Background/Objective: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has limited treatment options, and sulbactam MIC interpretation varies with the antimicrobial susceptibility testing (AST) method. This study compared sulbactam MICs determined using broth microdilution (BMD) and the E-test and examined their associations with 28-day mortality. Methods: This secondary analysis used data from a randomized controlled trial comparing colistin plus sulbactam at 9 g/day versus 12 g/day in adults with CRAB pneumonia. The sulbactam MICs of 134 isolates were determined using BMD and the E-test. The agreement between methods across MIC ranges and associations between MICs, dosing, and 28-day mortality were analyzed. Results: Sulbactam MICs determined using BMD were lower than those obtained with the E-test (MIC50/90: 32/128 μg/mL vs. 96/≥256 μg/mL). Overall, agreement between methods was limited and depended on MIC level, with better agreement at lower MICs and marked discrepancies at higher MICs, where the E-test frequently overestimated the MICs. Using the IDSA breakpoint (MIC ≤ 4 μg/mL), susceptibility was identified in 6% of isolates with BMD and 3% with the E-test. A significant survival benefit with high-dose sulbactam (12 g/day) was observed in patients with BMD-determined MICs≥128 μg/mL (HR 0.27; 95% CI, 0.077–0.956; p = 0.042), whereas no mortality association was seen when MICs were categorized using the E-test results. Conclusions: AST method selection substantially affects sulbactam MIC interpretation in CRAB pneumonia. BMD shows stronger correlation with clinical outcomes than the E-test, particularly at high MIC levels. High-dose sulbactam may benefit patients with highly resistant isolates, underscoring the need for accurate and standardized AST methods.
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