Clinical trial landscape for pneumonia: Evolving agents against bacterial pathogens

Du Feng; Huixin Jiang; Hao Deng; Gengda Huang; Yue Zhu; Rong Xiao; Gengjia Chen; Chengzhi Zhou

doi:10.1016/j.ijid.2025.107965

Clinical trial landscape for pneumonia: Evolving agents against bacterial pathogens

Int J Infect Dis. 2025 Jun 25:107965. doi: 10.1016/j.ijid.2025.107965. Online ahead of print.

Authors

Du Feng¹, Huixin Jiang¹, Hao Deng¹, Gengda Huang¹, Yue Zhu¹, Rong Xiao², Gengjia Chen¹, Chengzhi Zhou³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, P.R.China.
² Guangzhou Medical University, Guangzhou, Guangdong, 511436, P.R.China.
³ Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, P.R.China. Electronic address: doctorzcz@163.com.

PMID: 40578546
DOI: 10.1016/j.ijid.2025.107965

Abstract

Pneumonia remains a significant global health challenge, exacerbated by the escalating crisis of antimicrobial resistance. Through a comprehensive analysis of clinical trials spanning three decades, this study reveals the evolving landscape of anti-pneumonia drug development. Through analysis of clinical trial volumes and therapeutic mechanisms, our findings demonstrate a substantial increase in early-phase clinical trials over the past decade, reflecting intensified efforts to combat growing antimicrobial resistance, while research focusing on DNA topoisomerase inhibition has declined after an initial development surge. Although carbapenems serve as a cornerstone in pneumonia treatment, they face increasing risks of resistance-related mortality, particularly in hospital-acquired pneumonia (HAP) dominated by drug-resistant pathogens. Given the varying pathogen susceptibility across different age groups, we conducted age-stratified analyses. While traditional mechanisms like cell wall synthesis inhibition remain dominant, innovative approaches are emerging to enhance drug delivery and antimicrobial action, exemplified by phage therapy, non-ionic silver nanoparticles, and antibody-drug conjugates. This landscape analysis not only synthesizes historical and current therapeutic trends but also highlights promising directions for combating resistance, emphasizing the urgent need for novel agents in the post-antibiotic era.

Keywords: Antimicrobial resistance; Clinical trial landscape; Pneumonia.