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

<b>Background/Objective</b>: Carbapenem-resistant <i>Acinetobacter baumannii</i> (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. <b>Methods</b>: 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. <b>Results</b>: 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; <i>p</i> = 0.042), whereas no mortality association was seen when MICs were categorized using the E-test results. <b>Conclusions</b>: 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.