RESUMO
BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Estados Unidos , Rifampina/efeitos adversos , Linezolida/efeitos adversos , Antituberculosos/efeitos adversos , Tuberculose/tratamento farmacológico , Diarilquinolinas/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Humanos , Linezolida/uso terapêutico , África do Sul/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Estados Unidos/epidemiologiaRESUMO
The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug (Cmins) of 2 and 7 mg/liter as thresholds for toxicity. The PK/PD breakpoint was defined as the highest MIC at which the probability of target attainment is >90%. A total of 104 patients with pulmonary TB were included, with a median age and weight of 37 years and 60 kg. Eighty-one percent had drug-resistant TB. The PK data were best described by a one-compartment model. The PK/PD breakpoint was 0.125 mg/liter for a total daily dose of 300 mg, while daily doses of 450 to 600 mg and 900 to 1,200 mg had PK/PD breakpoints of 0.25 and 0.50 mg/liter, respectively. The probability of achieving a Cmin of ≤2 mg/liter was higher when the dose was given at once than when dividing it into 2 doses. Linezolid at a daily dose of 300 mg may not be optimal. We predicted an excellent and comparable efficacy of linezolid using total daily doses of 900 and 1,200 mg for MICs of ≤0.5 mg/liter but with the potential for more toxicity than with 600 mg daily. The increase in Cmin was noticeable when the daily dose was divided and may incur greater toxicity.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antibacterianos/uso terapêutico , Brasil , Georgia , Humanos , Linezolida , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
Ethionamide (ETA), an isonicotinic acid derivative, is part of the multidrug-resistant tuberculosis (MDR-TB) regimen. The current guidelines have deprioritized ETA because it is potentially less effective than other agents. Our aim was to develop a population pharmacokinetic (PK) model and simulate ETA dosing regimens in order to assess target attainment. This study included subjects from four different sites, including healthy volunteers and patients with MDR-TB. The TB centers included were two in the United States and one in Bangladesh. Patients who received ETA and had at least one drug concentration reported were included. The population PK model was developed, regimens with a total of 1,000 to 2,250 mg daily were simulated, and target attainment using published MICs and targets of 1.0-log kill and resistance suppression was assessed with the Pmetrics R package. We included 1,167 ethionamide concentrations from 94 subjects. The final population model was a one-compartment model with first-order elimination and absorption with a lag time. The mean (standard deviation [SD]) final population parameter estimates were as follows: absorption rate constant, 1.02 (1.11) h-1; elimination rate constant, 0.69 (0.46) h-1; volume of distribution, 104.16 (59.87) liters; lag time, 0.43 (0.32) h. A total daily dose of 1,500 mg or more was needed for ≥90% attainment of the 1.0-log kill target at a MIC of 1 mg/liter, and 2,250 mg/day led to 80% attainment of the resistance suppression target at a MIC of 0.5 mg/liter. In conclusion, we developed a population PK model and assessed target attainment for different ETA regimens. Patients may not be able to tolerate the doses needed to achieve the predefined targets supporting the current recommendations for ETA deprioritization.
Assuntos
Etionamida , Tuberculose Resistente a Múltiplos Medicamentos , Antibacterianos/uso terapêutico , Antituberculosos/uso terapêutico , Bangladesh , Etionamida/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoAssuntos
Antituberculosos , Mycobacterium tuberculosis , Nitroimidazóis , Tuberculose , Antituberculosos/uso terapêutico , Humanos , Nitroimidazóis/efeitos adversos , Nitroimidazóis/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Estados UnidosRESUMO
Mycobacterium bovis bacillus Calmette-Guérin (BCG) is used as a vaccine to protect against disseminated tuberculosis (TB) and as a treatment for bladder cancer. We describe characteristics of US TB patients reported to the National Tuberculosis Surveillance System (NTSS) whose disease was attributed to BCG. We identified 118 BCG cases and 91,065 TB cases reported to NTSS during 2004-2015. Most patients with BCG were US-born (86%), older (median age 75 years), and non-Hispanic white (81%). Only 17% of BCG cases had pulmonary involvement, in contrast with 84% of TB cases. Epidemiologic features of BCG cases differed from TB cases. Clinicians can use clinical history to discern probable BCG cases from TB cases, enabling optimal clinical management. Public health agencies can use this information to quickly identify probable BCG cases to avoid inappropriately reporting BCG cases to NTSS or expending resources on unnecessary public health interventions.
Assuntos
Vacina BCG/efeitos adversos , Notificação de Doenças , Tuberculose/epidemiologia , Tuberculose/microbiologia , Vacina BCG/genética , Notificação de Doenças/estatística & dados numéricos , Feminino , Genótipo , História do Século XXI , Humanos , Masculino , Vigilância da População , Tuberculose/diagnóstico , Tuberculose/história , Estados Unidos/epidemiologiaRESUMO
Transplant recipients are at increased risk of tuberculosis (TB). We describe a case of pulmonary and vertebral multidrug-resistant TB (MDR-TB) in a kidney transplant patient who required neurosurgical intervention and unfortunately developed fatal nosocomial complications. Thirteen transplant recipients with MDR-TB were previously reported in the literature (one hematopoietic cell transplant, one heart transplant, one lung transplant, one heart-lung transplant, and nine kidney transplant recipients). Extrapulmonary disease, severe treatment complications, and deaths were observed in patients who developed MDR-TB after transplantation.
Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/fisiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose da Coluna Vertebral/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Infecção Hospitalar/complicações , Infecção Hospitalar/microbiologia , Nefropatias Diabéticas/complicações , Farmacorresistência Bacteriana Múltipla , Evolução Fatal , Transplante de Células-Tronco Hematopoéticas , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Procedimentos Neurocirúrgicos , Pneumonia Bacteriana/microbiologia , Reação em Cadeia da Polimerase , Insuficiência Respiratória/etiologia , Choque Séptico/microbiologia , Transplantados , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/diagnóstico , Tuberculose da Coluna Vertebral/complicações , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/cirurgiaRESUMO
BACKGROUND: The Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. METHODS: We conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. RESULTS: Our study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. CONCLUSION: While the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.
Assuntos
Genótipo , Tuberculose Latente , Mycobacterium tuberculosis , Humanos , Masculino , Mycobacterium tuberculosis/genética , Feminino , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Fatores de Risco , Adolescente , Análise por Conglomerados , Idoso , Prevalência , Tuberculose/epidemiologia , Tuberculose/microbiologia , Criança , Pré-Escolar , Lactente , Florida/epidemiologiaRESUMO
Background: Concern for drug-drug interactions leading to treatment failure and drug-resistant strains have discouraged clinicians from attempting concomitant treatment of hepatitis C virus (HCV) and tuberculosis (TB). Increased metabolism of direct-acting antivirals (DAAs) by rifamycins has hindered concurrent use. Development of an assay for ledipasvir and sofosbuvir (LDV/SOF) serum concentrations for therapeutic drug monitoring (TDM) can ensure adequate therapy. We present the first cases of concomitant therapy of active TB and HCV with rifamycin-containing regimens and DAAs using TDM. Methods: Using TDM, we aim to determine whether concomitant therapy with rifamycin-containing regimens and DAAs is safe and effective for patients coinfected with TB and HCV. Five individuals with TB and HCV who experienced transaminitis before or during TB therapy were concomitantly treated with rifamycin-containing regimens and LDV/SOF. Therapeutic drug monitoring was performed for LDV, SOF, and rifabutin during therapy. Baseline laboratory tests and serial liver enzymes were performed. Hepatitis C virus viral load and mycobacterial sputum cultures were obtained upon completion of therapy to determine efficacy of therapy. Results: All patients were found to have nondetectable HCV viral loads and negative mycobacterial sputum cultures upon completion of therapy. No clinically significant adverse effects were reported. Conclusions: These cases illustrate concomitant use of LDV/SOF and rifabutin in patients with HCV/TB coinfection. Utilizing serum drug concentration monitoring to guide dosing, correction of transaminitis were achieved, which allowed the use rifamycin-containing TB therapy. These findings suggest that concomitant therapy of TB/HCV is possible, safe, and effective.
RESUMO
BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Intervalos de Confiança , Feminino , Humanos , Masculino , Razão de Chances , Recidiva , Falha de TratamentoAssuntos
Tuberculose Latente , Tuberculose , Feminino , Infecções por HIV , Humanos , Gravidez , Complicações Infecciosas na GravidezRESUMO
Background: Tuberculosis (TB) is the leading cause of death in human immunodeficiency virus (HIV)-infected people worldwide. Currently there are no studies examining the use of Rifabutin (RBN) and Dolutegravir (DTG) in co-infected persons. This is a case series of 4 co-infected patients receiving both agents who underwent Pharmacokinetic (PK) analysis. Methods and Results: This is a retrospective chart review study of four patients diagnosed with both HIV and TB, receiving RBN and DTG and undergoing therapeutic drug monitoring. All 4 cases had lower than expected DTG concentrations at least once, including those on the current recommended dose of DTG with RBN, and even those receiving higher doses. Conclusions: Given the frequency of low DTG and RBN concentrations, therapeutic drug monitoring (TDM) for these drugs is advisable. Prospective clinical studies are needed to further determine the PK interactions between RBN and DTG, and virologic response to treatment.
Assuntos
Antibióticos Antituberculose/uso terapêutico , Infecções por HIV , Rifabutina , Tuberculose , Compostos Heterocíclicos com 3 Anéis , Humanos , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , Estudos Retrospectivos , Rifabutina/uso terapêuticoRESUMO
A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up.
Assuntos
Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Elefantes , Doenças Urogenitais Femininas/veterinária , Tuberculose Resistente a Múltiplos Medicamentos/veterinária , Tuberculose Pulmonar/veterinária , Animais , Antituberculosos/administração & dosagem , Feminino , Doenças Urogenitais Femininas/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologiaRESUMO
BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis is difficult to treat, given the propensity for drug interactions between the rifamycins and the antiretroviral drugs. We examined the pharmacokinetics of rifabutin before and after the addition of lopinavir-ritonavir. METHODS: We analyzed 10 patients with HIV infection and active tuberculosis in a state tuberculosis hospital. Plasma was collected for measurement of rifabutin, the microbiologically active 25-desacetyl-rifabutin, and lopinavir by validated high-performance liquid chromatography assays. Samples were collected 2-4 weeks after starting rifabutin at 300 mg thrice weekly without lopinavir-ritonavir, 2 weeks after the addition of lopinavir-ritonavir at 400 and 100 mg, respectively, twice daily to rifabutin at 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the normal range) 2 weeks after an increase in rifabutin to 300 mg thrice weekly with lopinavir-ritonavir. Noncompartmental and population pharmacokinetic analyses (2-compartment open model) were performed. RESULTS: Rifabutin at 300 mg without lopinavir-ritonavir produced a low maximum plasma concentration (C(max)) in 5 of 10 patients. After the addition of lopinavir-ritonavir to rifabutin at 150 mg, 9 of 10 had low C(max) values. Eight patients had dose increases to 300 mg of rifabutin with lopinavir-ritonavir. Most free rifabutin (unbound to plasma protein) C(max) values were below the tuberculosis minimal inhibitory concentration. For most patients, values for the area under the plasma concentration-time curve were as low or lower than those associated with treatment failure or relapse and with acquired rifamycin resistance in Tuberculosis Trials Consortium/US Public Health Service Study 23. One of the 10 patients experienced relapse with acquired rifamycin resistance. CONCLUSION: The recommended rifabutin doses for use with lopinavir-ritonavir may be inadequate in many patients. Monitoring of plasma concentrations is recommended.
Assuntos
Antibióticos Antituberculose/farmacocinética , Antivirais/farmacocinética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Pirimidinonas/farmacocinética , Rifabutina/farmacocinética , Ritonavir/farmacocinética , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Antibióticos Antituberculose/sangue , Antibióticos Antituberculose/uso terapêutico , Antivirais/sangue , Antivirais/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Pirimidinonas/sangue , Pirimidinonas/uso terapêutico , Rifabutina/sangue , Rifabutina/uso terapêutico , Ritonavir/sangue , Ritonavir/uso terapêuticoRESUMO
RATIONALE: Serial smear analysis to guide respiratory isolation (RI) of patients with suspected tuberculosis (TB), the majority of whom will be found not to have TB, leads to expensive and unnecessary isolation, and may potentially result in decreased vigilance of subjects with respiratory compromise. OBJECTIVES: To compare the performance of a single first-sputum, Mycobacterium tuberculosis-specific nucleic acid amplification (NAA) test with three sputum smears for assessing the need for RI. METHODS: Prospective evaluation of 493 patients with suspected TB (74% HIV positive) admitted to RI in a major county hospital in the United States, who had at least three sputum smears and material available from the first sample for additional NAA testing. MEASUREMENTS AND MAIN RESULTS: Accuracy of the first sputum NAA result and serial smears for identifying patients with potentially infectious TB who truly require RI was determined. Forty-six patients (9.3%) had TB confirmed by culture. First-sputum NAA test detected all patients with TB who had a positive smear (n = 35), even when the first of the three specimens was smear negative. In addition, when compared with serial smears, the first-sputum NAA had a higher sensitivity (0.87; 95% confidence interval [CI], 0.74-0.95) and specificity (1.0) in the detection of subjects with positive M. tuberculosis cultures (smear sensitivity, 0.76; 95% CI, 0.61-0.87; and specificity, 0.96; 95% CI, 0.94-0.98). CONCLUSIONS: A single first-sputum NAA testing can rapidly and accurately identify the subset of patients with suspected TB who require RI according to serial sputum smears. Its potential use to shorten RI time does not preclude the need to obtain subsequent specimens for culture.
Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Escarro/microbiologia , Tuberculose/diagnóstico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014. METHODS: All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services. RESULTS: A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services. CONCLUSION: RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States.