Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (P < 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (P < 0.01), 66% or 100% (P < 0.05), 30% or 50% (P ‫؍‬ 0.198), and 32% or 21% (P ‫؍‬ 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients. Diabetes mellitus (DM) is among the well-known major risk factors for tuberculosis (TB) (1-5), and the presence of DM affects the outcome of drug treatment negatively, reduces the cure rate, and enhances the risk of relapse and emergence of drug resistance (6-10). A recent study (11) has shown that DM is associated with slow response, and circulating levels of TB drugs (e.g., rifampin) are likely to be below the expected therapeutic ranges among diabetic TB patients. The circulating concentration of rifampin was also reported to decline in some (12) but not all (13, 14) studies in diabetic TB patients. Available data, however, are inconclusive with regard to whether DM affects serum therapeutic levels of anti-TB drugs.Hence, the present study was designed to determine plasma concentrations of isoniazid, rifampin, pyrazinamide, and ethambutol, the first line anti-TB drugs, in adult Turkish pulmonary tuberculosis patients with DM during the intensive phase of the short-course therapy under conditions of directly observed therapy (DOT).A total of 70 adult patients with newly diagnosed active pulmonary TB were enrolled in the study. Patients were divided into two groups. The first group consisted of 14 TB patients with type 2 DM who were receiving DM therapy with good glucose control (glycosylated hemoglobin level Ͻ 6.5%) at the time of recruitment, and they continued to use their antidiabetes drugs during the study. The second group consisted of 56 nondiabetic TB patients who were screened for DM, and patients with suspicious test results (fasting blood glucose Ͼ 100 mg/dl and/or hemoglobin A1c [HbA1c] Ͼ 6%) were excluded. Diagnosis of pulmonary TB was based on clinical symptoms, chest radiological examination, sputum microscopy, and culture. Patients with a comorbid disease (except for DM) as well as those using concomitant medications (except for antidiabetics) and having abnormal renal and/or hepatic function were excluded.Written informed consent was obtained from all patients before the commencement of the study. The study protocol and the contents of the written consent form were approved by the Institutional Ethics Committee (Acibadem University Ethical Committee, Istanbul, Turkey).All patients were administered orally identical drugs from a national manufacturer (Koçak Farma, Istanbul, Turkey) under conditions of DOT. Patients received daily administration of 300 mg of isoniazid, 600 mg of rifampin, 1,500 mg of pyrazinamide, and 1,000 mg ...

ÖZTÜRK 25 (Türkiye SUNRISE Çalışma Grubu; çalışmaya alınan hasta sayılarına göre isimler sıralanmıştır).

The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB).We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16–89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion.The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases.Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

No abstract

Our data show that the serum concentrations of anti-tuberculosis drugs varied considerably in the study patients. Therapeutic drug monitoring is necessary to identify patients with subtherapeutic INH and RMP serum concentrations.