The 60-year Development of Quinolones (I)

8 September, 2022

Professor Gao Xiwen

Chief Physician, Clinical Medicine Professor, Postdoctoral Fellow, Head of the Department of Respiratory and Critical Illness Medicine at Minhang Hospital of Fudan University (hospital situated at Shanghai Minhang district), Head of Internal Medicine, Head of Internal Medicine Teaching and Research Office. Head of Hospital Drug Good Clinical Practice (GCP) Institutional Office.
Member of Shanghai Medical Association Professional Committee for Respiratory
Member of China Research Hospital Association Professional Committee for Respiratory Medicine
Vice-chairman of Shanghai Grassroots Respiratory Disease Prevention and Control Alliance
Member of Shanghai Medical Society Allergy Association Committee
Member of Shanghai Rehabilitation Medicine Association Professional Committee for Respiratory Rehabilitation
Member of Shanghai Anti-Cancer Association Professional Committee for Tumour Respiratory Endoscopy
Standing Committee Member of Shanghai Pharmaceutical Association Drug Clinical Trial Committee


In 1962, the first fully synthetic quinolone antibiotic, nalidixic acid, was launched on the market. Since then, quinolone has been clinically applied for 60 years. Due to its various advantages, such as good bioavailability, high tissue concentration, convenient usage and good resistance, it has been widely used for treating respiratory tract infection, abdominal infection, skin infection, digestive tract infection and urinary tract infection. For this interview, we are interviewing Professor Gao Xiwen from the Department of Respiratory Medicine at Minhang Hospital of Fudan University, who will be discussing the clinical application of old and new quinolones over the past 60 years.


Traditional classic quinolone, leading the value and status of quinolone as anti-infective drugs

From the time the first generation of quinolones was launched in 1962, it has been clinically applied for 60 years. To date, the drug has evolved into its fourth generation. Respiratory quinolones dominate in clinical treatment of respiratory system infections. Conventional quinolones commonly used in clinical practice include ciprofloxacin, levofloxacin and moxifloxacin.

Ciprofloxacin: This is a second-generation quinolone with the longest application history and has strong antibacterial effectiveness1 against Pseudomonas aeruginosa. When dealing with bronchiectasis or chronic obstructive pulmonary infection, Pseudomonas aeruginosa presents a high risk of infection. Taking into consideration effectiveness and pricing, ciprofloxacin1 can be used, though it is commonly administered as an intravenous therapy at present.

Levofloxacin: a third-generation quinolone. It is currently the most widely used quinolone, with both intravenous and oral formulations. It has a broad antibacterial spectrum, which renders it to be highly effective against gram-positive and gram-negative bacteria. Exhibiting strong resistance against Mycobacterium tuberculosis, it is currently used as a second-line drug for tuberculosis in clinical practice1. To avoid any diagnostic delay of tuberculosis by use of empiric drug, imaging diagnosis becomes particularly important. For high-risk tuberculosis patients, risk assessment should be performed to select appropriate treatment options before the application of any initial empiric drug.

Moxifloxacin: In clinical practice, moxifloxacin is mostly considered for the treatment of community-acquired infections. However, it is not good at fighting Pseudomonas aeruginosa,2 hence it is generally not considered as a form of treatment for nosocomial-acquired infections. Sufficient attention is warranted for the cardiovascular toxicity of moxifloxacin, such as Q-T interval prolongation.


Levofloxacin and ciprofloxacin are clinically recognized quinolones with better tolerance, while the new quinolone sitafloxacin and levofloxacin have comparable tolerance.

Quinolones are well tolerated in clinical use. But with widespread clinical applications, there have also been many reports of adverse reactions to it, such as tendonitis and tendon rupture, QT-interval prolongation, and insomnia. In more severe cases, central nervous system reactions may even occur.1 Some manufacturers of moxifloxacin give rise to more central nervous system adverse reactions, especially those producing intravenous drugs.

Levofloxacin and ciprofloxacin are the more clinically recognised quinolones with better tolerance. Clinical studies have shown that the incidence of adverse reactions of both sitafloxacin and levofloxacin in patients with community-acquired pneumonia or acute exacerbation of chronic respiratory disease infection is comparable.3 At the same time, there is no age limit for the application of sitafloxacin.1 According to clinical drug practice, sitafloxacin has fewer occurrences of central nervous system adverse reactions and tendonitis as compared to levofloxacin. Based on the efficacy and stability of the original drug, coupled with the lack of sufficient clinical evidence to support domestically-manufactured fluoroquinolones,1 the original drug is generally preferred for severe infections detected in clinical practice.


The research and development of new quinolone drugs has been ongoing to provide better quinolone treatment solutions for clinical practice.

As the research and development of antibacterial drugs continues to progress, new quinolones have also been launched in China. For instance, nanofloxacin and sitafloxacin were respectively introduced in 2016 and 2019. Both display structural differences, with nanofloxacin being a fluoroquinolone-free drug,4 and the molecular structure of sitafloxacin containing fluorine atoms. Together with other fluoroquinolones, they are collectively referred to as fluoroquinolones-containing drugs, inheriting the advantages of conventional fluoroquinolones. However, nanofloxacin has weak efficacy against Mycobacterium tuberculosis.3

Due to their simple molecular structure, which enables new varieties to be formed by modification, quinolones have become the fastest developing anti-infective drugs in recent years. However, there are also a few quinolones that have been removed from the market owing to adverse reactions. For example, gatifloxacin was quickly eliminated from clinical practice owing to fluctuating blood sugar levels that resulted in glucose metabolism disorders, as well as other cardiac adverse events.2 Meanwhile, new quinolones with sufficient evidence-based evidence and vast clinical applications, such as sitafloxacin,3,5 have become the preferred choice for respiratory infections and secondary infections of underlying diseases in Japan.6

A phase III clinical study of sitafloxacin3,5 demonstrated good clinical curative effect on respiratory tract infection and urinary tract infection bacteria. In the study conducted on the antibacterial activity of recent clinically isolated strains obtained from 31 hospitals in China, sitafloxacin, compared with other quinolones, was found to have comparatively lower MICs, and yet was highly effective against ESBL-producing Escherichia coli, ciprofloxacin-resistant Escherichia coli, and Pseudomonas aeruginosa.7 It serves as an ideal choice for clinical treatment of respiratory tract infections and urinary tract infections.




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  6. Japanese Respiratory Society. Guidelines for the treatment of acquired pneumonia in adults. 2017.
  7. Wu S,  Yang Y, Yan G, et al.  Comparative activities of sitafloxacin against recent clinical isolates  in hospitals across China[J]. Eur J Clin Microbiol Infect Dis. 2021;40(11):2271-2283.