Sulbactam-Durlobactam in CRAB Infection: A Real-World Cohort Study

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат Sulbactam-Durlobactam
  Sulbactam-durlobactam administered according to routine clinical practice for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infection.

Первичные конечные точки

• 28-day All-Cause Mortality [Срок оценки: Up to 28 days after initiation of anti-CRAB therapy]

Вторичные конечные точки (4)

• Clinical Failure [Срок оценки: Up to 28 days after initiation of anti-CRAB therapy]
• Length of ICU stay [Срок оценки: Up to 90 days after ICU admission]
• Time to clinical improvement [Срок оценки: Up to 28 days after initiation of anti-CRAB therapy]
• Microbiological eradication [Срок оценки: Up to 14 days after initiation of anti-CRAB therapy]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Colonization without evidence of active infection.
• Missing key clinical data.
• Inability to determine treatment initiation time.
• Pregnancy or lactation.
• Patients considered unsuitable by investigators.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Sichuan Provincial People's Hospital — Чэнду

Публикации

• 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 tr PMID 37182534
• 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 bacter PMID 29276051
• 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. PMID 39234753

Идентификаторы

NCT: NCT07601711 · 2026-055

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗