Benjamin Albrecht's research while affiliated with Emory University and other places

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group ( P = .4), stage 2 or 3 AKI (15.9% vs 6%; P = .98), time to AKI development (1.7 vs 2 days; P = .5), time to return to baseline renal function (4 vs 3 days; P = .2), new requirement for RRT (4.5% vs 1.5%; P = .3), ICU length of stay (7.3 vs 7.4 days; P = .9), hospital length of stay (19.3 vs 20.1 days; P = .87), or in-hospital mortality (15.9% vs 10.8%; P = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings.

Introduction Increased demands on infectious diseases (ID) pharmacists and providers may result in targeted antimicrobial stewardship (AMS) interventions. Internal medicine (IM) pharmacists frequently intervene on antimicrobials for their patients during general clinical care, although little is known regarding their overall impact on AMS. Objective Characterize AMS interventions made by IM pharmacists to identify areas of AMS that can be expanded to patients not covered by ID teams. Methods This was a prospective, dual‐center, cross‐sectional study where IM pharmacists, and their trainees were recruited to document routinely made AMS interventions that happened during daily patient care activities. These interventions were classified based on infection source, stewardship intervention type, whether recommendations were accepted or rejected by providers, and any barriers incurred during the implementation of interventions. Results Four IM pharmacists documented 386 interventions from February 2021 through May 2021. Physicians accepted pharmacist interventions 95.6% of the time. The most common interventions were for respiratory ( n = 87, 22.5%), genitourinary ( n = 80, 20.7%), and skin and skin structure infections ( n = 65, 16.8%). The antimicrobials that IM pharmacists most frequently intervened on were vancomycin ( n = 89, 23.1%) and ceftriaxone ( n = 68, 17.6%). The most common interventions that were made were dose adjustment ( n = 105, 27.2%), shortened duration of therapy ( n = 86, 22.3%), and intravenous (IV) to oral (PO) conversions ( n = 38, 9.8%). Of the 17 interventions not accepted, the most common barrier to implementation was physician concerns ( n = 11, 52.4%), which were primarily associated with IV to PO recommendations ( n = 7, 63.6%). Conclusion IM pharmacists participate in AMS for their patients and intervene frequently to adjust dosing for antimicrobials, shorten duration of therapy, and facilitate IV to PO conversions. IM pharmacists could serve as AMS extenders where additional AMS coverage is needed.

Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Background The threat of inducible resistance and treatment failure positioned cefepime and carbapenems as the standard of care (SOC) treatment agents for infections due to AmpC-producing Enterobacterales regardless of antimicrobial susceptibility testing results. Recently published Infectious Diseases Society of America Guidance (IDSA) classifies the overall risk of clinically relevant AmpC expression for Serratia marcescens as low (< 5%). We aimed to compare the clinical outcomes of patients treated with a SOC antibiotic (carbapenem or cefepime) to those treated with an alternative beta-lactam agent for S. marcescens bloodstream infection (BSI). Methods This multisite, retrospective study included patients from five hospitals in the Atlanta-Metropolitan area with S. marcescens BSIs between January 1, 2018 and December 31, 2022. Patients were included if they received at least 72 hours of therapy with a beta-lactam antibiotic whose in vitro susceptibility was confirmed. Patients with polymicrobial bacteremia, those receiving combination therapy for > 72 hours, or those with a diagnosis of endovascular infection were excluded. We used a desirability of outcome ranking (DOOR) analysis to determine the probability of having a more desirable outcome receiving SOC antibiotics compared to receiving an alternative beta-lactam agent. The DOOR analysis includes counting undesirable events (Figure 1) and was performed using an online calculator (https://methods.bsc.gwu.edu).Figure 1:Primary endpoint - Desirability of outcome ranking. Abbreviations: AKI = acute kidney injury; CDI = Clostridioides difficile infection; EMR = electronic medical record; SCr = serum creatinine Results Of the 175 S. marcescens blood cultures reviewed, 66 patients met criteria for study inclusion, 43 in the SOC group and 23 in the alternative group. Baseline characteristics were comparable in both groups (Figure 2). The DOOR distribution between treatment groups was similar (Figure 3) and there was no significant difference in the probability of a more desirable outcome for patients who received an alternative beta-lactam compared to SOC (54.2% [95% CI, 40.3 - 67.5%]; Figure 4).Figure 2:Baseline patient characteristics. Abbreviations: BMT = bone marrow transplant within previous 12 months; Corticosteroid = ≥15 mg prednisolone daily equivalents; HIV = human immunodeficiency virus; ICU = intensive care unit; IQR = interquartile range; NS = non-significant; SOC = standard of care; SOT = any history of solid organ transplantFigure 3:Desirability of Outcome Ranking Distribution Summary Desirability of outcome ranking distribution for the standard of care and alternative beta-lactam treatment groups; SOC = standard of careFigure 4:Desirability of Outcome Ranking Probability Summary Forest plot of desirability of outcome ranking probabilities by overall treatment group and individual ranking components; CI = confidence interval, DOOR = desirability of outcome ranking, SOC = standard of care Conclusion The overall outcome of patients receiving alternative beta-lactam antibiotics was similar to those receiving SOC antibiotics in this study. These results support use of alternative beta-lactams for treatment of susceptible S. marcescens BSIs as recommended by IDSA guidance. Disclosures Joseph Torrisi, PharmD, BCIDP, Clinical Care Operations: Honoraria Ahmed Babiker, MBBS, Roche: Advisor/Consultant

Background Baricitinib (BARI) and tocilizumab (TOCI) are two FDA-approved immunomodulating agents for the treatment of COVID-19 patients with worsening respiratory status, but early studies suggest no differences in outcomes between the two therapies. Methods This is a single-center retrospective analysis of adult patients who received TOCI or BARI for severe COVID-19 from April 2021 to February 2022. Severe COVID-19 was defined as having a National Institute of Allergy and Infectious Disease (NIAID) Ordinal Scale (OS) score of 6 or 7 as described in the Table I. The primary outcome was days to clinical improvement defined as a reduction by ≥ 2 scores on the NIAID OS after the first dose of TOCI or BARI (Day 1) and analyzed using a stratified log-rank test with stratification by the Day 1 NIAID OS score of 6 or 7. Patients who did not show clinical improvement were removed from this analysis. Secondary outcomes include hospital and intensive care unit (ICU) length-of-stay (LOS) and adverse events (AE). Categorical variables were analyzed using Chi-square or Fisher’s exact test, and continuous variables were analyzed using Student’s t-test or Mann-Whitney U test as appropriate. Results A total of 258 patients met inclusion criteria (121 BARI; 137 TOCI). Of patients receiving NIV/HFO (n=224) or MV/ECMO (n=34) at baseline, 33.9% and 71% of patients did not show clinical improvement, respectively. The time to clinical improvement did not differ significantly between BARI and TOCI in patients with baseline NIV/HFO (11.9 vs. 12.6 days respectively; p=0.79). A significant difference in days to clinical improvement was observed in MV/ECMO patients who received BARI or TOCI (7.0 vs. 25.7 days respectively; p=0.04). Hospital LOS, ICU LOS, and AE were similar between groups. Mortality rates were higher in patients who had MV/ECMO at baseline compared to those who received NIV/HFO (50% vs 20.1%, p >0.05), but there were no significant differences in mortality between treatment groups. Conclusion Days to clinical improvement did not differ between TOCI and BARI. A significant difference in days to clinical improvement was observed in the MV/ECMO group. However, application of this finding to clinical practice in patients with MV/ECMO is limited due to a small subgroup size and low rates of survival. Disclosures All Authors: No reported disclosures

Background Ceftolozane-tazobactam (CT) and ceftazidime-avibactam (CZA) are front-line agents for treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa; however, real-world comparative-effectiveness data are lacking. Methods CACTUS is a retrospective, matched, multicenter study to compare the efficacy of CT and CZA among patients with bacteremia or pneumonia due to MDR P. aeruginosa. CT and CZA patients were matched 1:1 within each study site by the presence/absence of septic shock/severe sepsis, infection site, and time to treatment initiation. The primary outcome was clinical success at day 30 defined as survival, resolution of signs/symptoms with the intended treatment course, and absence of recurrent infections. Patients with cystic fibrosis or COVID-19 infection within 90 days were excluded. Results 234 patients were included from 20 sites. Patient demographics, severity of illness, infection types, and treatment durations were similar for patients treated with CT or CZA (Table 1). The overall median age was 61 years, 61% were male, and the median Charlson score was 5. At study drug initiation, 77% of patients were in the ICU, 67% received mechanical ventilation and the median SOFA score was 7. 79% of patients were treated for pneumonia; 72% of which occurred in ventilated patients. The median time from index culture to treatment initiation was 72 hours in both groups; CT patients were more likely to receive a prolonged infusion of ≥3 hours (36% vs 19%; P=0.005). Clinical success occurred in 62% and 55% of patients receiving CT and CZA, respectively (P=0.35; Table 1). Corresponding rates of success for pneumonia were 63% and 52%, respectively (P=0.13; Figure 1). All-cause, 30-day mortality rate was 20% and 19%, respectively. Microbiologic failures, recurrent infections, and development of resistance within 90 days were similar between groups. Time to a composite endpoint of recurrent infection or death within 90 days was similar between groups in the overall analysis and the subgroup of patients with pneumonia (Figure 2). Conclusion In this interim analysis of the CACTUS study, patients treated with CT and CZA had similar clinical outcomes. We plan to continue enrollment up to 420 patients to detect if any differences exist in the efficacy of CT and CZA for MDR P. aeruginosa infections. Disclosures Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Lilian M. Abbo, MD, MBA, Ferring: Advisor/Consultant|Pfizer: Advisor/Consultant|Regeneron: Grant/Research Support|Shionogi: Advisor/Consultant Ahmed Babiker, MBBS, Roche: Advisor/Consultant Kimberly C. Claeys, PharmD, Abbvie: Advisor/Consultant|bioMérieux Inc.: Advisor/Consultant|bioMérieux Inc.: Speaker|La Jolla Pharmaceuticals: Advisor/Consultant|Melinta Therapeutics: Advisor/Consultant Jason C. Gallagher, PharmD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant Emily L. Heil, PharmD, MS, Wolters Kluwer-LexiComp: Advisor/Consultant Wesley D. Kufel, PharmD, BCPS, BCIDP, AAHIVP, Merck and Co: Grant/Research Support Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Christopher Polk, MD, ViiVHealthcare: Job change to work for ViiV as Medical Director Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|SNIPRBiome: Grant/Research Support Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant

Background Infection is the leading cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). Prolonged suppressive therapy should be strongly considered and is often used in patients with recurrent infections when source control cannot be achieved. Dalbavancin is a promising option in patients with LVADs requiring prolonged durations of antibiotic therapy, especially when no oral alternatives are available. Methods This case series included 8 patients receiving dalbavancin for the long-term suppression of gram-positive infections at Emory University Hospital and Emory St Joseph's Hospital. Results The overall incidence of breakthrough infections occurred in 5 of the 8 patients included in the study. One patient experienced an early breakthrough infection within 1 month of dalbavancin initiation. Another experienced a breakthrough infection within 3 and 6 months of dalbavancin initiation, and the final 3 patients experienced a breakthrough infection within 6 and 12 months. The average duration of dalbavancin suppression therapy among all patients was 229 days, and no adverse effects were reported. Conclusions Dalbavancin is a promising option in patients who require long-term suppression for chronic gram-positive LVAD infections, given its unique pharmacokinetic profile and excellent tissue penetration. The use of biweekly dalbavancin infusions in our 8 patients prevented infection for an extended period of time despite some of the patients not being able to consistently receive infusions. Larger studies are needed to determine the efficacy and safety of using dalbavancin for long-term suppression of gram-positive LVAD infections.

Background While the available SARS-CoV2 vaccines are up to 94% effective at preventing COVID-19-related death or invasive mechanical ventilation, only 76% of the United States population aged ≥18 years have received a primary series and 49% have received a booster. Vaccine administration has been complicated by changing schedule recommendations, packaging in multi-dose vials, and federal reporting requirements that may have limited the locations offering vaccines. We therefore implemented a pharmacy-based initiative to provide SARS-CoV2 vaccination to patients admitted to an academic health center, in order to encourage vaccination when patients had presented for other care. Methods A pharmacy committee developed a protocol for administering the three authorized SARS-CoV2 vaccines to interested inpatients while minimizing vaccine waste, monitoring for safety events, and providing next dose education. Associated training included multidisciplinary education on requirements related to vaccine Emergency Use Authorization (EUA) status. While developing the protocol, the vaccine committee utilized a temporary procedure to administer vaccines once weekly through review by antimicrobial stewardship pharmacists during August 2021. The protocol went live in September 2021 for inpatient and emergency department sites, with subsequent tracking of the number of doses ordered (stratified by vaccine type and dose number) and number administered. Results From August 3 2021 to March 25 2022, a total of 389 vaccine orders were placed with 302 doses (78%) administered, including 126 Moderna (48 first, 20 second, 15 third, 42 booster, and 1 undesignated), 165 Pfizer/BioNTech (80 first, 24 second, 41 third, 14 booster, and 6 undesignated), and 11 Janssen COVID-19 vaccine doses. Only 18 vaccine orders were placed on patients in the ED, with 14 (78%) of those doses administered. Of the 87 vaccine orders not administered, 6 were placed but not given, and 81 were placed and then discontinued. Conclusion With multidisciplinary collaboration, SARS-CoV2 vaccination can be performed in inpatient and ED settings. However, orders should be monitored for protocol compliance and order discontinuation, as these may increase potential for waste. Disclosures All Authors: No reported disclosures.