Professor Ludong Qiao
Chief Physician, PhD. Department of Urology, Beijing Tongren Hospital, Capital Medical University
Task Force Member of the Expert Committee of Antimicrobial Drugs, National Health Commission of the People’s Republic of China
Deputy Leader of the Infection and Inflammation Group of the Division of Urology of the Chinese Medical Association
Vice Chairman and Secretary of the Chinese Urological Association National Alliance for Prevention and Treatment of Infection and Inflammation
Committee Member of the Expert Committee of Evidence-based Medicine and Transformation of Infectious Diseases of the Chinese Research Hospital Association
Deputy Leader of the Study Group for Infections of the Division of Urology of the Beijing Medical Association
Vice Chairman of the Youth Committee of the Expert Committee of Urology and Male Reproductive Tumours of the Beijing Anti-Cancer Association
Member of the North China Lithiasis Prevention and Treatment Base
Board Member of the 10th Editorial Board of the Chinese Journal of Urology
Contributed to editing multiple guidelines and consensus articles on urinary tract infections in China
Specializes in the diagnosis and treatment for minimally invasive treatment for urinary system lithiases, prostatectomy, urinary system infections, urinary dysfunctions, urinary incontinence, and other common diseases with high incidence rates; published over 20 academic papers

Introduction: Urinary tract infection ranks as the second most common infectious disease globally, with the rational selection of antibacterial drugs being key for effective treatment.

Urinary tract infection (UTI) stands out as one of the most common infectious disease globally¹, contributing to approximately 20% of healthcare-associated bacteremias, with mortality rates reaching as high as 10%². This imposes a significant burden on medical resources and the social economy. In this issue, ‘Medical Community’ is pleased to invite Professor Ludong Qiao, Chief Physician of the Department of Urology, Beijing Tongren Hospital, Capital Medical University, to join us in exploring pathways for UTI treatment among the local population.

Navigating Challenges with Urinary Tract Infections: Timely Intervention is Key
As UTI is not classified as an infectious disease requiring mandatory reporting, it is challenging to accurately calculate its incidence rate¹. Professor Ludong Qiao highlighted that UTIs affects a wide range of individuals, making it the second major infectious disease after respiratory tract infections.

UTIs can be categorized as community-acquired UTIs and Healthcare-associated UTIs. Professor Ludong Qiao highlighted  that the incidence rate of Healthcare-associated UTIs in China ranges from 10% to 50% according to local statistics. This broad statistical range reflects the need for clear diagnosis criteria for Healthcare-associated UTIs in clinical practice in China. There may be instances where bacteriuria detected in positive urine culture is universally regarded as UTIs and thus included in the Healthcare-associated infection statistics. This indicates that hospital managers and clinical doctors urgently need to improve their understanding of UTIs and refine the diagnostic criteria for the condition.

Regarding the etiology of UTIs, based on his own clinical experience, Professor Ludong Qiao observed a clear correlation with the patient’s gender and age. For example, certain children are prone to recurrent UTIs due to congenital underdevelopment of the urinary system. In addition, young women constitute the majority of patients with UTIs in outpatient clinics, followed by pre-menopausal and post-menopausal women with decreased estrogen levels and immunity. As age advances, the proportion of UTIs among the male population also increases, primarily due to urinary tract obstruction caused by prostatic hyperplasia.

Furthermore, UTIs can be classified into uncomplicated UTIs and complicated UTIs. Uncomplicated UTIs refers to acute sporadic or recurrent lower urinary tract infection (uncomplicated cystitis) and/or upper urinary tract infections (uncomplicated pyelonephritis), limited to non-pregnant women without known associated anatomical or functional urinary tract abnormalities or comorbidities. Complicated UTIs refers to all other UTIs aside from simple UTIs, specifically patients with UTIs experiencing concurrent complications, such as males or patients with urinary tract anatomical abnormalities, functional abnormalities, indwelling urinary catheters, kidney problems and/or other immunosuppressive diseases such as diabetes.³ According to the U.S. statistics, over 626,000 individuals are hospitalized annually due to complicated UTIs, constituting approximately 1.8% of hospitalized patients each year². The treatment of complicated UTIs poses challenges for clinicians.

To address these challenges, Professor Ludong Qiao emphasized the importance of coordination between medical and surgical departments in treating complicated UTIs. Surgical departments should strive to mitigate comorbid factors as much as possible to enhance the efficacy of antibacterial drugs, while medical departments should accurately identify the causative bacteria when selecting antibacterial drugs. However, the closed nature of information exchange among clinical doctors has led to a disconnection between the current bacterial spectrum and clinical practice.

The traditional belief holds that the bacterial spectrum of UTIs mainly consists of Gram-negative bacteria Escherichia coli. However, in China, the bacterial spectrum of complicated UTIs is characterized by a decrease of E. coli infections and an increase of bacterial strains that are positive for extended-spectrum beta-lactamases (ESBLs), alongside a rise of Enterococcus bacterial strains⁴. Despite these findings, some clinicians persist in selecting antibacterial drugs based on traditional concepts, disregarding the current bacterial spectrum and indiscriminately pursuing advanced antibacterial drugs. This has led to confusion in clinical antibacterial treatment, presenting a significant challenge in current anti-infective treatment practices.

Fresh Insights into the Utilization of Empirical UTI Treatment
In response to the challenges of UTI treatment, Professor Ludong Qiao provided guidance on the selection of antibacterial drugs, emphasizing that misuse of such drugs can result in the development of highly drug-resistant clinical environments. Therefore, the choice of antibacterial drugs should be based on specific situations, avoiding the indiscriminate use of presumed  ‘highest-grade’ antibacterial drugs.

Firstly, the selection process should consider the UTI patient’s history of antibacterial drug use. Patients who have not been administered antibacterial drugs within the past six months provide clinicians with a wider range of initial medication options. Secondly, the severity of the UTI should guide drug selection. For example, in cases of uncomplicated lower UTIs, antibacterial drugs with higher concentrations in urine may be preferable. For complicated UTIs, antibacterial drugs with a drug susceptibility rate of over 70%, based on published national drug susceptibility data, should be selected. For patients with severe UTIs, such as those with conditions like urosepsis, carbapenem antibacterial drugs should be used to suppress the condition and avoid unnecessary trial and error in treatment.

In addition, to improve the success rates of initial empirical clinical treatment, clinicians need an updated understanding of the bacterial spectrum in China. Professor Ludong Qiao underscored this point in the 2022 edition of the ‘Urinary Tract Infections Diagnosis and Treatment Handbook’, which he contributed to editing for the Chinese Urology Association (CUA). One of the most important updates in the handbook is the antibacterial drug recommendations for complicated UTIs, which differ entirely from those in the guidelines of the European Association of Urology’s (EAU). Based on the bacterial spectrum, research on UTIs, and the availability of antibacterial drugs in China, the CUA handbook provides more targeted recommendations for clinical antibacterial drugs, better suited for treating UTI patients within the local context of China³.

Additionally, the handbook updated information on the use of sitafloxacin, a new-generation fluoroquinolone antibacterial drug³. A randomised, double-blind, active-control, multicentre phase III clinical study in China demonstrated that sitafloxacin achieved an overall clinical cure rate of 89.2% and a bacterial clearance rate of 97.1% in patients with simple UTIs, and a clinical cure rate of 81.8% and bacterial clearance rate of 93.3% in patients with complicated UTIs⁵. In the case of ESBL-positive E. coli strains, the activity of sitafloxacin is notably higher than that of other quinolone drugs⁶, slightly surpassing that of cefoperazone-sulbactam but falling below that of meropenem and amikacin. This is consistent with the characteristics of the bacterial spectrum in China.

Professor Ludong Qiao also highlighted that sitafloxacin exhibit favourable treatment effects for patients with Proteus-induced infectious urinary tract lithiasis, and its oral administration option meets the long-term treatment requirements of patients. Based on clinical observations, patients with infectious urinary tract lithiasis have lower recurrence rates after maintaining 8-10 weeks of sitafloxacin treatment, thereby avoiding the need for subsequent surgical treatment, and significantly improving the quality of life of patients. It is noteworthy that, due to the high incidence rate of drug resistance, the available antibacterial drugs with distinct treatment effects for clinical use are limited. However, sitafloxacin demonstrates efficacy in treating challenging UTIs. Hence, it is imperative to implement a protective use strategy to mitigate the emergence of drug resistance.

Conclusion
There are notable distinctions between the UTI bacterial spectrum in China and traditional concepts. Clinical practitioners must diligently stay abreast of relevant information, continuously update their knowledge, and select suitable antibacterial drugs based on the UTI bacterial spectrum in China to improve the success rates of initial treatment. Sitafloxacin, with its string antibacterial activity, broad bacterial spectrum, and effectiveness against ESBL-positive drug-resistant bacterial strains, meets the medication needs of clinicians, rendering it a valuable treatment for UTIs. Nevertheless, prudent and rational utilization in clinical practice is crucial to curb the emergence of drug resistance.

References:

1. ÖZTüRK R, MURT A. Epidemiology of urological infections: a global burden [J]. World J Urol, 2020, 38(11): 2669-79.
2. SABIH A, LESLIE S W. Complicated Urinary Tract Infections [M]. StatPearls. Treasure Island (FL); StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC. 2024.
3. GUIDELINES FOR DIAGNOSIS AND TREATMENT OF URINARY TRACT INFECTIONS [J]. Chinese Guidelines for Diagnosis and Treatment of Urology and Andrology Diseases (2022 edition), 2022-11.
4. CHINESE EXPERT CONSENSUS EDITORIAL TEAM. Chinese expert consensus on diagnosis and treatment (2015 edition) – complicated urinary tract infection [J]. Chinese Journal of Urology, 2015, 36(4): 241-4.
5. LI Y, YIN Y, PENG X, et al. A randomized, active-controlled, multicentre clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated or complicated urinary tract infection [J]. Ann Med, 2021, 53(1): 217-26.
6. WU S, YANG Y, GUO Y, et al. Comparative activities of sitafloxacin against recent clinical isolates in hospitals across China [J]. Eur J Clin Microbiol Infect Dis, 2021, 40(11): 2271-83.