Patients with bedaquiline-resistant tuberculosis had prolonged time to microbiological recovery and poorer clinical outcomes compared with those with drug-susceptible infections, according to a matched cohort study conducted in South Africa.
The study included 82 patients with confirmed bedaquiline-resistant, rifampicin-resistant (RR) tuberculosis. These patients were matched 1:1 with 82 individuals who had bedaquiline-susceptible RR tuberculosis, based on age, HIV status, and baseline sputum culture results. All patients received care at the same tuberculosis referral center between 2018 and 2023.
The median time to sustained sputum culture conversion was 175 days (interquartile range [IQR], 100–254) in the bedaquiline-resistant group, compared with 32 days (IQR, 30–42) in the bedaquiline-susceptible group. In adjusted analysis, bedaquiline resistance was associated with longer time to culture conversion (adjusted hazard ratio, 0.03; 95% CI, 0.0023–0.29; P=0.003).
At 18 months, 43 of 82 patients (52%) with bedaquiline-resistant tuberculosis achieved tuberculosis-free survival, defined as being alive, culture-converted, and either in care or having completed treatment. Nineteen patients (23%) had died, and 50 of 63 survivors (79%) remained on treatment at 18 months. Tuberculosis-free survival was 57% at 12 months and 50% at 6 months.
Among 81 patients with outcome data, 54 (67%) experienced unfavorable treatment outcomes, including treatment failure in 35 patients (43%) and loss to follow-up in 8 (10%). These outcomes were notably worse than those typically observed in patients with bedaquiline-susceptible RR tuberculosis, although the difference in overall mortality between groups was not statistically significant (P=0.45).
Despite phenotypic resistance, 72 of 82 patients (88%) received bedaquiline. Among 71 patients with complete treatment data, bedaquiline was continued after resistance confirmation in 48 patients (68%), with a median duration of 65 days (IQR, 39–138). The total duration of bedaquiline use following detection of resistance was a median of 5.5 months (range, 4 d to 13.5 mo). The median overall treatment duration after the index sputum collection was 17.7 months (IQR, 10.4–20.4).
The most frequently co-administered drugs were linezolid, clofazimine, and terizidone. Meropenem combined with amoxicillin–clavulanate was prescribed for 32 of 82 patients (39%), initiated at a median of 156 days (IQR, 115–236) after resistance confirmation. Fewer than half of patients received carbapenem-based therapy, despite guideline recommendations.
At the time of resistance detection, 70 of 82 patients (85%) met criteria for extensively drug-resistant tuberculosis. Among 73 tested isolates, 67 (92%) showed resistance to clofazimine. Linezolid resistance emerged in 7 of 33 patients (21%) during follow-up, despite initially susceptible isolates.
Laboratory confirmation of phenotypic bedaquiline resistance occurred at a median of 4.5 months (IQR, 3.4–6.7) after sputum collection. During this time, most patients continued treatment without regimen change. Treatment modifications were made in 59% of cases after resistance confirmation.
Longer duration of bedaquiline use was associated with reduced mortality at 18 months (adjusted hazard ratio, 0.74; 95% CI, 0.62–0.88; P=0.0008), though the authors noted this finding may reflect survivor bias rather than a direct therapeutic benefit.
The study underscores the clinical challenges posed by bedaquiline-resistant tuberculosis and highlights the urgent need for rapid resistance testing, expanded use of targeted sequencing, and access to novel treatment options through clinical trials.
Full author disclosures and funding information are available in the original publication.
Source: The Lancet Infectious Diseases