Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

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.

Use of standard, contact, and droplet precautions with eye protection for the prevention of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission among home healthcare personnel in hospice and home healthcare settings-King and Snohomish counties, Washington, February-October 2020.

Among EvergreenHealth Home Care Service professionals, no coronavirus disease 2019 (COVID-19) cases were reported when they were instructed to use standard, contact, and droplet precautions with eye protection while providing home health care to patients diagnosed with laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2). These precautions might provide some level of protection against coronavirus disease 2019 (COVID-19) among home healthcare personnel.

Adverse pregnancy outcomes after in vitro fertilization due to undiagnosed urogenital tuberculosis and proposed screening algorithm for patients from tuberculosis-endemic countries.

Objective: To report 2 cases of adverse pregnancy outcomes due to delayed diagnosis of urogenital tuberculosis and propose a screening algorithm for patients from tuberculosis-endemic countries. Design: Case report. Setting: Academic medical center. Patients: Two patients with delayed diagnosis of urogenital tuberculosis leading to a fetal loss and a preterm delivery of an infant with congenital tuberculosis. Interventions: Endometrial biopsy, acid-fast bacilli culture of urine, and endometrium. Main outcome measures: Pregnancy outcomes. Results: Fetal loss at 19 weeks and preterm delivery of an infant with congenital tuberculosis before urogenital tuberculosis treatment. Conclusions: Patients who are at risk of urogenital tuberculosis should be screened in advance of infertility treatment to potentially prevent adverse pregnancy outcomes.

A Targeted Screening Program for Latent Tuberculosis Infection Among Hematopoietic Cell Transplant Recipients.

BACKGROUND: US hematopoietic cell transplantation (HCT) recipients have a low prevalence of latent tuberculosis infection (LTBI), but if latently infected they are at risk for progression to active tuberculosis. At our center, all HCT recipients underwent LTBI testing pretransplant by tuberculin skin testing (TST) until 2013 when we implemented a targeted screening program. Our objective was to assess the utility of our screening program that incorporated a pretransplant LTBI questionnaire to target TST and QuantiFERON TB Gold (QFT) testing. METHODS: We performed a retrospective cohort study of HCT recipients undergoing first transplant from 2014 to 2016. Patients with positive, indeterminate, and a subset with negative QFT results underwent electronic medical record (EMR) review to assess TST results and risk factors for LTBI. RESULTS: Among 1290 eligible recipients, 457 (35%) had at least 1 risk factor for LTBI on the pretransplant questionnaire; nonwhites were more likely to undergo LTBI testing (P < .0001). Overall, 16 of 1290 (1.2%) had at least 1 positive LTBI test. Of those screened by QFT, 14 of 457 (3%) were positive and 52 (11%) were indeterminate. Among those undergoing EMR review, 123 of 267 (46%) had TST records; 4 of 123 (3%) positive by both TST and QFT, and 2 (2%) by TST alone. Two or more risk factors were reported among the majority of LTBI-positive patients (15 of 16 [94%]). All patients with at least 1 positive test for LTBI (n = 16) were evaluated, and 11 of 16 (69%) were recommended to receive treatment. CONCLUSIONS: Incorporating a pretransplant LTBI questionnaire allowed for an approximate 65% reduction in LTBI testing when compared with universal testing among this low prevalence population.

Investigation and Serologic Follow-Up of Contacts of an Early Confirmed Case-Patient with COVID-19, Washington, USA.

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

First Case of 2019 Novel Coronavirus in the United States.

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

Tuberculosis in Older Adults: Seattle and King County, Washington.

BACKGROUND: In the United States, tuberculosis (TB) incidence rates are highest among adults aged ≥65 years. We performed this study to evaluate outcomes of older patients undergoing treatment for TB disease, including the frequency of adverse events related to TB treatment. METHODS: This study evaluated adult patients who were diagnosed with pulmonary TB from 2009 to 2014 in King County, Washington. Patient characteristics, manifestation of TB, and treatment outcomes in different age groups were compared. Frequency and type of adverse events that resulted in treatment interruption were evaluated and patients aged ≥65 years were compared with selected younger patients. RESULTS: There were 403 patients who met the study criteria, 111 of whom were aged ≥65 years. Older patients were significantly less likely to have cavitation on chest radiographs. Patients aged ≥65 years were less likely to complete TB treatment (76.6% vs 94.9%, P < .0001) and were more likely to die during treatment (18.9% vs 2.1%, P < .0001). The difference in these outcomes was heightened for those aged ≥75 years compared with those aged <75 years. Those aged ≥75 years were also more likely to have an adverse event attributable to TB medication and were more likely to have an adverse event later in therapy. Regardless of age, pyrazinamide was responsible for the majority of adverse reactions. CONCLUSIONS: Adults aged ≥65 years with pulmonary TB had less-advanced disease but a higher risk of complications during treatment such as death or adverse events. This effect was most pronounced among those aged ≥75 years.

Short-course isoniazid plus rifapentine directly observed therapy for latent tuberculosis in solid-organ transplant candidates.

BACKGROUND: Short-course directly observed isoniazid plus rifapentine (INH/RPT) combination could have potential advantages over a standard 9-month INH regimen for the treatment of latent tuberculosis infection in solid-organ transplant (SOT) candidates. METHODS: We prospectively assessed the safety and tolerability of 12 weeks of INH/RPT given directly observed therapy in 17 consecutive SOT candidates with latent tuberculosis infection. RESULTS: The median age was 57 years and 82% were men. Of the 17 patients, 13 (76%) successfully completed therapy and 4 (24%) eventually underwent SOT. Treatment was prematurely discontinued in four patients. One of these patients underwent a kidney transplant. The overall dose compliance was 83% (169/204 scheduled doses), and 12 (71%) of 17 patients received 100% of scheduled doses. No patient developed transaminase elevations greater than twice baseline or greater than four times the upper limit of normal or clinical hepatotoxicity. No cases of TB developed during 20.4 months after transplant among INH/RPT-treated recipients. CONCLUSIONS: For carefully selected SOT candidates, combination INH/RPT weekly given as directly observed therapy seems to be reasonably well tolerated and is associated with a relatively high completion rate. Future larger prospective studies to confirm the safety and high completion rates reported here and to identify the most appropriate SOT candidates for this regimen are warranted.

Challenging issues in tuberculosis in solid organ transplantation.

Solid organ transplant (SOT) recipients are at risk for opportunistic infections including tuberculosis. Although guidelines on the management of latent tuberculosis and active tuberculosis are available, there remain a number of clinical areas with limited guidance. We discuss challenges in the diagnosis, management, and treatment of latent and active tuberculosis in SOT candidates and recipients who reside in low-tuberculosis-prevalence areas. We discuss the diagnosis of latent tuberculosis in SOT candidates/recipients using tuberculin skin tests and interferon-γ release assays and risk stratification of SOT candidates/recipients that would identify individuals at high risk for latent tuberculosis despite negative test results. Through a careful review of posttransplant tuberculosis cases, we identify a history of treated tuberculosis in SOT recipients as a risk factor for development of posttransplant active tuberculosis. Finally, we include comparisons of recommendations by several large transplant organizations and identify areas for future research.

How soon should patients with smear-positive tuberculosis be released from inpatient isolation?

OBJECTIVE: In patients with smear-positive pulmonary tuberculosis who are hospitalized or reside in congregate settings, guidelines recommend airborne infection isolation until sputum smear results are negative. Studies have identified factors associated with delayed sputum smear and culture conversion in patients with tuberculosis. Because these studies did not use methods of survival analysis, estimates of time to sputum smear conversion that are based on initial patient characteristics are not available. The ability to predict time to sputum smear conversion could be useful for programmatic planning and patient counseling. METHODS: We performed a cohort study using survival analysis to identify factors associated with time to sputum smear and culture conversion. We defined the time to sputum smear conversion as the time elapsed from the start of treatment to the first date of sustained conversion. RESULTS: Ninety-eight patients had sputum smear samples positive for acid-fast bacilli. Lower initial smear grade (on 1+ to 4+ scale) and absence of cavitation on chest radiograph were associated with earlier sputum smear conversion in bivariate analysis. In multiple regression analysis, initial smear grade (hazard ratio, 0.45; 95% confidence interval, 0.35-0.57) and drug resistance (hazard ratio, 2.30; 95% confidence interval, 1.08-4.89) remained statistically significant; a model comprising only initial smear grade performed almost as well. Predictors of sputum culture conversion were similar. CONCLUSIONS: Initial smear grade was the strongest predictor of time to sputum smear and culture conversion in patients with pulmonary tuberculosis and may be a useful predictor for programmatic planning and patient counseling.

Unexpected pulmonary involvement in extrapulmonary tuberculosis patients.

BACKGROUND: This study aimed to assess the utility of sputum examinations and chest radiographs (CXRs) in patients with extrapulmonary tuberculosis (XPTB) to detect pulmonary involvement of tuberculosis (TB). METHODS: We studied 72 XPTB patients who were managed through the TB Program, King County, WA, from January 2003 through November 2004. RESULTS: The two most common sites of XPTB were the lymph nodes (36 [50%]) and pleura (12 [17%]). Thirty-five of 72 XPTB patients (49%) had abnormal CXR findings. Sputum was not obtained from 15 patients despite sputum induction. Of the 57 patients from whom sputum was collected, 30 (53%) had abnormal CXR findings, 5 (9%) had sputum smears that were positive for acid-fast bacilli, and 12 (21%) had sputum cultures that were positive for Mycobacterium tuberculosis. Weight loss was significantly associated with positive sputum culture findings in a multivariate analysis (odds ratio, 4.3; 95% confidence interval, 1.01 to 18.72; p = 0.049). There was no significant difference in the occurrence of positive sputum culture results between patients with abnormal CXR findings and those with normal CXR findings (7 of 30 patients [23%] vs 5 of 27 patients [19%], respectively; p = 0.656). Of 24 HIV-negative XPTB patients with normal CXR findings, 2 patients (8%) had positive sputum culture findings. CONCLUSIONS: CXR results did not reliably differentiate XPTB patients with and without positive sputum culture findings. Some XPTB patients had positive sputum culture results despite normal CXR findings and negative HIV status. Weight loss in XPTB patients was associated with positive sputum culture results. Sputum examinations in XPTB patients, regardless of the CXR results, may identify potentially infectious cases of TB.