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Background The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. Methods We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models; and all trial-defined safety outcomes using logistic regression. Results Our model-derived rifampicin exposure ranged from 4.57 mg · h/L to 140.0 mg · h/L with a median of 41.8 mg · h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to the weight-banded dose. Exposure-efficacy analysis (n = 680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared with those with exposure above the median. Exposure-safety analysis (n = 722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events or serious adverse events. Conclusions Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard-of-care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation. [ABSTRACT FROM AUTHOR]

Background A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14–86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen. [ABSTRACT FROM AUTHOR]

Background Few studies have examined the burden of postacute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in low- and middle-income countries. We sought to characterize PASC with self-reported questionnaires and clinical examinations of end-organ function in Lima, Peru. Methods From January to July 2021, we recruited participants at least 8 weeks after COVID-19 diagnosis from a case registry in Lima, Peru. We evaluated participants for PASC with questionnaires, neuropsychiatric evaluations, chest X-ray, spirometry, electrocardiogram, and echocardiogram. We used multivariable models to identify risk factors for PASC. Results We assessed 989 participants for PASC at a median 4.7 months after diagnosis. Clinically significant respiratory symptoms were reported by 68.3% of participants, particularly those who had been severely ill during acute COVID-19, and were associated with cardiac findings of ventricular hypertrophy or dilation on echocardiogram. Neuropsychiatric questionnaires were consistent with depression in 20.7% and cognitive impairment in 8.0%. Female sex and older age were associated with increased risk of respiratory (adjusted odds ratio [aOR], 2.36 [95% confidence interval {CI}, 1.69–3.31] and aOR, 1.01 [95% CI, 1.00–1.03], respectively) and neuropsychiatric sequelae (aOR, 2.99 [95% CI, 2.16–4.18] and aOR, 1.02 [95% CI, 1.01–1.03], respectively). Conclusions COVID-19 survivors in Lima, Peru, experienced frequent postacute respiratory symptoms and depression, particularly among older and female participants. Clinical examinations highlighted the need for cardiopulmonary rehabilitation among persons with severe COVID-19; psychosocial support may be required among all COVID-19 survivors. [ABSTRACT FROM AUTHOR]

We report severe acute respiratory syndrome coronavirus 2 antibody positivity among market and city bus depot workers in Lima, Peru. Among 1285 vendors from 8 markets, prevalence ranged from 27% to 73%. Among 488 workers from 3 city bus depots, prevalence ranged from 11% to 47%. Self-reported symptoms were infrequent. [ABSTRACT FROM AUTHOR]

Background Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking. Methods Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M abscessus disease in 2019. Results Four patients received omadacycline for the treatment of culture-positive M abscessus disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104–227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline's tolerability was acceptable for patients with M abscessus disease, with 1 patient discontinuing therapy in month 6 due to nausea. Conclusions Omadacycline is a novel oral option for the treatment of M abscessus disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline's definitive role in the treatment of M abscessus disease. [ABSTRACT FROM AUTHOR]

We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study of patients treated for multidrug-resistant tuberculosis in the Russian Federation, we found that monthly exposure to an aggressive multidrug-resistant tuberculosis regimen was a robust predictor of decreased risk of death or failure during treatment.Background. Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure.Methods. We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure.Results. Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis—MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents—we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29–.94]; P = .030).Conclusions. Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis is a dimorphic fungal infection endemic in Latin America. We report a patient with a history of pulmonary paracoccidioidomycosis who presented with relapsed disease in the central nervous system 4 years after initial treatment. We review current treatment strategies for paracoccidioidomycosis and neuroparacoccidioidomycosis. [ABSTRACT FROM AUTHOR]

We surveyed awardees of the Minority HIV Investigator Mentoring Program (MHIMP) of the AIDS Clinical Trials Group. Most reported clinical specialization in infectious diseases or HIV medicine (86%), and all but 1 (95%) are engaged in medical/health sciences research. The MHIMP helped retain early-career minority investigators in HIV/AIDS-related research. [ABSTRACT FROM AUTHOR]