Dr Charoen Chuchottavorn
Senior Medical Expert, Advisory Level
Central Chest Institute of Thailand

The World Health Organization (WHO) recently published updated guidance on the management of multi-drug resistant tuberculosis (MDR-TB).¹

Dr Charoen Chuchottavorn, a Senior Medical Expert at the Central Chest Institute of Thailand, provides insights into how the changes in the guidelines, as well as the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, have impacted his treatment of patients with MDR-TB.

Q1. COVID-19 and tuberculosis (TB) cause similar symptoms in patients (e.g., cough, fever and breathing difficulties). What strategies do you employ in your practice to differentiate between the two diseases? Is co-infection with COVID-19 and TB a concern in Thailand?

The clinical spectrum of COVID-19 ranges from asymptomatic disease to severe pneumonia with respiratory failure.² Patients with a mild case of COVID-19 may present with respiratory tract symptoms similar to pulmonary TB. Due to the high prevalence of both diseases in most countries, being able to differentiate between TB and mildly-symptomatic COVID-19 in clinical practice is very important.

All new patients visiting hospitals in Thailand are required to first have their risk of exposure to COVID-19 evaluated; their travel history is assessed, along with any potential contact with patients known to have been infected with COVID-19. All suspected patients are promptly isolated and respiratory specimens are obtained to facilitate diagnosis. Clinical signs and symptoms cannot be used to differentiate between TB and COVID-19. However, in some patients, chest x-rays could help differentiate between the two infections; patients with COVID-19 typically present with abnormal chest radiography in the lower and peripheral lung³, unlike patients with TB whose upper lungs are more affected.

Co-infection with COVID-19 and TB is not a concern in Thailand, as the country currently does not have local transmission of the virus. All new COVID-19 patients are individuals who have recently arrived from abroad and are quarantined in state camps or hotels.

Q2. Has the COVID-19 pandemic altered treatment of patients with TB at your practice? How has treatment of patients with TB changed?

The COVID-19 pandemic is under control in Thailand, and there has been no local transmission for the past 4–5 months. Hence, all healthcare systems have resumed pre-COVID-19 functions. Current treatment of patients with TB in Thailand has not altered or been affected by the pandemic. Newly diagnosed patients with drug-susceptible TB are treated with a standard 6 months short-course regimen which consists of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin.

Q3. What is the role of fluoroquinolones in the treatment of MDR-TB? The 2020 guidelines for the treatment of MDR-TB recommend the use of levofloxacin as part of a shorter treatment regimen in patients with MDR- and rifampicin-resistant TB. How does levofloxacin compare to moxifloxacin?

Fluoroquinolones are typically used as first-line treatment in patients with MDR-TB. In the updated guidance published by the WHO, patients with MDR-TB are recommended to receive a shorter (9–11 months) fully oral regimen as standard treatment.¹

Moxifloxacin was previously the fluoroquinolone of choice in the old amikacin-based shorter regimen for patients with MDR-TB. However, levofloxacin is currently preferred over moxifloxacin as the fluoroquinolone of choice as there is concern about prolonged QT interval (QTc) as a side-effect that arises from using bedaquiline, moxifloxacin and clofazimine.⁴

Q4. Is extensively drug-resistant TB (XDR-TB) common in Thailand? How frequently do you encounter patients with XDR-TB, and how would you treat these patients at your practice?

XDR-TB is not a common occurrence in Thailand. In 2019, only 21 cases of XDR-TB were registered in the national TB central registry (National TB Information Program). In 2019, I managed 4 patients with XDR-TB, and several patients with fluoroquinolone-resistant (FQ-R) pre-extensively drug-resistant TB (preXDR-TB). As patients with these infections are all resistant to fluoroquinolones, the drug is not included in the treatment regimen for these patients. The current approach to treating patients with XDR-TB, FQ-R preXDR-TB, is to use bedaquiline (6 months) and linezolid, clofazimine, cycloserine or delamanid for 18 months.

Q5. The use of fluoroquinolones is discouraged in patients with respiratory infections who have not yet received confirmation of TB.⁵ How do you use fluoroquinolones in your practice?

In my opinion, fluoroquinolones are the best antibiotics for the treatment of respiratory tract infections; they have broad-spectrum action against a wide range of causative organisms of respiratory tract infections.⁶ Fluoroquinolones also have favourable pharmacokinetic/pharmacodynamic and safety profiles.

In my practice, I am careful when prescribing fluoroquinolones for patients with respiratory tract infections, in whom TB is suspected or has not yet been ruled out. While fluoroquinolones have excellent efficacy in the treatment of TB, widespread use of the drug could also increase the risk of resistance in patients. As such, I do not prescribe fluoroquinolones for longer than 10 days, as longer duration of use is associated with increased risk of resistance in patients with respiratory tract infections which are later ascertained to be TB.

References

1. World Health Organization. WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment – Drug-Resistant Tuberculosis Treatment. Available at: https://www.who.int/publications/i/item/9789240007048. Accessed October 2020.
2. Cascella M et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2020 Aug 10]. In: StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK554776/. Accessed October 2020.
3. Durrani M et al. Pak J Med Sci 2020;36(COVID-19-S4):S22–6.
4. Harausz E et al. Int J Tuberc Lung Dis 2015;19:385–91.
5. Hogan AC et al. J Clin Tuberc Mycobact Dis 2017;6:1–7.
6. Cowling T, Farrah K. Fluoroquinolones for the Treatment of Respiratory Tract Infections: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Available at: https://www.ncbi.nlm.nih.gov/books/NBK543514/#:~:text=Fluoroquinolones%20(FQs)%20are%20a%20popular,%2C%20moxifloxacin%2C%20ofloxacin%20and%20delafloxacin. Accessed October 2020.