scholarly journals 67. Impact of a Pharmacist-Driven Collaborative Initiative on Staphylococcus aureus Bacteremia Management

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S52-S53
Author(s):  
Wesley D Kufel ◽  
Keri A Mastro ◽  
Dongliang Wang ◽  
Jeffrey Steele ◽  
Scott W Riddell ◽  
...  

Abstract Background Infectious diseases (ID) consultation has been associated with improved outcomes for Staphylococcus aureus bacteremia (SAB) largely by providing guidance to follow widely accepted standards. However, ID consultation may be delayed due to numerous factors. ID pharmacists may be able to facilitate timely and optimal management of SAB in collaboration with ID providers and microbiology. The primary outcome of this study was to evaluate the impact of a pharmacist-driven collaborative initiative for SAB. Methods This was a single-center, quasi-experimental study of patients with SAB before (8/1/16–7/31/17) and after (8/1/18-7/31/19) implementation of pharmacist-driven collaborative initiative for SAB management. After direct notification of SAB and penicillin-binding protein assay results from microbiology personnel, the ID pharmacist promptly contacted the primary team to facilitate ID consultation and identified opportunities to optimize treatment or diagnosis prior to consult. Recommendations were also collaboratively discussed with the ID consult service. Included patients were ≥18 years old with SAB. Excluded patients were < 18 years old, under palliative care or expired prior to S. aureus speciation, refused care against medical advice, pregnant, incarcerated, or had polymicrobial bacteremia. Results Ninety and 111 patients were included in the pre- and post-intervention cohort, respectively. Demographic data were similar between cohorts. Most SAB cases were community-acquired (72% vs 81%, p=0.137), complicated (83% vs 71%, p=0.059), and methicillin-susceptible (57% vs 65%, p=0.236). The most common sources were catheter (23%) and skin and soft tissue (30%) in pre- and post-intervention cohorts, respectively. Table 1 displays compliance with evidence-based SAB measures and clinical outcomes. Compliance with the SAB bundle was significantly higher in the post-intervention cohort (91% vs 50%, p< 0.001). Table 1. Compliance with Evidence-Based Staphylococcus aureus Bacteremia Management Bundle Elements and Clinical Outcomes Conclusion Increased compliance with evidence-based SAB recommendations decreased SAB duration, time to targeted antibiotics, and infection-related hospital length of stay after implementation of a pharmacist-driven collaborative initiative for SAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S201-S202
Author(s):  
Wesley D Kufel ◽  
Katie A Parsels ◽  
Jeffrey Steele ◽  
Robert Seabury ◽  
Kristopher M Paolino ◽  
...  

Abstract Background The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB. Methods This was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance. Results Of 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days. Conclusion To our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was < 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S52-S52
Author(s):  
Pegah Shakeraneh ◽  
Jeffrey Steele ◽  
Robert Seabury ◽  
Stephen J Thomas ◽  
Kristopher M Paolino ◽  
...  

Abstract Background Ceftriaxone and azithromycin are common empiric antibiotics for community-acquired pneumonia (CAP). Despite low suspicion for atypical infection, azithromycin is often continued for a full course. Negative laboratory data for atypical bacteria may assist with azithromycin de-escalation. Thus, a pharmacist-driven azithromycin de-escalation protocol was implemented for immunocompetent, non-intensive care unit (ICU) patients treated for CAP. The primary outcome was to compare azithromycin duration before and after protocol implementation. Secondary outcomes included hospital length of stay (LOS) and all-cause 30-day readmission. Methods This was a single-center, quasi-experimental study of hospitalized, non-ICU patients treated with azithromycin and a beta-lactam for CAP. The pre- and post-intervention cohorts were from 07/01/2018–04/30/2019 and 07/01/2019–04/30/2020, respectively. Patients were included if they were ≥18 years old, diagnosed with CAP, and had a negative Legionella pneumophila urinary antigen and negative nasopharyngeal swab PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Patients were excluded if they were immunocompromised, admitted to an ICU, prescribed azithromycin for an alternative indication, or had evidence of atypical bacteria. Results After exclusion criteria were applied, 90 and 100 patients were included in the pre- and post-intervention cohorts, respectively. Demographic and clinical characteristics were mostly similar between cohorts. This initiative was associated with a statistically significant decrease in azithromycin duration (2 days (IQR 1–2.75) vs. 5 days (IQR 3–6), p < 0.001) and hospital LOS (3 days (IQR 2–5) vs. 5 days (IQR 3–8.25), p < 0.001). No statistically significant difference was observed for all-cause 30-day readmission (14 days (15.6%) vs 13 days (13.0%), p=0.614). Conclusion Implementation of a pharmacist-driven azithromycin de-escalation protocol for CAP was associated with reduced azithromycin duration and hospital LOS, but not all-cause 30-day readmission. Disclosures Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member) Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S757-S758
Author(s):  
Olivia D Reese ◽  
Ashley Tippett ◽  
Laila Hussaini ◽  
Luis Salazar ◽  
Megan Taylor ◽  
...  

Abstract Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S366-S366
Author(s):  
Ashley H Marx ◽  
Vahini Chundi ◽  
Jill Zaccardelli ◽  
Timothy Angle ◽  
Jonathan Oriet ◽  
...  

Abstract Background Mortality associated with Staphylococcus aureus bacteremia (SAB) has prompted the development of “bundle”-based approaches to improve outcomes. Components of bundled strategies include appropriate antibiotic selection, early source control, documenting negative cultures, echocardiogram, and adequate treatment duration. In 7/2016, the UNC Antimicrobial Stewardship Program (ASP) began prospective monitoring of SAB patients. Here we describe the impact of these ASP efforts. Methods Quasi-experimental study of patients ≥16 years with SAB 9/2015-3/2016 (pre-intervention) and 9/201/2017 (post-intervention). Patients were excluded if the bloodstream infection was polymicrobial, therapy began at an outside hospital, or the patient was discharged or died within 72 hours of positive blood culture. Minimum adequate treatment duration was defined as 14 days for uncomplicated SAB; 28 days for complicated SAB; 42 days if endovascular disease or osteomyelitis present. Categorical variables were compared using the chi-squared test, significance level of P < 0.05. The study was approved by the UNC IRB. Results 217 treatment courses were included; 114 pre- and 103 post-intervention. Rates of adequate empirical antibiotics were consistently high throughout the study (Table 1). Pre-intervention, individual bundle components occurred frequently: negative culture documented (95%), echocardiogram (80%), and adequate duration of an appropriate antibiotic (71%; Table 2). After ASP intervention, echocardiography and adequate treatment duration rates increased to 92% (P < 0.05, both outcomes), as did ID consultation rates (59% to 67%; P = 0.04). Overall bundle achievement increased from 54% to 82%. ASP interventions were documented for 11 (10%) and 32 (31%) of patients during the periods. Mortality and readmission within 6 months of discharge were unchanged (12% and 11%; 41% and 42%, respectively). Conclusion ASP intervention was associated with increased rates of bundle achievement but did not impact mortality or 6-month readmission. Despite adequate empiric therapy and relatively high rates of adherence to best-evidenced practices, SAB continues to be associated with significant mortality and high rates of 6-month readmission. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S343-S344
Author(s):  
Jose Ramon Arribas ◽  
Jose Ramon Arribas ◽  
Arun J Sanyal ◽  
Alex Soriano ◽  
Bum Sik Chin ◽  
...  

Abstract Background Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Hydroxychloroquine (HQN) is an experimental treatment for COVID-19. Effects of coadministration of HQN with RDV have not been studied and are relevant given the long half-life (~22 days) of HQN. We report the impact of concomitant HQN and RDV use on clinical outcomes and safety in patients with moderate COVID-19. Methods We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation &gt;94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. We compared patients on concomitant HQN (HQNpos) vs not (HQNneg). Clinical recovery was evaluated using Cox proportional hazards. Covariate adjustment included age, sex, race, region, symptom duration, oxygen support status and obesity. Recovery and adverse events (AEs) were assessed through death, discharge, or d14. Results Of 584 patients, 199 (34%) received HQN (5d RDV: n=57 [30%]; 10d RDV, n=49 [25%]; SoC: n=93 [47%]). Through median follow-up of 13d (range 1-41d), HQNpos patients on 5d or 10d RDV had a lower recovery rate (adjusted HR [95% CI] 0.78 [0.59, 1.03], p=0.09) with longer median time to recovery (8 vs 6 days) compared to HQNneg. HQNpos compared to HQNneg patients in 5d RDV showed a trend of reduced recovery rate (HR: 0.69 [0.45,1.04], p=0.080); such an effect was not observed in 10d RDV or SoC (Table 1). More HQNpos than HQNneg patients had AEs in RDV (5/10d) or SoC arms evaluated separately, and all arms combined. This difference was significant for AEs and SAEs for all arms combined after covariate adjustment (Table 2). Table 1. Table 2. Conclusion In moderate COVID-19 patients, concomitant HQN may delay recovery on RDV and showed no impact on recovery with SoC alone. The AE profile of HQNpos patients was worse than that observed for HQNneg patients, regardless of RDV treatment. Disclosures Jose Ramon Arribas, MD, Alexa (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Janssen (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Merck (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Viiv Healthcare (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees) Jose Ramon Arribas, MD, NO DISCLOSURE DATA Arun J. Sanyal, MD, AbbVie (Consultant)Akarna (Shareholder)Amarin (Consultant)Ardelyx (Consultant)Astra Zeneca (Consultant, Research Grant or Support)Boehringer (Consultant)Bristol Myers Squibb (Research Grant or Support)Conatus (Consultant)Cumberland (Research Grant or Support)Durect (Shareholder)Elsevier (Other Financial or Material Support, Royalties)Exhalenz (Shareholder)Fibrogen (Consultant)Genfit (Shareholder)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Research Grant or Support)Haemoshear (Shareholder)Indalo (Shareholder)Intercept (Research Grant or Support)Jannsen (Consultant)Lilly (Consultant)Malinckrodt (Research Grant or Support)Merck (Research Grant or Support)Nimbus (Consultant)Nitto Denko (Consultant)Novartis (Consultant)Pfizer (Consultant)Salix (Consultant)Sanyal Biotechnology (Employee, Shareholder, Other Financial or Material Support, President)Shire (Research Grant or Support)Takeda (Consultant)Tiziana (Shareholder)Tobira (Consultant)UptoDate (Other Financial or Material Support, Royalties)Zafgen (Consultant) Bum Sik Chin, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Bum Sik Chin, MD, NO DISCLOSURE DATA Shirin Kalimuddin, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Stefan Schreiber, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Emon Elboudwarej, PhD, Gilead Sciences Inc. (Employee, Shareholder) Yuan Tian, PhD, Gilead Sciences Inc. (Employee, Shareholder) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Christoph Lübbert, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Chien Boon Lye, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Chien Boon Lye, MD, NO DISCLOSURE DATA Judith A. Aberg, MD, Theratechnology (Consultant) Enrique Navas Elorza, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Karen T. Tashima, MD, Bristol-Myers Squibb (Research Grant or Support)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)GlaxoSmithKline (Research Grant or Support)Merck (Research Grant or Support)Tibotec (Research Grant or Support)Viiv Healthcare (Research Grant or Support) Mark McPhail, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S633-S634
Author(s):  
Tyler Maxwell ◽  
James E Orban ◽  
Wesley D Kufel ◽  
Christopher Destache ◽  
Karen S Williams ◽  
...  

Abstract Background Daptomycin (DAP) has become an appealing treatment option for gram-positive infections, which are common in patients receiving hemodialysis (HD), due to frequent access and manipulation. The approved DAP dosing of 4 to 6 mg/kg every 48 hours (q48h) quickly becomes desynchronized from the patient’s HD schedule and requires the burden of additional IV access. Previous pharmacokinetic studies have suggested that DAP can be dosed three-times weekly following HD, but no studies have evaluated clinical outcomes of this regimen. Methods This was a multi-center, retrospective cohort study across 6 hospitals in the United States. Adult, nonpregnant patients who received HD and DAP between 2015 and 2020 were screened for inclusion. Electronic medical records were reviewed for relevant study data. The primary outcome was clinical and microbiological outcomes among patients who received DAP thrice weekly versus q48h dosing. Microbiological Failure was defined as positive cultures after 7 days and further study definitions are included under Table 3. Results Baseline characteristics are summarized in Table 1. Length of stay was similar between both groups at a median of 25 days and patients had a median QPitt score of 0 on admission. The average DAP dose used was 7 mg/kg and 7mg-7mg-9mg on HD days in the q48h dosing and thrice weekly dosing regimens, respectively. The majority of patients had bacteremia and the most commonly isolated bacteria was methicillin-resistant Staphylococcus aureus. No differences in clinical outcomes were observed (p=0.87). Microbiological failure was higher among patients who received DAP thrice weekly compared to q48h dosing (69.2% vs 34.8%, p=0.047). Conclusion DAP dosed thrice weekly on HD days offers similar clinical resolution compared to q48h dosing. While the thrice weekly dosing regimen did have a significantly higher rate of microbiological failure, the analysis was limited by a small sample size. As this is a retrospective analysis not accounting for confounding variables, additional prospective studies are warranted to confirm these findings. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker's Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)


2013 ◽  
Vol 57 (11) ◽  
pp. 5536-5542 ◽  
Author(s):  
So-Youn Park ◽  
In-Hwan Oh ◽  
Hee-Joo Lee ◽  
Chun-Gyoo Ihm ◽  
Jun Seong Son ◽  
...  

ABSTRACTVancomycin has been a key antibiotic agent for the treatment of methicillin-resistantStaphylococcus aureus(MRSA) infections. However, little is known about the relationship between vancomycin MIC values at the higher end of the susceptibility range and clinical outcomes. The aim of this study was to determine the impact of MRSA bacteremia on clinical outcomes in patients with a vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA bacteremia were divided into a high-vancomycin-MIC group (2 μg/ml) and a low-vancomycin-MIC group (≤1.0 μg/ml). We examined the relationship between MIC, genotype, primary source of bacteremia, and mortality. Ninety-four patients with MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC were analyzed. There was no significant difference between the presence ofagrdysfunction and SCCmectype between the two groups. A higher vancomycin MIC was not found to be associated with mortality. In contrast, high-risk bloodstream infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24 to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to 0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day mortality. Our study suggests that a high-risk source of bacteremia is likely to be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a susceptible range, as well as genotype characteristics, are not associated with mortality.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S131-S131
Author(s):  
Aisling Caffrey ◽  
Emily T O’Neill ◽  
Vrishali Lopes ◽  
Erlinda R Ulloa ◽  
George Sakoulas ◽  
...  

Abstract Background There is a growing body of evidence which suggests that P2Y12 inhibitors may have antibacterial properties in vivo. To our knowledge, this has not been previously examined using real world clinical data from patients with specific infections. Methods Our retrospective cohort study included patients admitted to Veterans Affairs hospitals between 2010–2018 with blood cultures positive for S. aureus and treated with appropriate antibiotics within 48 hours of culture collection. We included patients treated with P2Y12 inhibitors for at least the 30 days prior to admission and continued use for at least 5 days after admission. Non-users included patients without P2Y12 inhibitor use in the year prior to admission through discharge. We compared clinical outcomes during the S. aureus bacteremia admission among P2Y12 users and non-users using propensity score matched Cox proportional hazards regression models. Results We identified 371 P2Y12 inhibitor users (clopidogrel, prasugrel, ticagrelor, cangrelor) and 13,298 non-users. Mean age was 70 years and 69 years, respectively. Over 98% were male in both the groups, and the overall inpatient mortality rate was 8.7%. We were able to match 199 users and non-users, which were well matched in terms of baseline covariates. Inpatient mortality was significantly lower among P2Y12 inhibitor users (hazard ratio [HR] 0.08, 95% confidence interval [CI] 0.01–0.64), and 30-day mortality was non-significantly lower (HR 0.57, 95% CI 0.31–1.03). There was no difference between the groups in readmission or re-infection within 30 days of discharge. Conclusion Among patients with S. aureus bacteremia, those treated with P2Y12 inhibitors in the days leading up to admission and continuing through the initial period of antibiotic treatment, had a 92% lower risk of inpatient mortality. Identifying adjunctive therapies which improve clinical outcomes among patients with S. aureus bacteremia is highly important in order to improve patient outcomes and to increase the understanding of the pathophysiology of the disease. Prospective clinical studies are needed to further define the potential benefits of P2Y12 inhibitors in S. aureus bacteremia and possibly other infection types. Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Erlinda R. Ulloa, MD, MSc, Cidara Therapeutics (Consultant) Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve &gt;1 log10 decrease in CMV viral load (VL) and having VL &gt;1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p&lt; 0.001). In multivariable model, risk factors for R/R included TCD HCT (p&lt; 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S60-S60
Author(s):  
Noor F Zaidan ◽  
Rachel S Britt ◽  
David Reynoso ◽  
R Scott Ferren

Abstract Background Pharmacist-driven protocols for utilization of methicillin-resistant Staphylococcus aureus (MRSA) nares screenings have shown to decrease duration of empiric gram-positive therapy and rates of acute kidney injury (AKI) in patients with respiratory infections. This study evaluated the impact of a pharmacist-driven MRSA nares screening protocol on duration of vancomycin or linezolid therapy (DT) in respiratory infections. Methods Patients aged 18 years and older with a medication order of vancomycin or linezolid for respiratory indication(s) were included. The MRSA nares screening protocol went into effect in October 2019. The protocol allowed pharmacists to order an MRSA nares polymerase chain reaction (PCR) for included patients, while the Antimicrobial Stewardship Program (ASP) made therapeutic recommendations for de-escalation of empiric gram-positive coverage based on negative MRSA nares screenings, if clinically appropriate. Data for the pre-intervention group was collected retrospectively for the months of October 2018 to March 2019. The post-intervention group data was collected prospectively for the months of October 2019 to March 2020. Results Ninety-seven patients were evaluated within both the pre-intervention group (n = 50) and post-intervention group (n = 57). Outcomes for DT (38.2 hours vs. 30.9 hours, P = 0.601) and AKI (20% vs. 14%, P = 0.4105) were not different before and after protocol implementation. A subgroup analysis revealed a significant reduction in DT within the pre- and post-MRSA PCR groups (38.2 hours vs. 24.8 hours, P = 0.0065) when pharmacist recommendations for de-escalation were accepted. Conclusion A pharmacist-driven MRSA nares screening protocol did not affect the duration of gram-positive therapy for respiratory indications. However, there was a reduction in DT when pharmacist-driven recommendations were accepted. Disclosures All Authors: No reported disclosures


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