Outcomes and adverse events of pre- and extensively drug-resistant tuberculosis patients in Kinshasa, Democratique Republic of the Congo: retrospective cohort study

Abstract

Background: Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic.

Methods: A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored.

Results: Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV–TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy.

Conclusion: Bedaquiline based treatment improves patient survival in the DRC despite the still high mortality rate. The new anti-tuberculosis

drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.

Methods
Study design and participants

This is a retrospective study of all XDR TB and pre-XDR TB patients records who started their treatment with a bedaquiline-based regimen between January 1, 2015 and December 31, 2017 (with follow-up until December 2019). All patient records were coded by a number designated based on the date of treatment initiation; the number one was the first patient to be treated with bedaquiline containing treatment.

The confirmation of the diagnosis was made by the National Tuberculosis Laboratory of Mycobacteria of the DR Congo; the phenotypic drug susceptibility test (culture) and the molecular method (Xpert® MTB/RIF testing, Cepheid, Sunnyvale, CA, USA with the line probe assay (LPA) for first-line drug susceptibility and second-line drug susceptibility were performed.

Hospitalization was mandatory for all patients at the Specialized Center for the Management of Complications of Multidrug-Resistant Tuberculosis of Kinshasa called the ‘Centre d’Excellence Damien’ (CEDA). During hospitalization, all patients were evaluated daily by a general practitioner, stable patients were evaluated twice per week by a specialist in tuberculosis and respiratory diseases, and sick patients were evaluated daily (Annex 1). The DR TB regimen was modified by a doctor if severe adverse events were observed [26]. . A standardized classification of the severity of the adverse events (AEs) was used. The classification for grading AE severity in adults is based on the scale of ‘the Agence Nationale de recherche sur le SIDA’ [20]. The adverse events were attributed to bedaquiline if the QT interval corrected using the Bazett formula (QTcB) was >500 ms without another possible reason.

Ambulatory management in the health care center was provided for stable patients with three consecutive negative sputum smears or stable patients in the continuation phase. The duration of hospitalization was variable depending on the management of the side effects and clinical follow-up of the patients. Globally, paraclinical follow-up was performed monthly or in cases of emergency.

Monitoring and evaluation schedule of the patients during hospitalization and ambulatory care

Monitoring and Evaluation

Frequency

Evaluation by doctor

At baseline

Daily by general practitioner

Two times per week by a specialist for stable patients and daily for sick patients

Every month for outpatients after hospitalization

Evaluation by nurse

DOTS daily

Sputum smear and culture

At baseline

Monthly

Weight

At baseline and weekly

Monthly for outpatients after hospitalization

Height

At baseline

Drugs susceptibility testing

At baseline, monthly

For patient with continuously positive sputum smears

Chest radiograph

At baseline

At treatment completion

When requested by a doctor

Serum creatinine

Monthly

Serum potassium

Monthly

When requested by a doctor

ECG

Weekly during the intensive phase of bedaquiline treatment

When requested by a doctor

Thyroid stimulating hormone

At baseline

After the intensive phase if prothionamide is used

Liver serum enzymes

Monthly

HIV screening

At baseline, and repeated if clinically indicated

Pregnancy tests

At baseline for women

Audiometry

At baseline, monthly during the injectable phase and when requested by a doctor

Eye test

When requested by a doctor

Adapted from the World Health Organization: Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis ( WHO/HTM/TB/2005.361,World Health Organization: Geneva, Switzerland, 2008).