December 2018 Newsletter



Upcoming Webinar

Managing Side Effects to Drug-resistant TB Treatment – Hosted by RESIST-TB and The Union’s NAPS
On January 16th at 08:30 EST (14:30 CET, 15:30 SAST), RESIST-TB and The Union’s Nurses and Allied Professionals Sub-Section (NAPS) will be hosting a webinar to discuss the ICN/CITC Nursing Guide for Management of Side Effects of DR-TB Treatment. Nurses are often the first to hear of a patient’s side effects during TB treatment, making them well positioned to intervene. The information presented in this guide, which will be the topic of this webinar, was developed to help nurses assess for and respond appropriately to side effects related to anti-TB medications.

For more information on how to join the webinar, continue to check our website.



1. Acceptability of a Novel Levofloxacin Dispersible Tablet Formulation in Young Children Exposed to Multidrug-Resistant Tuberculosis.
Pediatr Infect Dis J. 2018 Dec 13. doi: 10.1097/INF.0000000000002268. [Epub ahead of print]
Purchase SE, Garcia-Prats AJ, De Koker P, Draper HR, Osman M, Seddon JA, Schaaf HS, Hesseling AC.

ABSTRACT: Levofloxacin is used for the treatment and prevention of multidrug-resistant tuberculosis in children, but current adult formulations are poorly palatable. A questionnaire administered to caregivers of 27 children taking a novel 100 mg dispersible taste-masked levofloxacin tablet found the new formulation to be more palatable (69%) and easier to prepare (81%) than the adult formulation. This formulation may assist children to better adhere to anti-tuberculous therapy.

This article is can be found here.

2. Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment.
Clin Infect Dis. 2018 Nov 28;67(suppl_3):S327-S335. doi: 10.1093/cid/ciy625
Bolhuis MS, Akkerman OW, Sturkenboom MGG,  Ghimire S, Srivastava S, Gumbo T, Alffenaar JC.

ABSTRACT: Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.

This article is can be found here.

3. Minimum inhibitory concentrations of fluoroquinolones and pyrazinamide susceptibility correlate to clinical improvement in MDR-TB patients – a nationwide Swedish cohort study over two decades.
Clin Infect Dis. 2018 Dec 18. doi: 10.1093/cid/ciy1068. [Epub ahead of print]
Davies Forsman L, Jonsson J, Wagrell C, Werngren J, Mansjö
M, Wijkander M, Groenheit R, Hammar U, Giske CG, Schön T,
Bruchfeld J.

INTRODUCTION: Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant
tuberculosis (MDR-TB) patients is unclear. Therefore, we correlated MICs of first-and second-line TB drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-TB patients.
MATERIALS/METHODS: Clinical and demographic data of MDR-TB patients in Sweden 1992-2014 including DST results were retrieved from medical records. MIC determinations were performed retrospectively for the stored individual Mtb isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results and clinical variables to tSCC and treatment outcome.                                                                                                                                                                                                                             RESULTS: Successful treatment outcome was observed in 83.5% (132/158) of MDR-TB patients. Increasing MICs of fluoroquinolones, diabetes and age > 40 years were significantly associated with unsuccessful treatment outcome. Patients treated with PZA had a significantly shorter tSCC compared to patients were not (median difference 27 days).
CONCLUSION: Increasing MICs of fluoroquinolones were correlated to unsuccessful treatment outcome in MDR-TB patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatmentwas associated with shorter tSCC, highlighting the importance of PZA DST.

This article can be found here.

4. Transmission of drug-resistant tuberculosis in HIV-endemic settings
Lancet Infect Dis. 2018 Dec 13. pii: S1473-3099(18)30537-1. doi: 10.1016/S1473-3099(18)30537-1. [Epub ahead of print]
Khan PY, Yates TA, Osman M, Warren RM, van der Heijden Y, Padayatchi N, Nardell EA, Moore D, Mathema B, Gandhi N, Eldholm V, Dheda K, Hesseling AC, Mizrahi V, Rustomjee R, Pym A.

ABSTRACT: The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis transmission. These interventions should include a combination of rapid molecular diagnostics and improved chemotherapy to shorten the duration of infectiousness, implementation of infection control measures, and activescreening of multidrug-resistant tuberculosis contacts, with prophylactic regimens for individuals without evidence of disease. Development and improvement of the efficacy of interventions will require a greater understanding of the factors affecting the transmission of multidrug-resistant tuberculosis in HIV-endemic settings, including population-based molecular epidemiology studies. In this Series article, we review what we know about the transmission of multidrug-resistant tuberculosis in settings with high burdens of HIV and define the research priorities required to develop more effective interventions, to diminish ongoing transmission and the amplification of drug resistance.

This article can be accessed for free here. (With a registered Lancet account, also free)

Science-based Dosing of Second Line Antituberculosis Agents for TB Programs – IDSA Clinical Infectious Disease Volume 67, Supplement 3 

1.Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs

2. Gatifloxacin Pharmacokinetics/Pharmacodynamics–based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis

3. Artificial intelligence–derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis

4. Levofloxacin Pharmacokinetics/Pharmacodynamics, Dosing, Susceptibility Breakpoints, and Artificial Intelligence in the Treatment of Multidrug-resistant Tuberculosis

5. Amikacin Dosing for MDR Tuberculosis: A Systematic Review to Establish or Revise the Current Recommended Dose for Tuberculosis Treatment

6. D-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal

7. Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis

8. Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment

9.  The Sterilizing Effect of Intermittent Tedizolid for Pulmonary Tuberculosis

10. Multiparameter Responses to Tedizolid Monotherapy and Moxifloxacin Combination Therapy Models of Children With Intracellular Tuberculosis

11. Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges

12.  Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

13. The Role of Novel Approaches and New Findings in the Pharmacology of Tuberculosis Medicines in Improving Treatment Outcomes

*The above links provide abstracts to the articles