The diagnostic accuracy of the GeneXpert ESBL- <i>ampC</i> prototype assay for rapid PCR-based detection of extended-spectrum beta-lactamase genes directly from urine
Bibliographic record
Abstract
ABSTRACT The emerging prevalence of extended-spectrum beta-lactamase (ESBL) producing Enterobacterales has implications for the empirical treatment of common infections, such as complicated urinary tract infections. To provide adequate treatment, while avoiding empirical therapy with last resort carbapenems, rapid identification of ESBL-containing pathogens is desirable. Routine urine samples were collected between February and July 2021 in two Dutch clinical medical microbiology laboratories according to a predefined list containing certain culture characteristics. All urine samples were screened for the presence of ESBL genes ( bla CTX-M2 , bla CTX-M14 , and bla CTX-M15 ) with random-access quantitative PCR (qPCR) using the Cepheid GeneXpert ESBL- ampC prototype assay. The qPCR and microbiological culture results were compared. After the calculation of the sensitivity and specificity, discrepancies were investigated by whole-genome sequencing. In total, 276 urine samples were available for ESBL analysis (94 ESBL culture positive and 182 ESBL culture negative). The sensitivity and specificity for detection of ESBL genes were 90.4% and 98.4%, respectively. In nine samples (9.6%), no ESBL genes were detected with GeneXpert, while in the microbiological culture, an ESBL-positive organism was isolated. This was mainly explained by non-GeneXpert ESBL genes: bla SHV -family ( n = 6; 75.0%), bla TEM -family ( n = 1; 12.5%), and bla SRT -family ( n = 1; 12.5%). The positive and negative predictive values in a hypothetical clinical scenario with a 15% ESBL prevalence were 0.91 and 0.98, respectively. Regarding ampC , the specificity appears to be satisfactory, but the sensitivity is low. The Cepheid GeneXpert ESBL assay could be beneficial for the fast and accurate detection of ESBL genes in regions where the epidemiology of ESBL genes coincides with the targets in the panel. IMPORTANCE Early identification of complicated urinary tract infections caused by ESBL-producing Enterobacterales has the potential to limit the use of carbapenems to those patients without alternative antibiotic options and avoid the empirical use of carbapenems in patients without ESBL-producing bacteria. The purpose for such a test will differ by setting and ESBL prevalence rates. Countries with low ESBL rates and cephalosporins as empiric treatment (e.g., The Netherlands) will need a rule-in test to decide to use carbapenems, while countries with high ESBL rates and empiric carbapenem treatment will need a rule-out test for ESBLs to de-escalate therapy early. Anyway, such as a test would—at least theoretically—improve patient care and reduce selective pressure for the emergence of carbapenem resistance.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".