Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis.

High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0-24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.).

Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.

Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.

Des patients adultes présumés atteints de TB (n = 1690) ont été dépistés à l'aide d'un questionnaire, d'une radiographie pulmonaire (CXR) et d'une microscopie de crachats à la recherche des bacilles acido-alcoolo-résistants; une culture de Mycobacterium tuberculosis a été réalisée chez 74% des patients et un test Xpert® MTB/RIF, chez 17,2%. Parmi les patients recrutés, 943 (55,8%) ont eu un diagnostic de TB, dont 870 (92,3%) ont été confirmés par bactériologie et 73 (7,7%) ont été diagnostiqués sur la CXR. Recourir à la CXR avant la culture ou le test Xpert réduit le nombre requis pour dépister un cas de 7,6 à 5,0. L'utilisation de la CXR pour le triage avant la culture ou le test Xpert réduit les cas manqués et augmente l'efficacité de l'utilisation de la culture et de l'Xpert.

Se investigó de la tuberculosis (TB) en pacientes adultos con presunción clínica de la enfermedad (n = 1690) mediante un cuestionario, la radiografía de tórax (CXR) y la baciloscopia del esputo; se practicó el cultivo para Mycobacterium tuberculosis en 74% de los pacientes y la prueba Xpert® MTB/RIF en 17,2%. De los pacientes que participaron se diagnosticó la TB en 943 (55,8%), de los cuales 870 (92,3%) con confirmación bacteriológica y 73 (7,7%) con diagnóstico clínico a partir de la CXR. El hecho de realizar la CXR o la prueba Xpert antes del cultivo disminuye de 7,6 a 5,0 el número de pacientes que deben someterse a detección. El uso de la CXR para seleccionar los casos en que se debe practicar el cultivo o la prueba Xpert disminuye los casos pasados por alto y aumenta la eficiencia del uso del cultivo y la prueba Xpert.

Mycobacterium tuberculosis genotypic drug resistance patterns and clustering in Jayapura, Papua, Indonesia.

BACKGROUND: Little is known about drug-resistant tuberculosis (TB) and its transmission in Papua, which has one of the highest rates of TB in Indonesia. DESIGN: We examined genotypic drug resistance patterns using multiplex ligation-dependent probe amplification and the degree of molecular clustering using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) among 199 consecutive pulmonary TB patients in Jayapura, Papua. RESULTS: Drug resistance mutations were present in 30/198 (15.2%) patients: 16/144 (11.1%) primary cases and 14/51 (27.5%) retreatment cases. Genotypic resistance to rifampicin was found in 15 (7.6%) patients, to isoniazid in 19 (9.6%), to ethambutol in 7 (3.5%), and to streptomycin and second-line injectable drugs in 5 (2.5%) patients. Eight (4.0%) patients had multidrug-resistant TB, while no mutations were found for fluoroquinolones. The most common lineage found among all isolates was East-African Indian (n = 66, 33.7%), followed by Euro-American (n = 38, 19.4%). Drug resistance mutations were more common among Beijing strains than other lineages. Of the 30 drug-resistant isolates, 12 (40.0%) fell into four clusters that were separate from drug-susceptible clusters as determined using MIRU-VNTR. CONCLUSIONS: These are the first genotypic drug resistance data from Jayapura, Papua, showing moderate rates of resistance to first-line drugs and likely transmission of drug-resistant TB.

The experience of older people living in nursing home (Panti Wredha) in DKI Jakarta, Indonesia

Inability to fulfil daily needs and natural aging process will affect both health and life satisfaction among older people. Services to older people in nursing home may be affected when cooperation between nurse, caregiver and older people are not optimal. Hence, the cooperation between them must be optimized to enhance services and maintain quality of life among the older people. The aim of this study was to develop a partner model between nurse, caregiver and older people in nursing home, Panti Wredha in Jakarta, to improve caring behavior, health status, satisfaction and quality of life of older people. This study's operational method consisted of three phases: (I) exploration phase, (II) model development phase, and (III) model trial phase to assess the model effectiveness. The first year was phase I and II. The second year was phase III model trial to assess the model effectiveness. This article will report the phase I findings. Qualitative design with a descriptive phenomenology approach was used. The population was older people living in Nursing Home (Panti Wredha) in Jakarta. The sample for phase I was selected according to some criteria until data saturation was achieved: eight older people. Data were collected using face-to-face interview to older people. Data were analyzed using Collaizi method. The result of 11 themes (older people). This result will be used further for development of model and module, and will test by readability and expert test

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