부산대학교 도서관

Background Based on prior studies, elderly patients and those with renal dysfunction are prone to cefepime (CFP) toxicity. The toxicokinetics and toxicodynamics for CFP are not well established. Lamoth et al. reported a 50% probability of CFP neurotoxicity at a serum trough concentration of ≥22 mg/L, whereas Huwyler et al. observed CFP neurotoxicity when concentrations exceeded 35 mg/L. The objectives of this study were to quantify the incidence of CFP neurotoxicity and to assess the association between CFP concentrations and neurotoxicity. Methods We conducted a retrospective review between March 2016 and May 2018, of adult patients with serum CFP trough concentrations ≥25 mg/L. To be considered a CFP neurotoxicity case, patients were required to fulfill at least two of the NCI criteria for neurological toxicity such as, presence of new-onset confusion, delirium, or drowsiness. Following this, cases were classified as (1) high likelihood of toxicity (HLT) if they either had a neurology consult or EEG findings consistent with CFP toxicity and if their symptoms improved after discontinuation of CFP, (2) possible toxicity (PT) if neurology consult or EEG was absent or if we were unable to assess improvement after CFP was discontinued, or (3) nontoxicity (NT). Cases were independently reviewed by an ID pharmacist and physician. Additional data such as comorbidities, renal function, and use of anti-epileptics were collected. Results One hundred and forty-two patients were included in the analysis. Neurotoxicity (HLT+PT) related to CFP occurred in 18/142 (13%) patients; 67% (12/18) were considered HLT. The median age in the HLT cohort was 68 years (interquartile range [IQR], 57–74), with toxicity occurring a median of 6 days (IQR, 5–8) after starting CFP. At the time of neurotoxicity, HLT patients had diminished renal function with a median SCr of 1.6 mg/dL (IQR, 1.2–2.4) and a corresponding CrCl of 35.8 mL/minute (IQR, 19.2–50.9). The median CFP trough concentration in the HLT patients was 62 mg/L (IQR, 50–73) vs. 70mg/L (IQR, 41–115) in the PT and 42 mg/L (IQR, 31–61) in the NT groups. Conclusion Our data emphasize the need for careful dosing in older patients with renal insufficiency. Interestingly, our study reveals higher cefepime troughs (~3-fold higher) associated with neurotoxicity than previously reported. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]