Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. RESULTS: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. DISCUSSION/CONCLUSION: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

Daily Naltrexone Use Does Not Adversely Affect Physical, Cognitive or Marksmanship Performance in U.S. Army Soldiers.

INTRODUCTION: Considering the potential of weaponized opioids, evaluating how prophylactic countermeasures affect military-relevant performance is necessary. Naltrexone is a commercially available Food and Drug Administration-approved medication that blocks the effects of opioids with minimal side effects. However, the effects of naltrexone on the health and performance of non-substance abusing military personnel are not well described in the existing literature. METHODS: Active duty U.S. Army Soldiers (n = 16, mean ± SD, age: 23.1 ± 5.3 y) completed a series of physical, cognitive, and marksmanship tasks during a 4-day pretrial, a 7-day active trial, and a 4-day post-trial phase. During the active trial, participants were administered 50 mg of oral naltrexone daily. Physiological and biological processes were monitored with a daily review of systems, sleep monitoring, biochemistry, and hematology blood panels. RESULTS: Naltrexone did not negatively affect physical performance, cognitive functioning, marksmanship, or sleep duration (P > 0.05). Improvements were observed during the active trial compared to the pretrial phase in cognitive tasks measuring logical relations (P = 0.05), matching to sample (P = 0.04), math speed (P < 0.01), math percent correct (P = 0.04), and spatial processing (P < 0.01). Results from biochemistry and hematology blood panels remained within clinically normative ranges throughout all phases of the study. No participants were medically withdrawn; however, one participant voluntarily withdrew due to nausea and reduced appetite. CONCLUSIONS: Temporary (7-day) daily use of naltrexone was safe and did not negatively affect physical performance, cognitive functioning, marksmanship ability, or sleep in a healthy cohort of U.S. Army Soldiers.

Plasma Blood Levels of Tafenoquine following a Single Oral Dosage in BALBc Mice with Acute Babesia microti Infection That Resulted in Rapid Clearance of Microscopically Detectable Parasitemia.

Previous studies of mice infected with Babesia microti have shown that a single dose of tafenoquine administered orally is extremely effective at decreasing microscopically detectable parasitemia. However, a critical limitation of studies to date is the lack of data concerning the plasma levels of tafenoquine that are needed to treat babesiosis. In the current study, we begin to address this gap by examining the plasma levels of tafenoquine associated with the rapid reduction of B. microti patent parasitemia in a mouse model of babesiosis. In the current study, we infected BALB/c mice with 1 × 107B. microti-infected red blood cells. Two days post-infection, mice were treated with 20 mg/kg of tafenoquine succinate or vehicle control administered orally by gavage. Parasitemia and plasma levels of tafenoquine were evaluated every 24 h post-treatment for 96 h. This allowed us to correlate blood plasma levels of tafenoquine with reductions in parasitemia in treated mice. Consistent with previous studies, a single oral dose of 20 mg/kg tafenoquine resulted in a rapid reduction in parasitemia. Plasma levels of tafenoquine 24 h post-administration ranged from 347 to 503 ng/mL and declined thereafter. This blood plasma tafenoquine level is similar to that achieved in humans using the current FDA-approved dose for the prevention of malaria.

Response and recovery of endocrine, behavioral, and neuronal morphology outcomes after different traumatic stressor exposures in male rats.

Preclinical models of organismal response to traumatic stress (threat of death or serious injury) can be monitored using neuroendocrine, behavioral, and structural metrics. While many rodent models of traumatic stress have provided a glimpse into select components of the physiological response to acute and chronic stressors, few studies have directly examined the potential differences between stressors and their potential outcomes. To address this gap, we conducted a multi-level comparison of the immediate and longer-term effects of two types of acute traumatic stressors. Adult male rats were exposed to either underwater trauma (UWT), predator exposure (PE), or control procedural handling conditions. Over the next 7 days, yoked cohorts underwent either serial blood sampling for neuroendocrine evaluation across the circadian cycle, or repeated behavioral testing in the elevated plus maze. In addition, a subset of brains from the latter cohort were assessed for dendritic spine changes in the prefrontal cortex and basolateral amygdala. We observed stressor-dependent patterns of response and recovery across all measures, with divergence between endocrine responses despite similar behavioral outcomes. These results demonstrate that different stressors elicit unique behavioral, neuroendocrine, and neuro-structural response profiles and suggest that specific stress models can be used to model desired responses for specific preclinical applications, such as evaluations of underlying mechanisms or therapeutic candidates.