Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides

Background: There remain concerns about the safety of once-daily dosing of aminoglycosides (AGs) in the elderly. Aim: To assess the safety of once-daily AGs in elderly patients and evaluate possible risk factors for nephrotoxicity. Design: Prospective, non-interventional surveillance study. Methods: All patients receiving AGs were monitored over 4 months. Clinicians determined the AG dose for each patient after estimating patient weight and calculating creatinine clearance (CrCl) using the Cockcroft-Gault formula. Parallel figures were calculated by the investigators using measured weight. Clinicians obtained an AG trough level 24 h after initiation of treatment, and, if non-toxic, every 5-7 days thereafter. AG toxicity was defined as an increase in serum creatinine of greater than or equal to50%. Results: In the study period, 249 consecutive patients received an AG: 116 (47%) males, mean+/-SD age 75+/-16 years. Forty-two (17%) received amikacin and 207 (83%) gentamicin. An increase of greater than or equal to50% in serum creatinine was detected in 31/249 (12.4%); maximal creatinine was less than or equal to177 mumol/l in 16/249 (6.4%), 186-265 mumol/l in nine (3.6%), and >265 mumol/l in six (2.4%). None developed oliguric renal failure. Renal damage correlated with a high AG trough level (>1.1 mug/ml) (p<0.001); haemoglobin level <10 g/dl (p<0.05); hospital admission >7 days prior to AG treatment (p<0.005); and AG treatment greater than or equal to11 days (p<0.05). Mean CrCl based on estimated weight was 52+/-18 ml/min; that based on actual weight was 71+/-37 ml/min. Despite this, mean AG dose was 1.3+/-0.6 higher than optimal. Conclusions: Oliguric and/or lasting renal toxicity is rare in elderly patients receiving once-daily aminoglycosides for <11 days, if regular trough drug levels are monitored.