May 2018 Newsletter

1. Linezolid-Containing Treatment Regimens for Tuberculosis in Children.
Pediatr Infect Dis J. 2018 May 10. doi: 10.1097/INF.0000000000002093. [Epub ahead of print]
Prieto LM, Santiago B(1), Del Rosal T(2), Carazo B(3), Jiménez AB(4), Pérez-Gorricho B(5), Rubio F(6), Tagarro A(7), Blázquez D(8), Moreno-Pérez D(3), Mellado MJ(2), Baquero-Artigao F(2); Spanish Paediatric TB Research Network (pTBred).

BACKGROUND: In recent years there is an increasing interest in the use of linezolid for the treatment of tuberculosis (TB).
METHODS: Patients under 18 years of age who received linezolid within the Spanish Pediatric TB Network (pTBred) from 2001 to 2016 were retrospectively included. Treatment characteristics, adverse events (AEs) and outcomes were analyzed.
RESULTS: Fifteen children were included (53% male) with a median age of 3.6 years (IQR: 1.6-6.2). Median follow up was 54 months (IQR: 38-76). The reasons for linezolid use were drug-resistant TB (DR-TB) in eight (53%) patients, drug-induced liver injury (DILI) in five (33%) patients and chronic liver disease (CLD) in two (13%) patients. Four children (26%) were on immunosuppressive therapy when TB was diagnosed. Five children (33%) were diagnosed with extrapulmonary TB. The median duration of linezolid treatment was 13 months (IQR: 7.5-17). Nine patients had 13 linezolid-related AEs. Hematologic toxicity was observed in eight patients (53%) and gastrointestinal intolerance in 3 patients (20%). In two patients linezolid dose was reduced and in two patients linezolid was discontinued because of AEs. A 2- year-old girl went back to her country of birth and was lost to follow-up. No relapses were observed among the other 14 patients (93%).
CONCLUSIONS: Linezolid may be considered when treating children with drug resistant TB but also in the cases of patients with chronic liver disease or drug induced liver injury. However, AEs should be closely monitored. Further studies are needed to determine the optimum dosage and the optimal duration of linezolid treatment in children.

Read abstract here.

2. Long Term Bedaquiline-Related Treatment Outcomes in Patients with Extensively Drug Resistant Tuberculosis from South Africa.
Eur Respir J. 2018 May 3. pii: 1800544. doi: 10.1183/13993003.00544-2018. [Epub ahead of print]
Olayanju O(1), Limberis J(1), Esmail A(1), Oelofse S(1), Gina P(1), Pietersen E(1), Fadul M(1), Warren R(2), Dheda K(1).

EXTRACT: The persistence of the multi-drug-resistant tuberculosis (MDR-TB) epidemic threatens to destabilise TB control [1, 2]. MDR-TB is defined as a TB strain with resistance to at least isoniazid and rifampicin. In 2016 ∼600 000 new cases of MDR- or rifampicin-resistant TB were estimated to have occurred globally. Detection rates have more than doubled in several countries such as China, India and Russia in the last several years, and almost 20% of Mycobacterium tuberculosisisolates globally are now resistant to at least one first or second line anti-TB drug [3]. Approximately 10% of global MDR-TB strains are thought to be extensively drug-resistant TB (XDR-TB), which is MDR-TB with additional resistance to a fluoroquinolone and a second line injectable drug.

Read extract here.

3. Prevalence of drug-resistant tuberculosis and imputed burden in South Africa: a
national and sub-national cross-sectional survey.
Lancet Infect Dis. 2018 Apr 20. pii: S1473-3099(18)30222-6. doi:
10.1016/S1473-3099(18)30222-6. [Epub ahead of print]
Ismail NA(1), Mvusi L(2), Nanoo A(3), Dreyer A(3), Omar SV(3), Babatunde S(4), Molebatsi T(2), van der Walt M(5), Adelekan A(6), Deyde V(6), Ihekweazu C(3), Madhi SA(7).

BACKGROUND: Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001-02 estimates.
METHODS: A cross-sectional survey was done between June 15, 2012-June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model.
FINDINGS: 101 422 participants were tested in 2012-14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5-2·7) among new tuberculosis cases and 4·6% (3·2-6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9-2·9) and 5·1% (3·7-7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5-5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0-3·6; p=0·01). Comparing the current survey with the previous (2001-02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25·9-63·6) and 59·1% (49·0-69·1), respectively. The prevalence of XDR tuberculosis was 4·9% (95% CI 1·0-8·8). Nationally, the estimated numbers of cases of rifampicin-resistant tuberculosis, MDR tuberculosis, and isoniazid mono-resistant tuberculosis for 2014 were 13 551, 8249, and 17 970, respectively.
INTERPRETATION: The overall prevalence of MDR tuberculosis in South Africa in 2012-14 was similar to that in 2001-02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management.
FUNDING: President’s Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of 1U19GH000571.

Read abstract here.

4. Pan-tuberculosis regimens: an argument for.
Lancet Respir Med. 2018 Apr;6(4):239-240. doi: 10.1016/S2213-2600(18)30096-1.
Wallis RS(1), Cohen T(2), Menzies NA(3), Churchyard G(4).

ABSTRACT: 600,000 cases of drug-resistant tuberculosis, causing 240 000 deaths, were estimated by WHO to have occurred worldwide in 2016.1 Cases are expected to increase over the next two decades, driven by the low likelihood that patients will initiate appropriate treatment and, in those who do, the low probability that treatment will succeed.2 Experience in Africa has highlighted the scope and complexity of this problem. In South Africa, where the Xpert MTB/RIF test has fully replaced sputum acid-fast bacilli smear for tuberculosis diagnosis, 59% of rifampicin-resistant patients have additional resistance to second-line drugs (eg, kanamycin, ethionamide, and ofloxacin).

Read abstract here.

5. Pan-tuberculosis regimens: an argument against.
Lancet Respir Med. 2018 Apr;6(4):240-242. doi: 10.1016/S2213-2600(18)30097-3.
Dheda K(1), Gumbo T(2), Lange C(3), Horsburgh CR Jr(4), Furin J(5).

ABSTRACT: In 1986, after publication of a seminal paper about the use of short-course regimens for tuberculosis treatment, there was great optimism that a universal regimen for tuberculosis had been discovered.1Pierre Chaulet described the short-course regimens as “highly effective and reliable with the minimum of constraints either for patients or for health personnel.”2 Unfortunately, the emergence of rifampicin-resistant Mycobacterium tuberculosis strains soon rendered these short-course regimens ineffective for many individuals.

Read abstract here.