Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery

Highlights

• Treating MDR-TB is complicated, long and expensive.

• Bedaquiline (BQ) is a new active drug to treat MDR-TB.

• No study evaluated safety and effectiveness of surgery in BQ-treated patients.

• 57 BQ-exposed cases resistant to 7 drugs (median) underwent surgery in 9 countries.

• 60% of cases initiated BQ after surgery, 36.4% before and completed it afterwards.

• 90% culture-converted and 69.1% achieved treatment success at the end of treatment.

Summary

Objectives

No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.

Methods

This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015.

Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.

Results

57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.

Conclusions

The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Introduction

With over 490,000 multidrug-resistant tuberculosis cases (MDR-TB; TB caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin) occurring globally each year, 6.2% of which are XDR-TB (extensively drug-resistant TB: MDR-TB with additional resistance to fluoroquinolones and one second-line injectable), the ‘white plague’ remains a major clinical and public health priority.1, 2, 3, 4

Although higher success rates are achievable,1, 2 the overall proportion of treatment success is sub-optimal, adverse events common, and treatment duration long and expensive.1, 2, 3, 4 Currently, scientific debate focuses on the role of new medications (bedaquiline and delamanid),5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and repurposed drugs for the optimal management of difficult-to-treat M/XDR-TB cases.16, 17, 18, 19

Few studies are presently available on the programmatic use of bedaquiline^1,4, 5, 6, 7 and no study has evaluated the contribution of adjunctive surgery in bedaquiline-treated patients.20, 21 The aim of this study is to describe treatment outcomes and complications in a cohort of drug-resistant pulmonary TB cases treated with bedaquiline-containing regimens having indication for surgical intervention (the vast majority of them have been operated).