Isoniazid/rifapentine (for latent TB infection)
A 1-month regimen of daily isoniazid plus rifapentine has been evaluated in a randomized, open-label, phase 3 trial and found to be noninferior to 9 months of isoniazid alone for preventing TB in patients with HIV who were living in areas of high TB prevalence or who had evidence of latent TB infection (LTBI).[117]Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-11.
https://www.doi.org/10.1056/NEJMoa1806808
http://www.ncbi.nlm.nih.gov/pubmed/30865794?tool=bestpractice.com
US guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV include the 1-month regimen as an alternative option for treatment of LTBI in people with HIV.[88]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Mycobacterium tuberculosis infection and disease. May 2024 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium-0?view=full
However, it is not currently recommended in the National Tuberculosis Controllers Association and Centers for Disease Control and Prevention guidelines.[95]Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020 Feb 14;69(1):1-11.
https://www.cdc.gov/mmwr/volumes/69/rr/rr6901a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/32053584?tool=bestpractice.com
Rifapentine and moxifloxacin (4-month regimen)
An international, randomized, controlled, open-label phase 3 noninferiority clinical trial (study 31/A5349) found that a 4-month daily treatment regimen containing high-dose (optimized) rifapentine with moxifloxacin is as effective as the standard daily 6-month regimen in the treatment of drug-susceptible pulmonary TB.[118]Dorman SE, Nahid P, Kurbatova EV, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-18.
https://www.doi.org/10.1056/NEJMoa2033400
http://www.ncbi.nlm.nih.gov/pubmed/33951360?tool=bestpractice.com
The US Centers for Disease Control and Prevention and the World Health Organization both now recommend the 4-month regimen (8 weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by 9 weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin) as a treatment option for patients aged ≥12 years with drug-susceptible pulmonary tuberculosis.[119]Carr W, Kurbatova E, Starks A, et al. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):285-9.
https://www.doi.org/10.15585/mmwr.mm7108a1
http://www.ncbi.nlm.nih.gov/pubmed/35202353?tool=bestpractice.com
[120]World Health Organization. WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment. May 2022 [internet publication].
https://www.who.int/publications/i/item/9789240048126
Guidelines for the prevention and treatment of opportunistic infections in those with HIV also recommend this regimen as an alternative option only for patients with pulmonary TB receiving an efavirenz-based antiretroviral therapy regimen.[88]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Mycobacterium tuberculosis infection and disease. May 2024 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium-0?view=full
This regimen is not currently recommended for most types of EPTB but could be an acceptable option for patients with EPTB that is likely to be paucibacillary, does not pose a substantial risk for death or disability, and does not require prolonged treatment (i.e., pleural or lymph node TB).[119]Carr W, Kurbatova E, Starks A, et al. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):285-9.
https://www.doi.org/10.15585/mmwr.mm7108a1
http://www.ncbi.nlm.nih.gov/pubmed/35202353?tool=bestpractice.com
[120]World Health Organization. WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment. May 2022 [internet publication].
https://www.who.int/publications/i/item/9789240048126
Additional studies are recommended for patients with EPTB.[119]Carr W, Kurbatova E, Starks A, et al. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):285-9.
https://www.doi.org/10.15585/mmwr.mm7108a1
http://www.ncbi.nlm.nih.gov/pubmed/35202353?tool=bestpractice.com
[120]World Health Organization. WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment. May 2022 [internet publication].
https://www.who.int/publications/i/item/9789240048126
Bedaquiline plus pretomanid and linezolid (BPaL)
Pretomanid is approved in the US for the treatment of extensively-drug resistant (XDR), treatment-intolerant, or nonresponsive multidrug-resistant (MDR) pulmonary TB, when used in combination with bedaquiline and linezolid (the BPaL regimen).[121]Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020 Mar 5;382(10):893-902.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6955640
http://www.ncbi.nlm.nih.gov/pubmed/32130813?tool=bestpractice.com
The Centers for Disease Control and Prevention now recommends that BPaL may be used in the treatment of adults with pulmonary XDR or pre-XDR (resistant to isoniazid, rifampin, and at least one fluoroquinolone or injectable medication [i.e., amikacin, kanamycin, capreomycin]) or treatment-intolerant/nonresponsive MDR TB when a safe and effective treatment regimen cannot otherwise be provided.[122]Centers for Disease Control and Prevention. Provisional CDC guidance for the use of pretomanid as part of a regimen [bedaquiline, pretomanid, and linezolid (BPaL)] to treat drug-resistant tuberculosis disease. Feb 2024 [internet publication].
https://www.cdc.gov/tb/hcp/treatment/bpal.html?CDC_AAref_Val=https://www.cdc.gov/tb/topic/drtb/bpal/default.htm
The World Health Organization (WHO) also recommends BPaL for patients with MDR-TB and BPaL with moxifloxacin (BPaLM) for those who do not have documented resistance to fluoroquinolones.[108]World Health Organization. WHO consolidated guidelines on tuberculosis, module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. Dec 2022 [internet publication]
https://www.who.int/publications/i/item/9789240063129
The WHO recommends the use of this 6-month regimen for adults and adolescents ages 14 and over with confirmed pulmonary TB and all forms of extrapulmonary TB (except for TB involving the CNS, osteoarticular and disseminated [miliary] TB), regardless of HIV status, who have less than 1 month exposure to bedaquiline, linezolid, pretomanid, or delamanid.[108]World Health Organization. WHO consolidated guidelines on tuberculosis, module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. Dec 2022 [internet publication]
https://www.who.int/publications/i/item/9789240063129
Guidelines for the prevention and treatment of opportunistic infections in those with HIV also now recommend BPaLM as the preferred option for rifampin-resistant pulmonary TB in people with HIV.[68]Crump JA, Reller LB. Two decades of disseminated tuberculosis at a university medical center: the expanding role of mycobacterial blood culture. Clin Infect Dis. 2003 Oct 15;37(8):1037-43.
http://www.ncbi.nlm.nih.gov/pubmed/14523767?tool=bestpractice.com
Some TB experts in the US are using BPaL and BPaLM for less severe forms of extrapulmonary TB (e.g., cervical lymphadenitis, pleural TB); however, pretomanid is not currently approved for treatment of extrapulmonary TB in the US.