Indiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice >70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing.

Background: Recent studies in gram-negative bacteremia (GNB) suggest intravenous (IV) to oral (PO) switch and short treatment durations yield similar clinical outcomes and fewer adverse events. Antimicrobial stewardship program (ASP) bundled initiatives have been associated with improved clinical outcomes for blood stream infections. Methods: This single-center retrospective cohort evaluation included inpatient adults from 11/2014-10/2015 and 10/2017-9/2018 with GNB. The pre-ASP period was prior to the establishment of an ASP program. In the post-period, the ASP promoted IV to PO switches, avoidance of repeat blood cultures, and short treatment durations for patients with uncomplicated GNB. The primary outcome was duration of antibiotic therapy. Secondary outcomes included associated process measures with the bundle and clinical outcomes. Results: 137 patients met criteria for inclusion, with 51 patients in the pre- group, and 86 patients in the post- group. Background characteristics were similar between groups. The median duration of therapy was 14 days (IQR = 10-16) in the pre- group and 10 days (7-14) in the post- group (p<0.001). The median day of IV to PO switch was on day 5 (4-6) in the pre- group versus day 4 (3-5) in the post- group (p=0.046). Average total hospital cost per case decreased by 27% in the post- group (p=0.19). Mortality rates and bacteremia recurrence were not significantly different between groups. Conclusions: An ASP bundle for uncomplicated GNB was associated with reduced durations of therapy and earlier PO switch. These findings highlight the synergistic role of ASPs in optimizing antibiotic use and promoting patient safety.

Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. We conducted an explanatory, sequential mixed-methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (P = .001), considered valuable team members (P = .001), and comfortable recommending antibiotic changes (P = .02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had 4 distinguishing characteristics: (1) robust knowledge of and access to antibiotic stewardship guidance; (2) high-quality clinical pharmacist–physician relationships; (3) tools and infrastructure to support stewardship; and (4) highly engaged infectious diseases physicians who advocated stewardship principles. This mixed-methods study demonstrates the importance of organizational context for high performance in stewardship and suggests that improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.

BACKGROUND: COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS: SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use. TRIAL REGISTRATION: ClinicalTrials.gov NCT04373460. FUNDING: Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

We describe a case of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient receiving ocrelizumab for multiple sclerosis. Viral RNA shedding, signs, and symptoms persisted for 69 days with resolution after administration of convalescent plasma and antiviral therapy. This case suggests risk for persistent SARS-CoV-2 infection in patients treated with anti-CD-20 monoclonal antibodies and supports a role for humoral immunity in disease resolution.