Pharmacodynamic characterization of nephrotoxicity associated with once-daily aminoglycoside.
OBJECTIVE
To characterize nephrotoxicity associated with an individualized serum concentration target-specific, once-daily aminoglycoside (ODA) program.


METHODS
Concurrent and retrospective study.


METHODS
University-affiliated trauma hospital.


METHODS
Two hundred patients treated with ODA and 100 treated with individualized traditional dosing (TDA).


METHODS
Empiric dosing for both groups was based on patient-specific pharmacokinetics and severity of infection. Regimens were modified according to predetermined target maximum and minimum serum concentrations for both groups.


RESULTS
Nephrotoxicity occurred in 7.5% patients treated with ODA and 14.7% receiving TDA (p=0.05). Minimum serum concentrations, length of aminoglycoside therapy, and cumulative area under the curve (AUC) were all dependently related to nephrotoxicity, and concomitant vancomycin and other nephrotoxic drugs were independently related to the disorder. The cumulative AUC was greatest in patients receiving TDA (p=0.03), and the modeled probability of becoming toxic at any given cumulative AUC was significantly greater with TDA than with ODA (p<0.01). Clinical and microbiologic outcomes were similar between groups. Maximum concentration:minimum inhibitory concentration ratios were higher (p<0.01) and number of days to organism eradication was shorter in the ODA group (p=0.04).


CONCLUSIONS
The trend was toward decreased nephrotoxicity in patients treated with ODA compared with TDA, and at any given cumulative AUC, the risk of toxicity was lower for ODA.
Murry
K R
KR
Department of Pharmacy Services, Detroit Receiving Hospital, Michigan 48201, USA.
McKinnon
P S
PS
Mitrzyk
B
B
Rybak
M J
MJ
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents