Tissue pharmacokinetics of ertapenem at steady-state in diabetic patients with leg infections.

OBJECTIVES Ertapenem pharmacokinetics were determined in the interstitium of healthy tissue and of infected tissue of patients suffering from diabetic foot infections, to evaluate if antibiotic concentrations at the target site are sufficient to achieve bacterial killing. PATIENTS AND METHODS Nine patients with diabetic foot infections received 1 g of ertapenem per day intravenously. At steady-state, ertapenem concentrations were measured over 8 h in plasma and in the interstitium of healthy subcutaneous adipose tissue and of soft tissue adjacent to the foot infection using microdialysis. RESULTS The maximum total concentration (Cmax) of ertapenem in plasma was 59.4 ± 12.9 mg/L. Free interstitial Cmax in the infected leg (4.5 ± 2.7 mg/L) was significantly higher (P=0.01) than in healthy subcutaneous tissue (2.4 ± 1.6 mg/L). For bacterial pathogens with an MIC of 1 mg/L, the free mean 'time above MIC' (T>MIC) in the interstitium of infected tissue was calculated to be 38%± 25% of the 24 h dosing interval. Accordingly, bacteriostatic (T>MIC >20%) and maximal bactericidal (T>MIC >40%) effects would be reached in 8/9 and 4/9 diabetic feet, respectively. CONCLUSIONS Although total plasma concentrations of ertapenem were lower in diabetics than reported for healthy subjects, free interstitial tissue concentrations in diabetics were similar to those known from healthy volunteers. Penetration of ertapenem into the interstitium of inflamed tissue of diabetic feet was not impaired in spite of angiopathy. Daily doses of >1 g of ertapenem might be considered to optimize bactericidal effects in diabetic foot infections caused by moderately susceptible strains.