Clinical Relevance of Antimicrobial Susceptibility Testing Methods in Carbapenem-Resistant Acinetobacter baumannii Pneumonia: A Secondary Analysis of a Randomized Controlled Trial

Background/Objective: Carbapenem resistant Acinetobacter baumannii (CRAB) pneumonia has limited treatment options, and sulbactam MIC interpretation varies by antimicrobial susceptibility testing (AST) method. This study compared sulbactam MICs determined by broth microdilution (BMD) and 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. Sulbactam MICs of 134 isolates were determined by BMD and E-test. Agreement between methods across MIC ranges and associations between MICs, dosing, and 28-day mortality were analyzed. Results: Sulbactam MICs determined by BMD were lower than those obtained by 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 E-test frequently overestimated MICs. Using the IDSA breakpoint (MIC ≤4 µg/mL), susceptibility was identified in 6% of isolates by BMD and 3% by 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 E-test results. Conclusions: AST method selection substantially affects sulbactam MIC interpretation in CRAB pneumonia. BMD shows stronger correlation with clinical outcomes than 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.