We investigated the pharmacokinetics of rifabutin in 15 male patients as part of a phase I trial of the treatment of early symptomatic human immunodeficiency virus infection. Six or more patients were studied at each of four different oral dosage levels: 300, 600, 900, and 1,200 mg/day. Twelve studies were also conducted with tracer doses of intravenous radiolabeled ['4C]rifabutin. Blood and urine samples were collected for at least 72 h after the first (day 1) and last (day 28) doses of rifabutin and analyzed by high-pressure liquid chromatography. The plasma concentration data were best described by a two-compartment open model with a terminal half-life of 36 h. Rifabutin was rapidly absorbed, reaching a peak concentration about 2 to 3 h after an oral dose. Peak and trough concentrations for the 1,200-mg dose were 907 and 194 ng/ml, respectively. Total body clearance was 10 to 18 liters/h. Oral bioavailability was 12 to 20%. The drug was moderately bound to plasma proteins with a free fraction of 29 + 2% (mean + standard deviation). About 10% of an administered intravenous dose of rifabutin is excreted into the urine unchanged. Renal clearance was 1.5 0.2 liters/h. The volume of distribution was large (8 to 9 liters/kg), suggesting extensive distribution into the tissues. The area under the curve for the last dose was smaller than that of the first dose, suggesting possible induction of drug-metabolizing enzymes.Rifabutin (ansamycin; LM427) is a semisynthetic rifamycin similar in structure and activity to rifampin (7). In addition to in vitro activity against a variety of gram-negative and gram-positive organisms, it also has activity against Mycobacterium tuberculosis and Mycobacterium avium complex (4, 9). Recent in vitro studies have shown 92% inhibition of reverse transcriptase activity in human immunodeficiency virus-infected lymphocytes when used at a concentration of 0.1 .g/ml (1). As part of a phase I study of rifabutin in patients with early symptomatic human immunodeficiency virus infections, we studied the pharmacokinetics of rifabutin in patients with acquired immunodeficiency syndrome-related complex at four different dosage levels: 300, 600, 900, and 1,200 mg/day. MATERIALS AND METHODSSubjects. Fifteen male patients, ages 28 to 44 years, with early symptomatic human immunodeficiency virus infections were studied after giving informed consent. All patients had either oral thrush or chronic lymphadenopathy but were otherwise in generally good health. Patients were excluded when they had evidence of impaired renal (creatinine clearance of <85% of expected value based on Cockcroft-Gault equation) or hepatic (serum glutamic oxalacetic transaminase or serum glutamic pyruvic transaminase of >60 or bilirubin of >1.2 mg/100 ml) function, known hypersensitivity to rifabutin or rifampin, or recent use of other antiviral agents or immunomodulating agents or of cytolytic or other agents for cancer treatment. All nonessential medications were discontinued prior to enrollment in the trial. Patients were allowed...
We reviewed 106 patients referred to our institution for treatment of peripheral tuberculous adenitis to establish the epidemiologic, clinical, and pathologic manifestations of this disease. Tuberculous lymphadenitis occurred predominantly in young, foreign-born women a mean of 5 years after arrival in the United States. Tuberculin skin tests were positive in 94% of cases. Lymphadenopathy occurred most frequently in the neck (57%) or supraclavicular area (26%) and involved 1-3 nodes. Forty (38%) patients had an abnormal chest radiograph consistent with granulomatous infection. Culture-positive pulmonary tuberculosis was diagnosed in 41% of those patients with abnormal chest radiographs. Fine needle aspiration was an essential step in the evaluation and diagnosis of tuberculous lymphadenitis. Granulomas were seen in 61% of fine needle aspirates and 88% of surgical biopsies. Positive cultures for Mycobacterium tuberculosis were obtained from 62% of fine needle aspirate samples and 71% of excisional biopsies. The presence of necrosis and/or neutrophilic inflammation in tissue samples correlated with culture positivity. Given the high yield of positive cultures from fine needle aspirates, surgery was rarely indicated as an initial step in immunocompetent adults. In this cohort, 101 patients received a final diagnosis of peripheral tuberculous lymphadenitis. Eighty-two percent received their entire therapy under direct observation, and response to antituberculous therapy was uniformly successful. Paradoxical expansion of adenopathy was seen in 20% of all patients and was more commonly noted in human immunodeficiency virus-seropositive patients. We present a diagnostic algorithm based on our experience.
BackgroundPatient adherence to isoniazid (INH) monotherapy for latent tuberculosis infection (LTBI) has been suboptimal despite its proven efficacy. Various strategies have been studied to improve adherence, but all have been based at a clinic or treatment program. At the Santa Clara Valley Tuberculosis Clinic, it was our practice to refer a subset of high-risk LTBI patients to the Public Health Department for monthly follow-up at home instead of at the clinic. Our goal was to assess whether house calls by community health workers and public health nurses affected INH adherence or frequency of adverse effects.MethodsWe retrospectively studied 3918 LTBI patients who received INH. At the discretion of the treating physician, 986 (25.2%) received house calls instead of clinic follow-up. Home-based follow-up included language translation, medication delivery, assessment of compliance with pill counts, monitoring for adverse effects, and active tracking of noncompliant patients. We assessed differences in patient characteristics, treatment completion, and reasons for treatment discontinuation between patients followed at home versus in the clinic. Multivariate analyses to address possible referral bias or confounding were performed using logistic regression.ResultsMore patients followed with house calls completed INH treatment (90% home versus 73.2% clinic). This was the case across all subgroups of patients, including those with historically the lowest adherence: patients from correctional and rehabilitation facilities (77.8% home versus 46.9% clinic), postpartum women (86.4% home versus 55.6% clinic), and patients aged between 18 and 35 years (87% home versus 63.1% clinic). After adjusting for age, place of birth, referral category (TB contacts/skin test converters, correctional/rehabilitation patients, postpartum women, tuberculin positive patients from other screening), and prescribed INH regimen duration (9 versus 6 months), home-based follow-up of LTBI patients was a significant predictor of treatment completion (AOR 2.94, 95% CI: 2.33, 3.71). Patients followed at home were 21% more likely to complete therapy (ARR 1.21, p<0.001). Risk of adverse effects was similar between the two types of follow-up.ConclusionHome-based follow-up of LTBI patients taking isoniazid was associated with improved treatment completion and no increase in adverse effects regardless of patient characteristics or prescribed duration of INH therapy.
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