Concomitant Treatment of Tuberculosis and Hepatitis C Virus in Coinfected Patients Using Serum Drug Concentration Monitoring.

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.

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.

Complication of Mycobacterium tuberculosis treatment: Isoniazid-induced pneumonitis.

Prolonged therapy with isoniazid is used for the treatment of pulmonary tuberculosis. Drug-induced lupus erythematosus is a rare, adverse event associated with isoniazid use and can complicate treatment, especially if it is associated with pneumonitis. The diagnosis is made by clinical suspicion, elevated serum titers of anti-nuclear antibody and anti-histone antibody, and new ground-glass opacities on chest tomography. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy of affected areas of the lung is useful to increase diagnostic accuracy and differentiate between drug-induced pneumonitis, concomitant infection, or other inflammatory processes. Treatment includes systemic corticosteroids and cessation of isoniazid therapy.

Seizure Induced by a Therapeutic Dose of Venlafaxine ER: A Case Report.

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor commonly used for the treatment of depression. Although listed as an adverse reaction, seizure activity associated with a therapeutic dose of venlafaxine has rarely been documented. A review of the literature reveals only 2 cases of venlafaxine-induced seizures, both of which were generalized tonic-clonic seizures in patients on doses at the higher end of the therapeutic range. We report the case of a 44-year-old woman undergoing antituberculosis therapy who suffered complex partial seizures after ingestion of a low therapeutic dose of venlafaxine extended release (ER). Her first seizure was observed soon after venlafaxine ER was titrated from 37.5 to 75 mg daily, with a total of 9 witnessed complex partial seizures. After titrating the dose of the venlafaxine ER back down to 37.5 mg daily and beginning lamotrigine anticonvulsant therapy, the patient exhibited no further seizures. The development of seizure activity under therapeutic dosing of venlafaxine should be brought to the attention of the health care prescriber. The potential for drug-drug interactions involving venlafazine, particularly in combination with multiple drugs, such as isoniazid and levofloxacin, needs to be recognized.