TB/Non-TB Mycobacterial Infections
Joint ATS/CDC/ERS/IDSA Guideline Recommends Shorter, All-Oral Regimens for Drug-Susceptible and Drug-Resistant TB
5 Jan, 2025 | 11:30h | UTCIntroduction: This summary outlines new clinical practice guidelines from the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America on updated treatment regimens for tuberculosis (TB) in low-incidence settings. These recommendations build on recent clinical trials, World Health Organization (WHO) guidance, and were developed using the GRADE and GRADE-ADOLOPMENT methodology. The guidelines aim to shorten treatment duration, reduce pill burden, and improve patient outcomes for both drug-susceptible (DS) and drug-resistant (DR) TB, and they apply to settings where mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies are routinely available. A separate news release from CIDRAP highlights the significance of these shorter, all-oral regimens for adults and children. Directly observed therapy (DOT) remains the standard of care.
Key Recommendations:
Four-Month Regimen for DS-TB in Adults:
- For people aged 12 years or older with isoniazid- and rifampin-susceptible pulmonary TB, a new four-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide (2HPZM/2HPM) is conditionally recommended. This shortened course is based on a large, randomized trial (Study 31/A5349) demonstrating noninferior efficacy compared to the standard six-month regimen (84.6% vs 85.4% cure, respectively), no increase in adverse events, and potential benefits in completion rates. Exclusions include TB meningitis and other complicated forms of extrapulmonary TB, and clinicians should obtain rapid fluoroquinolone susceptibility tests before initiating this regimen.
Four-Month Regimen for DS-TB in Children:
- For children and adolescents aged 3 months to 16 years with nonsevere, drug-susceptible pulmonary TB, a four-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for the initial phase, followed by isoniazid and rifampin, is strongly recommended. Evidence from the SHINE trial showed high success (97.1% vs 96.9%) and similar safety with the shorter course compared to the 6-month regimen. Nonsevere TB generally excludes extensive cavitary disease, advanced extrapulmonary TB, or complicated forms. Close clinical and radiographic follow-up is important to confirm effective cure.
Six-Month BPaL Regimen for Rifampin-Resistant, Fluoroquinolone-Resistant or Intolerant TB:
- For rifampin-resistant (RR) pulmonary TB with resistance or patient intolerance to fluoroquinolones in adolescents aged 14 and older and adults, a six-month all-oral bedaquiline, pretomanid, and linezolid (BPaL) regimen is strongly recommended, replacing much longer regimens that often included injectables. Clinical trials (Nix-TB, ZeNix) demonstrated higher cure rates and lower toxicity with this regimen compared to longer regimens, though vigilance is needed for linezolid-related adverse events (e.g., neuropathy, myelosuppression). Baseline and monthly lab and ECG checks are advised.
Six-Month BPaLM Regimen for Rifampin-Resistant, Fluoroquinolone-Susceptible TB:
- For RR pulmonary TB that remains fluoroquinolone-susceptible in adolescents aged 14 and older and adults, a six-month bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen is strongly recommended over traditional 15-month or longer regimens in patients with MDR/RR-TB. Data from the TB-PRACTECAL trial showed high success rates and fewer serious adverse events. BPaLM is the first-line recommendation for this group. Close monitoring of cardiac status (QTc prolongation) and blood counts is advised.
Both BPaL and BPaLM regimens require detailed drug susceptibility testing and cautious management of potential drug–drug interactions, particularly for patients with comorbidities or HIV infection. Of note, the certainty of evidence for the outcomes in the DR-TB trials was rated as very low, due to multiple factors including bias, small event numbers, lack of blinding, and inconsistent outcomes.
Conclusion: These new recommendations markedly shorten TB treatment courses for adults and children in low-incidence settings with access to appropriate diagnostic tools, while avoiding injectables and reducing serious toxicities. By replacing older, more complex regimens with all-oral, shorter-duration therapy, and using DOT as the standard of care, the guidelines aim to improve adherence, lessen the burden on healthcare systems, and enhance patient quality of life. Ongoing research will further refine dosing, safety for special populations (e.g., pregnant individuals), and the role of advanced drug susceptibility testing.
Reference:
Jussi J. Saukkonen, Raquel Duarte, Sonal S. Munsiff, et al. “Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine, (2025). https://doi.org/10.1164/rccm.202410-2096ST
News release commentary: “New guidelines expand recommendations for shorter, all-oral TB treatments” (CIDRAP). https://www.cidrap.umn.edu/tuberculosis/new-guidelines-expand-recommendations-shorter-all-oral-tb-treatments
RCT: Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam
24 Dec, 2024 | 12:53h | UTCBackground:
Multidrug-resistant (MDR) and rifampin-resistant tuberculosis pose significant global health challenges. Preventing active disease among contacts exposed to resistant strains is critical, yet limited evidence exists on targeted chemopreventive interventions. This study investigated whether a six-month course of daily levofloxacin could reduce the incidence of bacteriologically confirmed tuberculosis among household contacts of individuals with confirmed MDR or rifampin-resistant tuberculosis in Vietnam.
Objective:
To assess if levofloxacin prophylaxis decreases the 30-month incidence of active tuberculosis among high-risk contacts. Primary endpoints included bacteriologically confirmed disease, and secondary outcomes encompassed adverse events, mortality, and development of fluoroquinolone-resistant Mycobacterium tuberculosis.
Methods:
Researchers conducted a double-blind, placebo-controlled, randomized trial. Eligible participants were household contacts of persons who had started MDR tuberculosis treatment within the previous three months, had a positive tuberculin skin test or immunosuppressive condition, and showed no clinical or radiographic signs of active disease. Enrolled individuals received weight-based oral levofloxacin (up to 750 mg/day) or an identical placebo for 180 days. Monthly visits supported adherence and monitored adverse events. Participants underwent follow-up visits every six months until 30 months for tuberculosis screening, chest radiography, and sputum testing where indicated.
Results:
Of 2041 randomized contacts, 1995 (97.7%) completed 30 months of follow-up or reached a primary endpoint. Confirmed tuberculosis was diagnosed in 6 participants (0.6%) in the levofloxacin group and 11 (1.1%) in the placebo group (incidence rate ratio, 0.55; 95% CI, 0.19–1.62), a difference that did not achieve statistical significance. Severe (grade 3 or 4) adverse events were infrequent in both groups, while mild adverse events were more common with levofloxacin (31.9% vs. 13.0%). Acquired fluoroquinolone resistance was not detected.
Conclusions:
Daily levofloxacin for six months showed a numerically lower incidence of tuberculosis than placebo, but the difference was not statistically significant due to lower-than-expected case counts. Treatment was generally well tolerated; however, higher discontinuation rates occurred among levofloxacin recipients, often due to mild musculoskeletal complaints. Further studies may clarify the role of fluoroquinolone-based regimens in preventing MDR tuberculosis across diverse epidemiologic contexts.
Implications for Practice:
These findings suggest that levofloxacin prophylaxis could benefit contacts at high risk of MDR tuberculosis, albeit with caution regarding adherence challenges and low-grade side effects. Broader implementation would require diligent screening, consideration of background fluoroquinolone resistance, and strategies to manage mild adverse events that could undermine treatment completion.
Study Strengths and Limitations:
Strengths include a rigorous double-blind, placebo-controlled design, nearly complete follow-up, and thorough exclusion of prevalent tuberculosis at baseline. Limitations involve an unexpectedly low incidence of confirmed disease, limiting statistical power, and a study population with low HIV prevalence, which may reduce generalizability.
Future Research:
Further research is necessary to confirm these findings in diverse settings, explore alternative or shorter regimens (including newer agents like delamanid), and investigate optimal approaches for patients with fluoroquinolone-resistant strains. The long-term impact on transmission dynamics and microbiome shifts also warrants additional investigation.
Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test
27 Apr, 2024 | 18:53h | UTCStudy Design and Population:
This prospective diagnostic study analyzed the predictive accuracy of tuberculosis (TB) tests among 22,020 high-risk participants across 10 US sites from 2012 to 2020. Participants included individuals with close contacts to infectious TB cases, those born in or travelers to high-incidence countries, individuals living with HIV, or belonging to locally prevalent high-risk groups. Testing included two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and SPOT.TB (TSPOT), alongside the traditional tuberculin skin test (TST).
Main Findings:
The study found that both IGRAs, TSPOT and QFT-GIT, showed significantly superior positive predictive value (PPV) for predicting TB disease progression compared to the TST, with PPV ratios of 1.65 (95% CI, 1.35-2.02) and 1.47 (95% CI, 1.22-1.77) respectively. Additionally, when considering a positive TST result, further positive results from either IGRA significantly increased the PPV, emphasizing the enhanced predictive capability of IGRAs over TST alone.
Implications for Practice:
The superior predictive performance of Interferon-γ Release Assays (IGRAs) suggests they should be considered in clinical settings for high-risk populations, if available and feasible, to better identify individuals at increased risk of progressing to active tuberculosis (TB). This enhanced detection capability could guide more targeted preventive treatments, ultimately supporting global efforts toward TB elimination. Clinicians should assess the accessibility and cost-effectiveness of IGRAs to refine decision-making processes in TB prevention strategies, ensuring that the benefits of these advanced diagnostics are balanced against their costs.
Reference (free full-text):
M-A | Exposure to smoke, overcrowding, poor living conditions, and contact with TB cases identified as risk conditions for pediatric TB
24 Jul, 2023 | 12:43h | UTC
M-A | Risk factors for non-tuberculous mycobacterial pulmonary disease
27 Jun, 2023 | 13:27h | UTCCommentary: Comorbid respiratory disease key predictor of NTM-PD – MDedge
M-A | CRP at 5 mg/L cut-off efficient for tuberculosis screening in HIV outpatients
21 Jun, 2023 | 13:30h | UTC
Commentary on Twitter
ERR: C-reactive protein at a 5 mg cut-off and two newly developed clinical prediction models from this study show clinical utility for TB screening among outpatient PLHIV, while the WHO-recommended four-symptom screen showed suboptimal clinical utility https://t.co/msm13KXR0Y pic.twitter.com/O0wS1Xv4da
— ERS publications (@ERSpublications) June 11, 2023
M-A | Residual respiratory disability after successful treatment of pulmonary tuberculosis
2 Jun, 2023 | 12:20h | UTC
USPSTF Statement | Asymptomatic adults at increased risk should be screened for latent TB
5 May, 2023 | 15:34h | UTCEvidence Report: Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force – JAMA
Editorials:
Screening for Latent Tuberculosis Infection – JAMA Network Open
JAMA Patient Page: Screening for Latent Tuberculosis
Author Interview: USPSTF Recommendation: Screening for Latent Tuberculosis Infection in Adults
Brief Review | Management of latent tuberculosis infection
5 May, 2023 | 15:32h | UTCManagement of Latent Tuberculosis Infection – JAMA (free for a limited period)
Review | Transforming tuberculosis diagnosis
5 May, 2023 | 15:18h | UTCTransforming tuberculosis diagnosis – Nature Microbiology (if the link is paywalled, try this one)
Commentary on Twitter
Diagnosis is the weakest aspect of tuberculosis care and control. A Comment article in @NatureMicrobiol describes seven critical transitions that can close the diagnostic gap and enable TB programmes worldwide to recover from the pandemic setbacks. 🔒 https://t.co/hZyBmVJfRR pic.twitter.com/NDgXF8O9W5
— Nature Portfolio (@NaturePortfolio) May 2, 2023
Post-tuberculosis lung impairment: systematic review and meta-analysis of spirometry data from 14 621 people
26 Apr, 2023 | 14:11h | UTC
WHO releases first-ever Standard on universal access to rapid TB diagnostics
24 Apr, 2023 | 14:04h | UTCNews Release: WHO releases first-ever Standard on universal access to rapid TB diagnostics – World Health Organization
WHO Standard: Universal access to rapid tuberculosis diagnostics – World Health Organization
Improving cascade outcomes for active TB | A global systematic review and meta-analysis of TB interventions
30 Mar, 2023 | 14:17h | UTC
M-A | The natural history of untreated pulmonary tuberculosis in adults
28 Mar, 2023 | 14:42h | UTCThe natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis – The Lancet Respiratory Medicine (free registration required)
Commentary from the author on Twitter
https://twitter.com/bianca_sossen/status/1639143776613482497
SR | Post-tuberculosis sequelae in children and adolescents
27 Mar, 2023 | 13:16h | UTCPost-tuberculosis sequelae in children and adolescents: a systematic review – The Lancet Infectious Diseases (free registration required)
M-A | Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine
27 Mar, 2023 | 13:14h | UTCCompletion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis – The Lancet Respiratory Medicine (free registration required)
Invited Commentary: Shorter regimens for tuberculosis preventive treatment: piecing together the global implementation jigsaw – The Lancet Respiratory Medicine (free registration required)
Commentary on Twitter
NEW Research—3HP provided an increase in treatment completion vs 4R but was associated with a higher risk of adverse events. The trade-off between completion and safety must be considered when deciding TPT
From Prof Dick Menzies & colleagues#WorldTBDayhttps://t.co/UY7l9OuI03 pic.twitter.com/GoKnu9BXoi
— The Lancet Respiratory Medicine (@LancetRespirMed) March 24, 2023
M-A | Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis
23 Mar, 2023 | 12:50h | UTCNews Release: New Algorithms Could Improve Pediatric Tuberculosis Diagnosis – Yale School of Public Health
Commentary from the author on Twitter (thread – click for more)
1/ Excited to share our #openaccess work in @LancetChildAdol where we evaluate existing algorithms and develop pragmatic, evidence-based algorithms to support evaluation for #pediatric pulmonary #tuberculosis
Link: https://t.co/tjDkk9xJm2
A summary 🧵
— Kenneth Gunasekera (@kennyguna) March 16, 2023
Review | Evidence-based approach to diagnosis and management of abdominal tuberculosis
16 Mar, 2023 | 13:17h | UTCEvidence-based approach to diagnosis and management of abdominal tuberculosis – Indian Journal of Gastroenterology (if the link is paywalled, try this one)
Commentary from the author on Twitter
Our review on abdominal tuberculosis, where we summarise all the evidence on gastrointestinal tuberculosis and peritoneal tuberculosis, has been published in @ijg_journal
Great effort by @JhaDayakrishna and @menon_mythilihttps://t.co/spPXILGNw2 pic.twitter.com/SxnGs0n9DE— Vishal Sharma (@drvishal82) March 11, 2023
RCT | An initial 8-week bedaquiline-linezolid regimen shows promise for the treatment of rifampin-susceptible tuberculosis
22 Feb, 2023 | 12:50h | UTCSummary: This randomized trial compared a standard 6-month rifampin-based tuberculosis treatment to a strategy that involved shorter initial treatment with extended therapy for persistent disease, monitoring, and retreatment for relapse. The results showed that the strategy involving an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for clinical outcomes. The experimental strategy was associated with a shorter total duration of treatment with no evident safety concerns.
Article: Treatment Strategy for Rifampin-Susceptible Tuberculosis – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Shorter drug regimen shows promise in TB trial – CIDRAP
Review | Contemporary pharmacotherapies for nontuberculosis mycobacterial infections
17 Feb, 2023 | 13:03h | UTC
Review | Female genital tuberculosis
16 Feb, 2023 | 14:42h | UTCFemale Genital Tuberculosis – Open Forum Infectious Diseases
M-A | Assessing the diagnostic performance of new commercial IGRAs for Mycobacterium tuberculosis infection
24 Jan, 2023 | 14:25h | UTC
Commentary on Twitter
Assessing the diagnostic performance of new commercial IGRAs for Mycobacterium tuberculosis infection: a systematic review and meta-analysis
✅ Just Accepted
🔓 Open Access
🔗 https://t.co/8eO3ugZdfl pic.twitter.com/Fc2AjJyIw9— Clinical Infectious Diseases (@CIDJournal) January 23, 2023
Brief review and algorithm | Management of latent tuberculosis infection
23 Jan, 2023 | 13:35h | UTCManagement of Latent Tuberculosis Infection – JAMA (free for a limited period)
Consensus statement | Use of a 4-month treatment regimen for drug susceptible TB in children with uncomplicated disease
18 Jan, 2023 | 14:25h | UTC
RCT | A 24-week, all-oral regimen for rifampin-resistant tuberculosis
12 Jan, 2023 | 13:27h | UTCA 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis – New England Journal of Medicine
Commentary: Trial results show superiority of shorter, all-oral treatment for drug-resistant TB – CIDRAP