Drug susceptibility testing (DST) is essential for starting people on effective tuberculosis (TB) regimens.

Ethambutol, a longstanding treatment for tuberculosis (TB), lacks comprehensive pharmacokinetic (PK) data, particularly regarding covariates affecting exposure and their link to treatment outcomes. Using the largest data to date from Study 31/AIDS Clinical Trials Group A5349, we aimed to characterize ethambutol PKs, identify risk factors for lower exposure, quantify relationships between exposure and efficacy and safety outcomes, and explore dosing considerations that optimize risks and benefits.MethodsWe analyzed ethambutol PK data using nonlinear mixed-effect modeling. We evaluated the contribution of ethambutol exposure to efficacy outcomes using parametric time-to-event modeling and safety outcomes using logistic regression.ResultsIn 1493 participants with 3077 plasma samples, a one-compartment model with first-order elimination best described ethambutol PKs, with diabetes, higher creatinine clearance, and higher weight linked to increased clearance. Higher ethambutol exposure was modestly associated with grade 3 or higher adverse events and a reduced risk of TB-related unfavorable outcomes. Target exposures for 95% cure were 8.9 µg·h/mL in the 6-month control regimen and 25.6 µg·h/mL in the 4-month rifapentine regimen. Simulations showed that reducing doses in middle (1200 to 1000 mg) and highest (1600 to 1200 mg) weight bands could equalize median exposures, lowering toxicity risk while maintaining efficacy in the control regimen, but might not achieve target exposure in the rifapentine regimen.ConclusionsThe contribution of ethambutol exposure is regimen-dependent, with a higher efficacy target required for the 4-month rifapentine regimen. Dose reductions for patients above 55 kg may mitigate toxicity in standard therapy but risk compromising efficacy in the shorter regimen.

Limited data exist on the treatment outcomes of a two-drug daily regimen of macrolide and ethambutol in patients with Mycobacterium avium complex pulmonary disease (MAC-PD).

India on Monday advanced an anti-dumping investigation into imports from China and Thailand of Ethambutol Hydrochloride, an active pharmaceutical ingredient used in anti-tuberculosis drugs, by releasing a list of registered interested parties.

Current guidelines recommend ethambutol as a first-line agent for treating Mycobacterium avium complex pulmonary disease (MAC-PD) but can induce optic neuropathy. Previous studies suggest that low-dose ethambutol may reduce the incidence of optic neuropathy without compromising its effectiveness, but have not adequately adjusted for risk factors for optic neuropathy. We investigated the association between low-dose ethambutol therapy and optic neuropathy in patients with MAC-PD.MethodsThis retrospective cohort study included patients treated for MAC-PD at Kameda Medical Center between April 2003 and July 2024. Patients were categorized into low-dose (<12.5 mg/kg/day) and high-dose (≥12.5 mg/kg/day) ethambutol groups. The primary outcome was the incidence of optic neuropathy. Secondary outcomes included failure of negative culture conversion and macrolide resistance. Propensity score-based overlap weighting was used to adjust for patient characteristics and outcomes were compared using datasets generated through bootstrap resampling.ResultsOf 223 patients, 79 received low-dose (10.7 mg/kg/day) and 144 received high-dose ethambutol (15.4 mg/kg/day). None of the patients in the low-dose group and 4.8% in the high-dose group developed optic neuropathy. After adjustment, the risk of optic neuropathy was significantly lower in the low-dose ethambutol group (risk difference: −17.1%, 95% CI: −32.9% to −5.4%), but the risk difference for failure of negative culture conversion and macrolide resistance did not differ significantly between groups (−20.0%, 95% CI: −45.6% to 2.5%; and −4.9%, 95% CI: −13.5% to 0.0%, respectively).ConclusionsLow-dose ethambutol therapy may reduce the risk of optic neuropathy without compromising treatment outcomes, offering a safer option for MAC-PD.

Lupin Pharmaceuticals has reached a settlement with multiple states to resolve allegations that it conspired with G&W Laboratories Inc. to raise prices of the tuberculosis drug Ethambutol during a supply...

A clofazimine-ethambutol-macrolide regimen showed similar results to the standard rifampicin-ethambutol-macrolide regimen and should be considered in the treatment of MAC-PD. The frequency of adverse ...

Limited data exist on the treatment outcomes of a 2-drug daily regimen of macrolide and ethambutol in patients with Mycobacterium avium complex pulmonary disease (MAC-PD).MethodsAn outcome analysis was performed on 108 patients with MAC-PD who underwent at least 12 months of treatment with macrolides and ethambutol. Microbiological responses, antibiotic resistance rates, and recurrence rates linked to the regimen were analyzed.ResultsThe median overall treatment duration for 108 patients was 13.2 months (interquartile range 12.1–14.6 months). A total of 72 (67%) patients achieved culture conversion and microbiological cure, with a median time to culture conversion of 1.7 months (interquartile range 1.2–4.0 months). A clinical cure was observed in 11 patients; thus, 83 (77%) patients demonstrated a favorable overall response. In the multivariate analysis models adjusted for important clinical variables, no clinical factors were significantly associated with culture conversion. Among patients who failed to achieve culture conversion, macrolide resistance developed in 2 of 18 patients (11%) who had both pre- and posttreatment isolates available. In 2 other patients who failed culture conversion, the minimum inhibitory concentration for ethambutol in the posttreatment isolates increased to ≥8 μg/mL, which was considered resistant. Of the 72 patients who achieved a microbiological cure, 16 (22%) experienced recurrence during follow-up.ConclusionsThe 2-drug daily regimen of macrolides and ethambutol showed moderate efficacy in treating MAC-PD when used for >12 months. However, macrolide resistance occurred in some refractory cases, and recurrence was noted even after successful treatment, highlighting the need for close follow-up.

Tuberculosis (TB) and HIV infections remain global emergencies with co-infection frequently occurring (1). In 2023, an estimated 10.7 million people developed TB disease worldwide, 3.6 million of whom...