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

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).

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

Primary outcomes

• 28-day All-Cause Mortality [Up to 28 days after initiation of anti-CRAB therapy]: All-cause mortality occurring within 28 days after initiation of anti-CRAB therapy.

Secondary outcomes

• Clinical Failure [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.
• Length of ICU stay [Up to 90 days after ICU admission]: Duration of ICU stay measured from ICU admission to ICU discharge.
• Time to clinical improvement [Up to 28 days after initiation of anti-CRAB therapy]: Time from initiation of anti-CRAB therapy to predefined clinical improvement.
• Microbiological eradication [Up to 14 days after initiation of anti-CRAB therapy]: Microbiological eradication confirmed by follow-up culture negativity.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years.
* Hospitalized patients receiving anti-CRAB antimicrobial therapy, including:

  1. patients with confirmed carbapenem-resistant Acinetobacter baumannii (CRAB) infection based on microbiological testing in combination with clinical evidence of infection; or
  2. 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.

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