Epps, Kevin

Background: Piperacillin-Tazobactam (PTZ) is often used to treat community-acquired intra-abdominal infections (CA-IAIs) despite common causative pathogens being susceptible to more narrow-spectrum agents. However, susceptibility to PTZ among these predominant pathogens has been declining. Antibiotic de-escalation to non-antipseudomonal beta-lactams whenever possible is an important strategy to prevent the development of resistance to PTZ. Objective: The purpose of this study is to assess PTZ length of therapy in patients with CA-IAI, by comparing patients who received a pharmacist-led intervention involving the de-escalation of PTZ to narrow-spectrum regimens with those who did not receive the intervention. Methods: A retrospective analysis was conducted among patients >18 years old and admitted with CA-IAI empirically placed on PTZ between January 1, 2022, through June 30, 2022 (pre-intervention group), and January 1, 2024, through June 30, 2024 (post-intervention group). A total of 246 patients were included in the pre-intervention group and 129 patients in the post-intervention group. The utilization of PTZ, hospital length of stay (LOS), and treatment-associated complications were assessed using linear and logistic regression model, respectively. Results: Compared with patients in the pre-intervention group, those in the post-intervention group had a mean 1.2-day reduction in PTZ length of therapy (2.3 vs 1.2 days, P < 0.001). There was no difference in LOS, (β = 0.001, 98% confidence interval [CI] −1.29 to 1.29; P = 0.477), hospital readmission within 30 days due to IAI (odds ratio [OR] = 0.85, 98% CI = 0.51 to 1.44; P = 0.56), treatment-associated complications during current hospitalization (OR = 0.77, 98% CI = 0.45 to 1.32; P = 0.35), development of Clostridium difficile -associated diarrhea (OR = 3.29, 98% CI = 0.77 to 22.4; P = 0.14), or medication toxicity (OR = 2.07, 98% CI = 0.79 to 6.08; P = 0.15). Conclusion and relevance: The use of narrow-spectrum antibiotics for the empiric treatment of CA-IAI-reduced PTZ length of therapy and did not result in adverse clinical outcomes.

Background: Cefazolin is a preferred treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Recent studies have suggested a potential impact on clinical outcomes in patients with hypoalbuminemia treated with highly protein-bound antimicrobials. Objective: The purpose of this study was to determine if there are any differences in clinical outcomes between normoalbuminemic and hypoalbuminemic patients treated with cefazolin for bacteremia. Methods: A retrospective, multicentered cohort study of patients hospitalized between 2019 and 2023 with MSSA bacteremia treated with cefazolin for at least 24 hours prior to culture clearance. Patients were divided into hypoalbuminemia (serum albumin ≤2.5 g/dL) or normoalbuminemia groups. The primary outcome was time to culture clearance. Results: Of 69 patients included (50 in normoalbuminemia group and 19 in hypoalbuminemia group), the most common sources of bacteremia were line-related, osteoarticular, and infective endocarditis. Deep-seated infections were present in 24% of the normoalbuminemia group and 58% of the hypoalbuminemia group. Patients with hypoalbuminemia had a significantly longer mean hospital length of stay (12 vs 7 days, P = 0.016). After adjusting for deep-seated infection, hypoalbuminemia was associated with increased time to culture clearance by 1.2 days ( P = 0.039). In-hospital mortality was significantly higher in the hypoalbuminemia group (26% vs 4%, P = 0.015). Conclusion and Relevance: Limited research is available describing the relationship between serum albumin levels and clinical outcomes. Our study suggests patients with hypoalbuminemia treated with cefazolin for MSSA bacteremia have significantly longer time to culture clearance, increased mortality, and longer length of stay.

Objective: We evaluated the impact of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) protocol on the vancomycin length of therapy (LOT) for skin and soft tissue infections (SSTIs). Design: Retrospective quasi-experimental pre- and post- MRSA nasal PCR protocol implementation study. Setting: Tertiary-care academic medical center in Jacksonville, Florida. Patients: Eligible patients received empiric vancomycin for SSTIs from January 1st to September 30th 2020 (pre-implementation group) and from January 1st to September 30th 2022 (post-implementation group). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with SSTIs. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary outcomes were incidence of acute kidney injury (AKI), number of vancomycin levels collected, and hospital length of stay (LOS). Results: The study included 131 patients (pre-implementation, n = 86 and post-implementation, n = 45). There was no significant difference in vancomycin length of therapy (LOT) between implementation groups: mean LOT in days and standard deviation (SD) were 2.7 (1.9) and 2.6 (1.3), respectively, p-value 0.493. Of significance, in the post-implementation group, vancomycin LOT between patients with a negative and positive MRSA PCR were 2.3 (1.1) and 3.9 (1.6), p-value 0.006. There was no difference in secondary outcomes. Conclusion: The utilization of the MRSA nasal PCR to guide vancomycin de-escalation did not significantly change the vancomycin LOT, however in the post-implementation group there was a significant difference in vancomycin LOT between negative and positive MRSA PCRs.

Abstract Background Implementing effective antimicrobial stewardship interventions is an important component of antimicrobial stewardship programs. Recently, stewardship research has shown that clinician characteristics may have an impact on antimicrobial stewardship intervention methods and acceptance rates. Methods A multisite health system antimicrobial stewardship prospective audit and feedback program interventions performed by stewardship staff using a standardized electronic medical record (EMR) tool were compared by stewardship clinician profession (pharmacist, physician, or advanced practice provider, APP) from 7/1/2017 to 6/30/2022. Outcomes assessed were intervention rates, communication methods, and intervention acceptance by patient age and intensive care unit (ICU) status of patient. Generalized estimating equations utilizing logistic regression were used to assess for associations between staff. Associations were assessed both univariately and after adjusting for other factors. Results Of 69,503 prospective audit and feedback EMR based rules, there were 14,699 rules associated with an intervention. The majority of rules were reviewed by pharmacists (90.7%) followed by physician (9.2%) and APP (&lt; 1%). Of 9,034 interventions with an outcome documented, 7326 (85.5%) pharmacist interventions were accepted and 360 (77.3%) physician interventions were accepted (adjusted p=0.047). Pharmacists intervened by direct action (ie, adjust a medication order) in 6.6% of interventions; whereas, physicians did so rarely (0.4%). Pharmacists were more likely to use synchronous communication than physicians in the adjusted model (pharmacist vs. physician: 63.8% vs 52.5%; p=0.004). Patients in the ICU had a significantly lower intervention acceptance rate (non-ICU vs. ICU: 86.6% vs. 78.0%; adjusted OR 0.57 [95% CI 0.46-0.70], p&lt; 0.001).Table 1.Intervention Rate by Baseline Demographics of Stewardship Clinicians and Patients. *% are reported as row % **Multivariable model was also adjusted for day of week and time of day APP-Advanced practice provider; ICU-intensive care unitTable 2.Intervention Acceptance. *% are reported as row % **Multivariable model was also adjusted for day of week and time of day APP-Advanced practice provider; ICU-intensive care unit Conclusion Antimicrobial stewardship pharmacists and physicians are both effective at prospective audit and feedback but used different intervention styles. Advanced practice providers were vastly underrepresented. Patients in the ICU may benefit from tailored ASP efforts. Disclosures Sara Ausman, PharmD, Gilead: Honoraria Caitlin Brown, PharmD, Alexion: Grant/Research Support|Trevena: Advisor/Consultant Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

Abstract Purpose Surgical patients with a penicillin allergy label (PAL) are less likely to receive β-lactams for surgical site infection (SSI) prophylaxis and more likely to receive second-line antibiotics, which may increase the risk of SSI, drug toxicities, and associated costs. We assessed the impact of implementing a pharmacist-led quality improvement project to increase the use of cefazolin as a first-line agent in this population. Summary After implementation of a pilot project in December 2021, all patients with a PAL and orders for preoperative antibiotics were risk stratified into high- or low-risk categories by a pharmacist. For the low-risk group, cefazolin was recommended. For the high-risk group, cefazolin was avoided and a second-line agent was administered. Our analysis compared 422 preintervention patients (August 15 to November 15, 2021) to 492 postintervention patients (December 15 to March 15, 2022). During the postintervention period, β-lactam usage increased (from 12.6% to 37.8%, P &lt; 0.001), while usage of vancomycin (45.5% vs 29.5%, P &lt; 0.001) and other second-line antibiotics (87.4% vs 62.2%, P &lt; 0.001) declined. There were no adverse reactions reported in the preintervention cohort, with 2 potential adverse reactions reported after the intervention (0% vs 0.4%, P = 0.190). Medication costs based on claims data were 50% to 80% lower for patients receiving cefazolin. Conclusion In our cohort, a pharmacy-led antibiotic selection algorithm for patients with a PAL receiving perioperative antimicrobial prophylaxis resulted in increased use of β-lactam antibiotics, decreased use of second-line antibiotics, and decreased costs without a significant change in the incidence of adverse reactions.

Abstract Background Treating COVID-19 infection in SOT is challenging due to long-term use of immunosuppressive agents. REM is the only FDA-approved anti-viral for SARS-COV-2 infection. DEX showed decrease in mortality in the Recovery Trial. COVID-19 treatment guidelines for SOT patients are the same as NTP despite limited literature on those outcomes. Our primary objective was to determine if 30-day mortality was different between SOT and NTP matched cohorts using these 2 drugs. The secondary objectives included comparisons of length of stay (LOS), days on mechanical ventilation (DMV), and the use of other treatment modalities. Methods We retrospectively collected data for hospitalized SOT and NTP, 18 years and older, with pcr-confirmed SARS-CoV-2 infection receiving REM and DEX from May 1, 2020, to October 10, 2020, at Mayo Clinic Florida. IRB approval was obtained. Descriptive statistics were used to analyze the data. Continuous variables were summarized as mean (standard deviation) or median (range) where appropriate, while categorical variables were reported as frequency (percentage). Results Of 80 patients who met the inclusion criteria, 28 were SOT, and 52 were NTP. The SOT cohort was subcategorized below: SOT patients were significantly younger than NTP (p &lt; .001). Further, SOT patients had significantly longer LOS (p = 0.043) and more COVID-19 modalities (75% vs. 36.5%, p = 0.002) compared to NTP. Among the 28 SOT patients, 2 of them died within 30 days of admission, and among the 52 NTP patients, 7 of them died within 30 days. The 30-d survival estimate for SOT group is 92.9% (95% CI: 83.8% - 100.0%) and for NTP group is 86.5% (95% CI: 77.7% - 96.3%). The log-rank test was not significant between the groups (p=0.37), but the NTP has a worse survival curve from the figure below. SOT-NTP Survival Curve Conclusion SOT group was younger, had longer LOS, and more COVID-related modalities. The 30-d survival estimate for SOT group is 92.9% and for NTP group is 86.5%, but the survival curve for NTP was worse likely secondary to age. Use of REM & DEX in SOT recipients is a valid recommendation. Disclosures Claudia R. Libertin, MD, Gilead (Grant/Research Support)

Abstract Background The majority of human antimicrobial utilization occurs in the outpatient setting. Despite being mainly viral in etiology, upper respiratory tract infections (URIs) were the most common indication for outpatient antimicrobial prescriptions at our institution. Methods Through our electronic health record (EHR), we were able to determine our rate of antibiotic prescriptions for inappropriate URI diagnosis at our primary care practice sites. We selected staff volunteers from each our primary care practice sites to serve as stewardship champions. They were given training in stewardship best practices, and an URI stewardship toolkit which included viral URI prescription pad, EHR order panel, and patient education signage. They were tasked with providing education and feedback to their practice sites. We meet with them on a monthly basis to disseminate prescribing data and education. They also provided feedback from practice sites to the stewardship committee. Results Our decentralized model was put in place in November 2020. In the 6 months prior to the intervention, the average prescribing rate was 29.1%. In the 6 months after the intervention, the average prescribing rate decreased by 15% to 24.8%. During the intervention phase, there was an increase in number of non-COVID URIs diagnosed at our primary care sites. Temporal Trend in Inappropriate Antibiotics Prescribing Rates for Viral URIs Pre- and Post- Intervention Inappropriate antibiotic prescribing rate for viral upper respiratory tract infections from May 2020 until May 2021. Intervention started in December 2021 (arrow). Pre-intervention average was 29.1%. Post-intervention age was 24.8% which is a 15% decline in prescribing rate. Viral Upper Respiratory Infections Visits The total number of visits for presumed viral upper respiratory infections to primary care sites from May 2020 until May 2021. The majority of COVID-19 precautions in the area expired at the end of March 2021. Conclusion We have been able to lower our inappropriate prescriptions for URIs utilizing a decentralized model of stewardship champions. This result was especially notable as the intervention phase corresponded with the end of COVID-19 precautions and an increase in non-COVID URIs diagnosed. The advantage of this approach includes an advocate embedded at each practice site who is familiar with the opportunities and challenges of the site, and a two-way flow of information from practice sites to the stewardship committee. This model provided additional benefit during the COVID-19 pandemic as the ability of centralized staff to travel to off campus clinic sites was curtailed. Disclosures All Authors: No reported disclosures

AbstractAcute pulmonary exacerbations are complications of cystic fibrosis (CF) and are associated with increased morbidity and mortality. Methicillin‐resistant Staphylococcus aureus (MRSA) and Aspergillus fumigatus are organisms that have been detected in the lungs of CF patients. The focus of this review is to provide an overview of the classes of antimicrobials used for MRSA and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction caused by A. fumigatus. The current anti‐MRSA antibiotics and medications for ABPA dosing recommendations are discussed. This article also reviews the findings from the MRSA utilization surveys and the pharmacokinetic and pharmacodynamic differences between CF and non‐CF patients. Antimethicillin S. aureus antibiotics include ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim, and tetracycline derivatives (doxycycline, minocycline, tigecycline). Medications used for ABPA include corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, voriconazole), and a monoclonal antibody, omalizumab.