Delay in commencing treatment for MDR TB at a specialised TB treatment centre in KwaZulu-Natal

Background. According to the National Department of Health (NDoH) guidelines, patients diagnosed with multidrug-resistant tuberculosis (MDR TB) must be referred to a specialised treatment centre for initiation of effective therapy. MDR TB is difficult to diagnose and the centralised referral model is beset with challenges that contribute to treatment delays, increased patient morbidity and mortality, and MDR TB nosocomial transmission. Culture and drug sensitivity testing (DST) takes 8 weeks or longer to obtain results while line probe assays (LPAs) can give a result in hours. LPAs and the GeneXpert MTB/Rif (GX) are ground-breaking discoveries for TB diagnosis. However, they are not easily accessible or available to those needing it, so culture and sensitivity testing remains the gold standard for diagnosis.Aim. This study aimed to assess the delay in the initiation of MDR TB treatment and profiled the patients being referred to a specialised drug-resistant treatment centre in KwaZulu-Natal.Results. Of all the patients, 75% referred showed a mean delay of 12.4 weeks from the date of sputum collection for culture and drug sensitivity testing to the start of treatment. Most of the patients were symptomatic for TB and HIV-positive.Discussion. Our findings suggest that current policy on the initiation of effective treatment needs urgent revision. Staff should be appropriately trained in LPA and GX technology to reduce delays in initiating treatment for MDR TB. The NDoH’s plans for rapid diagnosis and reducing the treatment burden on centralised MDR TB management facilities are in the early phases of implementation and will take years to achieve favourable and significant outcomes.Conclusion. There is a significant delay in initiating definitive management for MDR TB. S Afr Med J 2012;102(6):360-36

Drug-resistant tuberculosis control in South Africa: scientific advances and health system strengthening are complementary.

CAPRISA, 2014.Abstract available in pdf

Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa.

CAPRISA, 2014.Abstract available in pdf

Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance

The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71; P = 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%; P = 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drug

Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: Long-term outcome, tolerability, and effect on emergence of drug resistance

The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71; P = 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%; P = 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs. Copyright © 2012, American Society for Microbiology. All Rights Reserved