Overview
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.
Description
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).
Eligibility
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.
