Treatment of tuberculosis infection (TBI) is a key pillar of the World Health Organization End TB Strategy. Two short-course rifamycin-based regimens—3 months of weekly isoniazid plus rifapentine (3HP) and 4 months of daily rifampicin (4RIF)—are widely recommended; however, they have not previously been directly compared in a randomized controlled trial. We compared treatment completion between 3HP and 4RIF among individuals with TBI.MethodsWe conducted a multicenter, open-label, parallel-group randomized controlled trial across 7 tuberculosis clinics in Sydney, Australia, between July 2019 and June 2024. Participants of any age with TBI were randomized 1:1, stratified by site, to receive either weekly 3HP or daily 4RIF. All doses were self-administered. Participants in the 3HP group received weekly Short Message Service (SMS) adherence reminders; both groups received standard clinic follow-up. The primary outcome was treatment completion, defined as ingestion of ≥90% of prescribed doses. Analyses were conducted on an intention-to-treat basis.ResultsA total of 210 participants were enrolled (106 assigned to 3HP and 104 to 4RIF). Treatment completion was significantly higher in the 3HP group (84.9%) than in the 4RIF group (65.4%; relative risk, 1.30 [95% confidence interval, 1.22–1.38]; P < .001). Adverse events of any grade occurred in 24.5% of participants receiving 3HP and 20.2% receiving 4RIF. No treatment-related deaths were reported.ConclusionsWeekly 3HP supported by SMS reminders achieved significantly higher treatment completion than daily 4RIF, with similar safety. These findings support broader implementation of 3HP to optimize adherence and outcomes in TBI treatment programs.Clinical Trials RegistrationAustralian New Zealand Clinical Trials Registry (ACTRN12618001672246).

Shortened all-oral regimens for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) combine multiple QTc prolonging agents, including bedaquiline and delamanid, which act partly through hERG potassium channel binding. Promethazine, a first-generation antihistamine used for nausea during TB therapy, shares this mechanism. Whether adjunctive promethazine further raises the risk of clinically relevant QTc prolongation in this setting is unclear.MethodsWe conducted secondary analyses from a prospective observational cohort study of patients ≥15 years in Lesotho who received a 9- to 12-month all-oral regimen (bedaquiline, linezolid, levofloxacin, clofazimine, delamanid) for pulmonary MDR/RR-TB. We modelled time-varying promethazine exposure using the Andersen-Gill formulation of Cox regression, with time-to-first grade ≥3 (>500 ms) QTc event as the outcome of interest. We conducted comparator analyses with time-varying exposure to metoclopramide, ondansetron, and episodes of nausea, dizziness, and vomiting.ResultsAmong 247 participants (median age 41, 63.2% living with HIV), 62 (25.1%) received promethazine. Grade ≥3 QTc prolongation occurred in 10 (4.0%). Incident clinically significant QTc prolongation was higher during promethazine-exposed than unexposed periods (7.4 versus 1.3 per 10 000 person-days; HR 7.0, 95% CI: 1.4–35.3). No comparable elevation was seen in analyses of exposure to metoclopramide (HR 1.0, 95% CI: 0.3–3.6), ondansetron, or episodes of nausea, dizziness, or vomiting (HR 1.5, 95% CI: 0.3–6.9).ConclusionsPromethazine use was associated with increased risk of clinically relevant QTc prolongation within a QTc-burdened all-oral MDR/RR-TB regimen. These findings provide preliminary evidence that clinicians may consider when selecting anti-emetics as part of MDR/RR-TB therapy with a shortened all-oral regimen and highlight the importance of evaluating adjunctive medications in DR-TB care.

Depletion of Wolbachia has proven to be a validated curative treatment for filariasis. This trial investigated alternatives to the current treatment regimen for onchocerciasis: 6 weeks of doxycycline (DOX) at 200 mg daily.MethodsThis randomized, placebo-controlled, double-blind, phase 2a trial with 5 treatment regimens was conducted in Ghana to determine (1) whether treatment times could be shortened as compared with 6 weeks of DOX at 200 mg daily by using a combination of DOX and rifampicin (RIF) for 3 weeks or (2) whether a dosage reduction to 6 weeks of DOX at 100 mg or a change to 6 weeks of RIF at 10 mg/kg daily would result in noninferior efficacy.ResultsThe primary outcome—the absence of onchocercomata with worms showing normal embryogenesis at 20 months—revealed that DOX at 200 mg or 100 mg for 6 weeks was superior to all other interventions. DOX + RIF for 3 weeks was less effective but superior to RIF alone and to placebo, suggesting that shorter regimens can be designed by combining antiwolbachials. Finally, depletion of Wolbachia in nodules 6 months after study onset strongly correlated with antiparasitic effects at 20 months.ConclusionsReduction of DOX from 200 to 100 mg daily facilitates implementation of this regimen, by aligning it to other regimens using 100 mg daily with a larger safety profile. The results also indicate that a combination of antiwolbachials might deliver effective regimens with shorter treatment times. Finally, the ability to predict 20-month end points of the slow-acting antiwolbachials by using Wolbachia depletion at 6 months will accelerate follow-up end points earlier than macrofilaricidal end points.

To the  Editor—Tuberculous meningitis (TBM) remains the deadliest form of infection caused by Mycobacterium tuberculosis. Early diagnosis and prolonged treatment are essential to reduce mortality and long-term neurological sequelae. Optimizing drug dosing to ensure adequate central nervous system (CNS) exposure is a key strategy to improve treatment outcomes [1]. Standard doses of rifampicin yield low cerebrospinal fluid (CSF) concentrations, prompting several studies to investigate whether higher rifampicin doses can enhance CNS penetration [2].

To  The  Editor—Hughes and colleagues report intensive pharmacokinetic (PK) and safety data for clofazimine in pregnant and postpartum women treated for rifampicin-resistant tuberculosis (RR-TB) in South Africa [1]. In 11 women receiving 100 mg daily (64% with HIV), third-trimester exposure was higher than early postpartum: AUClast and Cmax were ∼30% greater in paired comparisons [1]. Importantly, postpartum Cmax only modestly exceeded the commonly cited 0.25 µg/mL bactericidal concentration even after a median 35 weeks of therapy [1]. For clinicians, the headline is not “higher pregnancy exposure,” but a postpartum exposure dip that could mark a vulnerable window when treatment durability and adherence are most at risk.

3 key findings from the brucellosis trial: (1) Sitafloxacin matched dual-therapy efficacy; (2) Fewer adverse events & better tolerability; (3) Single-agent dosin…

Rifampicin-resistant tuberculosis (RR-TB) remains a major public health challenge in TB-endemic regions. While social determinants of health affect infectious disease outcomes, their impact on RR-TB remains poorly understood. This study evaluated the relationship between educational attainment, social disadvantage, and RR-TB outcomes.MethodWe conducted a retrospective cohort study using data from 4 Centre for the AIDS Programme of Research in South Africa RR-TB clinical trials. Social vulnerability was measured using an exploratory Social Disadvantage Score (SDS) that incorporated education, employment, and incarceration. We used a latent class analysis (LCA) to identify classes with shared social vulnerability indicators. Associations with treatment outcomes were assessed using Cox regression models, with the exploratory SDS, its component indicators, and derived latent classes as predictors.ResultsEducation was not independently associated with unfavorable treatment outcomes (adjusted hazard ratio [aHR] = 1.39, 95% confidence interval [CI]: 0.96–1.99, P = .077), whereas a history of incarceration doubled the hazard (aHR = 2.05, 95% CI: 1.33–3.16, P < .001). Restricting subsequent models to the subcohort with collected employment data, unemployment increased the hazard of unfavorable outcomes (aHR = 1.84, 95% CI: 1.20–2.82, P = .005). Using the same subcohort, increasing cumulative social disadvantage showed a strong dose–response relationship, with a 5-fold higher hazard for 3 disadvantages (aHR = 5.85, 95% CI: 2.73–12.56, P < .001). Latent class analysis revealed that Class 2 (moderate socioeconomic advantage) had a significantly higher hazard of unfavorable outcomes (aHR = 1.82, 95% CI: 1.19–2.79, P = .006).ConclusionsCumulative social risk score was associated with unfavorable RR-TB outcomes, supporting further evaluation of targeted support for disadvantaged populations.

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Contraception is a medical decision in its own right. Here is what the evidence actually shows about hormonal methods and HS, a method-by-method comparison, and the rifampicin interaction worth knowing before you decide.

HS is not primarily a bacterial infection, yet antibiotics remain one of its most common treatments. Here is why that isn't a contradiction, how doxycycline, clindamycin and rifampicin are actually used, and why antibiotic resistance deserves its own conversation.

500,000 people contract brucellosis annually, mostly in endemic regions. A landmark trial shows a simplified single-agent regimen could improve treatment outc…

In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced....

People living with HIV are significantly more likely to develop multi-drug or rifampicin- resistant tuberculosis (TB) during treatment, ... View article...

500,000 people contract brucellosis annually, mostly in endemic regions. A landmark trial shows a simplified single-agent regimen could improve treatment outc…

AbstractTuberculosis (TB) treatment in patients with acute intermittent porphyria (AIP) is challenging because several first-line antituberculous drugs can precipitate porphyric crises, and evidence to guide management is limited.We describe a 26-year-old woman with peritoneal TB who developed acute abdominal pain, hyponatraemia, seizures, and neuropsychiatric manifestations within 24 hours of standard isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E) therapy. AIP was confirmed by elevated urinary porphobilinogen levels, and the patient required hemin for the acute crises. Antituberculous therapy was modified to a rifampicin-free regimen including moxifloxacin, linezolid, and ethambutol; isoniazid was cautiously reintroduced once the patient had stabilised.Recurrent porphyric crises and treatment-related toxicity ultimately led to therapy discontinuation after 167 doses. The patient achieved substantial neurological recovery without TB relapse after one year of follow-up.This case illustrates the need to balance TB control with porphyria safety, and to consider acute hepatic porphyria when patients develop unexplained abdominal pain, hyponatraemia, or neurological symptoms after starting antituberculous therapy. Rifampicin and isoniazid carry the highest porphyrinogenic risk, whereas moxifloxacin, ethambutol, and linezolid appear to be safer alternatives. Given limited evidence and the absence of standardised protocols for this rare coexistence, we offer a pragmatic framework to support shared decision-making in tuberculosis and porphyria.

SVOA Microbiology (SVOA-MB) ISSN 2634-534X is a peer-reviewed journal welcomes original research articles, reviews, mini-reviews, perspectives, and commentaries. It encourages submissions from researc...

A multicenter RCT in The Lancet Regional Health – Western Pacific shows sitafloxacin monotherapy is non-inferior to doxycycline–rifampicin for acute uncompli…

The Journal of Antibiotics - From milk to rifampicin and back again: history of failures and successes in the treatment for tuberculosis

A multicenter RCT in The Lancet Regional Health – Western Pacific shows sitafloxacin monotherapy is non-inferior to doxycycline–rifampicin for acute … #Antibiotics #Brucellosis #Clinicaltrial #Fluoroquinolones #Infectiousdiseases