» Articles » PMID: 31041348

Randomized Trial of Ceftazidime-Avibactam Vs Meropenem for Treatment of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (REPROVE): Analyses Per US FDA-Specified End Points

Overview
Date 2019 May 2
PMID 31041348
Citations 22
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP; nosocomial pneumonia) due to Gram-negative pathogens are associated with significant morbidity and mortality; treatment options for multidrug-resistant infections are limited. The pivotal phase III REPROVE trial evaluated the efficacy of ceftazidime-avibactam (CAZ-AVI) vs meropenem in the treatment of patients with HAP/VAP. Study results for prespecified analyses per US Food and Drug Administration-recommended trial end points are reported here.

Methods: Hospitalized adults with HAP/VAP proven or suspected to be caused by a Gram-negative pathogen were randomized 1:1 to receive CAZ-AVI or meropenem for 7 to 14 days. The primary outcome was 28-day all-cause mortality in the intent-to-treat (ITT) population. Secondary outcomes included clinical cure at test of cure (TOC) in the ITT and microbiological ITT (micro-ITT) populations, and safety and tolerability throughout the study.

Results: hundred seventy randomized patients received treatment and were included in the ITT population (CAZ-AVI, n = 436; meropenem, n = 434). CAZ-AVI was noninferior to meropenem for the primary end point (28-day all-cause mortality; ITT) based on the prespecified 10% noninferiority margin (CAZ-AVI, 9.6%; meropenem, 8.3%; difference, 1.5%; 95% confidence interval [CI], -2.4% to 5.3%) and for the clinical cure end point in the ITT population based on a prespecified -10% noninferiority margin (CAZ-AVI, 67.2%; meropenem, 69.1%; difference, -1.9%; 95% CI, -8.1% to 4.3%). Clinical cure rates at TOC for patients infected with CAZ-nonsusceptible pathogens were similar (CAZ-AVI, 75.5%; meropenem, 71.2%; micro-ITT). Safety data were consistent with established safety profiles for both agents.

Conclusions: CAZ-AVI provides an important new treatment option for HAP/VAP due to Gram-negative pathogens, including CAZ-nonsusceptible strains.

Citing Articles

Estimating the value of new antibiotic treatment strategies in Zhejiang province, China: cost-effectiveness analysis based on a validated dynamic model.

Yang W, Zhen X, Sun X, Khatiwada S, Yang D, Chen Y BMJ Open. 2024; 14(8):e086039.

PMID: 39209783 PMC: 11367305. DOI: 10.1136/bmjopen-2024-086039.


Novel Siderophore Cephalosporin and Combinations of Cephalosporins with β-Lactamase Inhibitors as an Advancement in Treatment of Ventilator-Associated Pneumonia.

Viscardi S, Topola E, Sobieraj J, Duda-Madej A Antibiotics (Basel). 2024; 13(5).

PMID: 38786173 PMC: 11117516. DOI: 10.3390/antibiotics13050445.


Effectiveness of Ceftazidime-Avibactam in Gram-Negative Nosocomial Pneumonia: A Real-World Study in India.

Gupta N, Saseedharan S, Paliwal Y Cureus. 2024; 16(2):e54443.

PMID: 38510907 PMC: 10951683. DOI: 10.7759/cureus.54443.


Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pneumonia for Patients Who Are Morbidly Obese.

Kunz Coyne A, Orzol C, Veve M, Rybak M Open Forum Infect Dis. 2023; 10(9):ofad454.

PMID: 37720698 PMC: 10500045. DOI: 10.1093/ofid/ofad454.


The place of new antibiotics for Gram-negative bacterial infections in intensive care: report of a consensus conference.

Dequin P, Aubron C, Faure H, Garot D, Guillot M, Hamzaoui O Ann Intensive Care. 2023; 13(1):59.

PMID: 37400647 PMC: 10317910. DOI: 10.1186/s13613-023-01155-4.


References
1.
Capitano B, Nicolau D, Potoski B, Byers K, Horowitz M, Venkataramanan R . Meropenem administered as a prolonged infusion to treat serious gram-negative central nervous system infections. Pharmacotherapy. 2004; 24(6):803-7. DOI: 10.1592/phco.24.8.803.36070. View

2.
Lorente L, Lorenzo L, Martin M, Jimenez A, Mora M . Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to gram-negative bacilli. Ann Pharmacother. 2006; 40(2):219-23. DOI: 10.1345/aph.1G467. View

3.
Joshi M, Metzler M, McCarthy M, Olvey S, Kassira W, Cooper A . Comparison of piperacillin/tazobactam and imipenem/cilastatin, both in combination with tobramycin, administered every 6 h for treatment of nosocomial pneumonia. Respir Med. 2006; 100(9):1554-65. DOI: 10.1016/j.rmed.2006.01.004. View

4.
Siempos I, Vardakas K, Manta K, Falagas M . Carbapenems for the treatment of immunocompetent adult patients with nosocomial pneumonia. Eur Respir J. 2007; 29(3):548-60. DOI: 10.1183/09031936.00080206. View

5.
Wang D . Experience with extended-infusion meropenem in the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2008; 33(3):290-1. DOI: 10.1016/j.ijantimicag.2008.09.012. View