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

Research output: Contribution to journalArticle

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 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
Volume63
Issue number8
DOIs
Publication statusPublished - 2019 Jan 1

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Cefoperazone
Sulbactam
Pneumonia
Delivery of Health Care
Therapeutics
Cephamycins
Confidence Intervals
cefepime
Arm
Thorax
Cell Membrane
Safety
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Liu, Jien Wei ; Chen, Yen Hsu ; Lee, Wen Sen ; Lin, Jung Chung ; Huang, Ching Tai ; Lin, Hsi Hsun ; Liu, Yung Ching ; Chuang, Yin Ching ; Tang, Hung Jen ; Chen, Yao Shen ; Ko, Wen Chien ; Lu, Min Chi ; Wangn, Fu Der. / Randomized noninferiority trial of cefoperazone-sulbactam versus cefepime in the treatment of hospital-acquired and healthcare-associated pneumonia. In: Antimicrobial agents and chemotherapy. 2019 ; Vol. 63, No. 8.
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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 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.",
author = "Liu, {Jien Wei} and Chen, {Yen Hsu} and Lee, {Wen Sen} and Lin, {Jung Chung} and Huang, {Ching Tai} and Lin, {Hsi Hsun} and Liu, {Yung Ching} and Chuang, {Yin Ching} and Tang, {Hung Jen} and Chen, {Yao Shen} and Ko, {Wen Chien} and Lu, {Min Chi} and Wangn, {Fu Der}",
year = "2019",
month = "1",
day = "1",
doi = "10.1128/AAC.00023-19",
language = "English",
volume = "63",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
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}

Liu, JW, Chen, YH, Lee, WS, Lin, JC, Huang, CT, Lin, HH, Liu, YC, Chuang, YC, Tang, HJ, Chen, YS, Ko, WC, Lu, MC & Wangn, FD 2019, 'Randomized noninferiority trial of cefoperazone-sulbactam versus cefepime in the treatment of hospital-acquired and healthcare-associated pneumonia', Antimicrobial agents and chemotherapy, vol. 63, no. 8, e00023-19. https://doi.org/10.1128/AAC.00023-19

Randomized noninferiority trial of cefoperazone-sulbactam versus cefepime in the treatment of hospital-acquired and healthcare-associated pneumonia. / Liu, Jien Wei; Chen, Yen Hsu; Lee, Wen Sen; Lin, Jung Chung; Huang, Ching Tai; Lin, Hsi Hsun; Liu, Yung Ching; Chuang, Yin Ching; Tang, Hung Jen; Chen, Yao Shen; Ko, Wen Chien; Lu, Min Chi; Wangn, Fu Der.

In: Antimicrobial agents and chemotherapy, Vol. 63, No. 8, e00023-19, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized noninferiority trial of cefoperazone-sulbactam versus cefepime in the treatment of hospital-acquired and healthcare-associated pneumonia

AU - Liu, Jien Wei

AU - Chen, Yen Hsu

AU - Lee, Wen Sen

AU - Lin, Jung Chung

AU - Huang, Ching Tai

AU - Lin, Hsi Hsun

AU - Liu, Yung Ching

AU - Chuang, Yin Ching

AU - Tang, Hung Jen

AU - Chen, Yao Shen

AU - Ko, Wen Chien

AU - Lu, Min Chi

AU - Wangn, Fu Der

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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