A retrospective cohort study of prescribing outcomes in outpatients treated with nirmatrelvir-Ritonavir for COVID-19 in an interdisciplinary community clinic.

BACKGROUND: Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting. METHODS: We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir. RESULTS: There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths. INTERPRETATION: Nirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.

Evaluating Antimicrobial Use and Spectrum of Activity in Ontario Hospitals: Feasibility of a Multicentered Point Prevalence Study.

BACKGROUND: Antimicrobial stewardship, a key component of an overall strategy to address antimicrobial resistance, has been recognized as a global priority. The ability to track and benchmark antimicrobial use (AMU) is critical to advancing stewardship from an organizational and provincial perspective. As there are few comprehensive systems in Canada that allow for benchmarking, Public Health Ontario conducted a pilot in 2016/2017 to assess the feasibility of using a point prevalence methodology as the basis of a province-wide AMU surveillance program. METHODS: Three acute care hospitals of differing sizes in Ontario, Canada, participated. Adults admitted to inpatient acute care beds on the survey date were eligible for inclusion; a sample size of 170 per hospital was targeted, and data were collected for the 24-hour period before and including the survey date. Debrief sessions at each site were used to gather feedback about the process. Prevalence of AMU and the Antimicrobial Spectrum Index (ASI) was reported for each hospital and by indication per patient case. RESULTS: Participants identified required improvements for scalability including streamlining ethics, data sharing processes, and enhancing the ability to compare with peer organizations at a provincial level. Of 457 patients, 172 (38%) were receiving at least 1 antimicrobial agent. Beta-lactam/beta-lactamase inhibitors were the most common (18%). The overall mean ASI per patient was 6.59; most cases were for treatment of infection (84%). CONCLUSIONS: This pilot identified factors and features required for a scalable provincial AMU surveillance program; future efforts should harmonize administrative processes and enable interfacility benchmarking.

Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use.

BACKGROUND: The success of antimicrobial stewardship is dependent on how often it is completed and which antimicrobials are targeted. We evaluated the impact of an antimicrobial stewardship program (ASP) in three non-ICU settings where all systemic antibiotics, regardless of spectrum, were targeted on the first weekday after initiation. METHODS: Prospective audit and feedback (PAAF) was initiated on the surgical, respiratory, and medical wards of a community hospital on July 1, 2010, October 1, 2010, and April 1, 2012, respectively. We evaluated rates of total antibiotic use, measured in days on therapy (DOTs), among all patients admitted to the wards before and after PAAF initiation using an interrupted time series analysis. Changes in antibiotic costs, rates of C. difficile infection (CDI), mortality, readmission, and length of stay were evaluated using univariate analyses. RESULTS: Time series modelling demonstrated that total antibiotic use decreased (± standard error) by 100 ± 51 DOTs/1,000 patient-days on the surgical wards (p = 0.049), 100 ± 46 DOTs/1,000 patient-days on the respiratory ward (p = 0.029), and 91 ± 33 DOTs/1,000 patient-days on the medical wards (p = 0.006) immediately following PAAF initiation. Reductions in antibiotic use were sustained up to 50 months after intervention initiation, and were accompanied by decreases in antibiotic costs. There were no significant changes to patient outcomes on the surgical and respiratory wards following intervention initiation. On the medical wards, however, readmission increased from 4.6 to 5.6 per 1,000 patient-days (p = 0.043), while mortality decreased from 7.4 to 5.0 per 1,000 patient-days (p = 0.001). CDI rates showed a non-significant declining trend after PAAF initiation. CONCLUSIONS: ASPs can lead to cost-effective, sustained reductions in total antibiotic use when interventions are conducted early in the course of therapy and target all antibiotics. Shifting to such a model may help strengthen the effectiveness of ASPs in non-ICU settings.

Point-of-Care ß-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

Background: ß-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

Reducing co-administration of proton pump inhibitors and antibiotics using a computerized order entry alert and prospective audit and feedback.

BACKGROUND: Antibiotics and proton pump inhibitors (PPIs) are associated with Clostridium difficile infection (CDI). Both a computer order entry alert to highlight this association as well as antimicrobial stewardship directed prospective audit and feedback represent novel interventions to reduce the co-administration of antibiotics and PPIs among hospitalized patients. METHODS: Consecutive patients admitted to two General Internal Medicine wards from October 1, 2010 until March 31, 2013 at a teaching hospital in Toronto, Ontario, Canada were evaluated. The baseline observation period was followed by the first phase, which involved the creation of a computerized order entry alert that was triggered when either a PPI or an antibiotic was ordered in the presence of the other. The second phase consisted of the introduction of an antibiotic stewardship-initiated prospective audit and feedback strategy. The primary outcome was the co-administration of antibiotics and PPIs during each phase. RESULTS: This alert led to a significant reduction in the co-administration of antibiotics and PPIs adjusted for month and secular trends, expressed as days of therapy per 100 patient days (4.99 vs. 3.14, p < 0.001) The subsequent introduction of the antibiotic stewardship program further reduced the co-administration (3.14 vs. 1.80, p <0.001). No change was observed in adjusted monthly CDI rates per 100 patient care days between the baseline and alert cohorts (0.12 vs. 0.12, p = 0.99) or the baseline and antibiotic stewardship phases (0.12 vs. 0.13, p = 0.97). CONCLUSIONS: Decreasing the co-administration of PPIs and antibiotics can be achieved using a simple automatic alert followed by prospective audit and feedback.

Growing a "positive culture" of antimicrobial stewardship in a community hospital.

BACKGROUND: Promoting the appropriate use of antimicrobials is a core value of antimicrobial stewardship. Prospective audit and feedback constitute an effective strategy for reducing the cost and use of antimicrobials, as well as their adverse effects, such as infection with Clostridium difficile. OBJECTIVE: To evaluate the antimicrobial stewardship program in the intensive care unit at the authors' hospital, in order to determine the cost and utilization of antimicrobials, as well as the rate of nosocomially acquired C. difficile infection. METHODS: An infectious diseases team, consisting of a physician and a pharmacist, performed prospective audit and feedback during a pilot study (April to June 2010). The team met with the intensive care unit team daily to discuss optimization of therapy. The cost and utilization of antimicrobial drugs, as well as rates of C. difficile infection, were compared between the pilot period and the same period during the previous year (April to June 2009). For 3 months after the pilot phase (i.e., July to September 2010), the strategy was continued 3 days per week. RESULTS: AFTER INTRODUCTION OF THE ANTIMICROBIAL STEWARDSHIP PROGRAM, THERE WAS A SIGNIFICANT REDUCTION IN THE COST OF ANTIMICROBIAL DRUGS: $27 917 less than during the same period in the previous year, equivalent to a reduction of $15.45 (36.2%) per patient-day ($42.63 versus $27.18). Utilization of broad-spectrum antipseudomonal antimicrobial agents was also significantly lower, declining from 63.16 to 38.59 defined daily doses (DDDs) per 100 patient-days (reduction of 38.9%). After the pilot period, the rate declined further, to 28.47 DDDs/100 patient-days. During the pilot period, there were no cases of C. difficile infection, and in the post-pilot period, there was 1 case (overall rate 0.42 cases/1000 patient-days). This rate was lower than (but not significantly different from) the rate for April to September 2009 (1.87 cases/1000 patient-days). There were no differences in mortality rate or severity of illness. CONCLUSION: The antimicrobial stewardship program in this community hospital was associated with significant decreases in antimicrobial costs and in utilization of antipseudomonal antimicrobial agents and a nonsignificant decrease in the rate of C. difficile infection. Knowledge exchange, peer-to-peer communication, and decision support, key factors in this success, will be applied in implementing the antimicrobial stewardship program throughout the hospital.