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Background Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Summary Objectives We examined VRE colonization, bacteremia (VREB) incidence and outcomes within 100 days of allogeneic hematopoietic cell transplantation (HCT). Methods HCT recipients screened for VRE were assessed, and colonization and VREB incidence compared over time using linear regression. Cox proportional hazards models were constructed to assess the relationship between mortality, pre-HCT colonization, and underlying disease. Results Of 1492 HCT recipients, 204 (14%) patients were colonized pre-HCT, while 90 (6%) acquired colonization post-HCT. Forty-two patients (2.8%) developed VREB within 100 days post-HCT; the majority, 32 (76%), were previously colonized. The cumulative incidence of VREB was 2.9 per 10,000 patient-days. Over the study period there were no significant changes in incidence of VRE colonization or VREB despite a number of interventions (p > 0.1). Patients with pre-HCT colonization had increased mortality compared to non-colonized patients (HR 2.1; 95% CI: 1.5, 3.3). Conclusions We found a low burden of VRE at our center with no significant changes observed over a 10-year study period. VRE, while responsible for substantial resource consumption from routine screening and isolation, was an infrequent cause of bacteremia.

Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.Funding: NoneDisclosures: Scott Bergman reports a research grant from Merck.

We examined vancomycin-resistant enterococci (VRE)-directed antimicrobial use and VRE bacteremia in a cohort of allogeneic hematopoietic cell transplantation patients from a center where VRE screening is standard prior to transplant. In this cohort, VRE bacteremia (VREB) was infrequent. In patients without VREB, colonized patients received VRE therapy more often than noncolonized patients.Infect Control Hosp Epidemiol2018;39:730–733

Background Inappropriate outpatient antibiotic prescribing for acute upper respiratory infections (URIs) is a high priority target for antimicrobial stewardship and has not been described for cancer patients. The goal of this study was to characterize patterns of and factors associated with antibiotic prescribing among ambulatory oncology patients with URIs. Methods We selected outpatients >18 years old seen at an ambulatory cancer center with ICD-10 diagnosis code consistent with URI from October 1, 2015 to September 30, 2016 for chart review. Patients without documented active URI symptoms or with lower tract infection at the first clinical encounter for the URI (day 0) were excluded. We obtained demographic, clinical, antimicrobial prescribing and viral testing data for days 0–14. We used generalized estimating equations to test for associations of baseline factors with a ≥1 antibiotic prescription for URI while accounting for correlation among patients seen by the same provider. Results Of the 341 charts reviewed, 251 (74%) patients, seen by 99 providers were eligible for analysis. A total of 162/251 (65%) had an underlying hematologic malignancy or disorder; of those, 51% had a prior hematopoietic cell transplant. Eighty-four (33%) received ≥1 antibiotic prescription for URI with 63% ordered on day 0. Azithromycin (47%) and fluoroquinolones (25%) were most often prescribed. One hundred thirteen (45%) patients had respiratory viral testing performed; 85 (75%) tested positive (Figure 1). Both antibiotic prescribing (P = 0.005) and viral testing (P < 0.001) varied by clinical service (Figure 2). Viral testing on day 0 was associated with lower risk of antibiotic prescribing while sputum production or chest congestion was associated with higher risk of antibiotic prescribing (Figure 3). Conclusion Antibiotics were prescribed in one in three oncology outpatients with URI, although viral etiologies were identified in most who were tested. Respiratory viral testing was associated with reduced antibiotic prescribing though collinearity between clinical service and viral testing limited our ability to separate these effects on antibiotic prescribing. It is important to further explore the role of viral testing in antibiotic prescribing for URI in outpatient oncology settings. Disclosures All authors: No reported disclosures.

Background Despite available prophylaxis, Pneumocystis jirovecii pneumonia (PJP) still occurs in immunocompromised hosts. We set out to determine the overall burden of PJP among cancer patients in the modern era at our cancer center. Furthermore, we sought to describe reasons for failure to use prophylaxis among these patients. Methods In this retrospective cohort study, we identified PJP cases among patients admitted between January 2007 and December 2016 at our center. PJP was defined as any positive test (immunofluorescence or PCR) from sputum and/or bronchoalveolar lavage. Patient demographics, underlying malignancy, anti-pneumocystis antibiotics and mortality were assessed through electronic medical records. Current National Comprehensive Cancer Network (NCCN) guidelines were used to determine who should have received prophylaxis. Cases not on prophylaxis at the time of diagnosis were reviewed to determine reasons why prophylaxis was not administered. Incidence of PJP for the last 5 years of the study was estimated based on a Poisson distribution. Results A total of 37 patients had confirmed PJP over the 10-year study period. The majority were male (68%) with a median age of 60 years (IQR: 47, 67). The most common underlying malignancy was acute myeloid leukemia (24%); 24/37 (65%) were bone marrow transplant recipients. The 5-year incidence between 2012 and 2016 was 2.28 per 10,000 inpatient days (95% CI, 1.50–3.32). There was no evidence of clustering of PJP diagnoses. Overall, 26/37 (70%) of PJP patients were not on prophylaxis at the time of diagnosis, 12 of whom met NCCN criteria for use. Twenty-three were deceased by the end of the study with 11/23 (48%) deaths occurring within 30 days of diagnosis. The main reason prophylaxis was not administered was neutropenia (19%). A documented sulfa allergy was noted in seven PJP cases (19%); 2/7 (29%) were not administered alternate prophylaxis despite recommendations for use. Conclusion PJP incidence in this large cohort of cancer patients was low, but one-third of patients who developed PJP were not on recommended prophylaxis in accordance with NCCN guidelines. Infection Prevention and Antimicrobial Stewardship teams should enhance efforts to address missed opportunities for PJP prophylaxis in high-risk patients. Disclosures S. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee.

Background The gut microbiome of hematopoietic cell transplant (HCT) recipients correlates with the risk of acute graft- vs.-host disease (aGVHD). IV vancomycin is the most commonly used nonprophylactic antibiotic in HCT recipients at our center. We evaluated indications for vancomycin use and impact of vancomycin exposure on the microbiome. Methods Antibiotic exposures and provider-documented indications for vancomycin use were assessed through chart review. We assessed adherence to guideline-based recommendations for vancomycin use for courses during neutropenic fever. Weekly stool samples collected from HCT patients before and up to 100 days post-transplant in a previously described cohort had bacterial composition determined from 16S rRNA amplicons analyzed with a phylogeny classifier and was correlated with vancomycin exposure using mixed effects modeling to correct for overlapping and repeated antibiotic exposures. Results Thirty-seven of 70 (53%) of patients received vancomycin over 61 courses with a mean duration of 8 days; 14 (23%) of these courses were with neutropenic fever. No indication was documented by the provider for 21 (34%) vancomycin courses (Figure 1). Almost half of all courses given for neutropenic fever did not meet guideline indications (Figure 2). Adverse effects occurred in 19 (31%) of vancomycin courses, including 11 (18%) associated with acute kidney injury. Vancomycin was associated with reduced relative abundance of organisms correlated with reduced risk of subsequent severe acute graft vs. host disease and Clostridium scindens, an organism protective against C. difficile infection (CDI) (Figure 3, in bold). Conclusion Indications for vancomycin were poorly documented and infrequently guideline based. Adverse events occurred in 1 in 3 courses of vancomycin. Vancomycin correlated with microbiome changes which have been associated with increased risk for aGVHD and CDI. Disclosures S. Pergam, Merck: Consultant, Consulting fee.

Background Antibiotics have contributed significantly to advances in cancer therapy and hematopoietic cell transplantation, but rising antibiotic resistance threatens this progress. Little is known about knowledge and perceptions surrounding antibiotic use and resistance among staff at cancer centers. Methods We conducted a brief cross-sectional survey of healthcare professionals (HCP) at a large ambulatory cancer center to assess knowledge of antibiotic prescribing and resistance during Antibiotic Awareness Week, November 13–19, 2017. A convenience sample of providers and staff who participated in one of two 2-hour Antimicrobial Stewardship Program “open house” events was used. Questions evaluated knowledge about antibiotic use for upper respiratory tract infections (URIs). Results There were 179 respondents. The proportion of correct responses to each question by employee type is displayed in Table 1. There was a statistically significant decreasing trend in the proportion correctly answering all four questions by employee type from providers, to pharmacists, to nurses, to others (P

Background Pre-transplant screening for VRE is commonly performed among patients prior to hematopoietic cell transplantation (HCT) although its role in prevention of horizontal transmission is controversial. The impact of pre-transplant VRE colonization on antimicrobial stewardship and use of VRE therapy is unknown. The purpose of this investigation is to determine whether pre-transplant VRE colonization affects the use of VRE therapy among patients during the first 100 days post-transplant. Methods We analyzed patients >18 years old within the first 100 days post- allogeneic HCT at a cancer center from September 1, 2007 to August 31, 2016 from a prospectively collected database. We performed retrospective chart review among patients who did and did not develop VRE bacteremia to obtain antimicrobial utilization data for agents with in vitro activity against VRE based on colonization status. Patients colonized post-HCT and those with positive surveillance blood cultures were excluded from analysis. Continuous variables were assessed using t-tests or Mann–Whitney U tests for normal or non-normal data respectively. Results Of 1402 allogeneic HCT patients, 203 (14%) were colonized pre-transplant. Among 22 (1.6%) patients who developed VRE bacteremia, 19 (86%) were colonized pre-transplant. Eight (42%) colonized patients received empiric VRE therapy within 24 hours of blood culture collection compared with 0 (0%) of non-colonized patients (P = 0.23). Among the 1371 patients who did not develop VRE bacteremia, 66 (5%) received VRE therapy. 32/179 (18%) of the colonized group received VRE therapy compared with 34/1192 (3%) non-colonized (P