Clinical Symptom Resolution Following PCR-Guided vs. Culture and Susceptibility-Guided Management of Complicated UTI: How Time-To-Antibiotic Start and Antibiotic Appropriateness Mediate the Benefit of Multiplex PCR—An Ad Hoc Analysis of NCT06996301
Notice bibliographique
Résumé
Background: Rapid multiplex PCR assays promise faster and broader detection of uropathogens and resistance markers than conventional quantitative urine culture and susceptibility testing (C&S), but trial evidence linking PCR-guided management to patient-centered outcomes and the mechanisms of any benefit is limited. We performed an ad hoc analysis of the randomized, multicenter NCT06996301 trial to evaluate whether PCR-guided diagnostic management improves clinical symptom resolution in complicated urinary tract infection (cUTI) and to quantify mediation by time-to-antibiotic start and antibiotic appropriateness. Methods: Paired PCR and C&S were collected for all participants; treating investigators received and acted on randomized results from one diagnostic modality and remained blinded to the comparator. The modified intention-to-treat (Mod-ITT) cohort at end-of-study (EOS) included 362 participants (PCR n = 193; C&S n = 169). The primary outcome was complete clinical cure at EOS (absence of all baseline symptoms). Secondary outcomes included partial cure (≥50% symptom reduction) and per-symptom changes. We used mixed-effects logistic regression (site random intercept) to estimate associations, and causal mediation analysis with nonparametric bootstrap (B = 2000) to decompose PCR’s total effect into indirect effects via time-to-antibiotic (log-transformed) and antibiotic appropriateness (binary, adjudicated at EOS) for complete clinical cure and partial cure. Results: Median time-to-first antibiotic was substantially shorter in the PCR arm (20 h; IQR 12–36) than in the C&S arm (52 h; IQR 30–66; p < 0.001). Antibiotic appropriateness was higher after PCR-guided care (161/193; 83.4%) versus C&S (105/169; 62.1%; p < 0.001). Complete clinical cure occurred in 143/193 (74.1%) PCR versus 106/169 (62.7%) C&S (p = 0.020); partial cure in 161/193 (83.4%) versus 121/169 (71.6%; p = 0.014). In a total-effect mixed model (no mediators), PCR assignment was associated with higher odds of cure (adjusted OR 1.95; 95% CI 1.12–3.39; p = 0.018). In the mechanistic model including mediators, antibiotic appropriateness (OR 2.48; 95% CI 1.45–4.24; p = 0.001), and time-to-antibiotic (per 1 h, OR 0.95; 95% CI 0.926–0.975; p < 0.001) were independently predictive, while the direct arm effect was attenuated (OR 1.10; 95% CI 0.33–3.71). Mediation analysis estimated a statistically significant combined indirect effect (ACME) of 0.0648 (95% CI 0.0343–0.0977), ADE 0.0207 (95% CI −0.0282–0.0784), total effect 0.0796 (95% CI 0.0419–0.1225), and proportion mediated ≈ 74%. Both time-to-antibiotic and appropriateness contributed, with ACME_time ≈ 0.046 and ACME_appropriateness ≈ 0.019. Exploratory analysis using partial cure as the outcome confirmed the robustness and internal validity of the complete-cure findings. Conclusions: In this ad hoc analysis of a randomized trial, PCR-guided management of cUTI improved patient-centered symptom outcomes compared with culture-guided care. Most of the benefit was mediated through faster initiation of antibiotics and, to a lesser extent, increased probability of an appropriate initial antibiotic. These results support stewardship-integrated, rapid molecular diagnostics (used alongside culture) to shorten time-to-effective therapy and improve clinical outcomes in cUTI.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».