Archive for February 21, 2013

Current Concepts: Tuberculosis

N Engl J of Medic February 21, 2013 V.368 P.745-755

Review Article

A. Zumla, M. Raviglione, R. Hafner,

From the Department of Infection, Division of Infection and Immunity, University College London Medical School, London (A.Z.); STOP TB Department, World Health Organization, Geneva (M.R.); the Tuberculosis Clinical Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (R.H.); and the Section of Infectious Disease and International Health, Geisel School of Medicine at Dartmouth, Hanover, NH (C.F.R.).

Despite the availability of a cheap and effective treatment, tuberculosis still accounts for millions of cases of active disease and deaths worldwide. The disease disproportionately affects the poorest persons in both high-income and developing countries. However, recent advances in diagnostics, drugs, and vaccines and enhanced implementation of existing interventions have increased the prospects for improved clinical care and global tuberculosis control….


February 21, 2013 at 3:55 pm

Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers.

Antimicrob Agents Chemother. 2012 May;56(5):2627-34.

Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Kuti JL, Nicolau DP.


Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.


This study assessed the pulmonary disposition of tedizolid, an oxazolidinone, in adult volunteers receiving 200 mg of the prodrug tedizolid phosphate orally every 24 h for 3 days to steady state. Plasma samples were collected over the dosing interval, and participants were randomized to undergo bronchoalveolar lavage (BAL) at 2, 6, 12, or 24 h after the last dose. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods followed by compartmental population pharmacokinetics. Penetration was calculated as the area under the concentration-time curve during the dosing interval (AUC(0-24)) for ELF and AM relative to the free AUC(0-24) (fAUC(0-24)) in plasma. The half-life and volume of distribution in plasma were 9.23 ± 2.04 h and 108.25 ± 20.53 liters (means ± standard deviations), respectively. Total AUC(0-24) in plasma was 25.13 ± 5.78 μg · h/ml. Protein binding was 89.44% ± 1.58%, resulting in a mean fAUC(0-24) of 2.65 ± 0.72 μg · h/ml in plasma. Mean concentrations (μg/ml) at 2, 6, 12, and 24 h were 9.05 ± 3.83, 4.45 ± 2.18, 5.62 ± 1.99, and 1.33 ± 0.59 in ELF and 3.67 ± 1.02, 4.38 ± 2.18, 1.42 ± 0.63, and 1.04 ± 0.52 in AM. ELF and AM penetration ratios were 41.2 and 20.0. The mean ELF penetration ratio after population analyses was 39.7. This study demonstrates that tedizolid penetrates into ELF and AM to levels approximately 40-fold and 20-fold, respectively, higher than free-drug exposures in plasma.


February 21, 2013 at 3:54 pm

Nosocomial Pneumonia in Patients with Acute Respiratory Distress Syndrome

Am. J. Respir. Crit. Care Med. April 1, 1998  V.157  N.4 P.1165-1172


1 Services de Réanimation Médicale, Microbiologie, and Pneumologie, Hôpital Bichat, Paris, France

To describe the epidemiologic and microbial aspects of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS), we prospectively evaluated 243 consecutive patients who required mechanical ventilation (MV) for  48 h, 56 of whom developed ARDS as defined by a Murray lung injury score > 2.5. We did this with bronchoscopic techniques when VAP was clinically suspected, before any modification of existing antimicrobial therapy.

For all patients, the diagnosis of pneumonia was established on the basis of culture results of protected-specimen brush (PSB) ( 103 cfu/ml) and bronchoalvelolar lavage fluid (BALF) ( 104 cfu/ml) specimens, and direct examination of cells recovered by bronchoalveolar lavage (BAL) ( 5% of infected cells). Thirty-one (55%) of the 56 patients with ARDS developed VAP for a total of 41 episodes, as compared with only 53 (28%) of the 187 patients without ARDS for a total of 65 episodes (p = 0.0005). Only 10% of first episodes of VAP in patients with ARDS occurred before Day 7 of MV, as compared with 40% of the episodes in patients without ARDS (p = 0.005).

All but two patients with ARDS who developed VAP had received antimicrobial treatment (mostly with broad-spectrum antibiotics) before the onset of infection, as compared with only 35 patients without ARDS (p = 0.004).

The organisms most frequently isolated from patients with ARDS and VAP were methicillin-resistant Staphylococcus aureus (23%), nonfermenting gram-negative bacilli (21%), and Enterobacteriaceae (21%). These findings confirm that microbiologically provable VAP occurs far more often in patients with ARDS than in other ventilated patients. Because these patients are often treated with antibiotics early in the course of the syndrome, the onset of VAP is frequently delayed after the first week of MV, and is then caused mainly by methicillin-resistant S. aureus and other multiresistant microorganisms.


February 21, 2013 at 3:52 pm


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