Optimizing preoperative antibiotics in patients with ß-lactam allergies: A role for pharmacy.

PURPOSE: Patients with a reported ß-lactam allergy (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSIs), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview service in the preoperative setting. METHODS: A pharmacist performed BLA clarification telephone interviews before elective procedures from November 2018 to March 2019. On the basis of allergy history and a decision algorithm, first-line preoperative antibiotics, alternative antibiotics, or allergy testing referral was recommended. The pharmacist intervention (PI) group was compared to a standard of care (SOC) group who underwent surgery from November 2017 to March 2018. RESULTS: Eighty-seven patients were included, with 50 (57%) and 37 (43%) in the SOC and PI groups, respectively. The most common surgeries included orthopedic surgery in 41 patients (47%) and neurosurgery in 17 patients (20%). In the PI group, all BLA labels were updated after interview. Twenty-three patients were referred for allergy testing, 12 of the 23 (52%) completed BLA testing, and penicillin allergies were removed for 9 of the 12 patients. Overall, 28 of the 37 (76%) pharmacy antibiotic recommendations were accepted. Cefazolin use significantly increased from 28% to 65% after the intervention (P = 0.001). SSI occurred in 5 (10%) patients in the SOC group and no patients in the PI group (P = 0.051). All of these SSIs were associated with alternative antibiotics. Incidence of AKI and CDI was similar between the groups. No allergic reactions occurred in either group. CONCLUSION: Implementation of a pharmacy-driven BLA reconciliation significantly increased ß-lactam preoperative use without negative safety outcomes.

GSK983: a novel compound with broad-spectrum antiviral activity.

GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC(50) values of 5-20 nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and Epstein-Barr virus (EBV) are susceptible to GSK983. The compound does not inhibit all viruses; herpes simplex virus (HSV-1), human immunodeficiency virus (HIV), and lytic replication of EBV were not susceptible at concentrations below 1 microM. GSK983 does inhibit the growth of cell lines immortalized by HTLV-1, EBV, HPV, SV40 and Ad-5, with EC(50) values in the range of 10-40 nM. Depending on the cell line, the compound induces either apoptosis or cytostasis at concentrations over 20 nM. GSK983 also inhibits cell lines immortalized by non-viral mechanisms, but has little effect on primary cells. The CC(50) values for keratinocytes, fibroblasts, lymphocytes, endothelial, and bone marrow progenitor cells are all above 10 microM. The pattern of inhibition, which includes diverse viruses as well as growth of immortalized cells of varied origins, suggests the target is a host cell protein, rather than a viral protein. Preliminary mechanism studies indicate that GSK983 acts by inducing a subset of interferon-stimulated genes.

Naphthyl piperazines with dual activity as 5-HT1D antagonists and 5-HT reuptake inhibitors.

SAR around a known molecule with dual 5-HT(1D) antagonist and 5-HT(transporter) inhibitory activity has led to the discovery of molecules with improved dual activity and reduced cross-reactivity toward other aminergic receptors (5-HT(1B), alpha(1), and D(2)).

Weekly paclitaxel infusion as salvage therapy in ovarian cancer.

The majority of women diagnosed with epithelial ovarian cancer will have persistent or recurrent disease after initial treatment. We evaluated response and toxicity in women with advanced stage disease given salvage paclitaxel as a low-dose, weekly infusion. We performed a retrospective review of 22 women with advanced stage epithelial ovarian (19 women) or primary peritoneal carcinoma (3 women) who had received low-dose, weekly paclitaxel salvage therapy. All women had refractory, persistent, or recurrent disease following first-line treatment with paclitaxel and platin chemotherapy. Response and toxicity were assessed. Measurable disease present on physical or radiologic exam and serum carbohydrate antigen-125 levels were used to assess disease response. Overall response rate to low-dose, weekly paclitaxel salvage therapy was 50% (27% complete, 23% partial). Median progression-free interval (PFI) in responders was 27 weeks (range, 14-68 weeks). Stabilization of disease occurred in an additional 27% of patients with a median PFI of 22 weeks (range, 15-89 weeks). No difference in response was detected between the 7 women with platin-sensitive disease and the 15 women with platin-resistant disease (P = 0.19). The median dose of paclitaxel was 80 mg/m2 (range, 60-80 mg/m2). During a total of 325 weeks of paclitaxel treatment (median per patient, 12 weeks; range, 6-49 weeks), 13 treatment delays occurred (hematologic indication, 9; nonhematologic indication, 4). No cases of grade 4 hematologic toxicity, sepsis, or worsening neuropathy were documented. Weekly paclitaxel infusion given as salvage therapy results in significant clinical response, even in women previously treated with paclitaxel. The regimen is well tolerated with no cases of grade 4 neutropenia or worsening neuropathy in our population.