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Purpose Burnout in healthcare can have serious consequences, as it decreases patient care quality. Recent studies have found pharmacy employees have high rates of burnout, but formalized pharmacy well-being programs are not reported in the literature. Methods We developed a departmental pharmacy well-being program and focused residency well-being program in October and July 2020, respectively. The program committees sent anonymous surveys to all pharmacy employees to identify opportunities to improve well-being. The feasibility and impact of ideas were assessed by committee members and presented to pharmacy leadership who endorsed and supported all proposed initiatives prior to implementation. Pharmacist distress scores were measured using the Well-Being Index (WBI). Results The WBI was completed by 49% of invited pharmacists (137 of 278) in November 2020 and 41% (116 of 283) in June 2021. There was a numerical improvement in mean (SD) WBI scores from 2.06 (2.47) in November 2020 to 1.52 (2.49) in June 2021 (P = 0.09). Pharmacy residents had significantly higher distress scores than nonresident pharmacists (P = 0.01). However, pharmacy resident scores improved by almost 50% between the 2 time points, from 4.43 (2.13) to 2.40 (2.42); P = 0.03. Conclusion The development of a system-wide pharmacy well-being program creates a structure to collect ideas from employees, implement well-being initiatives, measure burnout using a validated tool such as the WBI, and continue to build, evaluate, and adapt new interventions. Importantly, the program went beyond addressing individual needs and addressed institutional opportunities that impact well-being. This can serve as a model for other pharmacy departments looking to implement similar programs.

Background: Carbapenem-resistant Enterobacterales (CRE) are difficult to treat and can cause significant morbidity and mortality, however most data reflect carbapenemase-producing infections. Objective: Our objective was to evaluate clinical outcomes of non-carbapenemase-producing CRE (nCP-CRE) compared with carbapenem-susceptible Enterobacterales (CSE) infections. Methods: This was a retrospective, multicenter, observational study (January 1, 2018 to December 31, 2020). The primary outcome was clinical success at 30 days with secondary outcomes, including clinical success at 90 days, clinical success based on treatment for nCP-CRE, persistent bacteremia, intensive care unit (ICU) admission, length of stay, and rate of Clostridioides difficile or multidrug resistant infections. Results: The final analysis included 211 patients: 142 (67%) with CSE and 69 (33%) with nCP-CRE infections. Prior carbapenem exposure was more common with nCP-CRE (15% vs 4%, P = 0.01). Clinical success at 30 days was similar between groups (77% vs 74%, P = 0.73). There were no differences in secondary outcomes. There was an overall low use of carbapenems (empiric 6%, definitive 7%). Most nCP-CRE infections were treated with a monotherapy carbapenem-sparing regimen (empiric 88%, definitive 90%). Limitations include the retrospective design and the high rate of urinary infections. Conclusion and Relevance: Our study found no difference in clinical outcomes between nCP-CRE and CSE infections. Application of this study with future studies would help in determining optimal regimens for these infections.

BACKGROUND Most patients who report a penicillin allergy can tolerate cefazolin, the preferred prophylaxis in a total joint arthroplasty (TJA). Regardless, patients with a reported penicillin allergy are less likely to receive first-line perioperative antibiotics as a result of inaccurate penicillin allergy documentation and misconceptions regarding cross-reactivity between penicillin and cephalosporins. The over-reporting of penicillin allergies and the safety of cephalosporins in patients with reported penicillin allergies have been well established throughout the evidence [13]. QUESTIONS/PURPOSES The study sought to answer two questions: (1) Do antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA? (2) What is the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy? METHODS This was a single-center, retrospective study of orthopaedic patients older than 18 years who underwent a primary elective TJA at a 261-bed community hospital. The study had two periods: the preintervention period ran from March 1, 2017 to August 30, 2017 and the postintervention period was from March 1, 2019 to August 30, 2019. A total of 396 patients with a history of a documented penicillin allergy underwent a THA or TKA during the study periods. After reviewing every fourth patient with a history of a documented penicillin allergy who met study inclusion criteria and excluding those patients who had a codocumented cephalosporin allergy, a total of 180 patients with a documented penicillin allergy were evaluated (90 patients in the preintervention group and 90 patients in the postintervention group). To answer our first study question, regarding whether antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA, we evaluated appropriate antibiotic usage pre- and postintervention. To answer our second study question, concerning the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy, we reviewed signs of allergic reactions in patients who received cefazolin for a primary TJA and had a documented penicillin allergy. RESULTS Postintervention antibiotic use was more appropriate (91% [82 of 90] versus 54% [49 of 90], risk ratio 1.67 [95% confidence interval 1.37 to 2.04]; p < 0.01), particularly in patients with nonsevere allergy (preintervention: 47% [36 of 76] versus postintervention: 96% [76 of 79]; p < 0.01). No patients had signs of an allergic reaction related to cefazolin, including eight patients with severe penicillin allergy. CONCLUSION A multifaceted antibiotic stewardship intervention increased the appropriateness of antibiotic prophylaxis in elective primary TJA. Patients with nonsevere penicillin allergies, even those reporting hives or local swelling, tolerated cefazolin. Antibiotic stewardship interventions can be implemented across institutions to expand cephalosporin use in patients with a reported penicillin allergy within orthopaedic TJA patients. LEVEL OF EVIDENCE Level III, therapeutic study.

Background: Literature suggests that antibiotic prescribing in COVID-19 patients is high. Currently, there are insufficient data on what drives antibiotic prescribing practices throughout the COVID-19 pandemic. Objective: This study sought to determine antibiotic use rates and identify risk factors for antibiotic prescribing in hospitalized patients. It was the first study to assess risk factors for receiving more than 1 course of antibiotics. Methods: This was a retrospective, multi-center, observational study. Patients admitted from March 1, 2020, to May 31, 2020, and treated for COVID-19 were included. The primary endpoint was the rate of antibiotic use during hospitalization. Secondary endpoints included risk factors associated with antibiotic use, risk factors associated with receiving more than 1 antibiotic course, and rate of microbiologically confirmed infections. Results: A total of 208 encounters (198 patients) were included in the final analysis. Eighty-three percent of patients received at least 1 course of antibiotics, despite low rates of microbiologically confirmed infection (12%). Almost one-third of patients (30%) received more than 1 course of antibiotics. Risk factors identified for both antibiotic prescribing and receiving more than 1 course of antibiotics included increased hospital length of stay (median 12 days), intensive care unit admission, and the necessity for mechanical ventilation. Conclusion and Relevance: There were high rates of antibiotic prescribing with low rates of microbiologically confirmed bacterial co-infection. Many patients received more than 1 course of antibiotics during hospitalization. This study highlights the importance and demand for appropriate antibiotic stewardship practices in COVID-19 patients.

To determine if aztreonam as initial empiric treatment of adult septic shock is associated with increased mortality compared to the use of anti-pseudomonal beta-lactam agents.This was a multicenter, retrospective cohort study of 582 adult emergency department patients admitted to 12 acute care facilities within a single health system from January 2014 to December 2017 with septic shock receiving either aztreonam or an anti-pseudomonal beta-lactam for empiric treatment and discharged with an infection-related ICD-9 or ICD-10 code. The primary endpoint was in-hospital mortality.Initial exposure to aztreonam was associated with increased hospital mortality compared to treatment with an anti-pseudomonal beta-lactam agent (22.7% vs. 12.9%, OR = 1.98, 95% CI: 1.27-3.11). When adjusted for APACHE II score, the treatment group effect on mortality remained statistically significant (OR = 1.74, 95% CI: 1.08-2.80). Aztreonam use was also associated with increased utilization of aminoglycosides (28.9% vs. 12.4%, p0.0001) and fluoroquinolones (50.5% vs. 25.8%, p0.01). There was no difference in hospital or intensive care unit length of stay in surviving patients between the two groups.Compared to anti-pseudomonal beta-lactams, empiric treatment with aztreonam is associated with increased mortality and greater antibiotic exposure among patients with acute septic shock. These findings suggest that treatment with anti-pseudomonal beta-lactams should be prioritized over allergy avoidance whenever feasible.

BackgroundLiterature suggests that antibiotic prescribing in COVID-19 patients is high, despite low rates of confirmed bacterial infection. There are little data on what drives prescribing habits.ObjectiveThis study sought to determine antibiotic prescribing rates and risk factors for antibiotic prescribing in hospitalized patients. It was the first study to assess risk factors for receiving more than one course of antibiotics.MethodsThis was a retrospective, multi-center, observational study. Patients admitted from March 1, 2020 to May 31, 2020 and treated for PCR-confirmed COVID-19 were included. The primary endpoint was the rate of antibiotic use during hospitalization. Secondary endpoints included risk factors associated with antibiotic use, risk factors associated with receiving more than one antibiotic course, and rate of microbiologically confirmed infections.ResultsA total of 208 encounters (198 patients) were included in the final analysis. Eighty-three percent of patients received at least one course of antibiotics, despite low rates of microbiologically confirmed infection (12%). Almost one-third of patients (30%) received more than one course of antibiotics. Risk factors identified for both antibiotic prescribing and receiving more than one course of antibiotics were more serious illness, increased hospital length of stay, intensive care unit admission, mechanical ventilation, and acute respiratory distress syndrome.Conclusion and relevanceThere were high rates of antibiotic prescribing with low rates of bacterial co-infection. Many patients received more than one course of antibiotics during hospitalization. This study highlights the need for increased antibiotic stewardship practices in COVID-19 patients.

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51&ndash, 1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Background Antimicrobial stewardship program (ASP) guidance from the Centers for Disease Control and Prevention recommends co-leadership of both an infectious-diseases (ID) physician and ID-trained pharmacist. Pharmacists play a key role in the therapeutic management, administration, and implementation of ASP interventions. The purpose of this study, conducted on behalf of the Society of Infectious Diseases Pharmacists, was to describe the involvement of pharmacists in publications of ASP interventional research. Methods A PubMed search was conducted to identify publications in the United States and Canada from 1990–2019 including “antimicrobial (or antibiotic) stewardship” or “antimicrobial (or antibiotic) intervention.” Articles were screened for active interventions with comparator arms. A random subset of 100 pharmacist-authored manuscripts were selected using a time-based clustering strategy to review specific study designs, populations, interventions, and endpoints. Results Of 1,426 publications, 340 met inclusion. Two-thirds (228/340) of all interventional antimicrobial stewardship studies included a pharmacist author. Pharmacists were lead authors in 59% (135/228) of studies that included a pharmacist. Among the randomized subset of pharmacist-authored manuscripts (n=100), the average impact factor of journals with pharmacists as the first author was 3.52, compared to 5.25 as middle authors. Most studies were inpatient focused (89%), included adults (81%), and conducted in a single-site setting (84%). Pediatrics, immunocompromised, post-acute care, and ambulatory populations comprised less than 10% of the publications. The most common interventions described were audit and feedback (55%), guideline implementation (49%), and education (40%). Endpoints included drug utilization (66%), clinical outcomes (57%), safety events (46%), cost (40%), and appropriateness of therapy (35%). Figure 1. Conclusion Pharmacists have an integral role in publication and dissemination of ASP research. Opportunities exist in multi-site collaboration as well as research in ambulatory, pediatric, and immunocompromised groups. Future research endpoints should be practical, generalizable, and patient-centered. Disclosures Kelly E. Pillinger, PharmD, BCIDP, Pharmacy Times (Other Financial or Material Support, Speaker) Haley Appaneal, PharmD, Shionogi (Grant/Research Support)

Background Broad-spectrum antibiotics are often chosen for OPAT due to the convenience of once daily dosing. Current literature suggests that at least 20–30% of these regimens could be narrowed, but this has not been well-defined. Methods This was a multicenter, retrospective cohort study of adult inpatients evaluated by the infectious diseases (ID) team with culture positive infections with susceptibilities (C&S) on select intravenous (IV) antibiotics (ampicillin, ampicillin-sulbactam, cefazolin, ceftriaxone, daptomycin, ertapenem, meropenem, nafcillin, penicillin, piperacillin-tazobactam, and vancomycin) enrolled in OPAT and discharged from January 1 - June 30, 2019. Susceptibilities were not required for Actinomyces, Streptococcus spp., Haemophilus spp., anaerobes, Corynebacterium spp., or coagulase-negative Staphylococcus spp. when considered a contaminant by ID. Patients were excluded if the regimen included oral antibiotics (not including rifampin or metronidazole). Primary outcome was the percent of broad-spectrum regimens that could’ve been narrowed based on C&S (alternative available therapy or AAT group). Secondary outcomes included comparison of baseline characteristics and 30-day readmission rates between patients on narrow-spectrum IV antibiotics (NSA) vs AAT group, and the documented reason(s) for broad-spectrum antibiotic selection. Results 113 patients met study criteria; majority were male (56%), and median age was 60 years. Sixty-four patients were discharged on a broad-spectrum regimen, and 32 (50%) met our AAT definition. Ceftriaxone was used in 75% of these cases (24/32), and mono-microbial Streptococcus spp. infection was the primary indication (54%). AAT group patients were more likely to have Enterobacterales (24.1% vs 1.9% p=< 0.001) or polymicrobial infections (28.1% vs 8.2% p=0.019) compared to NSA group. Reasons for broad-spectrum antibiotic selection were largely undocumented (71%). No significant differences were seen in 30-day readmission rates. Conclusion At our institution, 50% of select IV broad-spectrum OPAT regimens had the potential to be narrowed based on C&S data. This rate is higher than previously reported. It warrants further investigation into the barriers to narrower-spectrum antibiotic prescribing in OPAT. Disclosures Kelly E. Pillinger, PharmD, BCIDP, Pharmacy Times (Other Financial or Material Support, Speaker)

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on “Implementing an Antibiotic Stewardship Program” were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Background The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. Methods A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. Results A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, P = 0.85), re-escalation (4.2% versus 4.8%, adjusted odds ratio = 1.57, P = 0.64), and Clostridioides difficile-associated infections (4.2% versus 2.4%, adjusted odds ratio = 2.27, P = 0.43). No patient experienced in-hospital mortality, intensive care unit admission, or bacteremia. Conclusion Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization.

Introduction: Acute bacterial skin and skin structure infection (ABSSSI) represents a major burden for healthcare systems. The increased prevalence of Methicillin-resistant Staphylococcus aureus, combined with the limited availability of microbiologic data when treating ABSSSI, has led to a need for more convenient, less toxic anti-MRSA agents. Recent approvals have added several agents to the antibiotic armamentarium that provide an expanded spectrum of activity and ease of administration compared to older agents. Areas covered: In this review, the authors discuss updated approaches to the management of ABSSSI. They also provide a review of recent FDA approved antibiotics and emerging investigational agents for treatment of ABSSSI. Expert opinion: Several new antibiotic agents have received FDA approval through the revised guidance on ABSSSI clinical trials with advantages of activity against MRSA and ease of administration. In theory, this may translate to reducing the utilization of healthcare resources by allowing for earlier discharge and reducing the need for outpatient parenteral therapy. While the approval of new agents offers the opportunity to improve and simplify treatment of ABSSSI, it is more important now than ever to use these agents in a responsible manner.

Infectious complication is a known cause of morbidity and mortality among hematopoietic cell transplant recipients. Prophylactic strategies have impacted the epidemiology of infections over decades during which infections previously seen in early posttransplant period are now observed in the late transplant period. Many such interventions have also improved infectious outcomes in HCT recipients by drastically influencing the frequency of infections. More recently, increasing efficient diagnostics has helped in earlier directed therapies for many infections. Transplant techniques are rapidly evolving along with the use of newer immunotherapies in transplant setting. Data are lacking on the impact of these immunotherapies on the epidemiology of posttransplant infection, making care of HCT recipients more complex. Management of infections requires an understanding of a net state of immunosuppression of the host in posttransplant period and frequency of specific infections during different phases of this period. This chapter focuses on understanding epidemiology of most common infection, new diagnostic methods available, and their management relevant to current clinical practices.

Background Most patients reporting a penicillin (PCN) allergy can tolerate cefazolin, the preferred prophylaxis in a total joint arthroplasty (TJA). The purpose of this study was to evaluate surgical prophylaxis in patients with a reported PCN allergy undergoing a TJA following a stewardship intervention that included updates to institutional guidelines, reclassification of severe PCN allergy, standardization of ordering processes, and participation of a physician champion. Methods This was a single center, retrospective study of adult orthopedic patients greater than 18 years old who underwent a primary elective TJA at a 261-bed community hospital from March 1, 2017 to August 30, 2017 (pre-intervention) and from March 1, 2019 to August 30, 2019 (post-intervention). The primary outcome was the difference in the composite rate of the following: 1) Patients with a reported non-severe PCN allergy without MRSA risk factors who received cefazolin; 2) Patients with a non-severe PCN allergy with MRSA risks factors who received cefazolin plus vancomycin; and 3) Patients with a severe PCN allergy who received vancomycin prior to a primary elective TJA. Results A total of 180 patients with a documented PCN allergy were evaluated (90 patients in the pre-intervention group and 90 patients in the post-intervention group). Rash and hives were the most commonly reported allergies in both groups (71% vs 61%, P=0.2076). Post-intervention revealed a significant increase in the primary outcome of appropriate perioperative antibiotic (55% vs 91%, P< 0.001), largely driven by patients with non-severe allergy [47% (36/76) vs 96% (73/76), P< 0.001]. No patients had signs of an allergic reaction thought to be due to cefazolin, including 8 patients with severe PCN allergy. No patients in either group developed a surgical site infection or C. difficile infection within 90 days post-procedure. Conclusion A multifaceted antibiotic stewardship intervention increased preferred prophylaxis in elective primary TJA. Patients with non-severe PCN allergies, even those reporting hives or local swelling, can tolerate cefazolin without issue. Patients with severe PCN allergy should undergo further evaluation as cefazolin may be a safe option. Disclosures Katelyn Quartuccio, PharmD, BCPS, AstraZeneca (Consultant) Kelly E. Pillinger, PharmD, BCIDP, Pharmacy Times (Other Financial or Material Support, Speaker)

Background Aztreonam is often given to patients with a documented β-lactam allergy in lieu of a first-line anti-pseudomonal β-lactam (APBL). However, aztreonam offers no gram positive coverage and data suggest that gram negative organisms have lower susceptibility rates to this antibiotic than to APBLs. Septic patients are especially vulnerable to poor outcomes since inappropriate initial antimicrobial therapy has been shown to be an independent predictor of increased mortality. The purpose of this study was to determine whether septic patients treated with aztreonam experience inferior outcomes compared to those treated with an APBL. Methods This was a retrospective, multicenter, cohort study of all adult patients in metro Charlotte Atrium Health facilities treated for sepsis or septic shock from January 2014 to October 2017. Patients receiving either aztreonam or an APBL were identified using the system-wide sepsis database and enrolled in a 1:2 ratio. Patients were excluded if there was no infection-related discharge ICD-9 or ICD-10 code, if they received both aztreonam and an APBL in the first 8 hours, or if they received fewer than 2 doses of the study antibiotic. The primary endpoint was in-hospital mortality. Results A total of 194 patients received aztreonam and 388 patients received an APBL. β-lactam allergies were more common in patients who received aztreonam compared to APBL (97% vs. 14.2%, p < 0.01). In-hospital mortality rates were greater in the patients who received aztreonam vs. APBL (22.7% vs. 12.9%, p = 0.0025). After adjusting for APACHE II score, initial aztreonam exposure remained independently associated with hospital mortality (OR = 1.74, 95% CI: 1.0 – 2.8, p = 0.02). Additionally, we identified an increase in combination therapy with the use of aminoglycosides (28.9% vs. 12.4%, p < 0.0001) and fluoroquinolones (50.5% vs. 25.8%, p < 0.0001) in patients receiving aztreonam. No difference was found in overall length of stay or ICU length of stay. Conclusion In septic patients, the use of aztreonam as the backbone of antimicrobial therapy may result in increased mortality. This highlights the importance of stewardship interventions that obtain an accurate allergy history and encourage the use of APBL antibiotics whenever feasible. Disclosures Kelly E. Pillinger, PharmD, BCIDP, Pharmacy Times (Other Financial or Material Support, Speaker)

Background: Acute bacterial skin and skin structure infections (ABSSSI) are a leading cause of hospitalization, but are often treated inappropriately in the inpatient setting. A multifaceted stewardship intervention was implemented to encourage prescribing of guideline-concordant therapy (GCT). Objective: To examine the impact of this initiative on antimicrobial prescribing practices and patient outcomes. Methods: This was a single-center, retrospective study of adult inpatients admitted with a primary or secondary diagnosis of ABSSSI, classified by type and severity based on signs of systemic infection. Patients treated during the pre-intervention period (pre-IP) were compared with patients treated during the post-intervention period (post-IP). The primary endpoint was receipt of GCT. Secondary endpoints included receipt of anti-anaerobic antibiotic (AAA) or broad-spectrum antibiotics (BSA). Results: A total of 125 patients were included, 64 in the pre-IP and 61 in the post-IP. There was a statistically significant increase in prescribing of GCT during the post-IP compared with the pre-IP (14% versus 56%, p < 0.0001) and a decrease in use of AAA (56% versus 34%, p = 0.01). No difference was observed with use of BSA (16% versus 15%, p = 0.89). Use of the computerized order set during the post-IP was low (18%). There was a numerical, but non-significant reduction in 30-day readmission (14.1% versus 6.6%, p = 0.17). Conclusion: The multifaceted intervention was effective for improving prescribing of GCT for ABSSSI. Given low use of the computerized order set, improved prescribing seemed to be driven by provider education. Strategies around ongoing education may be key to sustain positive results of stewardship interventions.

Background While current guidelines suggest a total treatment duration of 7 to 14 days for gram-negative bloodstream infections (GN-BSI), there is mounting evidence to suggest that shorter durations may be sufficient. This study compared the treatment outcomes of patients who received short duration therapy (6–10 days) with those who received long durations (11–15 days). Methods This was a retrospective study of adult patients who grew an aerobic gram-negative organism from a blood culture while admitted at Strong Memorial Hospital between May 2016 and May 2018. The primary outcome was a composite of mortality and relapsed GN-BSI with the same organism within 90 days of index culture. Secondary outcomes included clinical resolution at end of therapy (EOT), length of stay (LOS), 30-day readmission rate, Clostridoides difficile infection (CDI), development of recurrent GN-BSI resistant to prior antibiotic therapy, and development of multi-drug-resistant (MDR) GN-BSI within 90 days. Appropriate therapy was defined as an antibiotic with confirmed in vitro susceptibility that was either parenteral or a highly bioavailable oral antibiotic (fluoroquinolones or sulfamethoxazole–trimethoprim). Results Of 600 patients screened, 116 were included in the long duration group and 34 patients in the short-duration group. The majority of patients had a urinary source of infection (59.3%). The primary composite outcome occurred in 11.8% of the short duration group compared with 10.3% in the long (P > 0.999). There was no difference in clinical resolution at EOT, LOS, or rates of CDI, MDR GN-BSI, recurrent GN-BSI resistant to prior therapy, or 30-day readmission. Patients in the long duration group were discharged with longer appropriate outpatient courses (8 days vs. 0.5 days, P < 0.001), which remained significant when including lower bioavailability agents (e.g., oral β lactams) (8 days vs. 5 days, P < 0.001). Conclusion There was no difference in clinical outcomes between the long and short duration therapy for treatment of GN-BSI. This study may support shorter treatment durations for uncomplicated GN-BSI, but should be interpreted cautiously given the smaller sample size. Disclosures All authors: No reported disclosures.

Background One of the major challenges in Clostridioides difficile infection (CDI) is preventing recurrence, particularly in the setting of risk factors, such as systemic antibiotics that impact the gut microbiome. There are little data to demonstrate the impact of secondary prophylaxis with oral vancomycin and due to the lack of evidence, the IDSA guidelines do not make a recommendation. Methods This was a multi-site, retrospective cohort study of adult inpatients within the University of Rochester Medical Center who received either a high- or medium-risk systemic antibiotic between July 1, 2013 and September 30, 2018 and had a positive C. difficile test within one year prior to admission. The primary endpoint was incidence of recurrent CDI within 90 days from the start of antibiotics in patients who received oral vancomycin prophylaxis (OVP) vs. those who did not receive prophylaxis (control). Results Of 425 patients screened, 153 patients were included in the control and 78 patients in the OVP group. The OVP group was more likely to be immunosuppressed (P < 0.001), have increased hospital length of stay (P < 0.001), receive a proton pump inhibitor (P = 0.049), have a prior episode of CDI within the previous 90 days (P < 0.001), and have > 1 prior episode of CDI (P = 0.038). The control group was more likely to have received metronidazole for the most recent CDI episode (P < 0.001), likely reflecting mild-moderate severity. Recurrent CDI within 90 days was 10.3% in the OVP group compared with 17.6% in the control (P = 0.175). A subgroup analysis of the patients with recurrent CDI found the time to recurrence from initiation of systemic antibiotics was similar in the OVP group compared with control (43 vs 30 days, P = 0.223). Conclusion While there was not a statistically significant difference in recurrent CDI within 90 days, the OVP group had numerous risk factors that made these patients at higher risk for recurrence compared with the control group. This may be clinically important and certain risk factors, such as timing of previous CDI episode, could be used to guide which patients should receive OVP. Prospective studies are needed to better elucidate the role of OVP and better define the patients that may benefit the most. Disclosures All authors: No reported disclosures.

Background: Guideline recommendations from the Infectious Diseases Society of America (IDSA) and the 4th European Conference on Infections in Leukemia (ECIL-4) for the optimal duration of empiric antimicrobial therapy in patients with hematological malignancies and febrile neutropenia (FN) of unknown origin (FUO) vary given limited available evidence. Recent studies involving hematology patients and hematopoietic cell transplantation (HCT) recipients with FN have demonstrated that de-escalation of broad-spectrum antimicrobials (BSA) prior to hematopoietic recovery is associated with greater antibiotic-free days, but without increased risks, such as recurrent fever, bacteremia, intensive care unit (ICU) admission, or inpatient mortality. However, the safety of this de-escalation approach has not been extensively studied in autologous and haploidentical HCT recipients within the United States as most prior studies were conducted in Europe. The main purpose of this study was to compare rates of recurrent fever, re-escalation of therapy, and Clostridium difficile-associated infection (CDI) in autologous and allogeneic HCT recipients with FUO who received early de-escalation of BSA prior to hematopoietic recovery versus those who continued BSA until hematopoietic recovery. Methods: This retrospective, observational study assessed HCT recipients with FN admitted to Carolinas Medical Center in Charlotte, North Carolina between March 2014 to April 2018. Patients were included if they were ≥ 18 years of age, had an active hematologic malignancy and underwent allogeneic or autologous HCT, experienced their first episode of FN after HCT, and were initiated on appropriate BSA for ≥ 48 hours. Patients were excluded if they had microbiological or radiological diagnosis of active bacterial, fungal, or viral infection during the FN episode. Patients were enrolled into either cohort 1, which represented patients who were de-escalated to prophylactic antimicrobials prior to hematopoietic recovery (early de-escalation group), or cohort 2, which represented patients who continued BSA until hematopoietic recovery (hematopoietic recovery de-escalation group). Fisher's exact test was conducted to make cohort comparisons for categorical patient characteristics, while Mann-Whitney U test was employed for continuous variables. Multivariate logistic regression was utilized to evaluate rates of recurrent fever, re-escalation of therapy, and CDI between the 2 cohorts. Results: A total of 107 patients were included with 24 (22.4%) in cohort 1 and 83 (77.6%) in cohort 2. Most patients (87.5%) in cohort 1 received haploidentical HCT, whereas 84.3% of patients in cohort 2 received autologous HCT (P < 0.001). The median duration of neutropenia following the first FN episode was significantly shorter in cohort 2 (15 vs 4 days in cohorts 1 and 2, respectively, P < 0.001). There were no significant differences in rates of recurrent fever (4.2% vs 7.2%, adjusted OR (AOR) = 0.63,P = 0.684) and re-escalation of therapy (4.2% vs 4.8%, AOR = 1.26, P = 0.853) within 72 hours following de-escalation between the 2 cohorts. Rates of CDI within 30 days from hematopoietic recovery were also similar (4.2% vs 2.4%, AOR = 2.25, P = 0.582). No patients experienced inpatient mortality, ICU admission, or bacteremia. There were no significant differences in days of antimicrobial use per 1000 transplant days (P = 0.071). In a subgroup analysis of only allogeneic HCT recipients, haploidentical was the most common transplant type with 91.3% (n = 21/23) in cohort 1 and 69.2% (n = 9/13) in cohort 2. Recurrent fever was very infrequent among allogeneic HCT recipients (n = 1 in cohort 1 vs n = 0 in cohort 2, P > 0.999). However, a significant reduction in days of antimicrobial use per 1000 transplant days (P = 0.002) was observed in cohort 1 compared to cohort 2. Conclusion: HCT recipients with FUO who received de-escalation of BSA prior to hematopoietic recovery did not experience increased rates of recurrent fever, re-escalation of therapy, CDI, bacteremia, ICU admission, or inpatient mortality. These results concur with recently published studies and the ECIL-4 guidelines. An early de-escalation approach in haploidentical HCT recipients specifically appears to be safe and may result in a reduction in antimicrobial utilization. Disclosures Grunwald: Forma Therapeutics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medtronic: Equity Ownership; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy.

Background Infections caused by carbapenem resistant Enterobacteriaceae (CRE) are associated with high mortality. Optimal treatment for CRE bacteremia remains unclear, including the role of combination therapy, carbapenem-containing regimens, or newer antimicrobials, such as ceftazidime-avibactam (CAZ-AVI). The objective of this study was to evaluate risk factors associated with mortality in patients with CRE bacteremia, with a focus on antimicrobial therapy. Methods This was a multicenter, retrospective cohort study of inpatients within Carolinas HealthCare System who had a positive blood culture with CRE (Klebsiella spp., Enterobacter spp., or Escherichia coli) between January 1, 2010 and September 30, 2016. CRE isolates were identified as pathogens with an ertapenem MIC ≥ 1 mcg/mL. The primary endpoint was death within 28 days after the first positive blood culture in patients with CRE bacteremia. Clinical variables, including the use of specific antimicrobials and combination therapy, were compared between 28-day survivors vs. non-survivors. Results A total of 73 patients were included with CRE bacteremia. The most common sources of infection identified were urine (42.5%) and intra-abdominal (38.4%). The overall 28-day mortality was 26%. Fifty-three (72.6%) patients received combination antibiotic therapy and 20 (27.4%) received monotherapy. Combination therapy with in vitro active agents (36.8% vs. 33.3%, P = 0.87) and the use of carbapenem-containing regimens (47.4% vs. 46.3%, P = 0.74) did not differ between those who died and survived, respectively. One patient treated with CAZ-AVI as monotherapy died, but only eight patients received this antibiotic. There was a trend towards higher use of tigecycline in the group that died compared with the group that survived (73.7% vs. 59.3%, P = 0.26). Conclusion There did not appear to be a difference in mortality at 28 days with the use of combination therapy or a carbapenem-containing regimen. While a statistically significant difference was not demonstrated, tigecycline-containing regimens may be associated with increased mortality in the treatment of CRE bacteremia. Larger prospective studies are necessary to further elucidate the role of combination therapy and newer agents, such as CAZ-AVI, in this patient population. Disclosures C. Polk, The Medicines Company: Investigator, Research support.