A prospective study to evaluate high dose daptomycin pharmacokinetics and pharmacodynamics in spp. infective endocarditis.

BACKGROUND

Daptomycin pharmacokinetics and pharmacodynamics data relative to higher doses in patients are necessary for clinical practice.

OBJECTIVES

A monocentric, prospective study that enrolled patients with a diagnosis of spp. infective endocarditis treated with daptomycin according to clinical practice, to evaluate the pharmacokinetics/pharmacodynamics of different daptomycin daily doses (group A: 8-10 and group B: 11-12 mg/kg).

DESIGN AND METHODS

A monocentric, prospective, cohort study that enrolled patients with a diagnosis of spp. infective endocarditis treated with daptomycin. Daptomycin was administered by intravenous infusion over a 30-min period for at least five consecutive days before PK study.

RESULTS

Twenty-two patients were included. Native valve infectious endocarditis (IE) was diagnosed in 9 patients, prosthetic valve IE was diagnosed in 10 patients and 3 patients had concomitant intracardiac device infections. All patients showed a microbiologic response with negative blood cultures by day 5 (1-3 interquartile rate (IQR) 3-8). The median calculated AUC was 1298 (1-3 IQR 1069-1484) and 1459 (1-3 IQR 1218-1711) µg*h/mL, with the corresponding clearance of 0.49 (1-3 IQR 0.37-0.57) and 0.57 (1-3 IQR 0.40-0.71) L/h, respectively. A value of area under the curve/minimum inhibitory concentration (AUC/MIC) > 666 was reached by all patients; however, 4 out of 15 patients in group A and 1 out of 14 patients in group B did not reach the pharmacokinetic/pharmacodynamic (PK/PD) target of 1061; therefore, AUC/MIC equal to or above 1061 was reached by 73.3% in group A and 92.9% in group B.

CONCLUSION

From a PK/PD point of view, all patients reached the value of AUC/MIC > 666, while roughly 70% of patients in group A and 90% in group B reached the target value of AUC/MIC>1061. Even if this cut-off value is arbitrary, 11-12 mg/kg daily dose could be taken into consideration in case of serious infections characterised by a high inoculum or in cases of prosthetic valve infections.