Professor Zheng Bo
Deputy director of Institute of Clinical Pharmacology, Peking University
Professor and Chief Physician of Peking University First Hospital
Doctoral supervisor

• Person-in-charge of North Area Technical Centre, China Antimicrobial Resistance Surveillance System
• Leader of Statistics Analysis Group and vice-chairman of Academic Committee on China Antimicrobial Resistance Surveillance
• Deputy secretary-general of Chinese Society of Infectious Diseases, Chinese Medical Association
• Committee member of Expert Committee on the Clinical Application of Antimicrobial Drugs and Bacterial Resistance Evaluation, National Health and Family Planning Commission
• Vice-chairman of Professional Committee on Evidence-based and Translational Infectious Diseases, Chinese Research Hospital Association
• Vice-chairman of Professional Committee on Infectious Diseases, Beijing Medical Award Foundation
• Committee member of Bacterial Infection and Resistance Prevention and Control Branch, Chinese Medical Association
• Committee member of Inflammation and Infection Group, Chinese Urological Association, Chinese Medical Association
• Committee member of Infection Cooperative Group, Chinese Society of Obstetrics and Gynaecology, Chinese Medical Association

Q1: What is the epidemiology of urinary tract infection in China?

Currently, urinary tract infection is one of the most frequently seen infectious diseases in China, second only to respiratory tract infection. Urinary tract infection occurs more frequently in females compared with males of the same age. In addition, the incidence rate of complicated urinary tract infection is 12 times higher than uncomplicated urinary tract infection. In recent years, due to the large volume of antimicrobials use, there have been changes to the distribution of urinary tract infection pathogens and also to antimicrobial resistance.

Q2: How can physicians ensure the appropriate selection of antibiotics for the treatment of patients with urinary tract infection?

The management of urinary tract infections is similar with treating other infectious diseases – three factors influence treatment decision: causative pathogen, patient, and antimicrobial agent.

There are distinct differences in the aetiology of urinary tract infection among genders.

The most common pathogen isolated in female urine samples is Escherichia coli (60%), followed by Enterococcus faecium, Klebsiella pneumoniae, Enterococcus faecalis, and Proteus mirabilis. There is a great difference in the causative pathogens isolated in male urine samples. While E. coli remains the most common pathogen, the prevalence is significantly lower compared with those in females – at about 30%. Other common pathogens include E. faecalis, E. faecium, and K. pneumoniae – which occur significantly higher compare with those in females, i.e. approximately 9% to 10%. In addition, Pseudomonas aeruginosa is the fifth most common pathogen in males instead of P. mirabilis as that in females.

The aetiology as well as the current situation of antimicrobial resistance are important factors when considering treatment strategy. For example, I have mentioned E. coli earlier, which has a relatively high drug resistance rate against cephalosporins and quinolones. For patients with complex urinary tract infection or pyelonephritis, urine cultures should be performed before drug administration, and empirical treatment should be adjusted based on drug susceptibility.

Furthermore, antibiotic selection should not be solely based on the results of in vitro drug susceptibility results but should also take into consideration the pharmacokinetic properties of each drug. For instance, levofloxacin retains its original form when excreted in the urine, causing high levels in the urine. Therefore, this class of drug is particularly advantageous in the treatment of patients with urinary tract infection.

Q3: Could you provide an overview of complicated urinary tract infection?

Complicated urinary tract infection refers to urinary tract infections that are accompanied by complications that may lead to acquired infections or risk of treatment failure. The management of patients with complicated urinary tract infection are more challenging than patients with uncomplicated urinary tract infection as the former often presents with a history of antibiotic use for the treatment of other diseases such as urinary tract obstruction, increased residual urine in the bladder, or urinary diversion. This could potentially lead to higher occurrence of antimicrobial resistance. According to our surveillance among these patients, the occurrence of extended spectrum beta-lactamases (ESBL)-producing E. coli is higher. The occurrence of Enterococcus in these patients is also higher than in patients with uncomplicated urinary tract infection.

As such antibiotic selection for patients with complicated urinary tract infection should be based on the results of urine culture and drug susceptibility tests, in addition to the consideration of the spectrum of pathogens and regional drug resistance data. Meanwhile, for patients with underlying urinary system diseases, it is worthwhile evaluating the severity of their underlying diseases.

Q4: What is your opinion on the use of fluoroquinolones for the treatment of patients with urinary tract infection?

Fluoroquinolones are currently one of the more commonly used drugs in the treatment of patients with urinary tract infection. The 2015 expert consensus on complicated urinary tract infection also recommends 500 mg levofloxacin for the initial treatment due to its antibacterial spectrum coverage and characteristic of high urine drug concentration.

We are currently more concerned about the issue of drug resistance. In recent years, although the drug resistance of Enterobacteriaceae against fluoroquinolones is relatively stable, the drug resistance rate is already high, so it is necessary to ensure and maintain reasonable drug usage. Newer fluoroquinolones such as sitafloxacin are emerging in the market. Based on in vitro antimicrobial activity evaluation results, these newer fluoroquinolones have stronger antimicrobial activity against E. coli, in particular ESBL-producing strains. As such, I hope that these newer fluoroquinolones become a new drug of choice in the clinical setting.

References:

1. China Antimicrobial Resistance Surveillance System statistics
2. Hu Fupin et. al. 2018 Chinet China Antimicrobial Surveillance Network, Chinese Journal of Infection and Chemotherapy, 20 January 2020, Issue 20, No. 1
3. Chen Shan et. al. Chinese expert consensus on the diagnosis and treatment of urinary tract infection (2015 edition) – complex urinary tract infection, Chinese Journal of Urology, April 2015, Issue 36, No. 4
4. Wang M, et al. Antimicrob Agents Chemother. 2004.
5. Kanda H, et al. Japanese Journal of Chemotherapy. 2008, 56(S-1):1-17.