Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.
BackgroundCerebrospinal fluid (CSF) polymerase chain reaction (PCR) technology can be used as a rapid diagnostic tool that has the potential to more rapidly facilitate targeted antimicrobial therapy and reduce overall time to de-escalation and/or discontinuation of inappropriate antimicrobial usage in patients with suspected meningitis/encephalitis.MethodsThis was a single-center, retrospective cohort analysis with a primary objective focusing on time to de-escalation or discontinuation of inappropriate antimicrobials before and after implementation of a rapid diagnostic meningitis/encephalitis (ME) panel (BioFire FilmArray®). The pre-implementation group, containing 84 patients, examined individuals who had CSF cultures performed in the 6-months prior to implementation. The post-implementation group, containing 88 patients, examined individuals who had an ME panel done in the 6 months following a transitionary 1-month period following implementation. Categorical data analysis was performed using χ2 or Fisher’s exact test and continuous data was analyzed using the Mann–Whitney U test.ResultsTime to de-escalation/discontinuation of inappropriate ampicillin reported in median hours (IQR) was 47.5 (55) for pre-PCR group compared with 39.5 (23.5) in post-PCR group (P = 0.004). Time to de-escalation/discontinuation of Cefotaxime for pre-PCR group was 50.5 (42) compared with 45 (10) for post-PCR (P = 0.027). Using a subgroup analysis based on age, the results for ampicillin and cefotaxime were mirrored in the pediatric population; however, results were insignificant in the adult population. Subgroup analysis of the adult population showed significance in terms of de-escalation/discontinuation of acyclovir reported (in median hours) as 49 (68) in pre-PCR and 19 (18) in post-PCR group (P = 0.002).ConclusionTime to de-escalation and/or discontinuation of ampicillin and cefotaxime was significantly reduced after implementation of the ME panel suggesting clinical significance in high-risk populations such as neonates. Time to de-escalation and/or discontinuation of acyclovir was significantly reduced in the adult population.Disclosures
All authors: No reported disclosures.
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