Effectiveness and Safety of High-Dose versus Standard-Dose Cefoperazone-Sulbactam in Severe Infections: A Multicenter Retrospective Study

Cheng-Han Li,1 Chi-Kuei Hsu,2 Chih-Cheng Lai,3 Jin-Wei Liu,1 Hung-Jen Tang,1 Kuang-Ming Liao,4 Ping-Chin Chang,5 Yee-Huang Ku,5 Yu-Hsin Chiu,5 Chien-Tung Chiu2 1Division of Infectious Diseases, Department of Medicine, Chi Mei Medical Center, Tainan, 710402, Taiwan; 2Division of Pulmonary Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824005, Taiwan; 3Division of Intensive Care Medicine, Chi Mei Medical Center, Tainan, 710402, Taiwan; 4Department of Internal Medicine, Chi Mei Medical Center, Tainan, 722013, Taiwan; 5Division of Infectious Disease, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 736002, TaiwanCorrespondence: Chien-Tung Chiu, Division of Pulmonary Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824005, Taiwan, Email [email protected]: This study aimed to evaluate the clinical effectiveness and safety of high-dose versus standard-dose cefoperazone-sulbactam in patients with severe infections, particularly those caused by multidrug-resistant organisms (MDROs).Patients and Methods: A multicenter retrospective cohort study was conducted across four hospitals from January 2020 to October 2024. Adult patients who received cefoperazone-sulbactam for severe infections, defined as admission to the intensive care unit (ICU), requirement for mechanical ventilation, or an increase in Sequential Organ Failure Assessment (SOFA) score of more than 2, or MDROs were categorized into high-dose (2 g-2 g q8h) and standard-dose (2 g-2 g q12h) groups. The primary outcome was clinical cure at day 14. Secondary outcomes included microbiological eradication, in-hospital mortality, and adverse events (AEs). Multivariate logistic regression and subgroup analyses were performed to identify treatment-associated factors.Results: A total of 383 patients were included: 141 in the high-dose group and 242 in the standard-dose group. The high-dose group demonstrated significantly higher clinical cure rates (49.7% vs 38.8%; adjusted odds ratio [aOR]: 1.61, 95% CI: 1.05– 2.50) and microbiological eradication rates (46.1% vs 20.3%; aOR: 3.85, 95% CI: 2.37– 6.26). There was no significant difference in in-hospital mortality (17.7% vs 21.1%, aOR: 0.71; 95% CI: 0.41– 1.25). Subgroup analyses showed greater benefit of high-dose therapy in patients with pneumonia, acute respiratory failure, ICU admission, and Charlson Comorbidity Index > 4. Changes in liver function tests, renal function (serum creatinine), and coagulation parameters over the course of therapy did not differ significantly between the high-dose and standard-dose groups.Conclusion: High-dose cefoperazone-sulbactam showed superior clinical and microbiological efficacy compared to the standard dose without increased safety concerns. These findings support the use of high-dose regimens in critically ill patients or those with MDRO infections.Keywords: cefoperazone-sulbactam, severe infection, multidrug-resistant organism, carbapenem-resistance