It is clear that in this relatively new study area the knowledge space is already occupied by poor studies and potentially unreliable data. We would www.selleckchem.com/products/ABT-263.html like to encourage investigators to design studies that are methodologically robust and provide reliable mechanistic data. ICU researchers should work towards developing valid surrogate endpoints to allow robust and reliable translational research, although we acknowledge that previous success at improving organ performance has not always improved outcomes [12-14]. Once validated, these surrogate endpoints should be used to establish the biological effectiveness of new treatments (and probably some existing ones) before moving on to pragmatic studies using mortality as outcome measure .
Without demonstrating first biological and then functional (for example, organ performance) effectiveness, we run the risk of wrongly adding statins to the wasteland of ICU pharmacotherapy. On the positive side, the pleiotropic effects of statins and extensive experience with these agents in cardiology mean that we may be less likely to fall into a trap constructed of an insufficient understating of mechanisms combined with a single-target therapy .AbbreviationsCPB: cardiopulmonary bypass; IL: interleukin.Competing interestsThe authors declare that they have no competing interests.NotesSee related research by Morgan et al., http://ccforum.com/content/13/5/R165
Aminoglycosides are broad-spectrum antibiotics active against most Gram-negative pathogens responsible for ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) or healthcare-associated pneumonia (HCAP), even those with multidrug-resistance patterns .
However, the systemic use of this antibiotic class is limited by its toxicity and poor penetration into the lung [2-4]. Also, minimum inhibitory concentrations (MIC) of still active antibiotics on multidrug-resistant Gram-negative bacteria, mainly aminoglycosides, are higher. Aerosol administration offers the theoretical advantage of achieving high antibiotic concentrations at the infection site and low systemic absorption, Batimastat thereby avoiding renal toxicity . Although available data are abundant for cystic fibrosis, data on aerosolized antibiotics for mechanically ventilated patients are scarce, even for aerosolized aminoglycosides, which are the most studied . Moreover, during mechanical ventilation, high amounts of the particles dispersed by conventional nebulizers remain in the ventilatory circuits and the tracheobronchial tree before reaching the distal lung and, therefore, less drug is available in the alveolar compartment.