Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique

Bastard, Mathieu; Molfino, Lucas; Mutaquiha, Cláudia; Galindo, Miriam Arago; Zindoga, Pereira; Vaz, Deise; Mahinça, Ivan; Cros, Philipp du; Rusch, Barbara; Telnov, Alex

doi:10.1093/cid/ciz196

Cited by 6 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Niger, the combination of monthly audiometry with replacement of Km by linezolid was effective in preventing severe hearing loss [ 6 ]. Another study shows that bedaquiline can also be used to replace Km [ 23 ]. However, bedaquiline resistance is acquired in up to 5% of patients [ 24 , 25 ], which is used as an argument to save this drug for patients with FQ-resistant-TB [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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

Ciza

Gils

Sawadogo

et al. 2020

JCM

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Ciza

Gils

Sawadogo

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…Updated WHO guidelines for RR/MDR-TB conditionally recommend a shorter bedaquiline containing regimen for patients without previous exposure to second-line treatment and without fluoroquinolone resistance. [25][25][28]Outcomes of substituting bedaquiline for the injectable agent when toxicity occurred are promising [36]. Further operational research using SSRs incorporating more efficacious drugs including bedaquiline and linezolid, and removing drugs with high rates of resistance globally including ethionamide, pyrazinamide and ethambutol, would yield important real-world results whilst waiting for ongoing randomised trials to finish [37].…”

mentioning

confidence: 99%

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

Cros

Khamraev²,

Tigay

et al. 2020

ERJ Open Res

View full text Add to dashboard Cite

BackgroundIn 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility.

show abstract

“…Apart from two conference abstracts from Belarus in 2016 [65,66], up to April 2019 no results on the frequency and type of AEs reported through aDSM had been published. However, there are a limited number of reports on prospectively collected data on AEs in patients treated with ND&R in programmatic settings [14,17,18,23,[67][68][69][70]. These eight reports describe partially overlapping cohorts ( ND&R: new drugs and regimens; SAE: serious adverse event; AE: adverse event; MSF: Médecins Sans Frontières; NR: not reported; MDR: multidrug-resistant; TB: tuberculosis; STR: shorter (9-month) treatment regimen; Km: kanamycin; Bdq: bedaquiline; AST: aspartate transaminase; ALT: alanine transaminase; Dlm: delamanid; ERS: European Respiratory Society; WHO: World Health Organization; PiH: Partners in Health; XDR: extensively drug-resistant; Lzd: linezolid; Cfz: clofazimine; QTcF: Fridericia-corrected QT interval; FQ-R: fluoroquinolone resistance; SLID-R: second-line injectable drug resistance; ADR: adverse drug reaction; Lfx: levofloxacin; BL: baseline; Mer: meropenem; PAS: para-aminosalicylic acid; Cm: capreomycin; Cs: cycloserine; Mfx HD : high-dose moxifloxacin (dose not specified in paper); Imp: imipenem; GI: gastrointestinal.…”

Section: Why Active Drug Safety Monitoring?mentioning

confidence: 99%

“…one report describes this for Dlm [68], two reports for two cohorts receiving both Bdq and Dlm [23,70], and one report describes the safety and efficacy of a modified STR in which kanamycin was replaced with Bdq [67]. The safety data obtained from these reports are summarised in table 1.…”

mentioning

confidence: 99%

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences

et al. 2019

View full text Add to dashboard Cite

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014–2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

show abstract

Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique

Cited by 6 publications

References 7 publications

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

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

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences

Contact Info

Product

Resources

About