We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with neurological manifestations

Background: The protection against aerosol transmission provided by masks vs face shields or in combination when speaking indoors is not well understood. Methods: To simulate a human source, an aerosol generating system was made using a bacterial suspension in a nebulizer attached to an oxygen cylinder. A fan connected to the nebulizer created aerosols. Transmitted aerosols were detected using blood agar plates at 0.1524 and 1.8288 meters from source, simulating exposed person. The study was performed under controlled conditions at room temperature in a biohazard hood with high-efficiency particulate air (HEPA) filter and UV light. Results: When face shields were used alone, significant numbers of bacterial colonies grew on blood agar plates. When a mask used alone for both the subjects (source and exposed), the blood agar yielded minimal colony forming units at both distances. When face shields were used in combination with masks, no signifi-cant improvement was observed as compared to masks alone. Discussion: Our results were similar to what have been observed in related studies. Conclusions: Surgical masks alone provided good protection, surpassing the protection provided by face shields alone. Both used together provided the best protection, although the combined protection was similar to surgical masks use alone. (c) 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. Background: The protection against aerosol transmission provided by masks vs face shields or in combination when speaking indoors is not well understood. Methods: To simulate a human source, an aerosol generating system was made using a bacterial suspension in a nebulizer attached to an oxygen cylinder. A fan connected to the nebulizer created aerosols. Transmitted aerosols were detected using blood agar plates at 0.1524 and 1.8288 meters from source, simulating exposed person. The study was performed under controlled conditions at room temperature in a biohazard hood with high-efficiency particulate air (HEPA) filter and UV light. Results: When face shields were used alone, significant numbers of bacterial colonies grew on blood agar plates. When a mask used alone for both the subjects (source and exposed), the blood agar yielded minimal colony forming units at both distances. When face shields were used in combination with masks, no significant improvement was observed as compared to masks alone. Discussion: Our results were similar to what have been observed in related studies. Conclusions: Surgical masks alone provided good protection, surpassing the protection provided by face shields alone. Both used together provided the best protection, although the combined protection was similar to surgical masks use alone. ? 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All

Staphylococcus pettenkoferi (S.pettenkoferi), originally described in Germany in 2002 by Trueurolzsch et al, is a coagulase negative staphylococcus whose clinical relevance is yet to be determined. With about 10 case reports in the literature from several parts of the world, there is no data on S. pettenkoferi infection from the United States. This is a retrospective cohort study of 80 patients > 18 years of age who had at least 1 S. pettenkoferi-positive blood culture, identified by matrix-assisted laser desorption/ionization time-of -flight at a tertiary academic center in Detroit, Michigan. We describe the features of S. pettenkoferi-positive blood cultures in order to identify cases of true bacteremia. The mean age of the cohort was 66 16 years and 1 out of 3 had immunosuppressing conditions. No case of true S.pettenkoferi bacteremia was identified. More studies are needed to determine its role as a pathogen in the United States. (c) 2020 Elsevier Inc. All rights reserved.

Background. Bloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance. Methods. This was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene. Results. Four hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%-81% using the scoring tools (P < .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%-71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%-12%). Conclusions. Verigene significantly outperformed published ESBL scoring tools for identifying CRO- resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy.

Pooling of 1 positive sample with up to 5 negative samples prior to testing with the Cepheid GenXpert SARS-CoV-2 assay did not adversely impact detection of positive samples. At our current prevalence of 2%, it could save up to 70% of the test kits.

Purpose: Neutropenic fever in a pediatric oncology patient necessitates emergent initiation of efficacious broad spectrum antibiotics. We have utilized cefepime+/-vancomycin in this context for over two decades, and sough to evaluate the efficacy of this combination at our institution and, if necessary, to identify an optimal alternative regimen. Methods: Blood culture isolates from pediatric oncology patients were reviewed over 12 years. Antibiotic susceptibilities for all unique isolates were analyzed via minimum inhibitory concentration breakpoints and interpretive categories as per the Clinical and Laboratory Standards Institute M100/M45 manuals. Percentage susceptibility was calculated, antibiograms generated, and intraspecies antibiotic susceptibility comparisons made. Billing data was analyzed to identify the number of oncology patients admitted for fever during this interval. Results: 697 unique isolates were identified: 188 Gram-negative and 509 Gram-positive (155 Gram-positive and 343 total isolates, excluding coagulase negative Staphylococcal (CONS) species). Cefepime and meropenem each covered 95.7% of tested Gram-negatives. Stenotrophomonas (Xanthomonas) maltophilia was the most resistant Gram-negative organism; no antibiotic covered all Gram-negatives. No antibiotic offered significantly improved coverage compared to cefepime. 96.0% of total tested Gram-positives were vancomycin-susceptible (including all CONS); resistant organisms included Enterococcus faecium and Enterococcus faecalis. Linezolid did not offer significantly improved coverage, while daptomycin did. Including and excluding CONS, 46.3% and 72.5% of total Gram-positive isolates were cefepime-sensitive. Blood cultures were positive in 33.7% of admissions. Central venous catheters were routinely utilized in this patient population. Prophylactic antibacterial agents were not utilized. Conclusions: Cefepime+/-vancomycin remains efficacious as first-line empiric therapy for febrile neutropenia, with notable minor exceptions. Unit-specific surveillance of antibiotic resistance is warranted to ensure ongoing appropriate empiric antibiotic usage.

We compared the levels of hormones and metabolites in the plasma of 37 survivors of Reye's syndrome with the levels in 8 fatal cases, at four time periods within 72 hours of admission. The most prominent differences were found for norepinephrine (NE), which was significantly elevated in fatal cases compared with survivors at all periods. Lactate and dopamine were elevated in the earlier periods. Epinephrine and alpha-amino acid nitrogen were also elevated in fatal cases, but the differences usually were not significant. NE elevation may reflect an increased sympathoadrenal medullary output associated with brain edema, compounded by impaired hepatic clearance of monoamines. Skeletal muscle ischemia from NE-induced vasoconstriction may explain the association between lactic acidemia and the severity of encephalopathy.

Factor analysis of admission data from 209 Reye's syndrome patients yielded three factors. Factor 1 was associated with encephalopathy, blood ammonia, creatinine kinase (CK), uric acid and, to a lesser extent, bilirubin. This factor was linked to the encephalopathy and hypermetabolic changes in muscle, possibly prostaglandin-mediated proteolysis. Factor 2 was associated with serum alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT), and was identified as a hepatic lesion component. These factors correspond to two etiologic components of Reye's syndrome. Salicylate was only weakly associated with neuropathic and hypercatabolic indicators and not at all associated with the hepatic damage indicators.

ABSTRACT: Hepatic glutamate dehydrogenase (GDH) activity was measured in postmortem specimens obtained from two stage V Reye syndrome patients and in three postmortem specimens of normal human liver. The Reye syndrome specimens showed the hepatic mitochondrial enzyme deficits in GDH and monoamine oxidase activities that are characteristic of Reye syndrome. GDH activity was linear with the amount of supernatant fraction added, both for Reye and normal liver preparations: moreover, the activities of mixtures of Reye and control supernatant fractions were the sums of the activities of the individual components. This means that the activity difference between Reye and normal GDH activity is not due to a diffusible inhibitor in the Reye hepatocytes or to an activator of GDH in the normal control hepatocytes. Serum obtained from six Reye cases during neurologic deterioration was added to normal hepatic GDH preparations to test for a serum inhibitor of FDH. Highly variable effects were found, with two serum samples producing marked inhibition and others showing weak inhibition, no effect, or stimulation of GDH activity. The inhibitor was not removed by charcoal treatment and most of the activity was retained by a 10,000 dalton Diaflo membrane, signifying either that the compound had a high molecular weight or that it was bound to serum protein. We conclude that the decreased activity of GDH in Reye hepatocytes is not due to an intracellular diffusible inhibitor, and that serum effects are quite variable and are not directly related to intracellular changes in GDH activity.

Five enzymes were measured in 50 liver specimens (18 normal liver, 20 Reye liver, 12 diverse liver disorders other than Reye syndrome). The enzymes were: glutamic dehydrogenase (E.C. 1.4.1.3), monoamine oxidase (E.C. 1.4.3.4), lactate dehydrogenase (E.C. 1.1.1.27), D-glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49), catalase (E.C. 1.11.1.6). The Reye syndrome group showed significant decreases in glutamic dehydrogenase (56%) and monoamine oxidase (70%) compared to normal control tissue and these changes were not characteristic of the non-Reye liver disorder group as a whole. Neither catalase nor lactate dehydrogenase appeared to be altered significantly in the Reye or in the abnormal control group compared with normal controls. Thus, only the prominent decreases in the mitochondrial enzyme activities appeared to be highly characteristic of Reye syndrome. Paradoxically, the means of the five hepatic enzymes and the admission levels of two serum enzymes indicative of liver damage (alanine and aspartate aminotransferase) were remarkably similar for both survivors and nonsurvivors of Reye syndrome.

Factor analysis of admission data from 209 Reye9s syndrome patients yielded three factors. Factor 1 was associated with encephalopathy, blood ammonia, creatinine kinase (CK), uric acid and, to a lesser extent, bilirubin. This factor was linked to the encephalopathy and hypermetabolic changes in muscle, possibly prostaglandin-mediated proteolysis. Factor 2 was associated with serum alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT), and was identified as a hepatic lesion component. These factors correspond to two etiologic components of Reye9s syndrome. Salicylate was only weakly associated with neuropathic and hypercatabolic indicators and not at all associated with the hepatic damage indicators.

ABSTRACT: Following reports of a Reye-Iike syndrome in children resulting from Margosa oil (MO) ingestion, we administered MO to laboratory rats in an attempt to produce an animal model of Reye's syndrome. Male rats were injected intraperitoneally with either MO or corn oil and observed for clinical signs of a toxic response. After 15 h the animals were administered a second dose and the MO-treated animals developed florid neurological symptoms. The animals were then sacrificed and blood samples were analyzed for glucose, ammonia, aspartate aminotransferase, and alanine aminotransferase. Sections of liver, kidney, and brain were examined by light microscopy after Sudan black B, hematoxylin and eosin, and periodic acid- Schiff staining. Liver was additionally examined by electron microscopy. Liver samples were analyzed for hepatic enzyme levels and brain samples were analyzed for water content. There were greatly increased levels of ammonia, aspartate aminotransferase, and alanine aminotransferase and decreased glucose levels in the blood of MO-treated animals. Light microscopy of MO-treated livers revealed fatty infiltration, granularity of the cytoplasm with normal nuclei, and glycogen depletion; electron microscopy revealed mitochondrial pathology in the livers of MO-treated animals. There were no significant morphological changes in brain or kidney specimens although the kidneys did show some fatty infiltration. Hepatic mitochondrial enzyme levels were unchanged and there was no increase in brain water content in the MO-treated animals. Thus, many of the abnormalities seen in Reye's syndrome were seen in this model; however, there were no hepatic enzyme changes despite altered mitochondrial morphology and no evidence of cerebral edema despite a florid encephalopathy. Nonetheless, this model may have important implications for the understanding of the pathogenetic mechanisms of this Reye-like syndrome and, perhaps, Reye's syndrome.

Faraj et al1 recently reported a positive correlation between plasma tyramine levels and the number of days in coma, for patients with biopsy-proven Reye's syndrome. They suggested that the mitochondrial injury might have a disruptive effect upon hepatic monoamine oxidase, with a subsequent decrease in clearance of tyramine. We have reached a similar conclusion on the possible role of tyramine in the development of the encephalopathy, based on the finding that the hepatic monoamine oxidase activity was reduced about 60% in stage V Reye's syndrome patients.

Summary: The activities of nine enzymes in liver specimens obtained from four children who had died from Reye's syndrome were compared to the corresponding activities of a control group of four children who had died from unrelated causes. At the 95% significance level, the alterations could be classified into three groups. Five activities [lactate dehydrogenase, alanine aminotransferase, glucose 6-phosphatase, cytochrome oxidase, and malate dehydrogenase (mitochondrial plus cytosolic)] showed no change. Three enzymes [glutamate dehydrogenase, isocitrate dehydrogenase (NADP), and monoamine oxidase] were decreased. One activity (glucose 6-phosphate dehydrogenase) was increased.The malate dehydrogenase isozymes were resolved by electrophoresis, and the two bands were stained and measured. The ratio of cytosolic:mitochondrial enzyme was significantly greater in Reye's syndrome than in the control group. These results lend further support to the view that in Reye's syndrome the impairment of hepatic function is largely confined to the mitochondria. The lowered activity of monoamine oxidase means that the abnormalities extend to the outer mitochondrial membrane.Imbalances of the cytosolicrmitochondrial enzyme activities were evaluated in needle biopsy specimens from four other children under conditions where the neurologic abnormalities were less severe. Two patients had elevated ratios of both glutamate:lactate dehydrogenase and cytosolic:mitochondrial malate dehydrogenase activities, and a third had only an abnormal malate dehydrogenase ratio. In contrast to these Reye's syndrome patients, a fourth case admitted with a provisional diagnosis of Reye's syndrome showed no abnormality in either ratio in stage IV coma.Speculation: The decreased activities of hepatic mitochondrial enzymes in Reye's syndrome may reflect a generalized decrease in the steady-state level of mitochondrial enzymes due to a selective impairment of mitochondrial biogenesis. This may be the primary lesion. The low level of monoamine oxidase (a mitochondrial outer membrane enzyme) may contribute to the neurologic alterations and metabolic perturbations by promoting the synthesis of false neurotransmitters derived from tyramine and by promoting the release of catecholamines from chromaffin tissue.

Letter to the Editor: Cyclic Nucleotide Phosphodiesterase Activity of Human Liver: Is There an Altered Form in Reye's Syndrome?