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 Wangn

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22 Citations (Scopus)


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 openlabel, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazonesulbactam (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 (n=154), per-protocol (n=147), and safety (n=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 cefoperazonesulbactam 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.

Original languageEnglish
Article numbere00023-19
JournalAntimicrobial Agents and Chemotherapy
Issue number8
Publication statusPublished - Jan 1 2019


  • Cefepime
  • Cefoperazone-sulbactam
  • Healthcare-associated pneumonia
  • Hospital-acquired pneumonia
  • Noninferiority trial

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


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