Role of nemonoxacin as a therapeutic option for community-acquired pneumonia in the era of atypical pathogens

Abstract

Objective: To systematically summarize the clinical data from phase II-IV studies of nemonoxacin malate and comprehensively evaluate the clinical efficacy of nemonoxacin in treating pneumonia caused by atypical pathogens, so as to inform empirical antimicrobial selection in clinical practice.

Methods: A retrospective analysis was performed on the results of four phase II/III clinical studies of nemonoxacin malate in patients with community-acquired pneumonia (CAP) and on the composition and clinical outcomes of atypical pathogen-infected patients in one phase IV clinical study; subgroup efficacy analyses were conducted by age and by presence or absence of co-pathogen infection.

Results: This study included four phase II/III controlled trials and one phase IV single-arm trial, with a primary analysis population of 1769 CAP patients, of whom 994 were male (56.2%) and 775 were female (43.8%), with a mean age of 47.83 ± 16.39 years. In the phase II/III studies, 370 patients (27.8%) were positive for atypical pathogens, including Mycoplasma pneumoniae (MP) in 265 cases (19.9%), Chlamydia pneumoniae (CP) in 68 cases (5.1%), and Legionella pneumophila (LP) in 85 cases (6.4%). In the phase IV study, 172 patients (39.7%) were positive for atypical pathogens, including PM in 141 cases (32.6%), CP in 14 cases (3.2%), and LP in 50 cases (11.5%).Efficacy analysis showed that nemonoxacin 500 mg oral and injectable formulations had clinical success rates against atypical pathogens of 98.0% vs levofloxacin 95.5% (oral) and 97.7% vs levofloxacin 95.8% (injectable), respectively; against MP the rates were 99.0% vs 94.1% (oral) and 97.6% vs 100.0% (injectable), respectively, suggesting that the clinical efficacy of the two formulations of nemonoxacin is slightly superior to or comparable with levofloxacin. Additionally, subgroup analyses stratified by age and by presence of co-pathogen infection showed that nemonoxacin demonstrated good clinical efficacy in patients aged both < 60 years and ≥ 60 years, regardless of whether the infection was solely due to atypical pathogens or accompanied by other pathogens.

Conclusion: Nemonoxacin demonstrated good clinical efficacy in CAP patients with atypical pathogen infections, with effects comparable to or superior to levofloxacin, and may be considered as one of the options for empirical CAP treatment or as a therapeutic choice after confirmation of atypical pathogen infection.

Keywords

Nemonoxacin / Community-acquired pneumonia / Atypical pathogens / Clinical efficacy

Declarations

Not applicable.

CRediT authorship contribution statement

Xiaoping Zhang: Conceptualization, Data curation, Formal analysis, Writing - original draft preparation. Guoli Mo: Methodology, Investigation, Data curation. Fengjia Zhu: Investigation, Data curation, Validation. Kaiwen Zhang: Investigation, Resources, Validation. Lijie Tian: Data curation, Software, Formal analysis. Yueran Lv: Investigation, Resources. Jing Chen: Conceptualization, Methodology, Project administration, Supervision, Writing - review & editing.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Huashan Hospital Fudan University (Approval No. 2017-366). All study participants have signed informed consent forms.

Consent for publication

All authors have read and agreed to the published version of the manuscript and give their consent for publication in this journal.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Declarations of Competing Interest

The authors declare no competing interests.

Acknowledgements

Not applicable.

Authors' other information

Not applicable.

References

[1] Medical Chinese, Respiratory Association, Branch Disease. Guidelines for the diagnosis and treatment of community-acquired pneumonia in Chinese adults (2016 edition). Chin J Tuberc Respir Dis. 2016; 39(4):253-279. https://doi.org/10.3760/cma.j.issn.1001-0939.2016.04.005

[2] Chen R.C., Zhong N.S., Liu Y.N., editors. Respiratory Medicine. 3rd ed. Beijing: People's Medical Publishing House; 2022.

[3] Wang J.Y., Ge J.B., Zou H.J., editors. Practical Internal Medicine. 16th ed. Beijing: People's Medical Publishing House; 2022.

[4] Shen CM, Leng BZ, Liu YJ, et al. Analysis of pathogen infection in adult patients with atypical community-acquired pneumonia. Lab Med. 2020; 35(1):29-32. https://doi.org/10.3969/j.issn.1673-8640.2020.01.007

[5] Arnold FW, Summersgill JT, Lajoie AS, et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med. 2007; 175(10):1086-1093. https://doi.org/10.1164/rccm.200603-350OC

[6] Shi DY, Li YP, Zhang GR, et al. Etiological investigation and bacterial drug resistance analysis of 452 cases of community-acquired pneumonia. Clin Focus. 2011; 26(24):2181-2183.

[7] Liu C, Ye F, Jiang QQ, et al. Etiological analysis of 620 cases of adult community-acquired pneumonia in southeastern Beijing. China Mod Med. 2022; 28(7):139-150. https://doi.org/10.3969/j.issn.1674-4721.2022.07.038

[8] Zhu DM, Wu PC, Hu FP, et al. vitro antibacterial activity of nemonoxacin. Chin J Infect Chemother. 2015; 15(2):16.

[9] Chotikanatis K, Kohlhoff SA, Hammerschlag MR. vitro activity of nemonoxacin, a novel nonfluorinated quinolone antibiotic, against Chlamydia trachomatis and Chlamydia pneumoniae. Antimicrob Agents Chemother. 2014; 58(3):1800-1801. https://doi.org/10.1128/AAC.02263-13

[10] Zhao JJ, Xu XY, Zhu YJ, et al. Detection of nemonoxacin concentration in human lung tissue, bronchial mucosa and bronchial secretions by ultra-high performance liquid chromatography tandem mass spectrometry and clinical application. Chin J Infect Chemother. 2020; 20(2):146-152. https://doi.org/10.16718/j.1009-7708.2020.02.007

[11] Li JL, Liu LS, Zhang H, et al. Severe problem of macrolides resistance to common pathogens in China. Front Cell Infect Microbiol. 2023; 13:1181633. https://doi.org/10.3389/fcimb.2023.1181633

[12] Cai FQ, Li JL, Liang WJ, et al. Effectiveness and safety of tetracyclines and quinolones in people with Mycoplasma pneumonia: a systematic review and network meta-analysis. EClinicalMedicine. 2024; 71:102589. https://doi.org/10.1016/j.eclinm.2024.102589

[13] Jiang Y, Dou H, et al. Macrolide resistance of Mycoplasma pneumoniae in several regions of China from 2013 to 2019. Epidemiol Infect. 2024; 153:e75. https://doi.org/10.1017/S0950268824000323

[14] Sun Y, Li P, et al. Characterizing the epidemiology of Mycoplasma pneumoniae infections in China in 2022-2024: a nationwide cross-sectional study of over 1.6 million cases. Emerg Microbes Infect. 2025; 14:2482703. https://doi.org/10.1080/22221751.2025.2482703

[15] File TMJr, Ramirez JA. Community-acquired pneumonia. New Engl J Med. 2023; 389:632-641. https://doi.org/10.1056/NEJMcp2303286

[16] Chinese Medical Association, et al. Chinese Medical Association Journal, Chinese Medical Association General Practice Branch, Primary care diagnosis and treatment guidelines for adult community-acquired pneumonia (practice edition · 2018). Chin J Gen Pract. 2019; 18(2):127-133. https://doi.org/10.3760/cma.j.issn.1671-7368.2019.02.006

[17] Ma XG. Advances in the diagnosis and treatment of atypical pathogen pneumonia. Med Philos. 2015; 36(20):69-71.

[18] Yuan J, Zhang X, Chen J, et al. Safety of oral nemonoxacin: a systematic review of clinical trials and postmarketing surveillance. Front Pharmacol. 2022; 13:1067686. https://doi.org/10.3389/fphar.2022.1067686

[19] Li Y, Lu J, et al. Nemonoxacin dosage adjustment in patients with severe renal impairment based on population pharmacokinetic and pharmacodynamic analysis. Br J Clin Pharmacol. 2021; 87(12):4636-4647. https://doi.org/10.1111/bcp.14881

[20] Wang F., Zhang Y.Y., editors. Clinical Application Guidelines for Antimicrobial Agents. 3rd ed. Beijing: People's Medical Publishing House; 2020.

[21] Respiratory Department Team of Oriental Hospital. Unexplained fever and dry cough, diagnosis unclear after several attempts! The director's words revealed the truth [Internet]. Medical World Respiratory Channel; 2022 Nov 23 [cited 2025 Oct 14]. Available from: https://ysz-web.yxj.org.cn/ysz-h5/index.html#/articel?typeId=341828.]

[22] Fan Z, Wang SP, Zhao QY, et al. Epidemiological characteristics and etiological distribution of community-acquired pneumonia. Chin J Public Health. 2008; 24(7):825-827. https://doi.org/10.3321/j.issn:1001-0580.2008.07.041

[23] Chen YN, Chen S, Mao QS. Comparative analysis of pathogens in community-acquired pneumonia between young adults and middle-aged/elderly patients. Med Inf. 2019; 32(1):145-147. https://doi.org/10.3969/j.issn.1006-1959.2019.01.045