In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

To evaluate the frequency of unnecessary antibiotic prescribing for Tier 3 respiratory infection (URI) syndromes across the Mayo Clinic Enterprise before and after a multifaceted antimicrobial stewardship intervention, and to determine ongoing factors associated with antibiotic prescribing and repeat respiratory healthcare contact in the post-intervention period. This was a quasi-experimental, pre/post, retrospective cohort study from January 1^st, 2019– December 31^st, 2022, with 12-month washout during implementation from July 1^st, 2020–June 30^th, 2021. All outpatient encounters, adult and pediatric, from primary care, urgent care, and emergency medicine specialties with a Tier 3 URI diagnosis were included. The intervention was a multifaceted outpatient antibiotic stewardship bundle. The primary outcome was the rate of antibiotic prescribing in Tier 3 encounters. Secondary outcomes included 14-day repeat healthcare contact for respiratory indications and factors associated with persistent unnecessary prescribing. 165,658 Tier 3 encounters, 96,125 in the pre- and 69,533 in the post-intervention period, were included. Following intervention, the prescribing rate for Tier 3 encounters decreased from 21.7% to 11.2% (P<0.001). Repeat 14-day respiratory healthcare contact in the no antibiotic group was lower post-intervention (9.9.% vs 9.4%, P=.004). Multivariable models indicated that increasing patient age, Charlson comorbidity index, and primary diagnosis selected were the most important factors associated with persistent unnecessary antibiotic prescribing. Outpatient antibiotic stewardship initiatives can reduce unnecessary antibiotic prescribing for Tier 3 URIs without increasing repeat respiratory healthcare contact. Advancing age and number of comorbidities remain risk factors for persistent unnecessary antibiotic prescribing.

Posaconazole, a triazole antifungal commonly used for the treatment and prevention of invasive fungal infections, is available in IV, oral suspension and oral delayed-release (DR) tablet formulations.^1–3 Of the oral formulations, the DR tablet is favoured owing to its superior bioavailability, once-daily dosing and reliable absorption regardless of gastric acidity.⁴ Even when dosed appropriately, posaconazole oral solution often does not achieve therapeutic levels.⁵ This complicates administration in patients unable to swallow tablets whole and in whom long-term IV administration is undesirable. Posaconazole DR tablets are labelled as ‘do not crush,’ largely due to extrapolated concern that crushing the DR matrix may lead to a ‘dose dump’ and altered bioavailability.^6,7 Recently, several case series have demonstrated success with crushing and administering the DR tablets via enteral feeding tubes, thus prompting a practice change across our health system.^8–10 In August 2022, following the report by Dieringer et al.,⁹ our electronic health record entry for the DR tablets was modified to permit selection of per feeding tube routes and modification of the administration instructions to facilitate administration of crushed posaconazole DR tablets by feeding tube, when necessary. Between 1 August 2022 and 18 November 2022 a total of 22 adult patients received at least one dose of posaconazole DR tablets crushed and administered via feeding tube. This included 13 patients receiving the agent for antifungal prophylaxis and 9 patients receiving therapy for confirmed or suspected fungal infections. Ten patients had sufficient documentation confirming administration of the crushed DR tablets and therapeutic drug monitoring (TDM) performed. Of these, one patient was receiving crushed tablets per gastric tube upon hospital admission and had this continued, four patients were switched from alternative formulations to the crushed tablets, and five patients were initiated on new therapy with the crushed DR tablets. Patient age/sex, indications for therapy, previous formulation dosing regimens, crushed DR tablet regimens and routes, and TDM for the 10 included patients are displayed in Table 1.