Rivera, Christina G.

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A commentary on Canterino et al. (2024) and Munsiff et al. (2024), articles where clinicians from two large OPAT programs

Abstract Background Post-discharge culture and susceptibility review has been described in emergency department and urgent care settings, but there is a lack of published literature describing culture review after acute care hospitalizations. Awaiting microbiology results can impede timely patient discharge. However, discharging patients while microbiology results are pending may result in suboptimal therapy or lost opportunity for additional testing/follow up. We implemented an antimicrobial stewardship effort to identify microbiology tests that result post-discharge utilizing a custom report in the electronic medical record (EMR). Methods. This retrospective descriptive study included adult patients ( >18 years of age) at 4 sites within Mayo Clinic from 1/1/2019 to 2/28/2023. Eligible patients had a hospitalization with an ID consult and an abnormal culture that was reviewed by an antimicrobial stewardship pharmacist after discharge. Urine cultures were excluded. The details of pharmacist-initiated antimicrobial stewardship interventions based on the culture review were identified by an EMR based research report. Results A total of 6803 patient encounters with at least 1 microbiology result reviewed post-discharge were identified. Patients were 40% female with a median age of 62 years. Patient race was 89.8% white, 4% black/African American, 1.5% Asian, and < 1% other. Of these patients, 1983 (29%) had at least one pharmacist intervention. A total of 169 (2.5%) of these patients had multiple interventions. Interventions included modification of antimicrobial therapy, addition of susceptibility testing, or additional follow up (labs, imaging, or patient visits). Median time from culture update to pharmacist review was 27.2 hours. Median length of hospital stay was 5 days and discharge disposition was home with self care (65%), home with home health or hospice (22.7%), or discharge to another acute care or skilled nursing facility (12.3%). Conclusion Outpatient review of post-discharge culture updates utilizing EMR reporting led to substantial interventions impacting antimicrobial treatments. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria

Abstract Background Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared. Methods This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Results Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups. Conclusion This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In prior work, those who continued remdesivir in an outpatient setting had better outcomes. Here, we assessed patients’ perspectives and the economic impact of this outpatient practice. Methods During a one-year period, 3,029 patients received remdesivir for COVID-19 in the hospital; of them, 542 were dismissed to continue remdesivir in the outpatient setting and were surveyed. The cost of care was compared between those who remained in the hospital vs. those who were dismissed. Results 470 of 542 patients were surveyed, and 93 (19.8%) responded. Responders were older than non-responders (median, 63 vs. 58 years). The majority (70.5%) had symptoms resolved by the time of the survey. Ten patients (11.4%) had persistent symptoms attributed to long COVID-19, including fatigue (30.1%), brain fog (23.7%), and insomnia (18.3%). 73.8% were excited to learn about the outpatient remdesivir program. The majority (81.0%) felt that receiving therapy at home was the right decision; 79.5% had support and felt the benefits of completing treatment at home. The majority were satisfied with communication before (75.6%) and during (80.5%) the outpatient appointment, information on benefits (80.3%) and risks (58.5%), time spent at the infusion center (88.6%), quality of care (82.3%) and overall experience (76.0%). The benefits of treatment were high-value (82.6%), while the infusions' cost, inconvenience, and discomfort were unimportant for most responders. After adjusting for gender, comorbidity score, and WHO scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p< .01). During this study, we estimated a total of 1,077 hospital room-days were made available to other patients. Conclusion An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients hospitalized for COVID-19. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital rooms for other patients needing critical services. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Bijan J. Borah, Ph.D., Boehringer Ingelheim: Advisor/Consultant|Exact Sciences: Advisor/Consultant Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

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 (< 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< 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

Abstract Background Due to extensive protein binding, use of ceftriaxone in the setting of hypoalbuminemia may result in suboptimal drug exposure via higher concentrations of unbound drug resulting in increased volume of distribution and increased drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone for a bacterial infection. Methods This retrospective review included adult inpatients with weight > 100 kg or body mass index (BMI) > 40 who received ceftriaxone 2 grams intravenously every 12 hours for at least 72 hours for one of the following indications: bloodstream infection, pneumonia, urinary tract infection, non-enterococcal endocarditis, skin and soft tissue infection, or bone and joint infection. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Clinical cure was defined as resolution of signs and symptoms compatible with active infection without need to change or extend antibiotic therapy due to inadequate effect of ceftriaxone. Microbiologic cure was defined as negative repeat sterile site cultures, if applicable. Secondary outcomes included length of stay, mortality, and 30-day readmission. Outcomes were analyzed with Mann-Whitney U tests, Pearson’s chi-squared tests, and Fisher’s exact tests (α level = 0.05). Results 137 patients were included, 34 of whom had a serum albumin ≤ 2.5 g/dL. Patients were predominantly white (94.2%) and male (69.3%) with a median BMI of 48.6 (Table 1). Clinical success, a composite of clinical and microbiologic cure, was achieved in 76.5% and 92.2% (p = 0.013) of those with and without hypoalbuminemia, respectively. Clinical cure was significantly more common among those without hypoalbuminemia (93.2%) as compared to those with hypoalbuminemia (76.5%) (p = 0.007). Death during hospitalization was more common (14.7% vs. 0%, p < 0.001) and median length of stay was longer (14 vs. 9 days, p = 0.009) in the hypoalbuminemia group. No difference was seen in 30-day readmission (23.5% vs. 11.7%, p = 0.089). Conclusion Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 grams every 12 hours. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria

Abstract Background Non-diphtheriae Corynebacterium spp. are important human pathogens responsible for a broad spectrum of clinical syndromes. Data on species-specific susceptibility patterns is limited. In this study we aim to study these susceptibility patterns over time and summarize the species-specific resistance profile that could be used by clinicians to guide therapeutic decisions. Methods We conducted a retrospective review of all the Non-diphtheriae Corynebacterium isolates that were submitted for antimicrobial susceptibility testing (AST) between January-2012 and February of 2023 to our reference lab. Results A total of 1925 Corynebacterium isolates were submitted for susceptibility testing over the study period. The most commonly identified species was C. striatum (35.6%) followed by C. amycolatum (24.4%). Figure-1 outlines the species distribution. Temporal analysis showed decreasing susceptibility rates over the study period from 47.5% to 20.6% for penicillin & from 50% to 7.6% for clindamycin. Linezolid and vancomycin were universally active against all species (Table-1). Daptomycin non-susceptibility was reported in 25% of C. jeikeium isolates (MIC=2). High level resistance to daptomycin with MIC >256 were noted in seven C. striatum and single C. amycolatum isolate. Doxycycline has the highest susceptibility rates among the tested oral agents after linezolid for the non-striatum species. Significant variation in species-specific susceptibility pattern was noted and summarized in Table 1. C. striatum was associated with concerning resistance rates to beta-lactams, tetracyclines, trimethoprim-sulfamethoxazole & fluoroquinolones with limited reliable oral treatment options beside linezolid. C. kroppenstedtii (associated with granulomatous mastitis) showed high susceptibility rate to tetracyclines and trimethoprim-sulfamethoxazole despite prevalent penicillin resistance. Conclusion Non-diphtheriae Corynebacterium spp are commonly isolated from clinical specimens and are associated with various clinical syndromes. Significant variation in resistance profile exists between different species. Prevalent resistance among the most common species such as C. Striatum is associated with therapeutic challenges. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Audrey N. Schuetz, MD, Merck: Advisor/Consultant

Abstract Background Critically ill patients, particularly those treated with extracorporeal devices or at extremes of weight, experience pharmacokinetic variability which can compromise beta-lactam (BL) antibiotic target attainment and treatment response. Therapeutic drug monitoring (TDM) for BL antibiotics can improve precision pharmacotherapy but has had limited implementation. The objective of this study was to evaluate the frequency of BL target attainment among adult intensive care unit (ICU) patients who underwent TDM. Methods This observational study evaluated adults treated with cefepime, piperacillin/tazobactam or meropenem in ICUs at the Mayo Clinic in Rochester, Minnesota who underwent TDM from June-September 2022. During the study timeframe, multidisciplinary teams were encouraged to perform BL TDM on patients requiring extracorporeal membrane oxygenation, continuous kidney replacement therapy, or at an extreme of body weight (weight < 40 kg or >120 kg or BMI < 18 kg/m2 or > 40 kg/m2). Percentage of patients with initial serum trough concentrations within the therapeutic range was calculated (Table 1). Results During the study timeframe, 59 trough concentrations were performed on critically ill patients, of which 5 were excluded due to uninterpretable results. Of the remaining 54 BL trough concentrations analyzed, 49 (91%) were initial troughs during the antibiotic course, and 5 (9%) were repeat troughs. Thirty-six (73%) of the initial trough concentrations were within the therapeutic range. Among the trough concentrations outside the therapeutic range, 10 (77%) were too high, and 3 (23%) were too low (Table 2). Dose adjustment occurred in 19 (39%) of initial trough evaluations, including 6 which were adjusted despite a level within the therapeutic range. All of the repeat trough concentrations drawn during the same antibiotic course were within the therapeutic range (n = 5/5; 100%). Conclusion One-fourth of initial BL trough concentrations were outside of the therapeutic range. BL levels outside the therapeutic range prompted dose adjustment to improve the potential for effectiveness or limit the potential for toxicity. BL TDM appears to be a promising strategy to enhance precision pharmacotherapy in the critically ill. Disclosures Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria