High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss

Abstract

The short treatment regimen (STR) achieves over 80% cure in rifampicin-resistant tuberculosis (RR-TB) patients. However, ototoxicity induced by the injectable is a concern. This is the first study to evaluate the replacement of injectables by linezolid in patients with audiometry abnormalities at baseline or during the treatment.We conducted a retrospective cohort study of all RR-TB patients started on the STR between 2016 - June 2019 in Niger. Patients underwent audiometry every 2 months in 2016, and every month since 2017.Of 195 patients, 16.9% (33/195) received linezolid from the start (n=17), or switched from injectables to linezolid during treatment (n=16), based on audiometry abnormalities. In 2016 two patients developed severe ototoxicity despite switching to linezolid. Since 2017, no patient developed severe hearing loss or complete deafness. Severe hematologicalal toxicity was observed in 18.1% (6/33) of patients on linezolid, none of which was life threatening. The use of linezolid was associated with severe but manageable adverse events (hazard ratio 8.9; 95%CI 2.5–31.5; p=0.001). A total of 90.9% (30/33) of patients on a linezolid containing STR were cured, and none experienced treatment failure. Three died, but not due to adverse events.Baseline and monthly audiometry monitoring and using linezolid after detection of hearing abnormalities appears effective to prevent severe ototoxicity, while keeping high treatment success and manageable adverse events.

Bedaquiline can act as core drug in a standardised treatment regimen for fluoroquinolone-resistant rifampicin-resistant tuberculosis

“…Without core drug regimens are little effective. [8] On the other hand, in Niger linezolid was effectively used as companion drug in patients with fluoroquinolone-susceptible RR-TB and a contraindication for treatment with second-line injectable drugs [13] Our sample size was too small to conclude whether relapse-free cure was significantly higher with 95% certainty for the BDQ-STR compared to the LZD/GFX-STR. However, data on culture conversion showed that the BDQ-STR had an earlier killing effect than the LZD/GFX-STR in a cohort mainly consisting of patients with fluoroquinolone-resistant cohort.…”

“…Without core drugs, regimens are less effective [ 8 ]. On the other hand, in Niger linezolid was effectively used as companion drug in patients with fluoroquinolone-susceptible RR-TB and a contraindication for treatment with second-line injectable drugs [ 13 ].…”

Definitive outcomes in patients with rifampicin-resistant tuberculosis treated in Niger from 2012 to 2019: A retrospective cohort study

“…The study setting and procedures are published elsewhere. 4,7 The 9-11 mo STR was the standard treatment regimen and included a FQ (moxifloxacin or gatifloxacin), clofazimine, ethambutol and pyrazinamide throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid (10 mg/kg) during the first 4 mo (6 mo if conversion to smear microscopy was delayed). Since 2017, the second-line injectable kanamycin has been replaced by linezolid in case of any hearing disturbance on audiometry.…”

“…Since 2017, the second-line injectable kanamycin has been replaced by linezolid in case of any hearing disturbance on audiometry. 7 In case of failure or relapse, patients started a BDQ-regimen, including bedaquiline throughout treatment and, depending on drug susceptibility testing (DST) results, linezolid with either a second-line injectable or delamanid. The STR structure was respected.…”

Correlation of inflammatory cytokines on corrected QT interval in rifampicin-resistant tuberculosis patients

“…The presence of drug resistance is associated with poor treatment management. In 2020, the World Health Organization (WHO) reported 465,000 cases of rifampicin-resistant tuberculosis (RR-TB) with treatment success rates of 57% [ 1 ]. The combination of second-line anti-TB drugs to treat drug-resistant tuberculosis (DR-TB) is more toxic and leads to adverse effects.…”