Course of Adverse Events during Short Treatment Regimen in Patients with Rifampicin-Resistant Tuberculosis in Burundi

Abstract

The introduction of the nine-month short-treatment regimen (STR) has drastically improved outcomes of rifampicin-resistant tuberculosis (RR-TB) treatment. Adverse events (AE) commonly occur, including injectable-induced hearing loss. In Burundi we retrospectively assessed the frequency of adverse events and treatment modifications in all patients who initiated the STR between 2013–2017. Among 225 included patients, 93% were successfully treated without relapse, 5% died, 1% was lost-to-follow-up, 0.4% had treatment failure and 0.4% relapsed after completion. AE were reported in 53%, with grade 3 or 4 AE in 4% of patients. AE occurred after a median of two months. Hepatotoxicity (31%), gastro-intestinal toxicity (22%) and ototoxicity (10%) were most commonly reported. One patient suffered severe hearing loss. Following AE, 7% of patients had a dose reduction and 1% a drug interruption. Kanamycin-induced ototoxicity led to 94% of modifications. All 18 patients with a modified regimen were cured relapse-free. In this exhaustive national RR-TB cohort, RR-TB was treated successfully with the STR. Adverse events were infrequent. To replace the present STR, all-oral regimens should be at least as effective and also less toxic. During and after transition, monitoring, management, and documentation of AE will remain essential.

Effectiveness and Safety of a Shorter Treatment Regimen in a Setting with a High Burden of Multidrug-Resistant Tuberculosis

“…Such a pattern might be explained in that some DAE, such as ototoxicity, commonly are observed in patients receiving large cumulative doses of second-line injectable drug [ 4 ], while sharp decline between month 5 and 6 reflects the phasing out of the intensive phase of treatment. A similar pattern was shown among hospitalized RR-TB patients receiving conventional individualized treatment in Tashkent [ 33 ], but in other STR studies the median time to AE was reported earlier, usually during the first two months of treatment [ 11 , 32 , 34 ].…”

“…In our study, grade 3 or 4 DAE occurred in 22.1% (95%CI 14.2–31.9%) of participants. This is much higher compared to STR observational studies conducted in nine countries in Africa (10.7%) [ 9 , 11 ], Niger (6.6%) [ 26 ] and Burundi (4%) [ 32 ], but much lower compared to the 48.2% of grade 3–4 AE reported in the STR arm in the STREAM trial [ 25 ]. Our results are consistent with previous publications showing 21.9% grade 3 or 4 AE among RR-TB patients enrolled in STR in Karakalpakstan [ 13 ].…”

“…This is lower compared to a study conducted in Uzbekistan by Kalandarova et al among MDR/TB patients receiving conventional MDR-TB treatment in Tashkent showing that 55% of patients receiving ambulatory care and 86% of those receiving hospital-based care developed DAE using the conventional RR-TB regimen [ 33 ]. The proportion of patients developing at least one AE in STR studies conducted elsewhere has ranged from 50 to 89% [ 9 , 11 , 26 , 32 , 34 ]. Differences may be explained by differences in treatment regimens, AE definitions and the capacity and available resources for monitoring treatment.…”

Key factors influencing multidrug-resistant tuberculosis in patients under anti-tuberculosis treatment in two centres in Burundi: a mixed effect modelling study

“…In Burundi, the Rifampicin resistant tuberculosis (RR-TB) treatment started in 201 3[ 19 ]. Nine month short-treatment regimen improved outcomes of RR-TB treatment with only 8.2% of treatment failure [ 19 ].…”

“…In Burundi, the Rifampicin resistant tuberculosis (RR-TB) treatment started in 201 3[ 19 ]. Nine month short-treatment regimen improved outcomes of RR-TB treatment with only 8.2% of treatment failure [ 19 ]. Despite evident progress,recent survey have shown that only half of cases are detected, DR-TB form are spreading [ 20 ]…”