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Background Microneedle patches provide an alternative to conventional needle-and-syringe immunization, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability and safety. We describe safety, immunogenicity and acceptability of the first-in-human study on single, dissolvable microneedle patch vaccination against influenza. Methods The TIV-MNP 2015 study was a phase 1, partially blinded, placebo-controlled, randomized clinical trial conducted at Emory University that enrolled non-pregnant, immunocompetent adults (age 18–49 years) from Atlanta (USA) and naïve to 2014–2015 influenza vaccine. Participants were equally randomized among four groups and received a single dose of inactivated influenza vaccine 1) by microneedle patch or 2) by intramuscular injection, or received 3) placebo by microneedle patch, all administered by an unblinded healthcare worker; or received 4) inactivated influenza vaccine by microneedle patch self-administered by study participants. Primary safety outcomes were reactogenicity, grade 3 adverse events and serious adverse events within 8, 28 and 180 days and secondary safety outcomes were new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days all analyzed by intention to treat. Secondary immunogenicity outcomes were antibody titers at day 28 as well as seroconversion and seroprotection rates all determined by hemagglutination inhibition antibody. The trial is completed and registered with ClinicalTrials.gov, NCT02438423. Findings Twenty-five participants per group were enrolled between June 23 and September 25, 2015. There were no related serious adverse events, no related grade 3 or higher adverse events and no new-onset chronic illnesses. Overall incidence of solicited and unsolicited events was similar among vaccinated groups. Reactogenicity was mild, transient and most commonly reported as tenderness at 60% (95% CI, 39– 79%) and pain at 44% (95% CI, 24–65%) after intramuscular injection and tenderness at 66% (95% CI, 51–79%), erythema at 40% (95% CI, 26–55%) and pruritus at 82% (95% CI, 69–91%) after vaccination by microneedle patch application The geometric mean titers were comparable at day 28, between the microneedle patch administered by healthcare worker and the intramuscular route with values of 1197 (95% CI, 855– 1675) and 997 (95% CI, 703–1415) (p=0.5), respectively, for the H1N1 strain; 287 (95% CI, 192–430) and 223 (95% CI, 160–312) (p=0.4), respectively, for the H3N2 strain and 126 (95% CI, 86–184) and 94 (95% CI, 73–122) (p=0.06), respectively, for the B strain. Similar GMT titers were observed in participants who self-administered the microneedle patch. The seroconversion rates were significantly higher at day 28 after microneedle patch vaccination compared to placebo and were comparable to intramuscular injection. Interpretation Use of dissolvable microneedle patches for influenza vaccination was well-tolerated and generated robust antibody responses. Funding National Institutes of Health.

Background The objective of our study was to describe trends in U.S. outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). Methods We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies in January 2017-May 2020. We averaged estimates from 2017-2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017- 2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. Results From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. Conclusions From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected due to seasonal trends alone, possibly related to the COVID-19 pandemic and associated mitigation measures.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fitsall" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities. K E Y W O R D S antibiotic prophylaxis, ethics and public policy, health services and outcomes research, infection and infectious agents, organ transplantation in general How to cite this article: So M, Hand J, Forrest G, et al. White paper on antimicrobial stewardship in solid organ transplant recipients.

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The Food and Drug Administration warned against fluoroquinolone use for conditions with effective alternative agents. An estimated 5.1% of adult ambulatory fluoroquinolone prescriptions were for conditions that did not require antibiotics, and 19.9% were for conditions where fluoroquinolones are not recommended first-line therapy. Unnecessary fluoroquinolone use should be reduced.

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