The 2018 World Health Organization (WHO) treatment guidelines for multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) give preference to all-oral long regimens lasting for 18–20 months. The ...guidelines strongly recommend combining bedaquiline, levofloxacin (or moxifloxacin) and linezolid, supplemented by cycloserine and/or clofazimine. The effectiveness of this combination in a long regimen has not been tested in any study to date, with corresponding uncertainty. The guidelines indicate that, ideally, all MDR-TB patients should have – as a minimum – the isolate tested for fluoroquinolones, bedaquiline and linezolid susceptibility before the start of treatment. Unfortunately, the capacity for drug susceptibility testing is insufficient in resource-limited settings. The risk of acquired bedaquiline resistance cannot be ignored, especially in patients with undetected resistance to fluoroquinolones. Both linezolid and cycloserine are known for their high frequency of serious adverse events. The combination of bedaquiline, moxifloxacin and clofazimine in the same regimen may excessively increase the QT interval. These expected adverse effects are difficult to monitor and manage in resource-limited settings, and may result in frequent modifications and a less effective regimen. The final STREAM results have confirmed the non-inferiority of the short regimen compared with the long regimen. Before evidence on the all-oral long and modified all-oral short treatment regimens is available, the WHO-recommended short MDR-TB regimens, with monitoring for ototoxicity, remain a better treatment option for the management of MDR/RR-TB patients who are eligible for short regimens in low- and middle-income countries. National tuberculosis programmes should also strengthen their capacity in the detection and management of fluoroquinolone-resistant MDR-TB following the WHO guidelines.
The ideal number of drugs needed and treatment duration are crucial issues in the management of multidrug-resistant tuberculosis (MDR-TB). Thus, we read with interest the Article by the Collaborative ...Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017,1 the results of which support our proposal,2 from 2015, to classify anti-tuberculosis drugs on the basis of their toxicity, and sterilising or bactericidal activity.
In this study, we analyzed the M. tuberculosis complex (MTBc) population structure among multidrug-resistant TB (MDR-TB) patients in Niger and tested whether the Cameroon family displayed a slower ...response to MDR-TB treatment. We genotyped baseline clinical isolates that had been collected from pulmonary MDR-TB patients recruited consecutively between 2008 and 2016 in Niger. Spoligotyping was used to analyze the genetic diversity of mycobacterial lineages, and Kaplan Meier's analysis to compare treatment outcomes. A total of 222 MTBc isolates were genotyped; 204 (91,9%) were identified as the Euro-American L4 lineage, with the Ghana family (106, 47,4%) and the Cameroon family (63, 28,4%) being predominant. Patients infected by Cameroon family isolates 61(96,8%) showed faster conversion (log-rank p < 0.01) than those infected with Ghana family isolates (91,5%), and were more likely to experience favorable outcome (adjusted odds ratio aOR 4.4; 95%CI 1.1–17.9; p = 0.015). We found no association between MTBc families and second-line drug resistance profiles (p > 0.05). Our findings show that MDR-TB in Niger is caused by major spoligotypes of the Euro-American L4; with more rapid smear and culture conversion in patients infected with the Cameroon family. These first insights may alert clinicians that slow conversion may be associated with the type of infecting strain.
•Euro-American L4 predominate in the population structure of MDR-TB strains in Niger, mainly the Ghana and Cameroon families.•On the Short Treatment Regimen, the median time to sputum smear and culture conversion was two months.•Smear and culture conversion was faster for patients infected with Cameroon family than for patients with the Ghana family.
Aims and objectives: In 2016, Guinea had an estimated notification rate of 177 new tuberculosis (TB) cases per 100.000 population, with 360 estimated-number of rifampicin-resistant (RR) TB cases. In ...2014, Damien Foundation and the National Tuberculosis Programme (NTP) of Guinea started a biomedical-social-support to people treated by multidrug-resistant TB (MDR-TB) in one-pilot health-facility. The aim of this study is to analysis effectiveness of biomedical-social-support on MDR-TB-care.
Methods: All MDR-TB-cases treated during 2016 to 2017 were analysed. Treatment-outcomes were compared according to the provision of biomedical-social-support in one pilot-health-facility to two-health-facilities without it. In biomedical-social-support, all biological-tests, ancillary drugs were provided free of charge and a nutritional-kit and transport-refunds were monthly provided during the whole treatment. Treatment regimen included 20-month treatment regimen with Kanamycin (Km), Levofloxacin (Lfx), Cycloserine (Cs), Pyrazinamide (Z) and Prothionamide (Pto) during 6-month in the intensive-phase, followed by 12-18-month of same drugs but Km.
Results: We included 75 MDR-TB cases, 7(9%) HIV-positive. Mean-age was 26years (IQR 15-49). All cases were pulmonary-TB, from which 10(13%) were new-cases. There were 27 MDR-TB cases with biomedical-social support and 48 without it. Mean delay of treatment-start in days was 20(IQR 9-110) in the pilot health-facility compared to 34(IQR 9-111). Treatment outcomes in the group with biomedical-social support were: cured 22(82%), treatment-completion 0(0%), death 2(7%), failure 1(4%) and 2(7%) lost-to-follow-up compared to those without biomedical-social support 23(48%), 2(4%), 9(19%), 2(4%) and 12(25%) respectively. Treatment success to unfavourable- outcomes (failure, death and lost-to-follow-up) in the pilot health-facility was 82% and 18% respectively compared to 52% and 48% respectively in those health-facilities without biomedical-social support (p<0.01).
Conclusions: The introduction of biomedical-social support to people affected by MDR-TB was successful in Guinea. People who benefited from this strategy had more favourable treatment-outcomes. The biomedical-social support could improve treatment-success if extended to all MDR-TB people under treatment.
Aims and objectives: Niger is a challenging environment, with limited resources for TB control. Health staff are scarce, access to care is limited due to long distances between communities and health ...facilities and security threats.
The Short Treatment Regimen (STR) has been implemented nationwide for rifampicin resistant tuberculosis (RR-TB), since 2008. No previous publication has shown the results from countrywide programmatic implementation using few exclusion criteria.
The National Tuberculosis Programme and the Damien Foundation conducted a retrospective observational study to evaluate the management of RR-TB from 2008 to 2017.
Methods: Sputum specimens were collected before treatment initiation and monthly for smear and culture during treatment. Follow-up after cure continued up to one year after cure with smear and culture performed every 6 months.
Individuals with confirmed RR-TB were treated in the three national Units. Initially, the high-dose gatifloxacin-based Bangladesh regimen was used. In October 2013 high-dose gatifloxacin was replaced by normal-dose moxifloxacin when gatifloxacin became unavailable on the market. From October 2015, a modified STR, with linezolid replacing kanamycin during the intensive phase was used in patients with hearing loss on audiometry. Systematic clinical and laboratory monitoring of patients on treatment was introduced in 2008. From 2008 to September 2013, hearing loss was monitored clinically and with audiometry at the end of the intensive phase. Thereafter, bimonthly audiometry has been carried out in all patients given SLIs.
Results: Among 1,550 patients tested for rifampicin resistance, mainly previously treated patients, 411 (26.5%) were diagnosed with pulmonary RR-TB. The proportion of retreatment cases tested for RR-TB increased from 11.2% in 2008 to 60.5% in 2017. Of the 411 patients with confirmed RR-TB, 359 (87.3%) were enrolled on treatment and 324 (90.3%) started on STR. 24 patients received a modified STR mainly because of hearing loss at baseline or during treatment. Among 300 patients on standardised STR, 250 (83.3%) (IC95%: 78.7-87.1) were cured relapse-free, ten (3.3%) had failure, 28 (9.3%) died, eight (2.7%) were lost to follow-up and four (1.3%) relapsed. Among the 14 patients with bacteriological unfavourable outcome (failure and relapse), nine had initial resistance to fluoroquinolones (FQ) and five had susceptible strains. Among 251 patients with initial susceptibility to FQ there were 4 (1.6%) acquisition of resistance. Of 24 patients receiving a modified STR, 21 (87.5%) were cured relapse-free. Serious ototoxicity was reported in 6 of 120 patients (5%) with clinical monitoring, audiometry at the end of the intensive phase and switch from kanamycin to capreomycin and in 2 of 74 patients (2.8%) with bimonthly audiometry and reduction of kanamycin dose from daily to thrice a week.
In 130 patients with bimonthly audiometry and switch from kanamycin to linezolid, serious hearing loss was detected in 2 (1.5%) patients. Since 2016 onwards no serious hearing loss was recorded in Niger.
Conclusions: A comprehensive nationwide approach to multidrug-resistant tuberculosis management using the STR was feasible and successful. Hearing loss was manageable replacing the injectable with linezolid. Our study confirms the effectiveness and safety of the STR.
Aims and objectives: The standardized short treatment regimen (STR) is implemented in Niger to treat multidrug-resistant tuberculosis (MDR-TB) since 2008 with excellent outcomes. However, ototoxicity ...secondary to injectable is a concern and data on modified oral STR are limited. The aim of this study is to test if linezolid can replace the injectable. Both drugs have a similar mechanism of action and the use of linezolid in replacement of SLI may preserve bedaquiline as core-drug in a salvage regimen to treat possible failures and relapses. Linezolid is used only in the intensive phase to reduce the risk of peripheral neuropathy and optic neuritis.
Methods: A prospective longitudinal study was conducted on a modified STR replacing kanamycin with linezolid (600 mg/d) in case of hearing loss (grade 1) at baseline or during treatment. WHO definitions were used for outcomes and adverse events were assessed according to French National Agency for Research on AIDS. Audiometry was performed bimonthly from 2016 to 2017 and monthly from 2018 onwards.
Results: A total of 173 patients were treated with the STR for pulmonary MDR-TB from 2016 to June 2018. Among them, 22 (12.7%) had a modified STR, switching from kanamycin to linezolid during treatment (14) or starting with linezolid (8) because of hearing loss. Fourteen (63.6%) were males, 2 (9.1%) were HIV positive, the median age was 37.5 years (range 21-71) and the median BMI was 16.5 kg/m2 (range 13-24.2). No patients had strains resistant to fluoroquinolones and/or injectables. The median time from treatment start to switch kanamycin to linezolid was 2 months (range 0-3) and the median duration of treatment with linezolid was 2 months (range 1-5). All patients had smear and culture conversion with a median and range of 1 month (1-6) and 2 months (2-4) respectively.
Nineteen patients (86.4%) were cured and 3 died of respiratory failure (2) and severe immunosuppression (1). Eighteen patients were assessed for follow-up 6 months and 12 were assessed 12 months after cure. All remained smear and culture negative. Severe adverse events were anaemia in 5 cases (22.7%) with a median onset of 1 month (range 1-3) and thrombocytopenia in 1 case (4.5%). Linezolid was temporarily discontinued and these patients received blood transfusions. The drug was reintroduced at reduced dosage (300 mg) with no further problems. Seven patients (31.8%) had a reversible mild to moderate peripheral neuropathy which was reversible at the end of treatment. No patients had optic neuritis. From 2016 onwards no serious hearing loss secondary to SLI use was detected nationwide in Niger.
Conclusions: A modified STR with linezolid may achieve high cure rates with manageable adverse events.
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