DOSAGE ADJUSTMENT OF ANTIINFECTIVE THERAPY IN PATIENTS WITH RENAL IMPAIRMENT

Schematic dosage adjustments for aminoglycosides, vancomycin, and cipr ofloxacin were derived from published data on the prolongation of elim ination half-lives in patients with renal impairment. Therapeutic drug monitoring was retrospectively evaluated with 84 severely ill patient s, 29 of whom needed renal replacement therapy (35%). Mortality (n = 2 7) and antiinfective failures were high (n = 23). Toxicity was suspect ed in 5 patients, though it was demonstrated only in 1 case. As compar ed to the patients with normal renal function, patients with renal imp airment exhibited peak levels that tended to be lower, although their trough levels tended to be higher; the aminoglycoside troughs even wer e 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, ant iinfective failure was by far the greater problem even with dosage adj ustments at high trough levels. Multivariate analysis showed antiinfec tive failure to be significantly correlated to 10 canonical variables (age, weight, leucocyte count, peak level, trough level, initial creat inine, increase in creatinine, fever, change of dosage, and renal repl acement therapy). Among these variables, it were neither drug levels n or renal replacement, but only persistent fever and deteriorating rena l function that independently contributed to antiinfective failure. Fo r adjustment of antiinfective therapy, paradoxically we conclude that trough concentrations higher than normal must be allowed for to avoid underdosage in renal replacement patients.