Examining the risk of neurotoxicity in patients who receive unadjusted doses of oral beta-lactams in renal insufficiency: a retrospective cohort study.

BACKGROUND

In patients with reduced renal function, drug monographs recommend reduced doses of oral beta-lactams. However, dose reductions could result in suboptimal pharmacokinetic-pharmacodynamic target attainment, compromising efficacy. This study evaluated the safety of full doses of oral beta-lactams in patients with reduced renal function by assessing the incidence of neurotoxic symptoms.

METHODS

This single-site, retrospective cohort study included patients with renal insufficiency prescribed full dose or renally adjusted doses of oral beta-lactams. Neurotoxicity symptoms were graded via chart review using the Naranjo Adverse Drug Reaction Probability Scale. The primary outcome was incidence of 'probable' or 'definite' beta-lactam related neurotoxicity. Multivariate logistic regression was used to adjust for differences in baseline characteristics.

RESULTS

The cohort included 987 patients with renal insufficiency receiving 1001 full-dose courses and 122 renally adjusted dose courses. The rate of 'probable' or 'definite' neurotoxicity was 0.1% (1/1001) in the full dose group and 0.8% (1/122) in the renally adjusted group (p = 0.08). There was no difference between groups when stratified by early or late stage renal insufficiency. After adjustment for differences in baseline characteristics, receiving full dose oral beta-lactams was not associated with an increased odds of 'possible', 'probable' or 'definite' neurotoxicity as the aOR was less than 1 [aOR = 0.52, 95% CI 0.30-0.89, p = 0.02].

CONCLUSION

There was no increase in 'probable' or 'definite' neurotoxicities detected among patients with renal insufficiency receiving full dose as compared to renally adjusted doses of oral beta-lactams, suggesting that using full doses are a safe way to optimize the pharmacokinetic-pharmacodynamic parameters of these drugs.