N C I D E N C E O F H I G H G R A D E Q T C F P R O L O N G A T I O N A N D I T S M A N A G E M E N T A M O N G P A T I

Meseret Asfaw,Carole D Mitnick,Gene F Kwan,Kwanjune J Seung,Lawrence T Oyewusi,Davd Lee Holtzman

doi:10.21010/ajid.v15i2s.5

Abstract

Background: The World Health Organization (WHO) has approved the use of two new drugs, namely Bedaquiline (Bdq) and Delamanid (Dlm), for treatment of Drug Resistant Tuberculosis (DR-TB). One of the concerns raised with the use of these drugs was QT-interval prolongation. This condition could be serious and life threatening. Hence, knowing the magnitude and its management is very important. This case series identifies the incidence and discusses the management of clinically significant QT-interval prolongation amongst a cohort of patients who have been on these medicines. Materials and Methods: Patients with reports of high grade QT-Interval prolongation (i.e. Grade-3 and Grade-4) were identified from the cohort of 265 patients enrolled on bedaquiline and/or delamanid and discussion is made on the pattern, severity and management of each cases identified. Results: Only 4 (1.5%) out of all 265 patients enrolled on Bedaquiline and/or Delamanid have developed high grade QT-Interval prolongation. And all are managed without permanent discontinuation of both drugs. Conclusion: The Incidence of clinically significant QTcF-interval prolongation among DR-TB patients taking bedaquiline and /or delamanid in Lesotho is low. And almost all cases can be managed with more frequent Electrocardiogram (ECG) monitoring and management of other possible causes of QT-interval prolongation without the need to stop one or both drugs permanently.

Highlights

There were an estimated 500,000 new cases of rifampicin-resistant TB- Tuberculosis (TB) globally in 2018
We are reporting a case series of four patients with significant QT prolongation among a cohort of DR TB patients treated with bedaquiline and/or delamanid in Lesotho
The first case is a 57-year-old known Human Immunodeficiency Lfx- Levofloxacin (Virus) (HIV)-positive and chronic obstructive pulmonary disease (COPD) patient who was relatively stable and on treatment for both conditions. He was diagnosed with multidrug-resistant TB (MDR-TB) in January 2017 after two prior successful treatment courses for drug-susceptible TB in 2014 and 2018 respectively. He was started on a MDR-TB regimen of levofloxacin-delamanid-prothionamide-cycloserine and clofazimine after inpatient stabilization of initial respiratory distress

Summary

Introduction

There were an estimated 500,000 new cases of rifampicin-resistant TB globally in 2018. The approval and introduction of bedaquiline (Bdq) in 2012, delamanid (Dlm) in 2013 and repurposing of linezolid (Lzd) and clofazimine (Cfz) has improved DR-TB treatment outcomes (Expand New Drugs for TB, 2015). QT interval prolongation is one of the adverse effects of concern with the use of these drugs, for Bdq and Cfz and to a lesser degree Dlm. Other QT-interval prolonging medicines are frequently used along with these drugs to treat co-morbidities and manage certain side effects of DR-TB (WHO, 2014). We are reporting a case series of four patients with significant QT prolongation among a cohort of DR TB patients treated with bedaquiline and/or delamanid in Lesotho

Materials and Methods

Findings

Discussion

Conclusion