Treatment of life-threatening multiresistant staphylococcal and enterococcal infections in patients with end-stage renal failure with quinupristin/dalfopristin: preliminary report.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Schwenger
V
V
Dept. of Internal Medicine, University Hospital Heidelberg, Bergheimer Str. 56a, D-69115 Heidelberg, Germany. vedat.schwenger@med.uni-heidelberg.de
Mündlein
E
E
Dagrosa
E E
EE
Fahr
A M
AM
Zeier
M
M
Mikus
G
G
Andrassy
K
K
D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy*; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D016908:Gram-Positive Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy; D008297:Male; D016106:Methicillin Resistance; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012494:Sampling Studies; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D020713:Vancomycin Resistance; D014769:Virginiamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014769:Virginiamycin; C113825:quinupristin; C113826:dalfopristin