Pharmacokinetics of amphotericin B after accidental overdose in an adult critically ill patient treated with plasmapheresis: a case report and review of literature

Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

Diagnostic Accuracy of Procalcitonin and C-reactive Protein Is Insufficient to Predict Proven Infection : A Retrospective Cohort Study in Critically Ill Patients Fulfilling the Sepsis-3 Criteria

BACKGROUND: New Sepsis-3 definitions facilitate early recognition of patients with sepsis. In this study we investigated whether a single initial determination of procalcitonin (PCT) or C-reactive protein (CRP) in plasma can predict proven sepsis in Sepsis-3 criteria-positive critically ill patients. We also investigated whether a decline in serial PCT or CRP can predict outcome in 28-day mortality. METHODS: Patients, ≥18 years of age, at the intensive care unit with a suspected infection, a Sequential Organ Failure Assessment (SOFA) score of ≥2 points, and an index test PCT and CRP at admission were selected from a prospectively collected cohort. PCT and CRP were studied retrospectively with the Mann-Whitney U-test and ROC analysis. RESULTS: In total, 157 patients were selected; 63 of the 157 had proven sepsis, and sepsis could not be detected in 94 of the 157. Neither a single PCT nor CRP at admission was able to discriminate proven sepsis from nonproven sepsis (PCT, 1.8 μg/L and 1.5 μg/L, respectively, P = 0.25; CRP, 198 mg/L and 186 mg/L, respectively, P = 0.53). Area under the curve for both PCT and CRP for detecting proven sepsis was low (0.55 and 0.53). Furthermore, neither a decline from baseline to day 5 PCT nor CRP could predict 28-day mortality (PCT, 50% vs 46%, P = 0.83; CRP, 30% vs 40%, P = 0.51). CONCLUSION: PCT and CRP at admission were not able to discern patients with proven sepsis in Sepsis-3 criteria-positive critically ill patients. A decline of PCT and CRP in 5 days was not able to predict 28-day mortality

Diagnostic Accuracy of Procalcitonin and C-reactive Protein Is Insufficient to Predict Proven Infection : A Retrospective Cohort Study in Critically Ill Patients Fulfilling the Sepsis-3 Criteria

BACKGROUND: New Sepsis-3 definitions facilitate early recognition of patients with sepsis. In this study we investigated whether a single initial determination of procalcitonin (PCT) or C-reactive protein (CRP) in plasma can predict proven sepsis in Sepsis-3 criteria-positive critically ill patients. We also investigated whether a decline in serial PCT or CRP can predict outcome in 28-day mortality. METHODS: Patients, ≥18 years of age, at the intensive care unit with a suspected infection, a Sequential Organ Failure Assessment (SOFA) score of ≥2 points, and an index test PCT and CRP at admission were selected from a prospectively collected cohort. PCT and CRP were studied retrospectively with the Mann-Whitney U-test and ROC analysis. RESULTS: In total, 157 patients were selected; 63 of the 157 had proven sepsis, and sepsis could not be detected in 94 of the 157. Neither a single PCT nor CRP at admission was able to discriminate proven sepsis from nonproven sepsis (PCT, 1.8 μg/L and 1.5 μg/L, respectively, P = 0.25; CRP, 198 mg/L and 186 mg/L, respectively, P = 0.53). Area under the curve for both PCT and CRP for detecting proven sepsis was low (0.55 and 0.53). Furthermore, neither a decline from baseline to day 5 PCT nor CRP could predict 28-day mortality (PCT, 50% vs 46%, P = 0.83; CRP, 30% vs 40%, P = 0.51). CONCLUSION: PCT and CRP at admission were not able to discern patients with proven sepsis in Sepsis-3 criteria-positive critically ill patients. A decline of PCT and CRP in 5 days was not able to predict 28-day mortality