Extended follow-up on patients in a phase 3 clinical trial found that two bedaquiline-containing drug regimens for rifampicin-resistant tuberculosis (TB) maintained superiority compared with a 9-month injectable-based regimen at 132 weeks, researchers reported yesterday in the Lancet Respiratory Medicine.

The STREAM stage 2 trial randomized patients aged 15 years or older with rifampicin-resistant TB in seven countries to receive one of four treatments: the long regimen (the 20-month regimen recommended by the World Health Organization from 2011 to 2018), a control regimen (a 9-month regimen with the second-line injectable kanamycin), an oral regimen (9 months with bedaquiline replacing kanamycin), or a 6-month regimen (containing bedaquiline and supplemented with 8 weeks of kanamycin). 

Initial analysis at 76 weeks showed that the oral regimen and the 6-month regimen were superior to the control regimen for the primary outcome of favorable status (negative cultures for Mycobacterium tuberculosis). The long-regimen arm of the trial was terminated early.

Effective and safe treatments for drug-resistant TB

In the follow-up analysis, investigators examined unfavorable status (death or a positive culture from one of two most recent samples) at week 132 in the three remaining groups. Among 517 patients in the modified intention-to-treat population, the proportion with unfavorable status was 19.6% in the oral regimen arm, 29.3% in the control regimen arm, and 9.8% in the 6-month regimen arm. 

Few serious or severe adverse events were reported after week 76. Treatment-emergent hearing loss was recorded in significantly fewer participants on the oral regimen (3%) than the control regimen (8%), and there was no significant difference in severe hearing loss between the oral regimen and the 6-month regimen.

Death rates were low among participants allocated to the two bedaquiline-containing arms (1.01 per 100 person-years) compared with participants on the control regimen (1.52/1oo person-years).

"The findings of the STREAM stage 2 trial, combined with results of previous trials, show that shorter bedaquiline-containing regimens are an effective and safe treatment for patients with multidrug-resistant tuberculosis," the investigators wrote. "These data confirm the value of the 9-month regimen recommended in current WHO guidelines and support the use of a 6-month regimen."

In related developments, German officials are investigating symptoms in two train travelers, one of them a medical student who had arrived by plane from Rwanda where he had contact with a patient who was later diagnosed with Marburg virus infection, Bild reported today. The man and his girlfriend reportedly experienced flulike symptoms on a train from Frankfurt to Hamburg.

Officials cleared two tracks in Hamburg Central Station and evacuated the area, as emergency responders in protective suits boarded the train. The two people were taken to University Hospital Eppendorf in Hamburg. Health officials have identified about 200 passengers on the train and are working to determine if they had contact with the two sick passengers. 

In an outbreak notice earlier this week, the World Health Organization (WHO) said one of the contacts of a Marburg patient in Rwanda had traveled to Belgium, but the individual remains healthy, had completed the 21-day monitoring period, and is not a risk to public health.

The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) confirmed H5N1 avian flu in one more dairy herd in Idaho, pushing the national total to 244 across 14 states.

Idaho has now reported 34 H5N1 outbreaks on dairy farms, three of them since early September. 

The Idaho State Department of Agriculture said there are currently nine quarantined facilities across four counties: Twin Falls, Canyon, Cassia, and Jerome.