Carbapenem-Sparing Therapy of ESBL- Enterobacterales Pyelonephritis: A Retrospective Comparison of Cefoperazone-Sulbactam and Meropenem

Objective: To compare the real-world clinical outcomes, time to clinical cure of patients with Extended-spectrum b-lactamase-producing Enterobacterales (ESBL-E) pyelonephritis who received cefoperazone-sulbactam versus meropenem based on retrospective medical record review. Objective: To compare the real-world clinical outcomes, time to clinical cure of patients with Extended-spectrum b-lactamase-producing Enterobacterales (ESBL-E) pyelonephritis who received cefoperazone-sulbactam versus meropenem based on retrospective medical record review. Methodology: A retrospective cohort study was done at the Department of Infectious Diseases, Indus Hospital and Health Network (IHHN), Karachi, on adult patients with culture-proven ESBL-producing Enterobacterales pyelonephritis treated between January 2008 and December 2024. Data were collected using a structured questionnaire that captured demographic characteristics, clinical findings, and outcomes, including survival status, physician-assessed clinical improvement, infection-related complications, hospitalization, mortality, and clinical status at follow-up. Results: Overall mean age of 48.9+15.81 years and females were in majority 119 (73.5%) compared to males 43 (26.5%). Meropenem-treated patients had higher baseline severity, with higher SOFA scores (3.7 vs 2.3, p = 0.002), Charlson Comorbidity Index (3.6 vs 2.0, p = 0.001), compared to cefoperazone-sulbactam-treated cases. However, the primary and secondary outcomes were statistically comparable across the groups: in terms of composite clinical failure which occurred in 6.3% (meropenem) versus 6.1% (cefoperazone-sulbactam) p = 1.000, relapse in 12.6% versus 4.5% (p = 0.101), and 30-day mortality in 5.3% versus 0.0% (p = 0.077), with no significant differences in rehospitalization rate and microbiological non-response. Conclusion: Cefoperazone–sulbactam appeared to be a clinically feasible and effective carbapenem-sparing alternative to meropenem for the treatment of ESBL-producing Enterobacterales pyelonephritis. Although it was used more frequently in less critically ill patients, it was associated with clinical and microbiological outcomes comparable to those observed with meropenem. Results: Overall mean age of 48.9+15.81 years and females were in majority 119 (73.5%) compared to males 43 (26.5%). Meropenem-treated patients had higher baseline severity, with higher SOFA scores (3.7 vs 2.3, p = 0.002), Charlson Comorbidity Index (3.6 vs 2.0, p = 0.001), compared to cefoperazone-sulbactam-treated cases. However, the primary and secondary outcomes were statistically comparable across the groups: in terms of composite clinical failure which occurred in 6.1% (meropenem) versus 6.3% (cefoperazone-sulbactam) p = 1.000, relapse in 12.6% versus 4.5% (p = 0.101), and 30-day mortality in 5.3% versus 0.0% (p = 0.077), with no significant differences in rehospitalization rate and microbiological non-response. Conclusion: Cefoperazone–sulbactam appeared to be a clinically feasible and effective carbapenem-sparing alternative to meropenem for the treatment of ESBL-producing Enterobacterales pyelonephritis. Although it was used more frequently in less critically ill patients, it was associated with clinical and microbiological outcomes comparable to those observed with meropenem.