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The concentration at the site of action is also a key determinant in the activity of an antimicrobial agent. Arrigucci et al. 9 have shown that peritoneal concentrations at 3 h after a 1 g intravenous infusion of ertapenem in scheduled surgery patients were 83% of the plasma concentration. In our study, the ability to assay the unbound fraction was limited because of the low total plasma and peritoneal concentrations and the high protein-bound level of this antimicrobial agent. Even if the free fraction exceeded 50%, the C min of free ertapenem would not exceed the breakpoint in these patients. In most of our patients, total ertapenem plasma and perito-neal concentrations did not reach the target recommended for critically ill patients. 6 At 12 h after infusion, concentrations in peritoneal fluid were above the breakpoint for ertapenem susceptibility against Enterobacteriaceae and anaerobes, but at 24 h, concentrations were frequently below these thresholds. We found good peritoneal ertapenem diffusion, with concentrations equivalent to those measured in plasma, but they remained insufficient with regards to the breakpoints for susceptibility against causative bacteria. Despite the low total-plasma and peritoneal concentrations, a lack of efficacy to cure our patients could not be concluded, but the impact of such findings on clinical outcomes and the risk of selecting multiresistant bacteria are of concern. 4 In conclusion, at a fixed dose of 1 g/day, total plasma and peritoneal C min of ertapenem in patients who have severe secondary peritonitis were low with regards to breakpoint susceptibilities of this antimicrobial agent for the main bacterial types recovered in these infections. These findings suggest that dosing ertapenem at 1 g twice daily would be more suitable.

Gentamicin and acute kidney injury requiring renal replacement therapy in the context of a restrictive antibiotic policy