From our October 2019 Newsletter


1. Progress in global rollout of new multidrug-resistant tuberculosis treatments
This is an article published by The International Union Against Tuberculosis and Lung Disease (The Union) collaborating with RESIST-TB to demonstrate the implementation of new MDR-TB regimens among WHO regions.

2. Effect of tablet crushing on drug exposure in the treatment of multidrug-resistant tuberculosis.
Int J Tuberc Lung Dis. 2019 Oct 1;23(10):1068-1074. doi: 10.5588/ijtld.18.0775.

Court R(1), Chirehwa MT(1), Wiesner L(1), de Vries N(2), Harding J(3), Gumbo
T(4), Maartens G(1), McIlleron H(1).

SETTING: Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) are
poor. Due to drug toxicity and a long treatment duration, approximately half of
patients are treated successfully. Medication is often crushed for patients who
have difficulty swallowing whole tablets. Whether crushing tablets affects drug
exposure in MDR-TB treatment is not known.OBJECTIVE AND DESIGN: We performed a
sequential pharmacokinetic study in patients aged >18 years on MDR-TB treatment
at two hospitals in Cape Town, South Africa. We compared the bioavailability of
pyrazinamide, moxifloxacin, isoniazid (INH), ethambutol and terizidone when the
tablets were crushed and mixed with water before administration vs. swallowed
whole. We sampled blood at six time points over 10 h under each condition
separated by 2 weeks. Non-compartmental analysis was used to derive the key
pharmacokinetic measurements.RESULTS: Twenty participants completed the study: 15
were men, and the median age was 31.5 years. There was a 42% reduction in the
area under the curve AUC0-10 of INH when the tablets were crushed compared with
whole tablets (geometric mean ratio 58%; 90%CI 47-73). Crushing tablets of
pyrazinamide, moxifloxacin, ethambutol and terizidone did not affect the
bioavailability significantly.CONCLUSION: We recommend that crushing of INH
tablets in the MDR-TB treatment regimen be avoided. Paediatric INH formulations
may be a viable alternative if the crushing of INH tablets is indicated.

DOI: 10.5588/ijtld.18.0775
PMID: 31627771

Read the full article here.

3. What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?
Int J Tuberc Lung Dis. 2019 Oct 1;23(10):1060-1067. doi: 10.5588/ijtld.18.0649.

Bastard M(1), Sanchez-Padilla E(1), Hayrapetyan A(2), Kimenye K(3), Khurkhumal
S(4), Dlamini T(5), Fadul Perez S(6), Telnov A(7), Hewison C(8), Varaine F(8),
Bonnet M(9).

INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB)
treatment response is a necessary step on the path towards a surrogate marker to
reduce TB trial duration.METHODS: We performed a retrospective analysis on
routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture
conversion, defined as two consecutive negative cultures, was assessed, and
performance of culture conversion at Month 2 and Month 6 to predict treatment
success were explored. To explore factors associated with positive predicted
value (PPV) and the specificity of culture conversion, a multinomial logistic
regression was fitted.RESULTS: This study included 634 patients: 68.5% were
males; the median age was 35 years, 75.2% were previously treated for TB, 59.4%
were resistant only to isoniazid and rifampicin and 18.1% resistant to
fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while
specificity was much higher for culture conversion at Month 2: 91.3% (95%CI
86.1-95.1). PPV of culture conversion at Month 2 did not vary strongly according
to patients’ characteristics, while specificity was slightly higher among
patients with fluoroquinolone-resistant strains.CONCLUSION: Culture conversion at
Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the
advantage of using an earlier marker, further evaluation as a surrogate marker is
warranted to shorten TB trials.

DOI: 10.5588/ijtld.18.0649
PMID: 31627770

Read the full article here.

4. Advances in clinical trial design for development of new TB treatments-Translating international tuberculosis treatment guidelines into national strategic plans: Experiences from Belarus, South Africa, and Vietnam.
PLoS Med. 2019 Oct 18;16(10):e1002896. doi: 10.1371/journal.pmed.1002896.
eCollection 2019 Oct.

Brigden G(1), Nhung NV(2), Skrahina A(3), Ndjeka N(4), Falzon D(5), Zignol M(5).

DOI: 10.1371/journal.pmed.1002896
PMID: 31626628

Read the full article here.

5. Use of Second-line Medications and Treatment Outcomes in Children With Tuberculosis in a Single Center From 2007 to 2018.
Pediatr Infect Dis J. 2019 Oct;38(10):1027-1034. doi:

Chiappini E(1), Matucci T, Lisi C, Petrolini C, Venturini E, Tersigni C, de
Martino M, Galli L.

BACKGROUND: The incidence of drug-resistant forms of tuberculosis (DR-TB) and the
number of children treated with second-line drugs (SLDs) are increasing. However,
limited amount of information is available regarding the use of SLDs in this
METHODS: To describe the treatment of pediatric TB with SLDs and factors
associated with use of SLDs in children with and without documented DR-TB,
records of pediatric TB patients referred to a center in Italy from 2007 to 2018
were reviewed retrospectively.
RESULTS: Of 204 children diagnosed with active TB during the study period, 42
were treated with SLDs because of confirmed or probable drug resistance (42.8%),
adverse reactions to first-line drugs (7.1%), central nervous system involvement
(11.9%) or unconfirmed possible drug resistance (38.1%). There were no deaths or
adverse reactions to SLDs reported. Treatment was successful in 85.2% children
treated with first-line drugs and 92.9% children treated with SLDs. After
adjusting for calendar period, the only factor associated with DR-TB was <2 years
old [odds ratio (OR): 5.24 for <2 years vs. 5-18 years; P = 0.008]. Factors
associated with treatment with SLDs were TB at 2 or more sites (OR: 11.30; P <
0.001), extrapulmonary TB (OR: 8.48; P < 0.001) or adverse reactions to
first-line drugs (OR: 7.48; P = 0.002). No differences were noted in age or
region of origin.
CONCLUSIONS: A substantial proportion of TB children were treated with SLDs. The
main reason for using SLDs was failure of a first-line drug regimen, suggesting
possible DR-TB and underestimation of DR-TB in children. The use of SLD regimens
was associated with a high success rate and good tolerability profile.

DOI: 10.1097/INF.0000000000002410
PMID: 31397749

Read the full article here.