Nontraditional Treatment of Hepatic Encephalopathy.

The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.

Diagnostic Performance of the ICD-10 Code K76.82 for Hepatic Encephalopathy in Patients With Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is prevalent and is associated with increased morbidity and mortality among patients with cirrhosis. On October 1, 2022, a new, specific International Classification of Diseases-10 code for HE, K76.82, was introduced. We aimed to analyze the diagnostic accuracy of K76.82. METHODS: Diagnostic performance of K76.82 for HE (sensitivity, specificity, positive predictive ratio, and negative predictive ratio) was evaluated in 2 large health systems compared with lactulose, rifaximin, and K72.90. RESULTS: A total of 2,483 patients were analyzed. The combination term "lactulose or rifaximin" showed the highest sensitivity of >98% while K76.82 demonstrated a specificity of >87% in all cohorts. DISCUSSION: Although K76.82 is promising, the combination term "lactulose or rifaximin" identified patients with HE more accurately.

Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy.

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review.

SUMMARYRifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although in vitro testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant Enterococcus in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between in vitro resistance and rifaximin-α efficacy.

Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.

[Real-world analysis of the use of rifaximin 200 mg in the Campania Region.] / Analisi real world sull'utilizzo di rifaximina 200 mg nella Regione Campania.

INTRODUCTION: Since its approval in Italy in 1987, rifaximin has been licensed in over 30 countries for the treatment of a wide range gastrointestinal diseases. The aim of the study was to analyze the real world use of rifaximin 200 mg in the Campania region. METHODS: An observation retrospective study was conducted analysing the prescriptions of rifaximin received by the subjects ≥18 years old resident in the Campania Region. For each user the first rifaximin prescription in 2019 was defined as index date. All the prescriptions during the 12 months following the index date were analyzed. The subjects were categorized according to the number of packages/year received (1-4, 5-12, 13-24, >24). RESULTS: 231,207 subjects received at least one package/year of rifaximin 200 mg with a prevalence of use of 4.9% and a total annual expenditure of 9.2 million euros. The 73.9% of users received 1-4 packages/year, 16.4% between 5-12 packages/year and 7.7% between 13-24 packages/year. The 2.0% of the users received more than 24 packages/year with an incidence on total expenditure equal to 14.8% (5% is due to those who received more than 40 packages/year). DISCUSSION: About two thirds of rifaximin users received no more than three packages, presumably for the treatment of the infectious gastroenteritis or diarrheal syndromes, while 24% received 5-24 packages/year probably for the relapsing chronic intestinal pathologies. The 15% of the expenditure and consumption is related to subjects receiving more than 24 packages/year, probably due to the treatment of chronic liver diseases. CONCLUSIONS: The use of rifaximin 200 mg should be further investigated in different recurrent chronic diseases, especially to verify which schemes and dosages are used in real life compared to those tested in clinical trials.

Efficacy and Safety of Rifaximin in the Prevention of Recurrent Episodes of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal endotoxemia. We aimed to investigate the preventive role of rifaximin in recurrent episodes of hepatic encephalopathy in cases with a history of hepatic diseases. METHODS: We searched PubMed, Scopus, and Web of Science for the relevant studies using the following search strategy: "(Rifaximin) OR (Xifaxan) AND (cirrhosis) OR (encephalopathy)." We assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: recurrence of hepatic encephalopathy, adverse events, mortality rate, and time to the first episode of hepatic encephalopathy from the time of randomization (days). We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was performed under the random-effects model. RESULTS: We analyzed data obtained from 999 patients from 7 included trials. The overall risk ratio proved that the rifaximin group was associated with a lower recurrence rate than the control group (risk ratio [RR] = 0.61[0.50, 0.73], P = .001). We found no significant variation in both groups regarding adverse events (RR = 1.08 [0.89, 1.32], P = .41), and mortality rates (RR = 0.98 [0.61, 1.57], P = .93). The overall risk of bias results was low. CONCLUSION: The meta-analysis showed that in patients allocated to the rifaximin group, the incidence rate of hepatic encephalopathy was significantly lower when compared with those in the control group with no difference in both groups regarding adverse events and mortality rates.

Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy.

INTRODUCTION: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. RESULTS: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. DISCUSSION: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.

Lack of Access to Rifaximin Upon Hospital Discharge Is Frequent and Results in Increased Hospitalizations for Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis. Rifaximin, added to lactulose, effectively maintains remission and reduces hospitalizations from HE compared with lactulose alone. Although the clinical evidence supports the use of rifaximin, concerns remain regarding the financial implications and subsequent impact on medication access and outcomes. OBJECTIVE: The goal of this study was to determine whether medication access to rifaximin at hospital discharge reduces readmission and office visits related to HE. METHODS: A retrospective study was conducted in compliance with local institutional review board including cirrhotic patients discharged with a rifaximin prescription for HE. Patients were stratified into 2 groups: those able to obtain rifaximin and those unable to obtain rifaximin upon discharge. The primary outcome was to evaluate the rate of HE recurrence in each group as defined as a composite of readmission or office visit for acute HE within 12 months of discharge. RESULTS: Access to rifaximin significantly reduced the risk of hospital admission and office visit for acute HE over 12 months. A hospitalization or office visit occurred in 24.5% of patients in the medication access group compared with 50% in the group without medication access. Only 58% of patients had access to rifaximin at discharge. CONCLUSION AND RELEVANCE: Rifaximin use was associated with significantly reduced risk of hospitalization and office visits for HE. At discharge, 42% of patients did not have access to rifaximin regardless of being prescribed the medication, identifying that copay is a significant barrier in allowing patients to have access to rifaximin.

Evaluation of Mycobacterium Avium Complex Pulmonary Disease Treatment Completion and Adherence to ATS/IDSA Guidelines.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. METHODS: We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. RESULTS: We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. CONCLUSIONS: Overall, nearly half of new MAC therapy users were prescribed a non-guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources.

Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials.

BACKGROUND & AIMS: Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment. METHODS: Two phase II, randomized, double-blind, placebo-controlled trials were conducted. Trial 1: outpatients with early decompensated cirrhosis randomized to placebo or rifaximin SSD once-nightly: IR 40 or 80 mg, SER 40 or 80 mg, or IR 80 mg plus SER 80 mg, for 24 weeks. Trial 2: inpatients with OHE randomized to lactulose plus placebo or rifaximin SSD: IR 40 mg once or twice daily or SER 80 mg once or twice daily for ≤14 days. Primary efficacy endpoint: time to cirrhosis complication-related hospitalization/all-cause mortality (Trial 1) or time to OHE resolution (Trial 2). RESULTS: In Trial 1 (n = 516), no significant difference in time to cirrhosis complication-related hospitalization/all-cause mortality vs placebo. In a post hoc analysis, time to all-cause hospitalization/all-cause mortality was improved with IR 40 mg vs placebo (15.4% [12/78] vs 27.7% [26/94]; P = .03). A Trial 2 prespecified interim analysis (n = 71) showed lactulose plus rifaximin SSD IR 40 mg bid significantly reduced median time to OHE resolution (21.1 hours) vs lactulose plus placebo (62.7 hours; P = .02). Trial 2 was subsequently terminated. CONCLUSION: Rifaximin SSD IR 40 mg may reduce hospitalizations in patients with cirrhosis and shorten duration of OHE during hospitalization-considered a negative finding, yet also hypothesis-generating. (ClinicalTrials.govNCT01904409; NCT03515044).

Add-on Therapeutic Effects of Rifaximin on Treatment-resistant Hepatic Encephalopathy.

Objective Rifaximin is used to treat hepatic encephalopathy. However, whether or not rifaximin and lactulose combination therapy can enhance the treatment outcomes and reduce the hospitalization rate of patients with hepatic encephalopathy that are resistant to lactulose has yet to be determined. The present study investigated the hospitalization rate before and after rifaximin add-on therapy in patients resistant to lactulose. Methods A total of 36 patients who were resistant to lactulose with add-on rifaximin therapy were enrolled. Patients who were hospitalized and/or did not achieve normalization of ammonia levels under lactulose administration were defined as treatment-resistant. The primary outcome was the change in hospitalization rate due to hepatic encephalopathy at 24 weeks before and after rifaximin administration. Results Before rifaximin administration, 15 (41.6%) patients were hospitalized due to hepatic encephalopathy. After rifaximin administration, 8 (22.2%) patients were hospitalized due to hepatic encephalopathy. The hospitalization rates were significantly reduced after rifaximin administration (p=0.02). The median (interquartile range) ammonia levels upon rifaximin administration (baseline) and 8, 12, and 24 weeks after rifaximin administration were 124 (24-310) µg/dL, 78 (15-192) µg/dL, 67 (21-233) µg/dL, and 77 (28-200) µg/dL, respectively. Furthermore, the ammonia levels were significantly reduced by rifaximin add-on therapy (p=0.005, p=0.01, and p=0.01). Conclusion The addition of rifaximin to lactulose treatment in treatment-resistant patients decreases the hospitalization rate among patients with hepatic encephalopathy and may be used as an add-on treatment.

Clinical Outcomes of Oral Zinc Therapy in Hepatic Encephalopathy Treatment.

BACKGROUND: Additional therapies for hepatic encephalopathy (HE) treatment are warranted. There are data evaluating the use of zinc for HE; however, clinical outcomes, specifically in the United States, are unknown. OBJECTIVE: To compare 30-day and 1-year all-cause readmission rates in patients with cirrhosis complicated by HE on lactulose and rifaximin to those on lactulose, rifaximin, and zinc. METHODS: This retrospective study included patients admitted with documented cirrhosis and home medications of lactulose and rifaximin, with or without zinc. Patients were stratified into 2 groups: those receiving lactulose and rifaximin for HE (control) and those receiving lactulose, rifaximin, and zinc for HE (treatment). The primary outcomes were 30-day and 1-year all-cause readmission rates. RESULTS: One-hundred fifty-seven patients were included (102 in control group, 55 in treatment group). Regarding 30-day and 1-year all-cause readmission rates, there was no difference between the control and treatment groups. CONCLUSION AND RELEVANCE: This is the first study conducted in the United States evaluating zinc for HE treatment. Zinc did not impact 30-day or 1-year all-cause readmission rates. Further studies are warranted to evaluate the potential benefit of zinc for HE, possibly in correlation with Model for End-stage Liver Disease-Sodium (MELD-Na) scores.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

Latent tuberculosis infection: approach and therapeutic schemes.

Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid.

Testing and Treating Mycobacterium tuberculosis Infection.

After infection with Mycobacterium tuberculosis, a minority of individuals will progress to tuberculosis disease (TB). The risk is higher among persons with well-established risk factors and within the first year after infection. Testing and treating individuals at high risk of progression maximizes the benefits of TB preventive therapy; avoiding testing of low-risk persons will limit potential harms. Several treatment options are available; rifamycin-based regimens offer the best efficacy-safety balance. In this review, we present an overview of the diagnosis and treatment of TB infection, and summarize common clinical scenarios.

Therapeutic efficacy of rifalazil (KRM-1648) in a M. ulcerans-induced Buruli ulcer mouse model.

Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans infection that requires long-term antibiotic treatment and/or surgical excision. In this study, we investigated the therapeutic efficacy of the rifamycin derivative, rifalazil (RLZ) (also known as KRM-1648), in an advanced M. ulcerans infection model. Six-week-old female BALB/c mice were infected with 3.25 x 104 colony-forming units (CFU) of M. ulcerans subcutaneously into the bilateral hind footpads. At 33 days post-infection, when the footpads exhibited significant redness and swelling, mice were treated orally with 5 or 10 mg/kg of RLZ for up to 15 weeks. Mice were followed for an additional 15 weeks following treatment cessation. Untreated mice exhibited a progressive increase in footpad redness, swelling, and erosion over time, and all untreated mice reached to endpoint within 5-8 weeks post-bacterial injection. In the RLZ-treated mice, footpad redness and swelling and general condition improved or completely healed, and no recurrence occurred following treatment cessation. After 3 weeks of treatment, the CFU counts from the footpads of recovered RLZ-treated mice showed a 104 decrease compared with those of untreated mice. We observed a further reduction in CFU counts to the detection limit following 6 to 15 weeks of treatment, which did not increase 15 weeks after discontinuing the treatment. Histopathologically, bacteria in the treated mice became fragmented one week after RLZ-treatment. At the final point of the experiment, all the treated mice (5mg/kg/day; n = 6, 10mg/kg/day; n = 7) survived and had no signs of M. ulcerans infection. These results indicate that the rifamycin analogue, RLZ, is efficacious in the treatment of an advanced M. ulcerans infection mouse model.

Childhood tuberculosis.

PURPOSE OF REVIEW: We discuss the most recent literature to support the identification of children at risk for tuberculosis and optimal testing and treatment strategies. RECENT FINDINGS: The identification and management of children with tuberculosis has increased in complexity due to the recent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic, greater use of immunosuppressive agents, and the administration of shorter, rifamycin-containing treatment regimens. Advancements in the diagnosis and treatment of tuberculosis in children include: use of interferon gamma release assays (IGRAs); molecular-based tests; and shorter courses of treatment. While the essential steps to identify and treat children at risk for tuberculosis remain unchanged, providers must be aware of impact of these challenges. SUMMARY: The SARS-CoV-2 pandemic will likely have a negative impact on global tuberculosis control. It is important that countries maintain a comprehensive approach to the identification and management of children at risk for tuberculosis. Increasing evidence supports enhanced utilization of IGRAs and molecular-based testing to improve the diagnosis of tuberculosis in children. Shorter course, rifamycin-based treatment regimens are available to treat children with tuberculosis infection; however, their use is limited in some immunosuppressed children due to drug-drug interactions.