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.

Impact of two-step urine culture ordering in the emergency department: a time series analysis.

BACKGROUND: Despite evidence against the use of antimicrobials for asymptomatic bacteriuria (ASB), they are frequently prescribed leading to unnecessary adverse events. Prior studies have shown that reducing unnecessary urine cultures (UCs) results in decreased antimicrobial utilisation for ASB. Emergency departments (EDs) submit the largest volume of UCs, yet efforts to limit overordering in this patient setting have had limited success. METHODS: A new two-step model of care for urine collection, using a novel UC collection container, was implemented in the ED of a large community hospital. The collection system contains a preservative allowing UCs to be held at room temperature for up to 48 hours before processing. UCs were collected by front-line staff, but only processed in the microbiology lab if requested by ED physicians after clinical assessment. RESULTS: Following implementation there was a decrease in the percentage of weekly ED visits associated with a processed UC (5.97% vs 4.68%, p<0.001), a decrease in the percentage of monthly ED visits requiring a callback for positive urine culture (1.84% to 1.12%, p<0.001) and a decrease in antimicrobial prescriptions for urinary indication among admitted patients (20.6% to 10.9%, p<0.01). There was a false omission rate of 1.35% (95% CI 0.7% to 2.2%), yet no identified cases of untreated urinary tract infection (UTI), or significant change in repeat ED visits or ED length of stay. CONCLUSIONS: Changing to two-step urine culture ordering in the ED resulted in a decrease in UCs processed, callbacks for positive results and antimicrobial use without evidence of untreated UTIs. This model of care has strong potential to improve the use of hospital resources while minimising detection and inappropriate treatment of ASB.