The cell wall composition and autolytic properties of passage-selected glycopeptide-intermediate Staphylococcus aureus (GISA) isolates and their parent strains were studied in order to investigate the mechanism of decreased vancomycin susceptibility. GISA had relatively modest changes in peptidoglycan composition involving peptidoglycan interpeptide bridges and somewhat decreased cross-linking compared to that of parent strains. The cell wall phosphorus content of GISA strains was lower than that of susceptible parent strains, indicating somewhat lower wall teichoic acid levels in the GISA strains. Similar to whole cells, isolated crude cell walls retaining autolytic activity of GISA had drastically reduced autolytic activity compared to that of parent strains, and this arose early in the development of the GISA phenotype. This was due to an alteration in the autolytic enzymes of GISA as revealed by normal susceptibility of GISA-purified cell walls to parental strain autolysin extract and lower activity and altered peptidoglycan hydrolase activity profiles in GISA autolysin extracts compared to those of parent strains. Northern blot analysis indicated that expression of atl, the major autolysin gene, was significantly downregulated in a GISA strain compared to that of its parent strain. In contrast to whole cells, which showed decreased lysostaphin susceptibility, purified cell walls of GISA showed increased susceptibility to lysostaphin. We suggest that in our GISA strains, decreased autolytic activity is involved in the tolerance of vancomycin and the activities of endogenous autolysins are important in conferring sensitivity to lysostaphin on whole cells.

BackgroundRecent studies have demonstrated that several mineral products sold for medicinal purposes demonstrate antimicrobial activity, but little is known about the physicochemical properties involved in antibacterial activity.Methodology/Principal FindingsUsing in vitro mineral suspension testing, we have identified two natural mineral mixtures, arbitrarily designated BY07 and CB07, with antibacterial activity against a broad-spectrum of bacterial pathogens. Mineral-derived aqueous leachates also exhibited antibacterial activity, revealing that chemical, not physical, mineral characteristics were responsible for the observed activity. The chemical properties essential for bactericidal activity against Escherichia coli were probed by testing antibacterial activity in the presence of metal chelators, the hydroxyl radical scavenger, thiourea, and varying pH levels. Chelation of the BY07 minerals with EDTA or desferrioxamine eliminated or reduced BY07 toxicity, respectively, suggesting a role of an acid-soluble metal species, particularly Fe3+ or other sequestered metal cations, in mineral toxicity. This conclusion was supported by NMR relaxation data, which indicated that BY07 and CB07 leachates contained higher concentrations of chemically accessible metal ions than leachates from non-bactericidal mineral samples.Conclusions/SignificanceWe conclude that the acidic environment of the hydrated minerals significantly contributes to antibacterial activity by increasing the availability and toxicity of metal ions. These findings provide impetus for further investigation of the physiological effects of mineral products and their applications in complementary antibacterial therapies.

Purpose The use of buprenorphine, methadone, and long-acting naltrexone for treatment of opioid use disorder (OUD) is discussed, including a review of current literature detailing treatment approaches and action steps to optimize treatment in acute care and office-based settings. Summary The U.S. epidemic of opioid-related deaths has been driven by misuse of prescription opioids and, increasingly, illicit drugs such as heroin, fentanyl, and fentanyl analogs, necessitating a refocusing of treatment efforts on expanding access to life-saving, evidence-based OUD pharmacotherapy. Inpatient treatment of opioid withdrawal includes acute symptom control through a combination of nonopioid medications and long-term pharmacotherapy to lessen opioid craving and facilitate stabilization and recovery. Methadone and buprenorphine reduce opioid craving, increase treatment retention, reduce illicit opioid use, and increase overall survival. Buprenorphine has logistical advantages over methadone, such as greater flexibility of treatment setting and less risk of adverse effects. Studies have shown the efficacy of long-acting injectable naltrexone to be comparable to that of buprenorphine if patients are detoxified prior to initiation of therapy; however, patients with active OUD are often not able to complete the week-long period of opioid abstinence needed prior to initiation of naltrexone injections. Although buprenorphine is preferred by many patients and can be prescribed in office-based settings, there remains a paucity of physicians certified to prescribe it. Conclusion Buprenorphine has become the medication of choice for many patients with OUD, but its use is limited by the low number of physicians certified to prescribe the agent. Other agents studied for treatment of OUD include methadone and naltrexone.

Agitation and aggression are common in older emergency department (ED) patients, can impede the expedient diagnosis of potentially life‐threatening conditions, and can adversely impact ED functioning and efficiency. Agitation and aggression in older adults may be due to multiple causes, but chief among them are primary psychiatric disorders, substance use, hyperactive delirium, and symptoms of dementia. Understanding the etiology of agitation in an older adult is critical to proper management. Effective non‐pharmacologic modalities are available for the management of mild to moderate agitation and aggression in patients with dementia. Pharmacologic management is indicated for agitation related to a psychiatric condition, severe agitation where a patient is at risk to harm self or others, and to facilitate time‐sensitive diagnostic imaging, procedures, and treatment. Emergency physicians have several pharmacologic agents at their disposal, including opioid and non‐opioid analgesics, antipsychotics, benzodiazepines, ketamine, and combination agents. Emergency physicians should be familiar with geriatric‐specific dosing, contraindications, and common adverse effects of these agents. This review article discusses the common causes and non‐pharmacologic and pharmacologic management of agitation in older adults, with a specific focus on dementia, delirium, and pain.

Aqueous leachates prepared from natural antibacterial clays, arbitrarily designated CB-L, release metal ions into suspension, have a low pH (3.4–5), generate reactive oxygen species (ROS) and H2O2, and have a high oxidation-reduction potential. To isolate the role of pH in the antibacterial activity of CB clay mixtures, we exposed three different strains of Escherichia coli O157:H7 to 10% clay suspensions. The clay suspension completely killed acid-sensitive and acid-tolerant E. coli O157:H7 strains, whereas incubation in a low-pH buffer resulted in a minimal decrease in viability, demonstrating that low pH alone does not mediate antibacterial activity. The prevailing hypothesis is that metal ions participate in redox cycling and produce ROS, leading to oxidative damage to macromolecules and resulting in cellular death. However, E. coli cells showed no increase in DNA or protein oxidative lesions and a slight increase in lipid peroxidation following exposure to the antibacterial leachate. Further, supplementation with numerous ROS scavengers eliminated lipid peroxidation, but did not rescue the cells from CB-L-mediated killing. In contrast, supplementing CB-L with EDTA, a broad-spectrum metal chelator, reduced killing. Finally, CB-L was equally lethal to cells in an anoxic environment as compared to the aerobic environment. Thus, ROS were not required for lethal activity and did not contribute to toxicity of CB-L. We conclude that clay-mediated killing was not due to oxidative damage, but rather, was due to toxicity associated directly with released metal ions.

Purpose: To design and evaluate the accuracy and efficiency of a medication reconciliation workflow incorporating pharmacist home medication ordering. Methods: Designed and implemented an admission medication reconciliation workflow that expanded the pharmacists’ role to include an initial ordering of home medications. Performed a prospective, pre–post cohort analysis comparing preimplementation accuracy and efficiency data from inpatient medicine and cardiology patients to postimplementation accuracy and efficiency data from our emergency department observation unit. Accuracy for the preimplementation group was defined by the number of unintentional discrepancies identified by pharmacists between the prescriber admission orders and the reconciled home medication lists. Accuracy for the postimplementation group was defined by the prescriber acceptance of pharmacist-ordered home medications. Efficiency was measured by pharmacist time to complete the admission medication reconciliation process. Results: Prescribers accepted 98% of home medication orders placed by pharmacists, which correlated with a significant decrease in the occurrence of home medication orders containing a medication-related problem or discrepancy (46.4% vs 1.3%, P < .0001). The mean pharmacist time spent completing medication reconciliation per admission decreased from 64 to 23 minutes ( P < .0001). Conclusion: Implementation of an admission process that incorporates pharmacist ordering of home medications increased prescribing accuracy and efficiency.

Background: Antipsychotics and sedatives are used to treat agitation in the emergency department (ED) but carry significant risk in older adults. Our objective was to determine factors associated with their administration to older ED patients. Methods:This was an observational study using data from the 2014-2017 National Hospital Ambulatory Medical Care Survey. We identified ED visits for patients aged ≥65 years and determined whether an antipsychotic or sedative was administered. Visits related to substance use/withdrawal, other psychiatric complaints, and intubation were excluded. We performed multivariable logistic regression to identify risk factors for antipsychotic or sedative administration.Results: Of the 78.7 million ED visits that met inclusion criteria, 3.5% involved at least one dose of antipsychotic or sedative medication; 13% involved an antipsychotic and 92% a sedative. Factors associated with antipsychotic administration included nursing home residence (adjusted odds ratio [aOR]: 2.67; 95% CI: 1.05-6.80), dementia (aOR: 5.62; 95% CI: 2.44-12.94), and delirium (aOR: 7.33; 95% CI: 2.21-24.32). Sedative administration was positively associated with CT or MR imaging (aOR: 1.86; 95% CI: 1.42-2.43), urbanicity of ED (aOR: 1.46; 95% CI: 1.02-2.08), and female gender (aOR: 1.47; 95% CI: 1.08-1.99) and negatively associated with older age (age: 75-84; aOR: 0.67; 95% CI: 0.49-0.91; age: 85+; aOR: 0.63; 95% CI: 0.45-0.88; reference age: 65-74 years). Antipsychotic and sedative administration were associated with prolonged ED lengths of stay and hospital admission. Conclusion: We identified patient-and facility-level factors associated with sedative and antipsychotic administration in older ED patients. Antipsychotic and sedative administration were associated with prolonged ED lengths of stay and hospital admission. K E Y W O R D S antipsychotic agents, delirium, dementia, emergency medicine, hypnotics and sedatives See related editorial by Lee. in this issue.

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