Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline

Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals. Copyright © 2025 by the American Thoracic Society

Culture Conversion Among HIV Co-Infected Multidrug-Resistant Tuberculosis Patients in Tugela Ferry, South Africa

Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting.Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count.Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy.With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment

Towards better guidance on caseload thresholds to promote positive tuberculosis treatment outcomes:a cohort study

BACKGROUND: In low-incidence countries, clinical experience of tuberculosis is becoming more limited, with potential consequences for patient outcomes. In 2007, the Department of Health released a guidance 'toolkit' recommending that tuberculosis patients in England should not be solely managed by clinicians who see fewer than 10 cases per year. This caseload threshold was established to try to improve treatment outcomes and reduce transmission, but was not evidence based. We aimed to assess the association between clinician or hospital caseload and treatment outcomes, as well as the relative suitability of making recommendations using each caseload parameter. METHODS: Demographic and clinical data for tuberculosis cases in England notified to Public Health England's Enhanced Tuberculosis Surveillance system between 2003 and 2012 were extracted. Mean clinician and hospital caseload over the past 3 years were calculated and treatment outcomes grouped into good/neutral and unfavourable. Caseloads over time and their relationship with outcomes were described and analysed using random effects logistic regression, adjusted for clustering. RESULTS: In a fully adjusted multivariable model (34,707 cases)there was very strong evidence that management of tuberculosis by clinicians with fewer than 10 cases per year was associated with greater odds of an unfavourable outcome compared to clinicians who managed greater numbers of cases (cluster-specific odds ratio, 1.14; 95 % confidence interval, 1.05-1.25; P = 0.002). The relationship between hospital caseload and treatment outcomes was more complex and modified by a patient's place of birth and ethnicity. The clinician caseload association held after adjustment for hospital caseload and when the clinician caseload threshold was reduced down to one. CONCLUSIONS: Despite the relative ease of making recommendations at the hospital level and the greater reliability of recorded hospital versus named clinician, our results suggest that clinician caseload thresholds are more suitable for clinical guidance. The current recommended clinician caseload threshold is functional. Sensitivity analyses reducing the threshold indicated that clinical experience is pertinent even at very low average caseloads, which is encouraging for low burden settings

The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis

Tuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV. Meta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations from relevant articles, and reviewed conference proceedings. Multivariate hazard ratios (HR) of mortality in PLWH with and without tuberculosis, estimated in individual cohort studies, were pooled using random effect weighting according to "Der Simonian Laird method" if the p-value of the heterogeneity test was <0.05. Fifteen cohort studies were systematically retrieved. Pooled overall analysis of these 15 studies estimating the effect of tuberculosis on mortality in PLWH showed a Hazard Ratio (HR) of 1.8 (95% confidence interval (CI): 1.4-2.3). Subanalysis of 8 studies in which the cohort was not exposed to highly active antiretroviral therapy (HAART) showed an HR of 2.6 (95% CI: 1.8-3.6). Subanalysis of 6 studies showed that tuberculosis did not show an effect on mortality in PLWH exposed to HAART: HR 1.1 (95% CI: 0.9-1.3). These results provide an indication of the magnitude of benefit to an individual that could have been expected if tuberculosis had been prevented. It emphasizes the need for additional studies assessing the effect of preventing tuberculosis or early diagnosis and treatment of tuberculosis in PLWH on reducing mortality. Furthermore, the results of the subgroup analyses in cohorts largely exposed to HAART provide additional support to WHO's revised guidelines, which include promoting the initiation of HAART for PLWH co-infected with tuberculosis. The causal effect of tuberculosis on mortality in PLWH exposed to HAART needs to be further evaluated once the results of more cohort studies become availabl

Pharmacokinetic drug evaluation of rifaximin for treatment of diarrhea-predominant irritable bowel syndrome

Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-negative and -positive bacteria. It is active in the small intestine due to its high bile solubility, whereas in the aqueous environment of the colon, it shows limited efficacy against highly susceptible bacteria. These unique pharmacokinetic properties limit its systemic effects and can correct gut microflora imbalances. Thus, rifaximin has become a major therapeutic agent in several gastrointestinal diseases in which an imbalance in gut microflora may play a role, including diarrhea predominant irritable bowel syndrome (IBS-D). Area covered: This is an up-to-date review focusing on the efficacy of rifaximin in the treatment of IBS-D in both adult and pediatric populations. We will review the pharmacokinetic properties of rifaximin, including its absorption in health and disease, mechanisms of action, and interactions with other drugs. Expert opinion: Given its safety profile and its negligible absorption, rifaximin is a suitable treatment for IBS-D, in both adults and children. The possibility of modulating gut microbiota composition without side effects has made this drug an appealing therapeutic agent in highly prevalent gastrointestinal diseases. However, to date, monitoring for the development of resistant bacterial strains during long-term rifaximin use is still lacking