Pharmacist driven antibiotic redosing in the emergency department.

STUDY OBJECTIVE: Determine whether an expanded emergency medicine (EM) pharmacist scope of practice reduces the frequency of major delays in subsequent antibiotic administration in patients boarded in the emergency department (ED). METHODS: A pre-post, quasi-experimental study conducted from November 2019-March 2020 at a single-center tertiary academic medical center following the implementation of an expanded EM pharmacist scope of practice. Adult patients were included if they received an initial antibiotic dose in the ED and deemed to be high-risk. Subsequent antibiotic doses were reordered by EM pharmacists for up to 24-h after the initial order pending ED length of stay (LOS). The historical control group consisted of retrospective chart review of cases from the previous year. RESULTS: The study identified that of the 181 participants enrolled, major delays in subsequent antibiotic administration occurred in 13% of the intervention group and 48% of the control group (p < 0.01). When compared to the control group, the intervention group had a significant decrease in the number of delays among antibiotics dosed at 6-h (39% vs 13%) and 8-h (60% vs 8%) intervals. For antibiotics dosed at 12-h intervals, no statistically significant difference was observed between the control and intervention groups respectively (19% vs 5%). A statistically significant lower incidence of in-hospital mortality was observed in the intervention group (3% vs 11%, p = 0.02). In the intervention group, 97% of patients received subsequent antibiotic doses while boarded in the ED, compared to 65% in the control group (<0.01). CONCLUSION: Expanding EM pharmacist scope of practice was associated with a significant reduction in the frequency of major delays in subsequent antibiotic administration as well as a decreased incidence of hospital mortality.

Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia.

BACKGROUND: Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia. METHODS: We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment. RESULTS: Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab. CONCLUSIONS: Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.

Optimizing utilization of beta-lactam surgical prophylaxis through implementation of a structured allergy assessment tool in a presurgical clinic.

In patients with ß-lactam allergies, administration of non-ß-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report ß-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured ß-lactam allergy tool, was implemented to improve the utilization of preferred ß-lactam surgical prophylaxis.

Cefotetan-Induced Hemolytic Anemia: Case Series and Review.

PURPOSE: To raise awareness of cefotetan-induced hemolytic anemia, a known rare but serious side effect that occurred in 5 patients at our medical center. SUMMARY: Five cases of cefotetan-induced hemolytic anemia, which presented over the period of a single year at our center, are described. In each case, hemolytic anemia was confirmed by testing for the presence of anti-cefotetan antibodies. Each case occurred approximately 1 to 2 weeks following exposure to the drug. All five patients survived. A brief review of drug-induced immune hemolytic anemia (DIIHA) is also discussed. CONCLUSION: DIIHA may be difficult to distinguish from other causes of hemolytic anemia, but should be included in the differential in patients exposed to medications associated with DIIHA. Once suspected, antibody testing should be performed, and once diagnosed, further exposure should be avoided.

Effect of Thyroid Function on MNU-Induced Mammary Carcinogenesis.

Mammary cancer is a disease that affects many women. Extensive research has been conducted to elucidate which variables are involved in the development of this cancer. Studies have highlighted thyroid function as a modulator of tumor growth and development. Thyroxine and 3,3',5-triiodothyronine are responsible for regulating the development, differentiation, homeostasis, and metabolism of cells in the body including mammary tissue. Thyroid hormones also have estrogen-like effects on mammary cancer cell growth by regulating the estrogen receptor. The present study was designed to determine whether medically induced hyperthyroidism increases the multiplicity, prevalence, and mammary tumor burden in rats; and to elucidate whether surgically induced hypothyroidism conversely attenuates the rate of mammary cancer cell growth. Female Sprague-Dawley rats were randomly divided into three groups (euthyroid-control, hyperthyroid, and hypothyroid). Hyperthyroidism was induced via oral administration of levothyroxine; whereas, hypothyroidism was induced by thyroidectomy. Mammary carcinogenesis was induced with a single intraperitoneal injection of N-methyl-N-nitrosurea (MNU). Rats were sacrificed at 38 weeks, and the mammary tumors were excised, fixed for histology and analyzed. Analysis included evaluation of malignancy and immunohistochemistry for ER. MNU-induced mammary carcinogenesis among the groups resulted in a significant difference in tumor burden. The hyperthyroid group had a statistically higher tumor burden than did the euthyroid group, and the hypothyroid group had no tumors of mammary tissue origin at 38 weeks. All excised mammary tumors were ER alpha negative. These data support the hypothesis that thyroid function is one of potentially many factors that contribute to modulation of MNU-induced mammary tumor growth.

Mutagenic studies on histidine 98 of methylglyoxal synthase: effects on mechanism and conformational change.

Two detailed mechanisms [Marks et al. (2001) Biochemistry 40, 6805] have been proposed to explain the activity of methylglyoxal synthase (MGS), a homohexameric allosterically regulated enzyme that catalyzes the elimination of phosphate from DHAP to form enol pyruvaldehyde. This enol then tautomerizes to methylglyoxal in solution. In one of these mechanisms His 98 plays an obligate role in the transfer of a proton from the O(3) oxygen of DHAP to the O2 oxygen. To test this hypothesized mechanism, the variants H98N and H98Q were expressed and purified. Relative to the wild-type enzyme, the H98N variant shows a 50-fold decrease in k(cat) with all other kinetic parameters (i.e., K(m), K(PGA), etc.) being nearly the same. By contrast, the apparent catalytic rate for the H98Q variant is 250-fold lower than that of the wild-type enzyme. Inorganic phosphate acts as a competitive inhibitor (with a K(i) of 15 microM) rather than as an allosteric-type inhibitor as it does in the wild-type enzyme, and the competitive inhibitor phosphoglyolate (PGA) acts as an activator of this variant. These facts are explained by a shift in the conformational equilibrium toward an "inactive" state. When activation by PGA is accounted for, the catalytic rate for the "active" state of H98Q is estimated to be only 6-fold less than that of the wild-type enzyme, and thus His 98 is not essential for catalysis. Primary deuterium isotope effect data were measured for the wild-type enzyme and the two variants. At pH 7.0, the (D)V isotope effect (1.5) and the absence of a (D)(V/K) isotope effect for the wild-type enzyme suggest that the rate for the isotopically sensitive step is partially rate limiting but greater than the rate of substrate dissociation. Both the (D)V (2.0) and (D)(V/K) (3.4) isotope effects were more pronounced in the H98N variant, while the H98Q variant displayed an unusual inverse (D)V (0.8) isotope effect and a normal (D)(V/K) (1.5) isotope effect. The X-ray crystal structures of PGA bound to the H98Q and H98N variants were both determined to a resolution of 2.2 A. These mutations had little effect on the overall structure. However, the pattern of hydrogen bonding in the active site suggests an explanation as to how in the wild-type and H98N mutated enzymes the "inactive to active" equilibrium lies toward the active state, while with the H98Q mutated enzyme the equilibrium lies toward the inactive state. Thus, the role of His 98 appears to be more as a regulator of the enzyme's conformation rather than as a critical contributor to the catalytic mechanism.