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Predicting doripenem susceptibility based on meropenem and imipenem interpretation for Pseudomonas aeruginosa
Mao Hagihara1, Joseph L Kuti, David P Nicolau
1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.
Abstract:
Doripenem is not available on many automated susceptibility testing panels. We evaluated the surrogate predictive value (SPV) of meropenem and imipenem in predicting doripenem susceptibility using the different breakpoint definitions available globally. MIC data for 736 Pseudomonas aeruginosa were extracted, and categorical interpretations were performed using Clinical and Laboratory Standards Institute (CLSI) proposed 2012, European Committee on Antimicrobial Susceptibility Testing (EUCAST), and Food and Drug Administration (FDA) breakpoints. Regardless of the breakpoint applied, very major and major errors were observed in only 0.1-0.8% and 0.1-4.5% of isolates, respectively. Meropenem's SPV was 98.6% for CLSI 2012 breakpoints, 94.0% for EUCAST, and 95.0% for FDA. Imipenem's SPV was 98.6%, 90.9%, and 97.2%, respectively. These data indicate that meropenem and imipenem would be reliable surrogate markers of doripenem susceptibility when using CLSI 2012 and FDA breakpoints. Meropenem would be recommended over imipenem for EUCAST breakpoints. However, meropenem and imipenem nonsusceptible isolates should be directly tested against doripenem since the latter antibiotic may still retain susceptibility against these isolates.
Insights
Meropenem and imipenem can reliably predict doripenem susceptibility on automated panels, especially with CLSI 2012 and FDA breakpoints. Direct testing is advised for resistant isolates.
Area of Science:
- Clinical Microbiology
- Antimicrobial Resistance
- Pharmacology
Background:
- Doripenem susceptibility testing is often unavailable on automated systems.
- Evaluating surrogate markers is crucial for clinical decision-making.
Purpose of the Study:
- To assess the surrogate predictive value (SPV) of meropenem and imipenem for doripenem susceptibility.
- To compare SPV across different global breakpoint definitions (CLSI, EUCAST, FDA).
Main Methods:
- Analysis of MIC data for 736 Pseudomonas aeruginosa isolates.
- Categorical interpretation using CLSI 2012, EUCAST, and FDA breakpoints.
- Calculation of SPV and error rates for meropenem and imipenem.
Main Results:
- Meropenem and imipenem demonstrated high SPV across all breakpoints, with minimal major/very major errors.
- SPV for meropenem ranged from 94.0% (EUCAST) to 98.6% (CLSI 2012).
- SPV for imipenem ranged from 90.9% (EUCAST) to 98.6% (CLSI 2012).
Conclusions:
- Meropenem and imipenem are reliable surrogate markers for doripenem susceptibility with CLSI 2012 and FDA breakpoints.
- Meropenem is preferred over imipenem for EUCAST breakpoints.
- Direct doripenem testing is recommended for isolates nonsusceptible to meropenem or imipenem.
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