Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

Colistin; Phramacokinetic; Technique of nebulizationColistina; Farmacocinètica; Tècnica de nebulitzacióColistina; Farmacocinético; Técnica de nebulizaciónClinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.This research received no external funding

Stability of long-sustained oscillations induced by electron tunneling

Self-oscillations are the result of an efficient mechanism generating periodic motion from a constant power source. In quantum devices, these oscillations may arise due to the interaction between single electron dynamics and mechanical motion. Due to the complexity of this mechanism, these self-oscillations may irrupt, vanish, or exhibit a bistable behavior causing hysteresis cycles. We observe these hysteresis cycles and characterize the stability of different regimes in single and double quantum dot configurations. In particular cases, we find these oscillations stable for over 20 seconds, many orders of magnitude above electronic and mechanical characteristic timescales, revealing the robustness of the mechanism at play. The experimental results are reproduced by our theoretical model that provides a complete understanding of bistability in nanoelectromechanical devices.Comment: 11 pages, 10 figures, includes the complete paper and the Supplemental Materia

e-Pilly TROP Maladies infectieuses tropicales

L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence

Future Perspectives of Bone Tissue Engineering with Special Emphasis on Extracellular Vesicles

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