Treatment outcomes in multidrug resistant tuberculosis-human immunodeficiency virus Co-infected patients on anti-retroviral therapy at Sizwe Tropical Disease Hospital Johannesburg, South Africa

BackgroundMultidrug resistant-tuberculosis (MDR-TB) is a threat to global tuberculosis control which is worsened by human immune-deficiency virus (HIV) co-infection. There is however paucity of data on the effects of antiretroviral treatment (ART) before or after starting MDR-TB treatment. This study determined predictors of mortality and treatment failure among HIV co-infected MDR-TB patients on ART.MethodsA retrospective medical record review of 1200 HIV co-infected MDR-TB patients admitted at Sizwe Tropical Disease Hospital, Johannesburg from 2007 to 2010 was performed. Chi-square test was used to determine treatment outcomes in HIV co-infectedMDR-TB patients on ART. Multivariable logistic regression and Poisson models were used to determine predictors of mortality and treatment failure respectively.ResultsMortality was higher (21.8% vs. 15.4%) among patients who started ART before initiating MDR-TB treatment compared with patients initiated on ART after commencing MDR-TB treatment (p = 0.013). Factors significantly associated with mortality included: the use of ART before starting MDR-TB treatment (OR 1.65, 95% CI 1.02–2.73), severely-underweight (OR 3.71, 95% CI 1.89–7.29) and underweight (OR 2.35, 95% CI 1.30–4.26), cavities on chest x-rays at baseline (OR 1.76, 95% CI 1.08–2.94), presence of other opportunistic infections (OR 1.80, 95% CI 1.10–2.94) and presence of other co-morbidities (OR 2.26, 95% CI 1.20–4.21). Factors predicting failure were severe anaemia (IRR (OR 4.72, 95% CI 1.47–15), other co-morbidities (OR 2.39, 95% CI 1.05–5.43) and modified individualised regimen at baseline (OR 2.15, 95% CI 0.98–4.71).ConclusionsHigh mortality among patients already on ART before initiating MDR-TB treatment is a worrisome development. Management of adverse-events, opportunistic infections and co-morbidities in these patients is important if the protective benefits of being on ART are to be maximized. There is the need to intensify intervention programmes targeted at early identification of MDR-TB, treatment initiation, drug monitoring and increasing adherence among HIV co-infected MDR-TB patients

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Anti-Tuberculosis Drugs and Adverse Events

Anti-tuberculosis (TB) drugs can cause adverse drug reactions, particularly the older second-line drugs. Early intervention and adequate management of adverse drug reactions are important to prevent complications. Laboratory testing at baseline and during treatment, in addition to clinical monitoring, is protocolized to improve patient and treatment management. This chapter provides an overview of the most frequent and severe adverse effects caused by the first-and second-line drugs used for the treatment of tuberculosis. An approach on how to manage the adverse drugs effects is briefly described.</p

Factors influencing specialist care referral of multidrug- and extensively drug-resistant tuberculosis patients in Gauteng/South Africa : a descriptive questionnaire-based study

BACKGROUND: Sizwe Tropical Diseases Hospital is the only specialized hospital for the management of multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB cases in Gauteng Province. In South Africa, there is a mismatch between numbers of individuals with a laboratory diagnosis of drug-resistant tuberculosis (TB) and those being referred for the initiation of specialist treatment. We determined reasons for non-referral of MDR-TB and XDR-TB cases. METHODS: We conducted a descriptive questionnaire-based study amongst provincial primary health care facilities (PHC) and hospitals providing routine care for (drug-susceptible) TB, regarding specialist care referral of patients whose TB culture and susceptibility testing confirmed MDR-TB or XDR-TB diagnoses in the first half of 2008. RESULTS: In total 148 cases were analyzed; 144/148 (97%) had MDR-TB and 4/148 (3%) had XDR-TB. The main reason for non-referral to specialist care was loss to follow up, for patients diagnosed in-hospital (74/97; 76%) as well as in PHCs (11/21; 52%). Nineteen per cent (18/97) of patients diagnosed in hospital versus 33% (7/21) of patients diagnosed in PHCs deceased before referral. CONCLUSIONS: A significant problem in the fight to control DR-TB is follow-up after diagnosis with a delay in patient tracing. TB Focal Points in hospital need to be strengthened in order to improve on patient follow-up and care, and tracer teams should assist with community follow up.http://www.biomedcentral.com/1472-6963/13/268am2014ai201

Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa

BACKGROUND: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. METHODS: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)]. FINDINGS: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). CONCLUSION: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB

Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa : a retrospective cohort study

DATA SHARING : The data used for this analysis in the form of deidentified participant data and a data dictionary will be made available after publication. Investigators wishing to access these data will need to have an approved research proposal and complete a data access agreement. All inquiries should be sent to the corresponding author ([email protected] or [email protected]).SUPPLEMENTARY MATERIAL 1 : French translation of the abstract. SUPPLEMENTARY MATERIAL 2 : Appendices.BACKGROUND : There is a need for short and safe all-oral treatment of rifampicin-resistant tuberculosis. We compared outcomes up to 24 months after treatment initiation for patients with rifampicin-resistant tuberculosis in South Africa treated with a short, all-oral bedaquiline-containing regimen (bedaquiline group), or a short, injectable-containing regimen (injectable group). METHODS : Patients with rifampicin-resistant tuberculosis, aged 18 years or older, eligible for a short regimen starting treatment between Jan 1 and Dec 31, 2017, with a bedaquiline-containing or WHO recommended injectable-containing treatment regimen of 9–12 months, registered in the drug-resistant tuberculosis database (EDRWeb), and with known age, sex, HIV status, and national identification number were eligible for study inclusion; patients receiving linezolid, carbapenems, terizidone or cycloserine, delamanid, or para-aminosalicylic acid were excluded. Bedaquiline was given at a dose of 400 mg once daily for two weeks followed by 200 mg three times a week for 22 weeks. To compare regimens, patients were exactly matched on HIV and ART status, previous tuberculosis treatment history, and baseline acid-fast bacilli smear and culture result, while propensity score matched on age, sex, province of treatment, and isoniazid-susceptibility status. We did binomial linear regression to estimate adjusted risk differences (aRD) and 95% CIs for 24-month outcomes, which included: treatment success (ie, cure or treatment completion without evidence of recurrence) versus all other outcomes, survival versus death, disease free survival versus survival with treatment failure or recurrence, and loss to follow-up versus all other outcomes. FINDINGS : Overall, 1387 (14%) of 10152 patients with rifampicin-resistant tuberculosis treated during 2017 met inclusion criteria; 688 in the bedaquiline group and 699 in the injectable group. Four patients (1%) had treatment failure or recurrence, 44 (6%) were lost to follow-up, and 162 (24%) died in the bedaquiline group, compared with 17 (2%), 87 (12%), and 199 (28%), respectively, in the injectable group. In adjusted analyses, treatment success was 14% (95% CI 8–20) higher in the bedaquiline group than in the injectable group (70% vs 57%); loss to follow-up was 4% (1–8) lower in the bedaquiline group (6% vs 12%); and disease-free survival was 2% (0–5) higher in the bedaquiline group (99% vs 97%). The bedaquiline group had 8% (4–11) lower risk of mortality during treatment (17·0% vs 22·4%), but there was no difference in mortality post-treatment. INTERPRETATION : Patients in the bedaquiline group experienced significantly higher rates of treatment success at 24 months. This finding supports the use of short bedaquiline-containing regimens in eligible patients.WHO Global TB Programme.http://www.thelancet.com/infectionhj2023Medical Microbiolog