According to the World Health Organization (WHO), 10.0 million people worldwide contracted tuberculosis (TB) in 2019, with 1.4 million people dying from the disease. Multidrug-resistant tuberculosis is caused by Mycobacterium tuberculosis infection that is resistant to at least isoniazid, rifampin, and another chemotherapeutic treatment (MDR TB). Due to a paucity of infection monitoring and molecular testing, the frequency of treatment resistance in TB patients has been poorly characterised until recently.
The COVID-19 pandemic is affecting the countries with the greatest prevalence of tuberculosis, especially MDR tuberculosis. The detection of MDR TB necessitates close surveillance and the availability of resources for molecular testing. Previous therapy approaches necessitated lengthy intravenous infusions at a great expense. The WHO’s recommendations for the management of drug-susceptible TB and MDR TB in 2020 and 2021 included oral treatment regimens and shorter treatment periods. This Editorial aims to present the rationale for the 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB.
The treatment of patients with MDR TB and XDR TB has been challenging because of prolonged treatment duration of up to 24 months, drug toxicity, treatment cost, and poor clinical outcomes. After four decades of lack of drug development, three new drugs, bedaquiline, delamanid, and pretomanid, were approved for the management of patients with MDR TB and XDR TB and were also endorsed by the WHO, with the possibility of shorter treatment duration.
In 2019, the American Thoracic Society (ATS), the US Centers for Disease Control and Prevention (CDC), the European Respiratory Society (ERS), and the Infectious Diseases Society of America (IDSA) sponsored new clinical guidelines for the treatment of MDR TB. These guidelines were evidence-based from a review of published systematic reviews and meta-analysis data. The study group recommended the most effective oral drug regimen for treating MDR TB, the role of surgery in treating MDR-TB, treatment of patient contacts, and treatment of isoniazid-resistant TB.
These effects of the COVID-19 pandemic have come when TB cases, combined infections with TB, and MDR TB have all been increasing globally. It has recently been estimated that MDR-TB cases will rise in 2021 and 2022, further affecting already poor treatment outcomes. There is an urgent need for continued drug development and the use of shorter treatment regimens for patients with MDR TB.
New evidence and guidelines on the treatment of MDR TB
In November 2019, an independent international WHO expert panel reviewed new evidence on the treatment of MDR TB and rifampicin-resistant TB, and published new guidelines in June 2020. The WHO recommends a shorter treatment regimen of between 9 to 11 months for patients with MDR TB not resistant to fluoroquinolones, including oral bedaquiline. For patients with MDR-TB who also have fluoroquinolone resistance, a regimen composed of bedaquiline, pretomanid, and linezolid may be used for between 6 to 9 months.
The oral drug treatment regimens may be individualized based on the severity of TB and the MDR TB molecular profile. The data review from 2019 showed no safety concerns for the use of bedaquiline for more than 6 months’ duration, the use of delamanid combined with bedaquiline, or the use of bedaquiline during pregnancy. The WHO 2020 revised guidelines have highlighted the ongoing need for high-quality evidence from clinical trials to develop treatment guidelines.
Management of Drug Susceptible TB
On 14th June 2021, the WHO issued a rapid communication on the management of drug-susceptible TB, following a review of the evidence and status of available treatment regimens and considering the effects of the current COVID-19 pandemic. The WHO recommends a four-month regimen for drug-susceptible TB, with a shorter treatment regimen, oral dosing, and has evaluated the safety and efficacy of the recommended regimen. In support of these recommendations, in May 2021, the findings were published from an international phase 3 randomized, controlled trial funded partly by the US CDC.
The study compared patients with newly diagnosed TB treated with two four-month rifapentine-based regimens with a standard 6-month regimen. The efficacy of a four-month rifapentine-based regimen containing moxifloxacin was non-inferior to the standard six-month regimen in the treatment of TB. The shorter treatment regimens for both MDR TB and drug-susceptible TB, recently recommended by the WHO, would ease the burden on patients and healthcare systems, particularly during the COVID-19 pandemic.
The reduced duration of treatment may improve treatment compliance and reduce healthcare costs. Implementing the new first-line WHO regimen for drug-susceptible TB would be facilitated by improved availability and reduced cost of rifapentine. Also, patient monitoring will be required, as this regimen contains moxifloxacin, an antibiotic usually used to treat MDR TB.
The COVID-19 pandemic has had the greatest impact on countries with the highest prevalence of tuberculosis, notably MDR tuberculosis. The detection of MDR TB necessitates close surveillance and the availability of resources for molecular testing. In addition, earlier therapy regimens needed lengthy intravenous injections at a considerable expense. The WHO’s recommendations for the management of drug-susceptible TB and MDR TB in 2020 and 2021 included oral treatment regimens and shorter treatment periods.
As a result, the WHO’s clinical guidelines will have a worldwide impact, particularly in countries with a high and rising prevalence of drug-susceptible tuberculosis and multidrug-resistant tuberculosis (MDR-TB).
Source: Barbara D Alexander, Frédéric Lamoth, Claus Peter Heussel, Cornelia Schaefer Prokop, Sujal R Desai, C Orla Morrissey, John W Baddley, Guidance on Imaging for Invasive Pulmonary Aspergillosis and Mucormycosis: From the Imaging Working Group for the Revision and Update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC, Clinical Infectious Diseases, Volume 72, Issue Supplement_2, 15 March 2021, Pages S79–S88, https://doi.org/10.1093/cid/ciaa1855