International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Jun 2010
Case ReportsAugmented renal clearance in the Intensive Care Unit: an illustrative case series.
The substantial underlying disease burden, in combination with the therapeutic interventions provided, can result in significantly altered end-organ function in the critically ill. These changes can in turn affect key pharmacokinetic (PK) indices for many antibiotics, including drug clearance, promoting potentially subtherapeutic concentrations for lengthy periods of the dosing interval, therapeutic failure or the selection of resistant organisms. ⋯ We propose augmented renal clearance as a possible mechanism underlying this phenomenon, particularly in young post-operative, burns or head-injured patients with normal serum creatinine concentrations. TDM, or at least a measured creatinine clearance, should be considered early in this setting to allow the optimisation of antibiotic exposure.
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Int. J. Antimicrob. Agents · Jun 2010
2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia.
Acute lung inflammation (ALI) is a life-threatening pathology and can develop during the course of several clinical conditions such as pneumonia, acid aspiration or sepsis. Adenosine plays a significant role in controlling acute inflammation via binding to A(2A) receptors on inflammatory cells, i.e. neutrophils or macrophages. The present study was designed to evaluate the anti-inflammatory and immunomodulatory effects of 2-chloroadenosine (2-CADO), alone or in combination with amoxicillin/clavulanic acid (AMC), in Klebsiella pneumoniae B5055-induced acute lung infection in mice. ⋯ AMC), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFalpha and IL-1alpha along with elevation of IL-10 levels in the lung homogenate of mice with acute lung infection was observed upon treatment with 2-CADO alone, with no significant decrease in bacterial counts. Moreover, in combination with AMC, 2-CADO exhibited its immunomodulatory action in acute lung infection and prevented ALI, whilst an antibacterial action was exhibited by AMC.