The range of adverse events of linezolid is growing; new ones, such as nephro-toxicity and Bell's palsy, have been reported. Toxicity of linezolid is mostly related with the prolonged duration of treatment and the presence of predisposing factors. Physicians must be alerted when using linezolid for indications and duration different from the approved ones, and must be aware of the possible adverse events. In case of toxicity, the main option is the discontinuation of the drug; although, not all adverse events are fully reversible. Linezolid represents an important advance in therapeutics and is still considered safe enough, but anticipated benefits must always be counterbalanced by the possible toxicity.
BackgroundThere is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI).MethodsSixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations.ResultsHPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001).ConclusionsIn our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.
Pneumonia, along with influenza, is the leading cause of mortality associated with infectious diseases in the USA. Tigecycline is a novel antimicrobial agent that is active against a broad spectrum of pathogens. Our objective is to review the literature about the efficacy of tigecycline in community-acquired pneumonia (CAP). Data from various sources, including Pubmed, the European Medicines Agency (EMEA) and the US FDA were appraised. Tigecycline was found to be noninferior compared with levofloxacin for the treatment of patients with bacterial CAP requiring hospitalization. Recently, the drug was approved for the treatment of these patients by the FDA, but owing to some concerns, its application in the EMEA has been withdrawn. In addition, in a recent study concerns were expressed about the efficacy of tigecycline in the lungs using the current dosage. More data are needed about the pharmacokinetics of tigecycline in the lungs and its efficacy in severe CAP.
To cite this version:Matthew E. Falagas, Argyris Michalopoulos, Eugenios I. Metaxas. Pulmonary drug delivery systems for antimicrobial agents: facts and myths. International Journal of Antimicrobial Agents, Elsevier, 2009, 35 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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