapeutic alternatives in difficult situations.
Insights
Current cephalosporin breakpoints often miss extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae. Adjusting these breakpoints and focusing on minimum inhibitory concentrations (MICs) may improve treatment outcomes for resistant infections.
Area of Science:
- Microbiology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae are clinically significant but often undetected by standard cephalosporin breakpoints.
- Existing breakpoints in Europe and the USA are insufficient for detecting many ESBL-producing Enterobacteriaceae.
Purpose of the Study:
- To evaluate the relationship between minimum inhibitory concentrations (MICs), ESBL presence, and clinical outcomes of third-generation cephalosporin therapy.
- To advocate for revised antimicrobial susceptibility testing (AST) breakpoints for cephalosporins to improve detection of resistance mechanisms.
Main Methods:
- Analysis of clinical data correlating MIC values and ESBL detection with treatment success.
- Review of breakpoint harmonization efforts by regulatory bodies like EUCAST and CLSI.
Main Results:
- Clinical success of third-generation cephalosporins appears more closely linked to MIC values than to the mere presence or absence of ESBLs.
- Lowering cephalosporin breakpoints is necessary for accurate susceptibility testing and clinical interpretation.
Conclusions:
- Revised breakpoints, as implemented by EUCAST and considered by CLSI, are crucial for managing Enterobacteriaceae infections.
- A flexible interpretation of MICs, ESBLs, and clinical outcomes offers potential therapeutic strategies for increasing antimicrobial resistance.
