Randomized Noninferiority Trial of Cefoperazone-Sulbactam versus Cefepime in the Treatment of Hospital-Acquired and Healthcare-Associated Pneumonia.

Jien-Wei Liu, Yen-Hsu Chen, Wen-Sen Lee, Jung-Chung Lin, Ching-Tai Huang, Hsi-Hsun Lin, Yung-Ching Liu, Yin-Ching Chuang, Hung-Jen Tang, Yao-Shen Chen, Wen-Chien Ko, Min-Chi Lu, Fu-Der Wang

Journal: Antimicrobial agents and chemotherapy 2020;63(8):e00023-19

PMID: 31138577

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Abstract

Cefoperazone, a third-generation cephamycin with broad-spectrum antibacterial activity and the ability to permeate bacterial cell membranes, is active against commonly encountered multidrug-resistant pathogens for hospital-acquired pneumonia (HAP) and health care-associated pneumonia (HCAP). To clarify the clinical effects of cefoperazone-sulbactam in the treatment of HAP and HCAP, we conducted an open-label, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazone-sulbactam (2 g of each per 12 h) or cefepime (2 g per 12 h) arm. Clinical and microbiological responses were evaluated at early posttherapy and test-of-cure visits. Recruited patients were allocated to subpopulations for intent-to-treat ( = 154), per-protocol ( = 147), and safety ( = 166) analyses. Intent-to-treat analysis demonstrated that (i) at the early posttherapy visit, 87.3% of patients receiving cefoperazone-sulbactam and 84.3% of patients receiving cefepime achieved clinical improvement or cure (risk difference of 3.0%; 95% confidence interval [CI], -9.0% to 15.0%), and (ii) at the test-of-cure visit, 73.1% of patients receiving cefoperazone-sulbactam and 56.8% of patients receiving cefepime were assessed as cured (risk difference of 16.3%; 95% CI, 0.0% to 33.0%). These results indicated the noninferiority of cefoperazone-sulbactam to cefepime, which was confirmed by per-protocol analysis. The chest radiographic consolidation/infiltration resolution rate, microbiological eradiation rate, and percentage of adverse events were comparable in both groups. Serious adverse events were rare, and none was judged to be related to the study drugs. Cefoperazone-sulbactam at 2 g every 12 h was noninferior to cefepime at 2 g every 2 h for patients with HCAP.

Address: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.; Chang Gung University College of Medicine, Taoyuan, Taiwan.; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Medical Center, Taipei, Taiwan.; Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.; Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.; Division of Infectious Diseases, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan.; Department of Internal Medicine, Chi Mei Hospital, Tainan, Taiwan.; Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.; Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.; School of Medicine, National Yang-Ming University, Taipei, Taiwan.; Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.; College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Division of Infectious Diseases, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.; Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.; School of Medicine, National Yang-Ming University, Taipei, Taiwan [email protected].; Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

DOI: 10.1128/AAC.00023-19

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MeSH Terms: Aged, Aged, 80 and over, Anti-Bacterial Agents, Cefepime, Cefoperazone, Drug Therapy, Combination, Female, Haemophilus Infections, Healthcare-Associated Pneumonia, Humans, Male, Middle Aged, Pneumonia, Bacterial, Pseudomonas Infections, Sulbactam, Treatment Outcome