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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Background Remdesivir (RDV) is US FDA approved for coronavirus disease 2019 (COVID-19) but not recommended in severe renal impairment (SRI, Creatinine clearance <30mL/min or requiring renal replacement therapy). Few studies have evaluated RDV in patients with SRI. Methods Hospitalized patients who received RDV between 1 May 2020 and 31 October 2020 were analyzed in a retrospective chart review. We compared incident adverse events (AEs) in patients with and without SRI, including hepatotoxicity, nephrotoxicity, any reported AE, mortality, and length of stay. Results Of a total of 135 patients, 20 had SRI. Patients with SRI were significantly older (70 vs 54 years, P = .0001). The incidence of possible AEs was 30% among those with SRI vs 11% without (P = .06). Liver function test (LFT) elevations occurred in 10% vs 4% (P = .28), and serum creatinine (SCr) elevations in 27% vs 6% (P = .02) of patients with SRI vs without, respectively. LFT and SCr elevations were not attributed to RDV in either group. Mortality and length of stay were consistent with historical controls. Conclusions RDV AEs occurred infrequently and overall were not significantly different between those with and without SRI. While more of patients with SRI experienced SCr elevations, 3 (75%) patients had acute kidney injury prior to RDV. The use of RDV in this small series of patients with SRI appeared to be relatively safe, and the potential benefit outweighed the theoretical risk of liver or renal toxicity. Additional studies are needed to confirm this finding.

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Comparison of turnaround time and time to oseltamivir discontinuation between two respiratory viral panel testing methodologies Respiratory infections contribute to many Emergency Department visits and hospitalizations, resulting in a high healthcare burden (Neuzil et al., 2003; Schull et al., 2005). Rapid detection of respiratory pathogens in patients presenting with symptoms of an upper respiratory tract infection is crucial for timely determination of optimal antimicrobial management, avoidance of unnecessary evaluations and implementation of transmission-reducing infection control practices. Rapid viral testing can also result in cost savings to the healthcare system through reduction in Emergency Department boarding time and decreased duration of empiric antiviral therapy (Schull et al., 2005). With increased emphasis on antimicrobial stewardship in hospitals to facilitate improved clinical and economic outcomes with antimicrobial therapy, the implementation of rapid diagnostics for laboratory identification of pathogens is of great interest (Bauer et al., 2014).

Background Antimicrobial stewardship interventions utilizing real-time alerting through the electronic medical record enable timely implementation of the bundle of care (BOC) for patients with severe infections, such as candidemia. Automated alerting for candidemia using the Epic stewardship module has been in place since July 2015 at our medical center. We sought to assess the impact of these alerts. Methods All adult inpatients with candidemia between April 1, 2011, and March 31, 2012 (pre-intervention), and June 30, 2016, and July 1, 2017 (post-intervention), were evaluated for BOC adherence. We also evaluated the impact on timeliness to initiate targeted therapy, length of stay (LOS), and 30-day mortality. Results Eighty-four patients were included, 42 in the pre- and 42 in the post-intervention group. Adherence to BOC was significantly improved, from 48% (pre-intervention) to 83% (post-intervention; P = .001). The median time to initiation of therapy was 4.8 hours vs 3.3 hours (P = .58), the median LOS was 24 and 18 days (P = .28), and 30-day mortality was 19% and 26% (P = .60) in the pre- and post-intervention groups, respectively. Conclusions Antimicrobial stewardship program review of automated alerts identifying patients with candidemia resulted in significantly improved BOC adherence and was associated with a 1.5-hour reduction in time to initiation of antifungal therapy. No significant change was observed with 30-day mortality or LOS.

We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

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