Abstract
Background: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods: In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results: Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, -1.8%; 95% confidence interval [CI]: -8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, -7.6%; 97.5% CI: -15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions: Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration: NCT02019420.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E710-E718 |
| Journal | Clinical Infectious Diseases |
| Volume | 73 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2021 |
Funding
Acknowledgments. We thank the patients and their families and caregivers for participating in this study, along with all investigators and site personnel. A full list of primary investigators is provided in . Medical writing and/or editorial assistance was provided by Todd Waldron, PhD, CMPP, of The Lockwood Group, Stamford, Connecticut. This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA (MSD). Potential conflicts of interest. J. R. B., N. B., J. Y. K., and C. D. A. are employees of MSD who may own stock and/or hold stock options in Merck & Co, Inc. M. W. P. was previously an employee of MSD who may own stock and/or hold stock options in Merck & Co, Inc. R. G. W. reports grants and personal fees from MSD during the conduct of the study; grants and personal fees from Arsanis, Melinta, Polyphor, Shionogi, and the Medicines Company; personal fees from KBP Biosciences, Meiji Seika, and Microbiotix outside the presented work; and has received institutional research funding from MSD. A. R. reports grants and personal fees from MSD and from bioMerieux during the conduct of the study. D. R. G. reports grants and personal fees from MSD during the conduct of the study and from Bayer and Janssen outside the presented work. The remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Keywords
- Staphylococcal infections
- gram-positive cocci
- healthcare-associated bacterial pneumonia
- ventilator-associated bacterial pneumonia
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
