Dosage adjustment of antiinfective therapy in patients with renal impairment.

Schematic dosage adjustments for aminoglycosides, vancomycin, and ciprofloxacin were derived from published data on the prolongation of elimination half-lives in patients with renal impairment. Therapeutic drug monitoring was retrospectively evaluated with 84 severely ill patients, 29 of whom needed renal replacement therapy (35%). Mortality (n = 27) and antiinfective failures were high (n = 23). Toxicity was suspected in 5 patients, though it was demonstrated only in 1 case. As compared to the patients with normal renal function, patients with renal impairment exhibited peak levels that tended to be lower, although their trough levels tended to be higher; the aminoglycoside troughs even were significantly elevated in renal replacement patients (1.0 mg/l (0.6-1.4) versus 0.6 mg/l (0.3-0.8)). Seen in relation to toxicity, antiinfective failure was by far the greater problem even with dosage adjustments at high trough levels. Multivariate analysis showed antiinfective failure to be significantly correlated to 10 canonical variables (age, weight, leucocyte count, peak level, trough level, initial creatinine, increase in creatinine, fever, change of dosage, and renal replacement therapy). Among these variables, it were neither drug levels nor renal replacement, but only persistent fever and deteriorating renal function that independently contributed to antiinfective failure. For adjustment of antiinfective therapy, paradoxically we conclude that trough concentrations higher than normal must be allowed for to avoid underdosage in renal replacement patients.