Sulbactam-Durlobactam in CRAB Infection: A Real-World Cohort Study (SD-CRAB)
This is a Single-center Real-world Observational Cohort Study of Sulbactam-Durlobactam for Carbapenem-Resistant Acinetobacter Baumannii Infections: Effectiveness, Safety, and Exposure-Response Analysis
This is a multicenter real-world observational cohort study designed to evaluate the effectiveness and safety of sulbactam-durlobactam in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Patients receiving sulbactam-durlobactam will be compared with those receiving other anti-CRAB regimens during the same period.
The primary outcomes are 28-day all-cause mortality and clinical failure. Secondary outcomes include microbiological clearance, recurrence, length of hospital and ICU stay, duration of mechanical ventilation, and adverse events.
To reduce confounding inherent in observational studies, propensity score methods, including matching and inverse probability weighting, will be applied. A nested therapeutic drug monitoring (TDM) sub-cohort will be established to explore the relationship between drug exposure and clinical outcomes.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a single-center real-world observational cohort study including hospitalized adult patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Patients will be classified into two groups based on treatment exposure: those receiving sulbactam-durlobactam and those receiving alternative anti-CRAB regimens during the same period.
The study aims to evaluate the effectiveness and safety of sulbactam-durlobactam in high-risk populations, including transplant recipients and critically ill patients. The primary outcomes are 28-day all-cause mortality and clinical failure. Secondary outcomes include microbiological clearance, recurrence, ICU length of stay, duration of mechanical ventilation, and treatment-related adverse events.
To minimize bias inherent in observational studies, propensity score matching, inverse probability of treatment weighting (IPTW), and multivariable regression models will be applied to adjust for baseline differences between groups. Landmark analysis will be conducted to address time-related biases.
A nested therapeutic drug monitoring (TDM) sub-cohort will be included. Plasma samples will be collected at predefined time points within a dosing interval, and drug concentrations will be measured using validated LC-MS/MS methods. Population pharmacokinetic modeling will be performed to estimate exposure parameters, including Cmin, Cmax, and AUC. The relationship between drug exposure and clinical outcomes, as well as PK/PD target attainment, will be further explored.
Subgroup analyses will be conducted according to infection status (confirmed infection vs. donor-derived colonization or infection).
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Lieux d'étude
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Sichuan
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Chengdu, Sichuan, Chine, 610072
- Recrutement
- Sichuan Provincial People's Hospital
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Contact:
- Lingai Pan, MD
- Numéro de téléphone: +86 17708130236
- E-mail: panlingai2004@163.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
Hospitalized adult patients receiving anti-CRAB antimicrobial therapy in real-world clinical practice, including:
- patients with confirmed carbapenem-resistant Acinetobacter baumannii (CRAB) infection; or
- transplant recipients with donor-derived CRAB colonization or infection receiving early targeted therapy.
La description
Inclusion Criteria:
- Age ≥18 years.
Hospitalized patients receiving anti-CRAB antimicrobial therapy, including:
- patients with confirmed carbapenem-resistant Acinetobacter baumannii (CRAB) infection based on microbiological testing in combination with clinical evidence of infection; or
- transplant recipients with donor-derived CRAB colonization or infection who receive early targeted antimicrobial therapy.
- Treatment initiation time can be clearly determined.
- Availability of clinical outcome data.
Exclusion Criteria:
- Colonization without evidence of active infection.
- Missing key clinical data.
- Inability to determine treatment initiation time.
- Pregnancy or lactation.
- Patients considered unsuitable by investigators.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
Sulbactam-Durlobactam Group
Patients receiving sulbactam-durlobactam within 48 hours after treatment initiation.
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Sulbactam-durlobactam administered according to routine clinical practice for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infection.
|
|
Non-Sulbactam-Durlobactam Group
Patients receiving alternative anti-CRAB regimens during the same period without sulbactam-durlobactam.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
28-day All-Cause Mortality
Délai: Up to 28 days after initiation of anti-CRAB therapy
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All-cause mortality occurring within 28 days after initiation of anti-CRAB therapy.
|
Up to 28 days after initiation of anti-CRAB therapy
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Clinical Failure
Délai: Up to 28 days after initiation of anti-CRAB therapy
|
Clinical failure defined as lack of clinical improvement, need for escalation of antimicrobial therapy, or death.
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Up to 28 days after initiation of anti-CRAB therapy
|
|
Length of ICU stay
Délai: Up to 90 days after ICU admission
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Duration of ICU stay measured from ICU admission to ICU discharge.
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Up to 90 days after ICU admission
|
|
Time to clinical improvement
Délai: Up to 28 days after initiation of anti-CRAB therapy
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Time from initiation of anti-CRAB therapy to predefined clinical improvement.
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Up to 28 days after initiation of anti-CRAB therapy
|
|
Microbiological eradication
Délai: Up to 14 days after initiation of anti-CRAB therapy
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Microbiological eradication confirmed by follow-up culture negativity.
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Up to 14 days after initiation of anti-CRAB therapy
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Publications générales
- Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21.
- Kaye KS, Shorr AF, Wunderink RG, Du B, Poirier GE, Rana K, Miller A, Lewis D, O'Donnell J, Chen L, Reinhart H, Srinivasan S, Isaacs R, Altarac D. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis. 2023 Sep;23(9):1072-1084. doi: 10.1016/S1473-3099(23)00184-6. Epub 2023 May 11.
- Covvey JR, Guarascio AJ. Sulbactam-durlobactam for the treatment of Acinetobacter baumannii-calcoaceticus complex. Expert Rev Anti Infect Ther. 2024 Nov;22(11):925-934. doi: 10.1080/14787210.2024.2400703. Epub 2024 Sep 8.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
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Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 2026-055
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