International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · May 2009
Clinical TrialClinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion.
The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. ⋯ Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.
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Int. J. Antimicrob. Agents · May 2009
Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis.
Adequate data on the pharmacokinetics of once-daily administration of ertapenem in critically ill patients are largely lacking. This single-centre, prospective, open-label study was performed on a cohort of eight critically ill patients with severe sepsis with normal renal function treated with 1g of ertapenem once daily. Samples of venous blood and urine were collected before infusion and at specific time points in the 24-h post-infusion period. ⋯ Unbound levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than 7.1h (30%) of the dosing interval in two patients. The highly variable and unpredictable intersubject pharmacokinetic parameters documented in this study resulted in suboptimal unbound concentrations in some patients. This raises the question as to whether ertapenem is an appropriate agent for initial use in critically ill patients with severe sepsis.