Reverse MIC drift of nemonoxacin and its advantages against Gram-positive bacteria: A 10-year multicenter surveillance study

Abstract

Background: Antimicrobial resistance (AMR) threatens global health. Conventional fluoroquinolones have experienced accelerated resistance due to target-enzyme mutations and are further constrained by safety concerns. Nemonoxacin, as the first non-fluorinated quinolone, overcomes the aforementioned drawbacks by removing the fluorine atom at C-6 and introducing a methoxy substitution at C-8, but the trends in its antibacterial activity and the evolution of its antimicrobial spectrum remain unclear.

Objective: To assess the long-term evolution of the antibacterial activity of the novel non-fluorinated quinolone nemonoxacin against clinical isolates, evaluate its resistance risk, and compare it with conventional quinolones.

Methods: Clinical Gram-positive and Gram-negative isolates were collected from a multicenter network of 22 hospitals nationwide between 2015 and 2024. Minimum inhibitory concentrations (MICs) of nemonoxacin and comparator drugs were determined by agar dilution according to the Clinical and Laboratory Standards Institute (CLSI) standards; MIC trends were analyzed using Spearman's rank correlation coefficient and the Cochran-Armitage trend chi-square test.

Results: Nemonoxacin exhibited markedly superior antibacterial activity against Gram-positive bacteria compared with conventional quinolones. During the 10-year surveillance period, the isolation rate of methicillin-resistant Staphylococcus aureus (MRSA) was 34.95% and that of methicillin-resistant Staphylococcus epidermidis (MRSE) was 82.08%. The susceptibility rate of MRSA to nemonoxacin was 78.5%, and susceptibility rates among other staphylococci were all ≥ 80%, which is 19.4%-27.7% higher than that of conventional quinolones; for Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, and the viridans group streptococci, the MIC₅₀ and MIC₉₀ values were 1/2-1/64 those of fluoroquinolones, with a susceptibility rate of 99.4%. Among Gram-negative bacteria, Escherichia coli (extended-spectrum β-lactamase [ESBL]-positive rate 53.3%) and Klebsiella pneumoniae (ESBL-positive rate 23.5%) showed susceptibility rates to nemonoxacin of 41.0% and 60.9%, respectively, outperforming ciprofloxacin and levofloxacin; carbapenem-susceptible, ESBL-negative K. pneumoniae had a susceptibility rate up to 90.2%. For Haemophilus influenzae, nemonoxacin MICs ranged from 0.004 to 8 mg/L, which are 1/2-1/4 those of other quinolones; for Moraxella catarrhalis, the MICs were similar to those of fluoroquinolones. The resistance of Staphylococcus aureus and Escherichia coli to nemonoxacin showed a declining trend compared with the start year, manifesting as a “reverse MIC drift,” and the decrease in S. aureus resistance was not significantly correlated with the decline in MRSA isolation rate. Among Gram-positive bacteria, isolates from intensive care unit (ICU) patients and elderly patients, as well as S. aureus recovered from sputum and urine specimens, exhibited higher rates of resistance to nemonoxacin than isolates from other sources; among Gram-negative bacteria, ICU-isolated Klebsiella pneumoniae, Haemophilus influenzae isolated from adult patients, and Escherichia coli and K. pneumoniae isolated from urine specimens showed higher nemonoxacin resistance rates than isolates from other sources.

Conclusion: By virtue of its non-fluorinated structure and dual-target mechanism, nemonoxacin effectively curtailed the development of resistance over the 10-year period, demonstrating a sustained advantage particularly in infections caused by S. aureus, Streptococcus pneumoniae, and H. influenzae. The maintained or improved trend in its antibacterial activity suggests that, through the synergy of structural innovation and precision use, reversal of resistance evolution may be achievable, providing a new direction for optimizing anti-infective therapy.

Keywords

Nemonoxacin / Non-fluorinated quinolone / Reverse MIC drift / Antimicrobial resistance surveillance / Gram-positive bacteria

Declarations

Not applicable.

CRediT authorship contribution statement

Jie Wu: Conceptualization, Data curation, Writing - original draft. Yun Li: Methodology, Software, Writing - review & editing. Bo Zheng: Supervision; Validation.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Peking University First Hospital (Approval No. 2024-RD-394-001). 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

This study was supported by Zhejiang Medicine Co.,Ltd (Grant No. KYC-2024-0191).

Declaration of Competing Interest

The authors declare no competing interests.

Acknowledgements

Beijing Hospital; The Second Hospital of Jilin University; Tianjin Medical University General Hospital; Tianjin Third Central Hospital; Shanxi Children's Hospital; The Second Hospital of Hebei Medical University; Jinan Central Hospital Affiliated to Shandong University; The First Affiliated Hospital of Nanjing Medical University; Zhongshan Hospital, Fudan University; Sir Run Run Shaw Hospital, Zhejiang University; The First Affiliated Hospital of Xiamen University; Renmin Hospital of Wuhan University; Xiangya Hospital, Central South University; The Affiliated Hospital of Guizhou Medical University; Kunming First People's Hospital; The First Affiliated Hospital of Guangxi Medical University; Hainan Provincial People's Hospital; The First Affiliated Hospital of Army Medical University; Xijing Hospital, Air Force Medical University; Hanzhong Central Hospital; The Second Hospital of Lanzhou University; The First Hospital of Xinjiang Medical University.

Authors' other information

Not applicable.

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