榴莲视频

For three decades, the incidence of tuberculosis (TB) in the U.S. was on a steady downhill. Post-pandemic there was an uptick in U.S. cases, most likely because of reduced access to medical care and delayed diagnosis, resulting in TB cases that converted from . Fortunately, the CDC going in the opposite direction in early 2023, although Washington state had had its in 2 decades.

The TB treatment trajectory also has seen its share of shift. For some time, the U.S. standard of care for TB that is resistant to rifampin (Rifadin) included 15-24 months of an all-oral regimen (≥5 drugs in an intensive phase; four drugs in a continuation phase). In August 2019, the FDA approved BPaL, a shorter all-oral course of treatment for drug-resistant pulmonary TB.

BPaL is made up of a 6-month regimen of bedaquiline, pretomanid, and linezolid. FDA approval was based on results from the of BPal, showing that approximately 90% of patients with multi-drug resistant TB -- i.e., resistant to isoniazid (Hydra) and rifampin -- had a favorable outcome, as did approximately 90% of those with TB -- i.e., resistant to fluoroquinolones and injectable agents.

However, there was one caveat with BPaL: The recommended 1,200 mg linezolid starting-dose was linked with a neurologic toxicity rate of 81%. Fortunately, the 2022 demonstrated that a lower linezolid dose of 600 mg daily for 26 weeks could deliver comparable success rates and reduce rates of peripheral neuropathy to 24%.

In a 2023 review, the BPaL Implementation Group (BIG) offered reassurance that the low dose was the way to go. From 2019-2022, they looked at the clinical course of 70 U.S. patients with rifampin-resistant or rifampin-intolerant TB and reported that a 27-week regimen consisting of a 600-mg linezolid starting dose, along with careful therapeutic dose monitoring (TDM), was both effective and safe.

Notably, effective treatment required a course that was less than half the duration recommended in for drug-resistant TB, stated Connie A. Haley, MD, MPH, of the Southeastern National Tuberculosis Center/University of Florida in Gainesville, and co-authors.

"The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible," they wrote in . "Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion."

Specfially, the median BPaL duration was 6 months, and 97% of patients (n=66/70) treated with the modified BPaL regimen achieved cure. There were two patients who relapsed and two who were switched to rifampin-based therapy. Linezolid dose or frequency was successfully adjusted in 4.4% who developed hematologic toxicity and in 5.9% with neurotoxicity. TDM was performed in 97.1% of the patients, and the linezolid dose was changed from 600 mg daily for 61.6% individuals all together (52.9% based on TDM results; 8.8% based on provider decision). There were no deaths, according to Haley's group.

In an accompanying , Carlos Acuña-Villaorduña, MD, of Boston University, and Pranay Sinha, MD, of Boston Medical Center, called the findings "reassuring...drug resistance to the regimen components was low, which could partly explain the favorable outcomes reported." But they cautioned that "we cannot assume that resistance rates will remain low as bedaquiline resistance is already gaining ground in countries with widespread use," and that findings from the ongoing trial will refine short-course TB treatment even more.

In the following interview, Haley, who is also at the Vanderbilt Tuberculosis Center in Nashville, Tennessee, discussed the findings in greater detail.

Would you describe the BPaL regimen?

Haley: Treatment included bedaquiline 400 mg daily for 14 days then 200 mg thrice weekly; pretomanid 200 mg daily; and linezolid with provider-determined dosing, supervised with directly observed therapy. Providers used existing guidelines and protocols for treatment and monitoring of patients with drug-resistant TB, but management was not standardized.

What do the current findings add to your previous experience with BPaL?

Haley: It was validating for our BIG to see the way patients responded to the treatment, and how much easier it was for them to tolerate and complete this BPaL regimen compared to previous regimens. The shorter treatment regimen was easier to monitor, and proved to be a bonus for public health providers and staff, especially during the COVID-19 pandemic. Mostly, our team is just glad to help a group of patients who traditionally had a really tough time with treatment.

How significant are these results for future drug-resistant TB treatment?

Haley: With widespread implementation of these new, shorter, safe, and effective drug-resistant TB regimens, we can completely transform drug-resistant TB therapy for the vast majority of patients -- and we can do it in a way that reduces the burden on healthcare providers. I think there are profound benefits with these regimens that can be felt at all levels of the health system. Most important, the use of a BPaL regimen individualized for each patient is a significant advance towards person-centered medical care.

What is your take-home message for physicians?

Haley: Simply put, BPaL should be the standard of care for the vast majority of persons with pulmonary drug-resistant TB disease. The regimen not only leads to improved outcomes and patient experiences, but due to fewer pills, shorter duration, and reduced side effects, it's easier to administer than older treatments.

What do you consider the most important priorities for this research?

Haley: While the BPaL regimen represents significant and much needed progress in drug-resistant TB therapy, we are far from the finish line. We need to further simplify treatment and determine whether the regimen is effective for all forms of pulmonary and extrapulmonary TB. That said, work is ongoing to further optimize these new drug-resistant TB treatments, to explore the viability of these regimens, and to develop next-generation regimens for all forms of TB.

On a global research scale...coordinating the development of new treatments and new diagnostics should be a strategic priority. Investigation is needed into regimens that will provide safe and effective treatment for vulnerable populations not yet approved for new therapies. As I see it, the world also needs to invest in finding better ways to implement promising new TB treatment technologies to ensure they reach all those who need them. In addition, new TB treatment technologies must be used appropriately and with the requisite oversight to manage potential side effects and safeguard against the development of future drug resistance.

Can people contact you about implementing the BPaL regimen?

Haley: I want to emphasize that over the course of the last few years, our team has developed substantial experience in using the BPaL regimen and we are eager to share this. If you're a doctor, a policymaker, an insurer, or anybody with questions about the regimen or our findings, please contact us at connie.a.haley.1@VUMC.org.

You can read the study abstract here.