DOI: 10.5061/dryad.cnp5hqc29
title: Outcomes and adverse events of pre- and extensively drug-resistant tuberculosis patients in Kinshasa, Democratique Republic of the Congo: retrospective cohort study

description: 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.
description: <b>Study design and participants</b> 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 &gt;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).
description:   It is a hospital
 database. 
   Some control culture data
 is missing because it is not available or not
 relayed