Shorter regimen for resistant TB found effective with lower linezolid dose
New data presented today indicate that a shorter treatment regimen for highly drug-resistant forms of tuberculosis (TB) remains highly effective with reduced doses of one of its components.
The phase 3 ZeNix trial, conducted in Moldova, Georgia, Russia, and South Africa, assigned 181 patients with extensively drug-resistant (XDR)-TB, pre-XDR-TB, and failed or treatment-intolerant multidrug-resistant TB into four study arms. The patients were all treated with the BPaL (bedaquiline, pretomanid, and linezolid) regimen for 6 months, with each arm receiving a different dose of linezolid.
A previous trial, the Nix-TB trial, had found that treatment efficacy for the BPaL regimen was 89%, but with high rates of side effects, such as peripheral neuropathy and anemia, that were associated with linezolid.
Per the intent-to-treat analysis, the treatment success rate was 93% for patients who received the highest dose of linezolid (1,200 milligrams [mg] for 6 months), and was similarly high in the remaining arms—89% among patients receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% among those who treated with 600 mg for 2 months.
Reported side effects also declined with lower doses of linezolid. Peripheral neuropathy was reported in 38% of those receiving the highest dose, compared with 13% of those receiving the lowest dose. A similar downward trend in patients reporting anemia was observed.
“The results of the ZeNix trial support the observed high efficacy of the BPaL regimen as seen in the Nix trial,” principal trial investigator Francesca Conradie, MD, said at a press conference ahead of the International AIDS Society conference, where the results will be presented. “There appears to be a lower dose of adverse events of note, with a preservation of the high rate of efficacy of around 90%.”
The BPaL regimen was approved for use in patients with highly resistant TB in 2019. The 6-month, all-oral regimen is significantly shorter and more effective than previous treatment regimens, which lasted at least 18 months and had global success rates of only 43%.
“We now have evidence that the BPaL regimen can be optimized to make it even easier to use,” Mel Spigelman, MD, President and CEO of TB Alliance, which developed pretomanid for use in the regimen, said in a press release.
Jul 15 TB Alliance press release
CDC notes seasonal rise in Cyclospora cases: 208 cases in 22 states
In a regular update on domestically acquired Cyclospora cases, which typically rise in the spring and summer, the US Centers for Disease Control and Prevention (CDC) yesterday said 208 cases have been reported in 22 states and New York City.
So far, no food items have been linked to the illnesses, but cyclosporiasis in the past has been associated with fresh produce including basil, cilantro, mesclun lettuce, raspberries, and snow peas. Earlier cases have been linked to outbreaks, such as a bagged salad event in 2020, but often cases aren’t directly linked to outbreaks, because there is no validated genetic fingerprinting method for Cyclospora.
The latest total reflects an increase of 202 cases since the CDC’s last update in June. So far 21 patients were hospitalized, and no deaths have been reported.
For comparison, in 2020, multiple outbreaks and clusters were detected involving different produce items, including bagged salad. From May through September, the CDC reported 1,241 cases in 34 states and New York City.
The infections are caused by a parasite called Cyclospora cayetanensis, which is spread by eating food or drinking water contaminated with feces. The hallmark of the illness is profuse diarrhea that can last weeks to months.
Jul 14 CDC Cyclospora update