During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009.
Abstract 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.
A high prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections have been reported among persons with severe mental illness. In October, 2009, the Cook County Department of Public Health (CCDPH) initiated an investigation following notification of a cluster of HBV infections among mentally ill residents at a long term care facility (LTCF).LTCF staff were interviewed and resident medical records were reviewed. Residents were offered testing for HBV, HCV, and HIV. Serum specimens from residents diagnosed with HBV or HIV infection were sent to the Centers for Disease Control and Prevention (CDC) for analysis.Eleven newly diagnosed HBV infections were identified among mentally ill residents at the LTCF. Of these 11 infections, 4 serum specimens were available for complete HBV genome sequencing; all 4 genomes were found to be closely related. Four newly diagnosed HIV infections were identified within this same population. Upon molecular analysis, 2 of 4 HIV sequences from these new infections were found to be nearly identical and formed a tight phylogenetic cluster.HBV and HIV transmission was identified among mentally ill residents of this LTCF. Continued efforts are needed to prevent bloodborne pathogen transmission among mentally ill residents in LTCFs.
Abstract Background In August 2019 the U.S. FDA approved pretomanid as part of a 6-month all-oral BPaL (bedaquiline, pretomanid, and linezolid) regimen for treating pulmonary extensively drug-resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). In the study supporting approval, 89% of patients had a favorable outcome, and all reported ≥ 1 adverse event. We describe the reported use of BPaL in the United States. Methods Using the 2020 CDC Report of a Verified Case of Tuberculosis (RVCT) MDR TB supplemental form, TB programs and providers submitted data for patients who began taking BPaL between Aug 1, 2019 and May 1, 2020, for retrospective descriptive analysis. Results Programs and providers reported 17 TB patients aged a mean of 41 years (range 23–76) who received BPaL: 11 (65%) were male; 15 (88%) were non-U.S. born; 15 (88%) had pulmonary TB disease only; two (12%) had both pulmonary and extrapulmonary disease. Of all patients, 16 had Mycobacterium tuberculosis isolated from sputum and 7 (44%) had cavitary disease. The preliminary drug susceptibilities were 8 MDR patterns, 8 pre-XDR, and 1 unreported. Three patients received BPaL as their only treatment; six first received treatment for drug-susceptible TB, and eight received other regimens for MDR TB before BPaL. Eleven (65%) patients had ≥ 1 side effect reported during any TB treatment, including peripheral neuropathy (n=5), depression (n=4), vestibular dysfunction (n=3), and vision changes (n=3). Timing related to specific TB drug use was not reported. Sixteen (94%) patients received less than the approved initial dose of 1200 mg linezolid daily, and 15 (88%) patients underwent monitoring of linezolid exposure. All 16 patients with M. tuberculosis in initial sputa converted to negative culture results within 6 months of starting treatment. At 12 months after BPaL initiation, all patients had completed treatment, without TB recurrences or deaths reported. Conclusion In the early period after FDA approval, most U.S. patients received BPaL off-label with an initial linezolid dose lower than the approved 1200mg yet still achieved good outcomes. Most reported patients underwent some monitoring of linezolid exposure. Monitoring of BPaL use is important and should continue. Disclosures All Authors: No reported disclosures
The aim of this study is to assess whether choice of test for tuberculosis (TB) infection affects decisions to accept and complete treatment among contacts to TB cases.Retrospective study is conducted in which TB contacts, ⩾15 years old during 2005 and 2009, were tested for infection with either a tuberculin skin test (TST) or an interferon-gamma release assay test, the QuantiFERON-TB Gold In-Tube (QFT-GIT).Of 658 persons with valid test results, 185 (28%) had positive results, including 128 of 406 (32%) who had TST and 57 of 252 (23%) who received QFT-GIT. Treatment acceptance was 43 of 57 (75%) among QFT-GIT-positive and 97 of 128 (76%) among TST-positive persons (risk ratio [RR] = 1.0, 95% confidence interval [CI], 0.83-1.2). Treatment completion was 56% among QFT-GIT-positive (32 of 57) and 59% (75 of 128) among TST-positive persons (RR = 0.96, 95% CI, 0.73-1.26).Our study showed no difference in proportions of TB contacts ⩾15 years old with positive TST results who accepted or completed LTBI treatment compared with those with positive QFT-GIT results. Future studies should include high-risk persons with no known TB exposure, who constitute the main reservoir for TB cases in the United States.
Abstract 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.
