Associate Professor Pornpan Koomanachai
Faculty of Medicine Siriraj Hospital
Mahidol University, Thailand

Urinary tract infections (UTIs) remain one of the most prevalent bacterial infections worldwide, and the medical community is continually seeking effective treatment strategies in the face of rising antibiotic resistance. The judicious use of fluoroquinolone antibiotics, such as levofloxacin and ciprofloxacin, has become a critical consideration for healthcare providers globally.

In this interview, Associate Professor Pornpan Koomanachai, based in Thailand, discusses UTI management in Thailand, where fluoroquinolones have played a pivotal role in recent years, and proposes strategies, considerations and insights for navigating the treatment landscape.

Q1: Please provide an overview of the prevalent UTI pathogens in Thailand, including regional differences observed within Thailand.
In Thailand, prevalent UTI pathogens align with global patterns, in that they are primarily influenced by local microbiota. Consistent with international trends, the predominant causative agent in Thailand is Escherichia coli (E. coli), a member of the Enterobacterales spp.¹ The other common pathogens are Klebsiella pneumoniae, Coagulase-negative staphylococci, Streptococcus spp., Proteus mirabilis and Enterococcus faecalis.

The major difference in prevalence patterns noted between countries is related to the local antimicrobial resistance patterns of pathogens, particularly noteworthy for E. coli. The resistance of E. coli to fluoroquinolones is high, with an average prevalence of 40% to 50% and exhibiting a broad spectrum of resistance between 20% to 80%.²

Interestingly, while E. coli demonstrates substantial resistance to fluoroquinolones, there is a lack of significant regional variation in fluoroquinolone resistance among uropathogenic Enterobacterales throughout Thailand.^2-5 This uniformity in resistance rates across regions highlights a consistent challenge faced by healthcare providers in managing UTI, emphasising the need for cohesive and standardised strategies across the country.

Q2: How has the availability of fluoroquinolone antibiotics influenced treatment and patient outcomes in the context of UTI management?
In Thailand, fluoroquinolones are readily available throughout the country, dispensed even from pharmacies. General physicians are able to prescribe fluoroquinolones without restrictions, and individuals can also procure these antibiotics over the counter at the pharmacy without the need for a doctor’s prescription.

A variety of fluoroquinolones are available in Thailand including oral formulations of norfloxacin, ofloxacin, moxifloxacin, sitafloxacin, ciprofloxacin (available in both oral and intravenous forms) and levofloxacin (available in both oral and intravenous forms).

According to the drug profiles of fluoroquinolones, the outcomes of UTI treatment are generally favourable, often characterised as good or excellent. However, it is crucial to note that in cases where fluoroquinolone susceptibility is unknown, empirical treatment may result in suboptimal outcomes. Thus, obtaining susceptibility data is important to guide therapeutic interventions and improving overall patient outcomes in the context of UTI management.

Q3: What role does antibiogram data play in decision-making when selecting treatments for UTIs?
Local antibiogram data has a crucial role in shaping decisions regarding empirical treatment for UTI, by facilitating the identification of the most effective antimicrobial agents. Comparatively, guidelines from the USA or Europe, which primarily rely on their own local data supplemented by global data, are not always directly applicable to practice in diverse regions such as Asia, including Thailand.

For example, the Infectious Diseases Society of America (IDSA) Guideline for UTI suggest ciprofloxacin as a first-line antimicrobial for empirical treatment, provided the rate of fluoroquinolone resistance does not exceed 10%.⁶ However, this recommendation comes with the awareness of the “propensity for collateral damage” associated with ciprofloxacin use, and so recommends reserving its use for purposes other than “acute cystitis”.⁶

Q4: In which patient profiles or clinical scenarios do you find each specific fluoroquinolone show the most utility, and what are your preferences and sequencing approach?
All fluoroquinolones demonstrate effective penetration into the kidney-ureter-bladder (KUB) system, making them suitable for treating both upper and lower UTIs.

Fluoroquinolones are commonly used as empirical therapy in patients present with lower UTI, particularly when patients present with stable vital signs and have no contraindications or allergies to fluoroquinolones. In cases of upper UTI or complicated UTI, the prescription of fluoroquinolones is also recommended, especially when culture and susceptibility results are available. This targeted approach ensures a more precise selection of fluoroquinolones based on the specific pathogens identified. Fluoroquinolones are also suitable for de-escalation or transitioning from IV to oral therapy in certain cases.

Several fluoroquinolones are available in both intravenous (IV) and oral formulations, with ciprofloxacin and levofloxacin being notable options, accessible in both IV and oral forms.

Ciprofloxacin is considered a first-line choice for treating community-onset UTIs. However, it is important to note that in Thailand, Enterobacterales have shown resistance to fluoroquinolones ranging from 40% to 80%, even in community settings.² Therefore, the empirical use of ciprofloxacin is recommended for patients without sepsis or septic shock. Oral ciprofloxacin is suitable, provided there are no contraindications such as poor absorption, low serum albumin or a nil per os (NPO) requirement.

Levofloxacin, available in both IV and oral forms, may also be utilised for UTIs, although there is a preference for reserving this agent for respiratory tract infections. The once-daily dosing of oral levofloxacin may enhance patient compliance compared to ciprofloxacin. In contrast, moxifloxacin, a respiratory fluoroquinolone with documented good penetration into the prostate, is not recommended for UTIs to mitigate antibiotic pressure-induced drug resistance, considering the availability of alternative fluoroquinolones.

Sitafloxacin, an anti-ESBL (extended-spectrum beta-lactamase) fluoroquinolone, is valuable for de-escalation or transitioning from IV to oral therapy in UTI patients (without bacteraemia) caused by ESBL-producing Enterobacterales. However, the absence of Clinical and Laboratory Standards Institute (CLSI) breakpoints for sitafloxacin necessitates a reliance on susceptibility studies, which report sitafloxacin susceptibility rates from 80% to 90% among Enterobacterales strains.

Q5: What are the key factors and evidence that influence your choice of prescribing oral and intravenous fluoroquinolones for the treatment of UTI in your patients?
The decision to prescribe oral of intravenous fluoroquinolones for UTI treatment is influenced by three key factors:

1. Antibiogram data and accessibility of fluoroquinolones with robust supporting clinical evidence.
2. Culture and susceptibility results, which allow for individualised patient care. Despite potential disparities with the antibiogram, culture and susceptibility information help us choose the most appropriate fluoroquinolones based on the specific bacteria causing the UTI in each patient.
3. Adherence to antimicrobial stewardship principles, specifically de-escalation or transitioning from IV to oral therapy.⁸ For example, if a female patient had ESBL-producing E. coli-related acute pyelonephritis and sepsis (without bacteraemia), IV carbapenem would be recommended for initial treatment. If the patient stabilises and responds well to the initial treatment, we might then switch to an oral fluoroquinolone effective against ESBL-producing E. coli.^9,10

References

1. Sobel JD, Kaye D. 74 – Urinary Tract Infections. In: Bennett JE, Dolin R, Biaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8^th ed. Elsevier.2015:886.
2. National Antimicrobial Resistant Surveillance Center, Thailand. Citing websites: Antimicrobial Resistance 2000-2021(12M). Available from: http://narst.dmsc.moph.go.th/data/AMR%202000-2022-12M.pdf. Accessed 22 November 2023.
3. Wisutep P, et al. Sci Rep 2023;13:18013
4. Kotikula I, Chaiwarith R. Southeast Asian J Trop Med Public Health 2018;49:113-122.
5. Assawatheptawee K, et al. Antibiotics (Basel) 2022;11:1039
6. Gupta K, et al. Clin Infect Dis 2011;52:e103-20.
7. Tiengrim S, et al. J Med Assoc Thai 2017;100:1061-72.
8. Cunha CB. Med Clin North Am 2018;102:947-954.
9. Thamlikitkul V, Tiengrim S. J Med Assoc Thai 2014;97 Suppl 3:S7-12.
10. Malaisri C, et al. J Infect Chemother 2017;23:556-562.