Purpose <p>Carbapenemase-producing Enterobacterales (CPE), particularly OXA-48-producing Enterobacterales, represent a major diagnostic and therapeutic challenge due to their frequent low-level carbapenem resistance and delayed microbiological detection. Rapid confirmation of carbapenemase production is essential to optimize antimicrobial therapy and infection control measures.</p> Methods <p>This study evaluated the simplified carbapenem inactivation method (sCIM) for detection of OXA-48-producing Enterobacterales. Unlike the conventional mCIM, sCIM eliminates the preliminary carbapenem inactivation incubation step, simplifying the workflow and reducing turnaround time. A total of 150 OXA-48-producing Enterobacterales were analyzed, together with additional VIM-, KPC-producing, and non-carbapenemase-producing isolates collected from clinical specimens at the Hospital Central de la Defensa “Gómez-Ulla” in Spain. Carbapenemase production was confirmed using the Xpert^® Carba-R molecular assay.</p> Results <p>The sCIM detected all OXA-48-producing Enterobacterales with 100% sensitivity (95% CI: 97.6–100%) and no indeterminate results, including isolates with low ertapenem MICs. Results were available after 16–18&#xa0;h of incubation without previous 4-hour carbapenem inactivation step, simplifying laboratory workflow compared with the conventional mCIM.</p> Conclusions <p>The rapid detection of OXA-48-producing Enterobacterales remains a major diagnostic challenge due to their frequently low carbapenem MICs and subtle phenotypic expression. This study demonstrates that sCIM provides a simple, reliable, and highly sensitive method for detecting these isolates, even in cases with borderline susceptibility profiles. Given its low cost and ease of implementation, sCIM represents a valuable tool for routine clinical laboratories, particularly in high-prevalence or resource-limited settings.</p>