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Dosage adjustment of antiinfective therapy in patients with renal impairment
A Eckhardt1, K Borner, F Keller
1Medical Department, University Hospital Ulm, Germany.
Abstract:
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.
Insights
Dosage adjustments for antibiotics in renal impairment are complex. Higher trough levels may be necessary to prevent anti-infective failure, even with renal replacement therapy.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Renal impairment significantly alters drug elimination half-lives.
- Aminoglycosides, vancomycin, and ciprofloxacin require careful dosage adjustment in patients with kidney dysfunction.
- Therapeutic drug monitoring (TDM) is crucial for optimizing antimicrobial therapy in critically ill patients.
Purpose of the Study:
- To evaluate the effectiveness of schematic dosage adjustments for common antibiotics in severely ill patients with renal impairment.
- To identify factors contributing to anti-infective failure and toxicity in this patient population.
- To refine TDM strategies for antibiotics in patients undergoing renal replacement therapy.
Main Methods:
- Retrospective evaluation of TDM data from 84 severely ill patients.
- Analysis of dosage adjustments based on published data for prolonged elimination half-lives.
- Multivariate analysis to identify independent predictors of anti-infective failure.
Main Results:
- High rates of mortality (32%) and anti-infective failure (27%) were observed.
- Patients with renal impairment showed lower peak and higher trough drug levels compared to those with normal renal function.
- Persistent fever and deteriorating renal function, not drug levels or renal replacement therapy, were independent predictors of anti-infective failure.
- Aminoglycoside troughs were significantly elevated in patients on renal replacement therapy.
Conclusions:
- Current schematic dosage adjustments may not be adequate for preventing anti-infective failure in renal impairment.
- Higher trough concentrations than typically recommended may be necessary to avoid underdosage in patients on renal replacement therapy.
- Focusing on managing persistent fever and improving renal function is critical for successful anti-infective treatment in this population.