How to: ECOFFs—the why, the how, and the don'ts of EUCAST epidemiological cutoff values

Kahlmeter, Gunnar; Turnidge, John

doi:10.1016/j.cmi.2022.02.024

Cited by 34 publications

(27 citation statements)

References 14 publications

(15 reference statements)

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“…The clinical strains of P. aeruginosa ST3875 displayed a wild-type antimicrobial susceptibility profile [13]. However, resistance towards anti-pseudomonas drugs was discovered after antimicrobial treatment of single patients (data not shown).…”

Section: Discussionmentioning

confidence: 96%

Pseudomonas aeruginosa countrywide outbreak in hospitals linked to pre-moistened non-sterile washcloths, Norway, October 2021 to April 2022

Gravningen,

Kacelnik,

Lingaas

et al. 2022

Eurosurveillance

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In November 2021, a clonal outbreak of Pseudomonas aeruginosa of novel sequence type ST3875 was detected in three patients who died of bloodstream infections in one hospital. By 25 April 2022, the outbreak included 339 cases from 38 hospitals across Norway. Initial hospital reports indicate Pseudomonas infection as the main contributing cause in seven deaths. In March 2022, the outbreak strain was identified in non-sterile pre-moistened disposable washcloths, used to clean patients, from three lots from the same international manufacturer.

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Section: Discussionmentioning

confidence: 96%

Pseudomonas aeruginosa countrywide outbreak in hospitals linked to pre-moistened non-sterile washcloths, Norway, October 2021 to April 2022

Gravningen,

Kacelnik,

Lingaas

et al. 2022

Eurosurveillance

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“…However, similar to these studies, our MIC distribution was wide indicating poor reproducibility of individual MICs which was also observed in a systematic review by the WHO ( World Health Organization, 2018 ). Additionally, it has been pointed out that it is very difficult if possible to separate technically from biological variability within the wild-type MIC distribution of any drug ( Kahlmeter and Turnidge, 2022 ). Taking these caveats into account, our exploratory analysis showed that an MIC level close to the suggested breakpoint for Middlebrook 7H11 (≥0.25 mg/L), the recommended dosage may need further consideration.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients

Shao

Bao²,

Forsman³

et al. 2023

Front. Pharmacol.

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Aims: Bedaquiline is now recommended to all patients in the treatment of multidrug-resistant tuberculosis (MDR-TB) using standard dosing regimens. As the ability to measure blood drug concentrations is very limited, little is known about drug exposure and treatment outcome. Thus, this study aimed to model the population pharmacokinetics as well as to evaluate the currently recommended dosage.Methodology: A bedaquiline population pharmacokinetic (PK) model was developed based on samples collected from the development cohort before and 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 h after drug intake on week 2 and week 4 of treatment. In a prospective validation cohort of patients with MDR-TB, treated with bedaquiline-containing standardized regimen, drug exposure was assessed using the developed population PK model and thresholds were identified by relating to 2-month and 6-month sputum culture conversion and final treatment outcome using classification and regression tree analysis. In an exploratory analysis by the probability of target attainment (PTA) analysis, we evaluated the recommended dosage at different MIC levels by Middlebrook 7H11 agar dilution (7H11).Results: Bedaquiline pharmacokinetic data from 55 patients with MDR-TB were best described by a three-compartment model with dual zero-order input. Body weight was a covariate of the clearance and the central volume of distribution, albumin was a covariate of the clearance. In the validation cohort, we enrolled 159 patients with MDR-TB. The 7H11 MIC mode (range) of bedaquiline was 0.06 mg (0.008–0.25 mg/L). The study participants with AUC0-24h/MIC above 175.5 had a higher probability of culture conversion after 2-month treatment (adjusted relative risk, aRR:16.4; 95%CI: 5.3–50.4). Similarly, those with AUC0-24h/MIC above 118.2 had a higher probability of culture conversion after 6-month treatment (aRR:20.1; 95%CI: 2.9–139.4), and those with AUC0-24h/MIC above 74.6 had a higher probability of successful treatment outcome (aRR:9.7; 95%CI: 1.5–64.8). Based on the identified thresholds, simulations showed that the WHO recommended dosage (400 mg once daily for 14 days followed by 200 mg thrice weekly) resulted in PTA >90% for the majority of isolates (94%; MICs ≤0.125 mg/L).Conclusion: We established a population PK model for bedaquiline in patients with MDR-TB in China. Based on the thresholds and MIC distribution derived in a clinical study, the recommended dosage of bedaquiline is sufficient for the treatment of MDR-TB.

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“…The clinical utility is largely unexplored and adds an additional dimension to the recently highlighted use of ECOFF. 12 Epidemiological cut-off value zone sizes are provided by EUCAST and thus this could also be applied by laboratories that only use disk diffusion for AST, which is the recommended EUCAST method. This would require additional information to be provided on AST reports and concomitant education of clinicians as to the potential value thereof.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of Vitek-derived minimum inhibitory concentration values: Proof of concept study

Lowman

2023

Southern African Journal of Infectious Diseases

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Background: Minimum inhibitory concentration (MIC) values are useful in guiding appropriate antimicrobial therapy however, routine provision and interpretation of MIC values to guide clinical decision-making is challenging.Objectives: This proof of concept study aims to demonstrate the clinical utility and application of Vitek®-derived MIC values through categorisation of clinical isolates as wild type.Method: A random selection of clinically relevant Gram negative isolates routinely tested on the Vitek® instrument were included. The Vitek® MIC values, for selected antimicrobials at the lowest calling range of that card, were compared to the broth microdilution reference method. The specified end-point was concordance between the two results if the reference MIC was less than or equal to the EUCAST-defined epidemiological cut-off value (ECOFF) for that drug-bug combination.Results: A total of 525 isolates were included (468 Enterobacterales and 57 Pseudomonas aeruginosa), with an overall concordance rate of 96.4% (508/525). Correct ECOFF categorisation by the Vitek® was highest for ceftazidime and piperacillin (100%, n = 48 and n = 55, respectively) and lowest for cefepime (81.8%, n = 66).Conclusion: Vitek®-derived MIC values can be used to categorise organisms as wild-type if the MIC is reported at the card’s lowest calling range (≤) as there is high likelihood that the MIC is at or below the ECOFF. This has important implications for antimicrobial management, assisting in choice of agent and in improving probability of target attainment for desired pharmacodynamic targets which can translate into improved clinical outcomes.Contribution: Minimum inhibitory concentration data from an automated antimicrobial susceptibility testing instrument can be used to guide clinical decisions.

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How to: ECOFFs—the why, the how, and the don'ts of EUCAST epidemiological cutoff values

Cited by 34 publications

References 14 publications

Pseudomonas aeruginosa countrywide outbreak in hospitals linked to pre-moistened non-sterile washcloths, Norway, October 2021 to April 2022

Pseudomonas aeruginosa countrywide outbreak in hospitals linked to pre-moistened non-sterile washcloths, Norway, October 2021 to April 2022

Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients

Clinical application of Vitek-derived minimum inhibitory concentration values: Proof of concept study

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