Trends in Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia Trials. (11th November 2020)

• Record Type: Journal Article
• Authors: Bart, Stephen M; Rubin, Daniel; Kim, Peter; Farley, John J; Nambiar, Sumathi
• Is Part Of: Clinical infectious diseases. Volume 73:Number 3(2021)
• Page Start: e602
• Page End: e608
• Publication Date: 2020-11-11
• Subjects: hospital-acquired bacterial pneumonia -- ventilator-associated bacterial pneumonia -- clinical trials -- antibacterial drug development; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1712
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: New drug development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) is critical. Challenges remain in the conduct of HABP/VABP trials, especially in the contexts of enrollment, endpoints, nonstudy antibacterial drug therapy, and antimicrobial resistance. Methods: Four Phase 3 noninferiority trials (n = 2433 participants) submitted to the Food and Drug Administration after 2015 were analyzed for enrollment statistics, participant characteristics associated with 28-day all-cause mortality (ACM), microbiology, and receipt of nonstudy antibacterial drugs. All trials primarily enrolled patients with gram-negative bacterial infections. Results: The mean trial length was 2.7 years and the mean recruitment rate was 0.17 participants/site/month. ACM at 28 days was 17.1% and was higher among participants diagnosed with ventilated HABP (31.9%) or VABP (19.0%) than nonventilated HABP (9.9%). VABP participants tended to be younger, less likely to have chronic obstructive pulmonary disease, and more likely to have previously sustained an injury. Age, South American residence, diagnosis of ventilated HABP or VABP, and Acinetobacter baumannii infection were all associated with 28-day ACM in a multivariate logistic regression model. Infection by A. baumannii was most common in Eastern European and Asia/Pacific participants, and Eastern European isolates exhibited the highest levels of meropenem resistance. Concomitant nonstudy antibacterial drug therapy most commonly included beta-lactams and was initiated earliest in Western Europe. Conclusion: This analysis of recent trials may assist in trial considerations for HABP/VABP development programs and promote needed antibacterial drug development for patients with serious infections. Abstract : This study highlights that well-conducted hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) clinical trials are feasible, although difficult. Key aspects of recent HABP/VABP trials described can facilitate design and conduct of future trials and encourage development of antibacterial drugs to address patient needs.