Objectives Opioid pain reliever (OPR) prescribing at Emergency Department (ED) discharge has increased in the past decade but specific prescription details are lacking. Prior ED OPR prescribing estimates relied on national survey extrapolation or prescription databases. The main goal of this study was to utilize a research consortium to analyze the characteristics of patients and opioid prescriptions using a national sample of ED patients. We also aimed to examine the indications for OPR prescribing, characteristics of opioids prescribed both in the ED and at the time of discharge, and characteristics of patients who received OPRs compared with those who did not. Methods This observational, multi-centered, retrospective cohort study assessed OPR prescribing to consecutive patients presenting to the consortium EDs during 1 week in October 2012. The consortium study sites consisted of 19 EDs representing 1.4 million annual visits, varied geographically, and were predominantly academic centers. Medical records of all patients aged 18-90 years discharged with an OPR (excluding tramadol) were individually abstracted via standardized chart review by investigators for detailed analysis. Descriptive statistics were generated. Results During the study week, 27,516 patient visits were evaluated in the consortium EDs. 19,321 (70.2%) were discharged and 3,284 patients (11.9% of all patients and 17.0% of discharged patients) received an OPR prescription. For those prescribed an OPR, mean age was 41.1 (SD 14.7) years and 1,694 (51.6%) were female. Mean initial pain score was 7.7 (SD 2.4). The most common diagnoses associated with OPR prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity fracture (7.1%) or sprain (6.5%). The most common OPRs prescribed were oxycodone (52.3%), hydrocodone (40.9%) and codeine (4.8%). >99% were immediate release, 90.0% were combination preparations, and the mean and median number of pills was 16.6 (SD 7.6) and 15 (IQR=12-20) respectively. Conclusion In a study of ED patients treated over a single week across the country, 17% of discharged patients were prescribed OPRs. The majority of the prescriptions had small pill counts and almost exclusively immediate release formulations.

The dwindling repertoire of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum-quenching agents offer an alternative or an adjuvant to antibiotic therapy. Three biaryl hydroxyketone compounds discovered previously (F1, F12, and F19; G. Yu, D. Kuo, M. Shoham, and R. Viswanathan, ACS Comb Sci 16:85-91, 2014) were tested for efficacy in MRSA-infected animal models. Topical therapy of compounds F1 and F12 in a MRSA murine wound infection model promotes wound healing compared to the untreated control. Compounds F1, F12, and F19 afford significant survival benefits in a MRSA insect larva model. Combination therapy of these quorum-quenching agents with cephalothin or nafcillin, antibiotics to which MRSA is resistant in monotherapy, revealed additional survival benefits. The quorum-quenching agents sensitize MRSA to the antibiotic by a synergistic mode of action that also is observed in vitro. An adjuvant of 1 g/ml F1, F12, or F19 reduces the MIC of nafcillin and cephalothin about 50-fold to values comparable to those for vancomycin, the antibiotic often prescribed for MRSA infections. These findings suggest that it is possible to resurrect obsolete antibiotic therapies in combination with these novel quorum-quenching agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread bacterial pathogen, causing various infections, ranging from skin and soft tissue infections to serious invasive infections, such as pneumonia, endocarditis, bacteremia, and sepsis (1, 2). Rising antibiotic resistance and diminishing investment by the pharmaceutical industry in the development of new antibiotics have created an urgent need for novel anti-MRSA agents (3). Quorum-quenching agents provide an alternative and an adjuvant to conventional antibiotic therapy (4, 5). The mechanism of action of quorum-quenching agents is fundamentally different from that for antibiotics. Quorum-quenching agents are neither bactericidal nor bacteriostatic. They inhibit the production of disease-causing toxins by the pathogen, thereby disarming the pathogen of its capacity to inactivate host defense factors. An intact host immune system has a better chance to clear a bacterial infection. A quorum-quenching agent tips the balance of bacterial virulence factors and host defense factors in favor of the host.Virulence factor production in Staphylococcus aureus is regulated by a quorum-sensing mechanism predominantly under the control of the agr operon (6, 7). In previous work, we have identified small-molecule biaryl hydroxyketone compounds that target the response regulator AgrA and inhibit its interaction with promoter P3, curtailing the production of toxins and virulence factors (8). In a follow-up study, a combinatorial library of 148 compounds was synthesized based on the most efficacious hit compound (9). A member of this biaryl hydroxyketone library, named F12, was the most efficacious of the synthesized compounds, demonstrating 98% in vitro MRSA rabbit erythrocyte hemolysis inhi...

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