Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Why is the Implementation of Beta-Lactam Therapeutic Drug Monitoring for the Critically Ill Falling Short? A Multicenter Mixed-Methods Study.

BACKGROUND: Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM. METHODS: This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks. RESULTS: Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings. CONCLUSIONS: Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice.

CLinician and patient characteristics effect on Antimicrobial Stewardship Interventions (CLASI) study.

OBJECTIVE: To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate. DESIGN: A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes. SETTING: A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record. PARTICIPANTS: The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales). METHODS: Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient. RESULTS: Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted (P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001). CONCLUSIONS: Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

'How to' Guide for Pharmacist-led Implementation of Beta-Lactam Therapeutic Drug Monitoring in the Critically Ill.

Beta-lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta-lactam TDM program. This single-center experience forms the basis of the manuscript which outlines practical considerations involved with implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist-led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of 'individual internalization' seems to be uniquely important to beta-lactam TDM implementation compared with implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist led beta-lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program.

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019.

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.

A Framework for Outpatient Infusion of Antispike Monoclonal Antibodies to High-Risk Patients with Mild-to-Moderate Coronavirus Disease-19: The Mayo Clinic Model.

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.