quinupristin and Kidney-Failure--Chronic

To compare the pharmacokinetic profile of a single intravenous injection of quinupristin/dalfopristin, a new injectable streptogramin, in healthy young individuals and patients with severe chronic renal insufficiency. A secondary objective was to assess the relative tolerability of this dose in these patients compared with healthy individuals.. 13 patients with severe chronic renal insufficiency (creatinine clearance 6 to 28 ml/min/1.73m2) were individually matched for gender, bodyweight and age to a healthy volunteer.. Participants received a single dose of quinupristin/dalfopristin 7.5 mg/kg bodyweight as a continuous 1-hour intravenous infusion, followed by serial blood sampling.. The disposition profile of unchanged quinupristin was similar in the 2 groups. However, the elimination of quinupristin derivatives in patients with renal impairment tended to be decreased: mean peak plasma drug concentration (Cmax) and area under the concentration-time curve from zero to infinity (AUCinfinity) of quinupristin plus its active derivatives were about 1.4 times higher in the patients with renal impairment compared with healthy volunteers. The mean Cmax and AUCinfinity of both unchanged dalfopristin and dalfopristin plus its active derivatives were about 1.3 times higher in renally impaired patients than in healthy volunteers. Adverse events were generally mild and transient. No severe or serious adverse events were reported and no participants prematurely discontinued the study. Venous tolerability tended to be better in healthy volunteers than in the patients with renal impairment.. These results suggest that no formal reduction in the dosage of quinupristin/dalfopristin is necessary in patients with severe chronic renal impairment.

Topics: Adult; Aged; Anti-Bacterial Agents; Area Under Curve; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Virginiamycin

Life-threatening infections with multiresistant gram-positive bacteria are increasing. Treatment with quinupristin/dalfopristin (Q-D) has turned out to be effective against such resistant pathogens.. We report on treatment of six patients on dialysis (four with additional liver injury) and of one renal graft recipient with normal renal function who had severe infections caused by multiresistant Staphylococus epidermidis (1/7), methicillin-resistant Staphylococcus aureus (4/7) and vancomycin-resistant Enterococcus faecium (2/7).. Six out of seven patients were cured by therapy with Q-D in adjusted doses lasting for 10 to 34 days. Pharmacokinetics of Q-D and its metabolites were determined and remained within the therapeutic range, despite a modest increase of all compounds at the presumed steady state. The concentrations of the metabolites of Q-D were clearly lower than the parent drugs, including those of quinupristin-conjugated derivatives, which has not been reported previously.. These preliminary results suggest that: a) neither quinupristin nor dalfopristin or its metabolites accumulated despite the long duration of treatment; b) no adjustment of the standard dosage regimen (three times 7.5 mg/kg/day) is necessary in end-stage renal disease.

Topics: Aged; Aged, 80 and over; Bacteremia; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecium; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Kidney Failure, Chronic; Male; Methicillin Resistance; Middle Aged; Prospective Studies; Risk Assessment; Sampling Studies; Staphylococcal Infections; Treatment Outcome; Vancomycin Resistance; Virginiamycin