Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring.
Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN.
Bertino
J S
JS
Department of Pharmacy Services, Clinical Pharmacology Research Center, Cooperstown, New York 13326.
Booker
L A
LA
Franck
P A
PA
Jenkins
P L
PL
Franck
K R
KR
Nafziger
A N
AN
D000328:Adult; D000368:Aged; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003404:Creatinine