Dr Chan Chi Pang
Specialist in Emergency Medicine
St. Teresa’s Hospital
Hong Kong

The global rise in prevalence of multidrug-resistant (MDR) bacterial pathogens poses a significant threat to healthcare, associated with challenging and often fatal infections.¹ Although scientific evidence generally does not support routine combination therapy, the use of multiple antibiotics is common in MDR cases. For example, patients with sepsis from carbapenem-resistant Enterobacteriaceae (CRE) may benefit from a combination approach.²

In this interview, Dr Chan Chi Pang, a Specialist in Emergency Medicine from St. Teresa’s Hospital in Hong Kong, delves into the practical aspects and experiences of antibiotic use, particularly combination therapy, and provides a firsthand account of the decision-making process involved in the treatment of severe infections.

Q1: What are the current local or regional guideline recommendations for combination antibiotic therapy for severe infections?
In Hong Kong, there are currently no specific local or regional guidelines for combination antibiotic therapy in severe infections. The IMPACT guidelines, which address antibiotic resistance in hospital authority settings, serves as the primary reference, although it lacks specific recommendations for combination therapy.³ Notably, there are no guidelines available for private practice. In contrast, regions like the United States and the United Kingdom have established guidelines, such as those from the National Health Service (NHS).⁴ Even within university settings in Hong Kong, there is a lack of formal guidelines for clinicians. Consequently, healthcare practitioners rely heavily on personal and clinical experiences for decision-making regarding combination antibiotic therapy in severe infections.

Q2: Could you share your observations on the patterns and trends in the use of combination antibiotic therapy for severe infections in Hong Kong?
In Hong Kong, the approach to treating severe infections typically involves using meropenem as the primary antibiotic. Additional antibiotics, such as linezolid or vancomycin, may be added depending on factors such as intensive care unit (ICU) admission or the presence of sepsis. Treatment plans are also individualised based on the site of infection. For instance, in cases of transabdominal infections, clinicians may supplement meropenem with metronidazole. Similarly, for urinary tract infections or urosepsis, the addition of a quinolone such as intravenous ciprofloxacin is often considered as part of combination therapy.

Adjustments to therapy are made based on culture results and antibiotic susceptibility obtained from laboratory tests. Initially, meropenem combined with linezolid is often used within the first 48 hours to rapidly control sepsis. Subsequent treatment decisions are guided by the patient’s clinical response and overall condition.

Q3: Considering various clinical scenarios, including life-threatening infections, how do you determine the suitability of combination antibiotic therapy, and what factors guide your decision-making?
Determining the suitability of combination antibiotic therapy involves considering various clinical scenarios and patient factors. For meningitis, penicillin group antibiotics are commonly added to therapy. In cases of sepsis with an unknown cause, initiating treatment with meropenem plus linezolid is typical. Some clinicians may consider replacing linezolid with vancomycin, although vancomycin usage has declined owing to concerns about resistance and renal toxicity, as well as the need for frequent monitoring of vancomycin levels.⁵

Consideration of patient allergies to specific antibiotics is crucial, with penicillin and meropenem allergies being common. Cost considerations may also influence antibiotic choice.

Despite differences in antibiotic choices, efficacy is largely comparable, although meropenem appears to demonstrate favourable efficacy in controlling initial anti-inflammatory responses within the first 48 hours of treatment, even in cases where the cause of infection is unknown.

Q4: How do you approach adapting or customising combination therapy to suit the unique characteristics and microbial landscape of patients in your region?
In customising combination therapy for patients in our region, interdisciplinary collaboration between infectious disease specialists and microbiologists is key for decision-making. This ensures thorough evaluation and adjustment of therapy, particularly during initial stages when treatment direction may be uncertain. Following initiation of combination therapy, prompt monitoring for positive culture results from various sites like the skin or mucosal areas to identify specific pathogens allows for adjustments in antibiotic choices or dosages. For instance, if Staphylococcus is detected, we may incorporate vancomycin into the regimen.

Vigilant monitoring of renal function is crucial owing to potential adverse effects with vancomycin, and dosages are adjusted accordingly. We typically start with two-thirds of the standard dosage, reducing it further if necessary to safeguard renal function without compromising efficacy. Despite potential prolonged administration to minimise toxicity, extended treatment duration with vancomycin does not significantly impact antibiotic resistance rates, based on our clinical observations.

In cases of sepsis, the standard duration of combination therapy in Hong Kong is two weeks. However, we may extend treatment by an additional five days to one week without observing an increase in antibiotic resistance. Overall, our approach aims to balance life-saving treatment with minimising resistance, tailored to patient needs and microbial characteristics.

Q5: How do you approach the challenge of antibiotic resistance, particularly in the context of severe infections, and what role does combination therapy play in your strategy?
Despite encountering cases involving extensive antibiotic resistance profiles, we employ systematic testing of individual antibiotics based on culture results to determine the most suitable treatment option for each patient. Instead of employing numerous antibiotic combinations upfront, we adopt a more focused approach, initially starting with one to two antibiotics and adjusting them sequentially as necessary.

Accurate dosage adjustment is essential, taking into consideration factors such as renal function and body weight to optimise clinical outcomes while minimising treatment duration. Collaboration with microbiologists and pharmacists is essential, as their expertise provides valuable guidance in antibiotic selection and dosage optimisation.

From my clinical observations, instances of antibiotic resistance are relatively rare, particularly in the ICU setting. However, when faced with resistant pathogens, we rely on microbiologists’ insights to identify antibiotics with the highest likelihood of efficacy for individual patients. Despite the challenges posed by antibiotic resistance, informed decision-making remains crucial in ensuring optimal patient care and management of severe infections.

References

1. Mancuso G, et al. Pathogens 2021;10:1310.
2. Ahmed A, et al. Indian J Crit Care Med 2014;18:310–314.
3. PL Ho, et al. Reducing bacterial resistance with IMPACT. 5^th ed. Hong Kong; 2017.
4. MacGowan AP, et al. Citing websites: Antimicrobial Guidelines v7.2 2022. Available at: https://www.nbt.nhs.uk/sites/default/files/document/NBT%20Antimicrobial%20Guidelines%20v7.3_0.pdf. Accessed 12 February 2024.
5. Altowayan WM, et al. PLoS One 2023;18:e0284223.