Dr To Kim Chung
Specialist in Urology
St. Teresa’s Hospital
Hong Kong

Urinary tract infections (UTIs) are a serious public health concern, commonly caused by pathogens such as Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus.^1,2 High recurrence rates and increasing antimicrobial resistance to urinary pathogens threaten to increase the morbidity, hospital admission, and mortality rates, emphasising the need to explore the factors influencing antibiotic selection, effectiveness of new combination therapies and potential future therapeutic interventions.³

Dr To Kim Chung, a Specialist in Urology at St. Teresa’s Hospital, Hong Kong, provides an overview of the treatment strategies for UTI implemented in Hong Kong, and shares his clinical experience with levofloxacin for the treatment of UTI.

Q1: Please describe the etiology and epidemiology of UTIs in Hong Kong.

In Hong Kong, UTIs are a prevalent health issue in both community and hospital settings, regardless of gender and age.⁴ However, the most frequently encountered cases are among females during their reproductive years.⁵ Epidemiological studies have indicated that a significant proportion of young females will experience more than one UTI in their lifetime.⁶ The majority of UTI cases are uncomplicated cystitis, typically occurring in non-pregnant, premenopausal females without underlying medical or structural urological conditions.⁷ The risk factors contributing to these infections include sexual intercourse, the use of spermicides and delayed postcoital voiding.⁸ These factors can promote the proliferation of bacteria in the vagina, increasing the likelihood of UTIs.

The other patient groups affected by UTIs include children, males, individuals with underlying anatomical or functional urinary tract abnormalities and those with systemic diseases or presence of foreign body (e.g., urinary catheter) may be considered as complicated UTIs. Distinguishing between complicated and uncomplicated UTIs is crucial because patients with complicated infections have a higher risk of recurrence and potential complications stemming from the infection.⁷ Healthcare providers must investigate the underlying causes of the infection in complicated cases to improve treatment outcomes. This approach not only helps reduce healthcare costs, but also minimises the additional complications associated with UTIs.

In Hong Kong, the predominant causative agent of UTIs is Escherichia coli, which is responsible for both complicated and uncomplicated UTIs.¹² Other bacteria commonly implicated in UTIs include members of the Enterobacteriaceae family, Klebsiella, Pseudomonas, Enterobacter and Staphylococcus aureus.¹³ Additionally, in certain patient populations such as diabetics and immunocompromised individuals, UTIs can be caused by Candida.

 Q2: What are the current guideline recommendations for antibiotic selection for different UTIs?

 The current guideline recommendations for antibiotic selection for different UTIs in Hong Kong are based on the severity and complexity of the infection. For patients with uncomplicated UTIs that can typically be managed in outpatient settings with oral antibiotics, the Center for Health Protection of the Department of Health has established the Antibiotic Stewardship Program for Primary Care. This program provides evidence-based antibiotic prescribing guidance; the antibiotics recommended for uncomplicated UTIs are nitrofurantoin and amoxicillin/clavulanate. Nitrofurantoin is preferred due to its low antimicrobial resistance and low risk of selection by drug-resistant bacteria. Amoxicillin/clavulanate is well-tolerated, has intermediate antibiotic resistance, and achieves a high concentration in urine.¹¹ Levofloxacin and ciprofloxacin, which were commonly prescribed in the past, are now considered as second-line antibiotic therapies due to the high levels of antibiotic resistance observed in recent studies. These second-line antibiotics are primarily reserved for patients who are allergic to penicillin.

For patients with complicated UTIs, the management approach can vary based on the patient’s overall health status.¹² Factors such as the presence of severe sepsis, high fever and the results of urine culture play a significant role in decision-making. In cases where patients do not have severe sepsis, initial attempts can be made to manage them in an outpatient setting with oral antibiotics. Close clinical monitoring and follow-up are essential in these cases.

However, if a patient is found to harbour drug-resistant microorganisms based on urine culture results or if the infection progresses, there may be a need for parenteral (intravenous) antibiotics, and the patient may need to be admitted to the hospital. For complicated UTIs with fever or a high risk of sepsis, inpatient treatment with parenteral antibiotics is recommended.¹⁴ First-generation cephalosporins are the preferred choice of antibiotics for this group of patients, sometimes in combination with aminoglycosides, depending on the specific clinical presentation and susceptibility patterns.¹⁴

Q3: What is the prevalence of antibiotic resistance against urinary pathogens in Hong Kong? How has the emergence of antibiotic-resistant pathogens affected the way clinicians manage patients with UTIs?

Antibiotic resistance poses a significant global health concern, and Hong Kong is notably recognised for having high antibiotic resistance levels on a global scale. This situation has resulted in growing challenges in effectively managing patients with infectious diseases, leading to increased treatment failures and escalating healthcare costs.¹³ Data collected over the past decade, both from public and private healthcare facilities, consistently indicates a rising trend in antibiotic resistance rates.¹⁵

A careful evaluation of the antibiogram for Escherichia coli, the predominant pathogen causing UTIs, reveals alarming figures.¹¹ Resistance rates have surged to as high as 60%–80% for ampicillin, 40% for cotrimoxazole, and 40%–50% for levofloxacin and ciprofloxacin.¹⁶ Fortunately, some antibiotics like nitrofurantoin and amoxicillin/clavulanate still maintain relatively low resistance rates in Hong Kong (1% and 10%–20%, respectively).¹⁶.

The concerning rise in antibiotic resistance is largely attributed to the inappropriate use of broad-spectrum antibiotics in the treatment of UTIs. This misuse accelerates the development of antibiotic resistance and complicates the management of UTIs. To address this issue, a judicious approach to antibiotic selection is imperative to mitigate the upward trajectory of antibiotic resistance and preserve the effectiveness of available antibiotics for future use.

In clinical practice, a prudent strategy involves initiating antibiotic therapy based on urine culture results rather than resorting to broad-spectrum antibiotics as a first-line approach.⁷ Guided by the antibiogram, nitrofurantoin and amoxicillin/clavulanate are the recommended first-line antibiotics, given their lower resistance rates compared to other antimicrobial agents.⁷ While the use of ciprofloxacin and levofloxacin is not deemed inappropriate, it is noteworthy that many patients with Escherichia coli UTIs have been found to exhibit resistance to these agents.⁷ Consequently, clinicians may need to consider alternative antibiotics and potentially extend the duration of treatment for this subset of patients.

Q4: What is your opinion and experience on the use of levofloxacin for the treatment of patients with UTIs?

Levofloxacin, a fluoroquinolone antibiotic, offers broad-spectrum coverage against both Gram-positive and Gram-negative organisms. While levofloxacin has certain advantages, including high bioavailability and a favorable antimicrobial profile, it is no longer considered the first-line choice for UTI treatment. One primary concern associated with levofloxacin use is the growing prevalence of antimicrobial resistance. Additionally, there are notable side effects associated with levofloxacin that may warrant consideration. These include tendinitis or tendon rupture, central nervous system-related side effects such as convulsions and hallucinations, as well as the risk of peripheral neuropathy.^17-19

Despite these considerations, levofloxacin may still be prescribed as an alternative option for UTI treatment, particularly when guided by urine culture results that indicate its effectiveness. In my clinical experience, the incidence of the aforementioned side effects, such as tendinitis or tendon rupture, have been relatively low. This is partially attributed to the typically shorter duration of antibiotic treatment for UTIs, which is generally shorter than in cases of prostatitis, where treatment may extend to 4 to 6 weeks with levofloxacin. In cases where levofloxacin is prescribed, I would emphasise the importance of monitoring and prompt reporting of any side effects. This proactive approach helps ensure patient safety and allows for timely intervention if any adverse events occur during the course of treatment.

Q5: Once-daily ertapenem is emerging as a pragmatic and well-tolerated choice for outpatient parenteral antibiotic therapy to reduce the chances of prolonged hospital admissions.³ What is your opinion on the value of outpatient parenteral antibiotic therapy in treating complicated UTIs?

Once-daily ertapenem is a valuable option in the management of complicated UTIs, particularly those caused by extended-spectrum beta-lactamases (ESBL)-positive organisms.²⁰ ESBL-positive organisms often necessitate the use of carbapenems as the treatment of choice due to their broad spectrum of activity against these resistant pathogens.

Ertapenem offers several advantages that make it suitable for outpatient parenteral antibiotic therapy. Its once-daily dosing regimen and flexibility for administration via both intravenous and intramuscular routes make it a convenient choice in an outpatient setting. However, the decision to administer outpatient parenteral antibiotic therapy with ertapenem depends on the patient’s clinical status. Patients with severe sepsis or those in poor overall condition may still require inpatient treatment, typically with intravenous ertapenem. The transition to outpatient parenteral antibiotic therapy with ertapenem is typically considered when the patient’s clinical status stabilises and they express a desire to minimise their hospital stay. This approach aligns with the goal of providing effective treatment while optimising patient comfort and resource utilisation.

It is worth noting that, in Hong Kong, the utilisation of outpatient parenteral antibiotic therapy remains relatively uncommon. In my experience, I have managed patients with stable conditions, such as those with prostatitis who are not in severe sepsis, by administering once-daily ertapenem in an outpatient setting. However, this approach may not be widely followed across other clinical settings.

Q6: Switching from intravenous (IV) to oral (PO) therapy is associated with a shorter length of stay and fewer hospital antibiotic days compared with IV-only therapy – providing a viable treatment option for patients with bacteraemic UTIs.¹⁶ What is your opinion and experience on switching patients from IV therapy to oral levofloxacin?

Levofloxacin, available in both oral and intravenous formulations, offers flexibility in its administration for the treatment of bacteraemic UTIs. In my clinical practice, the approach to managing patients with bacteremia associated with UTIs typically involves initiating treatment with intravenous first-generation cephalosporins. This decision is backed by considerations related to the local antimicrobial resistance patterns, particularly the substantial resistance to levofloxacin observed in Hong Kong.

The decision to transition from intravenous therapy to oral levofloxacin is dependent on the patient’s clinical stability and the results of urine culture, indicating susceptibility to levofloxacin. Once these criteria are met, a shift to oral levofloxacin is considered. This transition facilitates an early discharge of the patient from the hospital, with a continuation of oral antibiotics for an extended duration, typically ranging from 10 to 14 days.²¹ The use of intravenous cephalosporins is maintained until specific clinical parameters, such as the resolution of fever and other pertinent clinical indicators, signal the patient’s improvement and readiness for the transition to oral therapy.

In cases involving complicated UTIs, additional diagnostic workup is imperative to uncover underlying factors contributing to the complexity of the infection. This may necessitate investigations to identify potential issues, such as urinary tract stones and obstructive lesions or foreign bodies, which may require surgical intervention to prevent recurrent UTIs in the future.

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