Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital.

Background: Studies have demonstrated improved clinical outcomes with extended infusion (EI) piperacillin/tazobactam (TZP) compared to standard infusion (SI). However, there is less evidence on its benefits in noncritically-ill patients. Hospital-wide EI TZP was implemented at our site on February 21, 2012. Our objectives were to compare clinical, safety and economic outcomes between EI and SI TZP. Methods: A retrospective cohort study of all adult patients who received EI TZP (3.375 g IV q8h infused over 4 hours and SI TZP for ≥ 48 hours during 3 years pre-and postimplementation was conducted. The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay (LOS), nursing plus pharmacy cost, occurrence of Clostridioides difficile infection, readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution for TZP. The primary outcome and binary secondary outcomes were analyzed using a logistic regression model. LOS was examined using time to event analysis. Cost was examined using linear regression modelling. Results: Overall, 2034 patients received EI TZP and 1364 patients received SI TZP. EI TZP was associated with lower odds of mortality (OR 0.76, 95% CI 0.63-0.91), lower odds of C. difficile infection (OR 0.59, 95% CI 0.41-0.84) and 8% lower cost (estimate 0.92, 95% CI 0.87-0.98) compared to SI TZP. Conclusions: Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C. difficile infection with cost savings at our institution.

Evaluating a pilot, structured, face-to-face, antimicrobial stewardship, prospective audit-and-feedback program in emergency general surgery service in a community hospital.

Background: Prospective audit and feedback (PAF) is an established practice in critical care settings but not in surgical populations. We pilot-tested a structured face-to-face PAF program for our acute-care surgery (ACS) service. Methods: This was a mixed-methods study. For the quantitative analysis, the structured PAF period was from August 1, 2017, to April 30, 2019. The ad hoc PAF period was from May 1, 2019, to January 31, 2021. Interrupted time-series segmented negative binomial regression analysis was used to evaluate change in antimicrobial usage measured in days of therapy per 1,000 patient days for all systemic and targeted antimicrobials. Secondary outcomes included C. difficile infections, length of stay and readmission within 30 days. Each secondary outcome was analyzed using a logistic regression or negative binomial regression model. For the qualitative analyses, all ACS surgeons and trainees from November 23, 2015, to April 30, 2019, were invited to participate in an email-based anonymous survey developed using implementation science principles. Responses were measured using counts. Results: In total, 776 ACS patients were included in the structured PAF period and 783 patients were included in the in ad hoc PAF period. No significant changes in level or trend for antimicrobial usage were detected for all and targeted antimicrobials. Similarly, no significant differences were detected for secondary outcomes. The survey response rate was 25% (n = 10). Moreover, 50% agreed that PAF provided them with skills to use antimicrobials more judiciously, and 80% agreed that PAF improved the quality of antimicrobial treatment for their patients. Conclusion: Structured PAF showed clinical outcomes similar to ad hoc PAF. Structured PAF was well received and was perceived as beneficial by surgical staff.

Evaluating the impact of mandatory indications on antibiotic utilization in a community hospital.

Objective: We evaluated the impact of introducing a mandatory indication field into electronic order entry for targeted antibiotics in adult inpatients. Design: Retrospective, before-and-after trial. Setting: A 400-bed community hospital. Interventions: All adult electronic intravenous (IV) and enteral orders for targeted antibiotics (moxifloxacin, ciprofloxacin, clindamycin, vancomycin, and metronidazole) had a mandatory indication field added. Control antibiotics (amoxicillin-clavulanate, ceftriaxone and piperacillin-tazobactam) were chosen to track shifts in antibiotic prescribing due to the introduction of mandatory indication field. Methods: Descriptive statistics were used to summarize the primary outcome, measured in Defined Daily Doses (DDD) per 1000 patient days (PD). Interrupted time-series (ITS) analysis was performed to compare levels and trends in antibiotic usage of targeted and control antibiotics during 24 months before and after the intervention. Additionally, a descriptive analysis of mandatory indication fields for targeted antibiotics in the postintervention period was conducted. Results: In total, 4,572 study antibiotic orders were evaluated after the intervention. Preset mandatory indications were selected for 30%-55% of orders. There was decreased usage of targeted antibiotics (mean, 92.02 vs 72.07 DDD/1000-PD) with increased usage of control antibiotics (mean, 102.73 vs 119.91 DDD/1000-PD). ITS analysis showed no statistically significant difference in overall antibiotic usage before and after the intervention for all targeted antibiotics. Conclusion: This study showed moderate use of preset mandatory indications, suggesting that the preset list of indications can be optimized. There was no impact on overall antibiotic usage with the use of mandatory indications. More prospective research is needed to study the utility of this intervention in different contexts.

Trends in hospital antibiotic utilization during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter interrupted time-series analysis.

Objective: To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic. Design: Retrospective interrupted time-series analysis. Setting: A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19. Methods: Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline. Results: Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76; 95% CI, 1.38-2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30; 95% CI, 1.16-1.46) and wave 2 of the pandemic (RR, 1.21; 95% CI, 1.11-1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions. Conclusions: After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.

Barriers and facilitators of implementing an antimicrobial stewardship intervention for urinary tract infection in a long-term care facility.

BACKGROUND: Fifty percent of antibiotic courses in long-term care facilities (LTCFs) are unnecessary, leading to increased risk of harm. Most studies to improve antibiotic prescribing in LTCFs showed modest and unsustained results. We aimed to identify facilitators, barriers and strategies in implementing a urinary tract infection (UTI)-focused antimicrobial stewardship (AS) intervention at a LTCF, with the secondary objective of exploring the pharmacist's potential roles. METHODS: The study used a qualitative descriptive design. Participants attended either a focus group or one-on-one interview. Data were analyzed inductively using a codebook modified in an iterative analytic process. Barrier and facilitator themes were mapped using the capability, opportunity, motivation and behaviour (COM-B) model. Similarly, themes were identified from the transcripts regarding the pharmacist's roles. RESULTS: Sixteen participants were interviewed. Most barriers and facilitators mapped to the opportunities domain of the COM-B model. The main barrier themes were lack of access, lack of knowledge, ineffective communication, lack of resources and external factors, while the main facilitator themes were education, effective collaboration, good communication, sufficient resources and access. For the pharmacist's role, the barrier themes were ineffective collaboration and communication. CONCLUSION: This study supports the importance of tailoring interventions to target factors underlying barriers to behaviour change. At this LTCF, an effective antimicrobial stewardship intervention should incorporate strategies to improve access, knowledge, communication and collaboration in its design, having sufficient resources and addressing external factors to optimize its success and long-term sustainability. Can Pharm J (Ott) 2021;154:xx-xx.

High versus low intensity: What is the optimal approach to prospective audit and feedback in an antimicrobial stewardship program?

BACKGROUND: Antimicrobial stewardship program (ASP) interventions, such as prospective audit and feedback (PAF), have been shown to reduce antimicrobial use and improve patient outcomes. However, the optimal approach to PAF is unknown. OBJECTIVE: We examined the impact of a high-intensity interdisciplinary rounds-based PAF compared to low-intensity PAF on antimicrobial use on internal medicine wards in a 400-bed community hospital. METHODS: Prior to the intervention, ASP pharmacists performed low-intensity PAF with a focus on targeted antibiotics. Recommendations were made directly to the internist for each patient. High-intensity, rounds-based PAF was then introduced sequentially to 5 internal medicine wards. This PAF format included twice-weekly interdisciplinary rounds, with a review of all internal medicine patients receiving any antimicrobial agent. Antibiotic use and clinical outcomes were measured before and after the transition to high-intensity PAF. An interrupted time-series analysis was performed adjusting for seasonal and secular trends. RESULTS: With the transition from low-intensity to high-intensity PAF, a reduction in overall usage was seen from 483 defined daily doses (DDD)/1,000 patient days (PD) during the low-intensity phase to 442 DDD/1,000 PD in the high-intensity phase (difference, -42; 95% confidence interval [CI], -74 to -9). The reduction in usage was more pronounced in the adjusted analysis, in the latter half of the high intensity period, and for targeted agents. There were no differences seen in clinical outcomes in the adjusted analysis. CONCLUSIONS: High-intensity PAF was associated with a reduction in antibiotic use compared to a low-intensity approach without any adverse impact on patient outcomes. A decision to implement high-intensity PAF approach should be weighed against the increased workload required.

High-dose methotrexate in adult oncology patients: a case-control study assessing the risk association between drug interactions and methotrexate toxicity.

INTRODUCTION: High-dose methotrexate, defined as dose ≥1 g/m(2), is commonly used in chemotherapy protocols. Certain drugs such as acyclovir, allopurinol, proton pump inhibitors and some antibiotics have been associated with delayed renal clearance of methotrexate and may predispose patients to toxicities. Currently, no specific recommendations exist on adjusting the high-dose methotrexate regimen in the presence of potential interacting drugs. This study aims to determine whether presence of interacting drugs is associated with delayed methotrexate clearance. METHODS: This was a case-control study of adult oncology patients who received their first cycle of high-dose methotrexate. Cases were defined as patients who experienced delayed methotrexate clearance, as indicated by serum methotrexate level ≥ 0.1 umol/L at 72 h. The primary endpoint was the frequency of presence of interacting drugs between cases and controls. These were compared using Fisher's exact test. Where possible, adjustment for significant baseline differences that can affect methotrexate clearance was made using logistic regression. The secondary endpoint was frequency of methotrexate-related clinical toxicities between groups and included myelosuppression, nephrotoxicity, hepatotoxicity and mucositis. RESULTS: From January 2004 to March 2011, 73 patients met study criteria, of which 23 were defined as cases. Significant baseline differences were methotrexate dose received (9116 mg ± 4339 versus 6054 mg ± 2874, p=0.012) and renal impairment (5 versus 0, p = 0.002). The presence of interacting drugs was not associated with delayed methotrexate clearance (OR 0.91, 95% CI 0.24-3.38, p > 0.999). After adjusting for methotrexate dose, drugs observed more frequently (allopurinol, proton pump inhibitors and sulfamethoxazole/trimethoprim) were not associated with delayed methotrexate clearance (p = 0.95, 0.59 and 0.20, respectively). Cases experienced more severe anemia (grade 2.52 versus 1.68, p = 0.007) and higher rates of mucositis (65.2% versus 20.0%, p < 0.001). CONCLUSION: This study showed no significant association between presence of interacting drugs and delayed methotrexate clearance. Patients who experienced delayed methotrexate clearance had higher incidence of severe anemia and mucositis.