Antimicrobial resistance is one of the world's top public health threats. Often termed a silent pandemic, antimicrobial-resistant bacteria have caused millions of deaths annually.

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.

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Clofazimine demonstrates an acceptable tolerability profile when used for the management of patients with NTM infections.

Clofazimine is commonly included in multidrug regimens for children with multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB), but accurate pediatric dosing has been limited by 100-mg soft-gel capsules that cannot be reliably divided. We evaluated the exposure and safety of a novel 50-mg clofazimine tablet using revised once-daily weight-banded dosing informed by a previous study (Clofazimine PK1).MethodsChildren <18 years weighing <30 kg receiving MDR/RR-TB treatment, including clofazimine, were enrolled. Sparse and semi-intensive pharmacokinetic sampling was completed at baseline and at weeks 2 and 12. Model-predicted weekly steady-state area-under-the-curve (wAUCss) was compared with an adult target of 111.79 mg·h/L. Safety monitoring included clinical, laboratory, and electrocardiogram (ECG) monitoring.ResultsTwelve children were included (median age 2.8 years; range 0.6–8.2). Median predicted wAUCss was 106 mg·h/L (range 76.9–274), within 25% of target. Two grade 3 adverse events (drug-induced liver injury and skin hyperpigmentation) possibly related to clofazimine, but no other clofazimine-related serious adverse events, were observed, The Fridericia corrected QT (QTcF) interval typically increased with 0.042 ms per1-µg/L increase in clofazimine concentration; five QTcF prolongations (>460–480 ms) occurred in three participants.ConclusionsThe revised once-daily dosing with the 50-mg clofazimine tablet achieved the predefined exposure target. Clinically important adverse events support cautious use with ECG and laboratory monitoring and further evaluation before broad adoption.Clinical Trials RegistrationSouth African National Clinical Trials Register (https://sanctr.samrc.ac.za/; DOH-27-0620-6415).

AbstractTuberculous meningitis causes substantial mortality due to limited penetration of antibiotics to the central nervous system and excessive neuroinflammation. This study evaluated clofazimine as an adjunct to the standard first-line tuberculosis regimen, in a mouse model. Mice were infected intracerebrally with Mycobacterium tuberculosis and treated for 6 weeks. Addition of clofazimine markedly reduced the brain bacterial burden, achieving measurable brain tissue concentrations despite minimal cerebrospinal fluid penetration, as well as attenuated brain tissue inflammation. These findings indicate that clofazimine enhances bactericidal activity of the standard regimen and mitigate neuroinflammation, supporting further investigation and clinical evaluation for tuberculous meningitis.

Journal of Mass Spectrometry, Volume 61, Issue 8, August 2026.

Bedaquiline, pretomanid, and linezolid (BPaL) is a 6-month regimen that has revolutionized treatment of multidrug-resistant (MDR) tuberculosis (TB). However, there is limited evidence of using BPaL to treat MDR tuberculous meningitis (TBM), a devastating illness that has high risk of mortality and permanent disability.MethodsA patient with fluoroquinolone-resistant pre–extensively drug-resistant (pre-XDR) TBM was cured with a 10-month regimen based on BPaL with clofazimine and cycloserine. Total concentrations of bedaquiline, pretomanid, and linezolid were measured in plasma and cerebrospinal fluid (CSF) via ultraperformance liquid chromatography. Unbound concentrations were estimated from plasma concentrations and CSF concentrations normalized to plasma protein concentrations using the Winter–Tozer formula. AUC24 (24-hour area under the curve) was calculated using the trapezoidal method.ResultsThe CSF:plasma unbound AUC24 was 1.48 and 0.99 for pretomanid and linezolid, respectively. Pharmacokinetic/pharmacodynamic targets were achieved for pretomanid with CSF concentration above the critical concentration of 0.5 mg/L throughout most of the dosing interval and linezolid AUC24/minimum inhibitory concentration (MIC) of 171 for an MIC of 0.5 mg/L. However, CSF concentrations of pretomanid and linezolid may be below target for strains with MICs >0.5 mg/L. Estimated unbound peak concentrations in CSF in week 21 were comparable to plasma (0.0034 mg/L and 0.0032 mg/L, respectively), suggesting that therapeutic central nervous system concentrations of bedaquiline were achieved.ConclusionsFluoroquinolone-resistant pre-XDR TBM was cured with 10 months of treatment based on BPaL with clofazimine and cycloserine. BPaL achieved therapeutic concentrations in CSF for most TB strains. Further research is required into optimal treatment and dosing of drug-resistant TBM.

The exposure and both Mycobacterium tuberculosis clearance rates and toxicity relationships of bedaquiline-pretomanid-linezolid- (BPaL), BPaL-clofazimine (BPaLC) and BPaL-moxifloxacin (BPaLM) for treatment of rifampicin-resistant tuberculosis remain understudied. Therefore, the relationship between the patients’ exposure to anti-TB drugs in TB-PRACTECAL trial investigational regimens and their treatment outcomes was investigated. PRACTECAL-PKPD was a prospective pharmacokinetics and pharmacodynamics study. Patients with rifampicin-resistant tuberculosis were enrolled from Belarus and South Africa. Antimicrobial exposures for bedaquiline, pretomanid, linezolid, moxifloxacin and clofazimine were adequately estimated, were within the ranges of previously published studies but did not correlate with the speed of sputum bacterial clearance. When compared to the standard of care (SoC) arm, a 20% increased bacillary killing rate with BPaLM was observed, whilst BPaL and BPaLC displayed a 15% d

The Phase III BEAT TB trial showed that a shorter, 6-month, all-oral treatment regimen (consisting of bedaquiline, delamanid, linezolid, and levofloxacin or clofazimine or both) demonstrated noninferiority to the longer 9-month standard-of-care regimen for patients with pulmonary rifampicin-resistant TB. The study confirmed that this new, simplified regimen can be safely utilized across entire households, including children and pregnant or breastfeeding women, expanding vital treatment options for these vulnerable populations. Read the full news story here. SEE ALSO: University of the Witwatersrand: South Africa’s TB research changes global medical practice GroundUp: Important advance in TB treatment The Clinical Trial Vanguard: The 6-month RR-TB trial the FDA should be studying as a pragmatic design blueprint For more TB updates, check out the TB CAB Weekly Newsletter (Issue #19, 30 June 2026)...

RIMOXCLAMIN, a new antibiotic regimen for Hansen's disease (HD), combines rifampicin, moxifloxacin, clarithromycin, and minocycline; the WHO-MDT combines rifampicin, dapsone, and clofazimine. To overcome limitations of WHO-MDT, we evaluated both regimens in a 2-arm cohort of multibacillary patients.MethodsTwo-arm observational cohort included 162 newly diagnosed multibacillary cases (103 RIMOXCLAMIN and 59 WHO-MDT) evaluated between 2015 and 2025. Patients were assessed at least quarterly (baseline and months 3, 6, and 12) for neurological and cutaneous findings, adverse events, tactile sensitivity, and physical disability grade (PDG).ResultsNeurological symptoms were frequent regardless of lesion count (≤5 vs > 5; P > .05). RIMOXCLAMIN demonstrated a greater reduction in nerve thickening than WHO-MDT (P < .0001) and increased PDG-0 from 18% to 82% (P < .0001), compared with 22%–53% in the WHO-MDT group (P = .0006). RIMOXCLAMIN reduced PDG-2 by 67% at month 6 (P = .002) and 83% at discharge (P < .0001), whereas WHO-MDT showed no change at month 6 and a 50% reduction at discharge. At month 3, neurological symptoms were greater in the RIMOXCLAMIN group than in the WHO-MDT, with no intragroup differences. WHO-MDT showed higher adverse events, including severe anemia (requiring dapsone discontinuation in 33.9% [20/59]). RIMOXCLAMIN adverse events were mild, requiring regimen adjustments in 19.4% (20/103) without additional medications. A general limitation is that the groups are not fully socioeconomically comparable.ConclusionsRIMOXCLAMIN was safe and clinically advantageous as a first-line HD regimen, offering faster neurological recovery, disability reversal, and minimal adverse event. These findings support incorporating neurological parameters of skin sensory changes, as lesion count alone does not appear to be a reliable marker of the clinical and neurological severity.

Two lung disease specialists are accusing Health Canada of shortening some patients' lives, by denying them access to an inexpensive, relatively harmless drug not sold in Canada.

There is limited experience of the all-oral 6-month regimens containing bedaquiline, delamanid, linezolid, and levofloxacin or clofazimine (BDLLfx/BDLCfz) in pregnant women with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We report maternal treatment, pregnancy, and infant outcomes to 12 months of age in a cohort of pregnant women treated with these regimens.MethodsWe included pregnant women treated for MDR/RR-TB from September 2023 to January 2025 in KwaZulu-Natal, South Africa, in a prospective observational study. Outcomes were collected through ongoing record reviews. Infant clinical assessments were conducted at 6 weeks, 6 months, and 12 months.ResultsOf 25 pregnant women with MDR/RR-TB, 21 received BDLLfx/BDLCfz; 12 (57%) were diagnosed with human immunodeficiency virus. Although 10 of the 21 (48%) treated women developed anemia, 18 (86%) had favorable treatment outcomes. All 21 infants were born alive, with a median gestational age 39 weeks (interquartile range [IQR], 38–40 weeks) and median birth weight 3160 g (IQR, 2818–3308 g). Three women had unfavorable pregnancy outcomes, with infants born prematurely (2 with low birth weight and 1 who developed respiratory distress syndrome). Of the 18 infants evaluated at 12 months, 10 (56%) had possible or confirmed unfavorable outcomes. Two infants had confirmed congenital anomalies and 3 possible congenital anomalies, but only 1 had first-trimester drug exposure. One infant died, another was diagnosed with MDR/RR-TB and started on treatment, and 3 infants had signs/symptoms of tuberculosis, necessitating referral for care.ConclusionsThese limited data suggest that in pregnant women, the BDLLfx/BDLCfz regimens have improved treatment and pregnancy outcomes compared to prior regimens. However, there is a high prevalence of unfavorable infant outcomes.

Nature Microbiology, Published online: 13 May 2026; doi:10.1038/s41564-026-02331-5Forward and reverse genetics identifies the mode of action of clofazimine in the parasite Cryptosporidium. The genomic locus encoding the target is heterogeneous, and a resistance-conferring allele is already widely distributed.