Abstract Background There is significant variability in patient serum posaconazole levels, and it is unclear what characteristics increase the risk for subtherapeutic levels. Higher levels have been associated with improved outcomes. The purpose of this study is to identify risk factors associated with subtherapeutic posaconazole serum levels. Methods Retrospective study of adult patients admitted to NewYork-Presbyterian Hospital who received posaconazole with at least one level obtained at steady-state. Levels were obtained after at least five consecutive days of therapy with no interruptions > 24 hours or dosage changes prior to initial level. Patients were grouped based on if the initial level was therapeutic, defined as a serum level > 1 mcg/mL. Risk factor assessment was performed using a logistic regression model. Baseline characteristics between therapeutic and subtherapeutic groups were compared via chi-squared test for categorical variables and independent t-test for continuous variables. Results 383 patients were included: 280 initial levels were therapeutic and 103 were subtherapeutic. Patients primarily consisted of those with solid organ transplant (48.8%) and hematologic malignancy (38.6%). Significant differences between therapeutic and subtherapeutic groups included median weight (73 vs 78 kg, p=0.017) and initial weight-based doses (4.4 vs 4.2 mg/kg, p=0.044), respectively. This prompted an exploratory analysis finding significant association with BMI > 35 (4.1% therapeutic vs 12.1% subtherapeutic, p=0.006). Initial dose thresholds of at least 3 mg/kg and 4 mg/kg showed nonsignificant increases in therapeutic levels (p=0.056 and p=0.107 respectively). On multivariable analysis, subtherapeutic levels were more likely in patients who are black or African American (OR 1.869, 95% CI 1.009, 3.465), had diarrhea (OR 1.978, 95% CI 1.149, 3.408), and had a BMI > 35 (OR 3.538, 95% CI 1.300, 9.628). Conclusion Patients who are Black or African American, have diarrhea, and have a BMI > 35 were identified as having increased risk for subtherapeutic levels at 300 mg daily dosing. Patients at risk may benefit from initial weight-based dosing of at least 4mg/kg, however this requires additional confirmatory studies. Disclosures All Authors: No reported disclosures

BACKGROUND:Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES:To understand optimal initial treatment of candidaemia. METHODS:We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS:A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS:These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.

Abstract Background Antibiotic exposure is a primary risk factor for Clostridioides difficile infection (CDI) and recurrence. We compared CDI recurrence in patients who received extended oral vancomycin (poV) after diagnosis of CDI, at a dose of q12-24h compared to q6h, while on concomitant systemic antibiotic therapy. Methods Retrospective study of adult patients admitted 2/2020-9/2022 to NewYork-Presbyterian Hospital, diagnosed with CDI, and received at least 14 days poV including initial CDI therapy, and at least 2 days of extension with concomitant systemic antibiotics with no interruptions. Patients were grouped based on vancomycin extended dosing to either q6h or q12-24h. Patients were excluded if CDI regimen included vancomycin pulse/taper or fidaxomicin, >1 day interruption between final day of CDI treatment and extended dosing, and incomplete resolution of CDI at day 14. The primary outcome of recurrent CDI at 90 days was compared between the two groups via chi-squared test. Predictors of CDI recurrence were assessed using a logistic regression model. Results 110 patients were included:77 received q6h and 33 received q12-24h extended poV. Median age was 63 years (IQR 55,74), 51% were hospital onset-CDI, and the median total duration of poV was 25 days (IQR 19,38 days). The only significant differences between q6h and q12-24h groups were total days of vancomycin (22 vs. 37 days; p< 0.001) and patients with previous CDI episodes (7% vs 24%; p=0.02). Recurrence at 90 days was similar between q6h and q12-24h groups (13.2% and 6.3% respectively; p=0.505). On multivariable analysis, while controlling for severe and fulminant CDI and patients with inflammatory bowel disease, poV regimen of q12h-24h did not impact recurrence (OR 0.428, 95% CI 0.08-2.21). Conclusion No significant differences were seen in CDI recurrence between extended poV q6h compared to q12-24h. For patients who require extended poV dosing beyond an initial treatment course, q12h-24h dosing may be an option with improved patient convenience and reduced drug cost. The long-term impact of this reduced dosing frequency remains to be determined. Disclosures All Authors: No reported disclosures

Abstract Background Candidemia is associated with mortality rates exceeding 40%. However, prior studies indicate mortality may be reduced when antifungal therapy is initiated within 12 hours. The T2Candida Panel is a diagnostic assay that detects Candida species directly from a whole blood specimen within 3-5 hours (T2 Biosystems, Lexington, MA). The objective of this study is to identify predictors of 30-day mortality in patients with candidemia identified by T2Candida Panel. Methods This is a retrospective, multicenter study of critically ill patients with candidemia identified by T2Candida Panel from January 2016 - December 2022. Critically ill patients were defined as those who developed candidemia during an intensive care unit (ICU) stay or within 72 hours of ICU admission or discharge. T2Candida sites were chosen across the United States based on T2Candida utilization. Exclusion criteria were patients < 18 years of age, those with prophylactic indications for antifungal therapy, prisoners and pregnant patients. Multivariate logistic regression was conducted to identify factors associated with 30-day mortality measured from the T2Candida draw time. Results There were 171 ICU patients from seven institutions with candidemia identified by T2Candida panel. The mean (standard deviation [SD]) age was 59.7 (14.8) years and 52.1% were male. Mean (SD) APACHE II and Charlson Comorbidity Index scores were 20.6 (7.1) and 4.9 (2.8), respectively. Empiric antifungal therapy was administered to 36.8% of patients and the majority received infectious diseases (ID) consult (92.4%). Echinocandins were the most common agents used for empiric (72.7%) and definitive therapy (62.6%). Overall, 30-day mortality occurred in 36.0% and was not associated with antifungal de-escalation. Administration of empiric therapy (aOR 0.457, 95% CI 0.199-1.054) and ID consult (aOR 0.225, 95% CI 0.056-0.913) were associated with reduced odds of 30-day mortality. Conclusion Empiric antifungal administration and ID consult were independently associated with reduced odds of 30-day mortality in patients with candidemia identified by T2Candida Panel. Future studies are needed to evaluate the impact of the T2Candida panel on antifungal stewardship. Disclosures Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant

Background: Penicillin allergy is commonly reported, but true allergy is rare. Inpatients with reported beta-lactam allergy are often treated with alternative antibiotics. Penicillin skin testing (PST) is not universally available for inpatients. Methods: We designed a four-phase quality improvement project aimed to increase the percentage of inpatients on medical services with reported beta-lactam allergy who safely receive beta-lactam antibiotics at two hospitals with limited access to PST. First, we updated our hospital guideline to allow for cephalosporin graded challenge without antecedent PST. Second, we educated physicians, physician assistants, and nurses about the new guideline and beta-lactam allergy classification and management. Third, we designed a pocket card to reinforce the education. Last, we used antimicrobial stewardship software to screen our daily census to identify opportunities to improve management of patients with reported beta-lactam allergies. Results: We observed a 29.2% increase in the percentage of patients who received beta-lactam antibiotics (excluding carbapenems) among those with reported beta-lactam allergy, from 42.2% (470/1,115) at baseline to 54.5% (379/696), p < 0.001, during the project period. There was a decrease in the use of alternative antibiotics, no change in hospital-onset Clostridioides difficile cases, and no increase in the number of infectious disease or allergy consults. The number of graded challenges increased during the project period, without any anaphylaxis events. Conclusion: A multiphase quality improvement project aimed to improve management of beta-lactam allergies and access to graded challenges led to an increase in beta-lactam utilization without an increase in anaphylaxis, even with limited access to PST.

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Purpose To share challenges and opportunities for antimicrobial stewardship programs based on one center’s experience during the early weeks of the coronavirus disease 2019 (COVID-19) pandemic. Summary In the spring of 2020, New York City quickly became a hotspot for the COVID-19 pandemic in the United States, putting a strain on local healthcare systems. Antimicrobial stewardship programs faced diagnostic and therapeutic uncertainties as well as healthcare resource challenges. With the lack of effective antivirals, antibiotic use in critically ill patients was difficult to avoid. Uncertainty drove antimicrobial use and thus antimicrobial stewardship principles were paramount. The dramatic influx of patients, drug and equipment shortages, and the need for prescribers to practice in alternative roles only compounded the situation. Establishing enhanced communication, education, and inventory control while leveraging the capabilities of the electronic medical record were some of the tools used to optimize existing resources. Conclusion New York City was a unique and challenging environment during the initial peak of the COVID-19 pandemic. Antimicrobial stewardship programs can learn from each other by sharing lessons learned and practice opportunities to better prepare other programs facing COVID-19 case surges.

A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.

Kidney transplant recipients are an immunocompromised population, many with comorbid diseases such as obesity, diabetes, and coronary artery disease, that may increase their risk for developing severe coronavirus disease 2019 (COVID-19).1Pereira M.R. Mohan S. Cohen D.J. et al.COVID-19 in solid organ transplant recipients: initial report from the US epicenter.Am J Transplant. 2020; 20: 1800-1808Crossref PubMed Scopus (593) Google Scholar During the pandemic in New York City, kidney transplant recipients requiring hospitalization for COVID-19 had a higher rate of mortality compared with patients who could be treated in the ambulatory setting.2Lubetzky M. Aull M. Craig-Schapiro R. et al.Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center.Nephrol Dial Transplant. 2020; 35: 1250-1261Crossref PubMed Scopus (62) Google Scholar Accounting for differences in baseline risk factors for progression in immunocompromised patients, avoidance of hospitalization would be beneficial given the added costs, limited hospital resources during a surge, and higher risk of complications when they are hospitalized. Although COVID-19 vaccination efforts are currently widespread and highly recommended for the prevention of severe COVID-19 infection, some transplant programs delay administering vaccinations immediately posttransplant to avoid alloimmune stimulation. Another challenging aspect of vaccinating this population is that immunosuppressed kidney transplant recipients may have impaired antibody responses.3Husain S.A. Tsapepas D. Paget K.F. et al.Postvaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplant recipients.Kidney Int Rep. 2021; 6: 1699-1700Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Emerging evidence of breakthrough infections among vaccinated kidney transplant recipients has been described, and therefore it is important to evaluate the efficacy and safety of available COVID-19 treatment options.4Tau N. Yahav D. Schneider S. et al.Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients.Am J Transplant. 2021; 21: 2910-2912Crossref PubMed Scopus (31) Google Scholar REGN-COV2, an antibody cocktail containing 2 SARS-CoV-2–neutralizing antibodies (casirivimab and imdevimab), has been shown to reduce COVID-19 viral load and received Emergency Use Authorization (EUA) by the US Food and Drug Administration for the treatment of mild to moderate COVID-19 infection in November 2020.5Weinreich D.M. Sivapalasingam S. Norton T. et al.REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19.N Engl J Med. 2021; 384: 238-251Crossref PubMed Scopus (1095) Google Scholar,6Casirivimab and imdevimab EUA letter of authorizationFood and Drug Administration.https://www.fda.gov/media/143891/downloadGoogle Scholar Casirivimab and imdevimab are 2 IgG1 antibodies that are noncompeting, and they target the receptor-binding domain of the SARS-CoV-2 spike protein, thereby neutralizing viral entry into human cells via the angiotensin-converting enzyme 2 receptor.5Weinreich D.M. Sivapalasingam S. Norton T. et al.REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19.N Engl J Med. 2021; 384: 238-251Crossref PubMed Scopus (1095) Google Scholar We provided REGN-COV2 to our kidney transplant recipients with mild to moderate COVID-19 infection—defined as presence of mild symptoms, oxygen saturation greater than or equal to 94%, and no additional oxygen supplementation from baseline. Herein we report our center’s experience. Over a 6-month period ending on June 25, 2021, a total of 14 kidney transplant recipients from our center received REGN-COV2 infusions for mild to moderate COVID-19 infection. Three recipients received the Moderna SARS-CoV-2 (mRNA-1273) vaccine prior to testing positive for COVID-19: 2 recipients completed the 2-dose series and the remaining recipients had completed 1 dose. To be eligible for REGN-COV2, all recipients must test positive by nasopharyngeal swab for SARS-CoV-2 via polymerase chain reaction. Single-dose infusions of casirivimab 1200 mg and imdevimab 1200 mg were given at an outpatient infusion center on campus to all with the exception of 1 individual who received the infusion in the emergency department. Eight recipients were white and 6 were nonwhite (Table 1). The median age of treated recipients was 62 years (interquartile range 52–69), and the median time from transplant was 5 years (interquartile range 1–9). Preexisting risk factors for severe disease were identified in our recipients and included age greater than 65 years, hypertension, coronary disease, and diabetes mellitus (Table 1). The median time to REGN-COV2 infusion was 5 days (interquartile range 4–7). The most common symptoms reported include fever, fatigue and myalgia, diarrhea, and upper respiratory tract complaints (Table 1). At presentation, maintenance therapy included tacrolimus and mycophenolate mofetil. Three of the 14 recipients also received corticosteroid maintenance therapy. Overall, immunosuppression was reduced in 6 of our kidney transplant recipients after COVID-19 diagnosis.Table 1Baseline demographics of renal transplant recipients receiving casirivimab-imdevimab (N = 14)Characteristicsn (%) or median (IQR)Male sex9 (64)Race White8 (57) Black2 (14) Hispanic2 (14) Asian1 (7) Other1 (7)Age, yr62 (52–69)Time since transplant, yr5 (1–9)Concomitant risk factors Hypertension14 (100) Coronary artery disease5 (36) Diabetes3 (21) Age >65 yr3 (21) Malignancy2 (14)Maintenance immunosuppression Tacrolimus tough, ng/dl6.3 (4.2–7.8) Mycophenolate > 1000 mg/d5 (36) Prednisone maintenance3 (21)Time from symptom onset to infusion, d5 (4-7)Symptoms Fever8 (57) Upper respiratory tract symptoms7 (50) Shortness of breath1 (7) Fatigue/myalgia10 (71) Diarrhea3 (21) Headache/confusion1 (7) Loss of taste/smell1 (7)Patients requiring additional COVID-19 therapy Remdesivir2 (14) Steroids2 (14) Tocilizumab1 (7)IQR, interquartile range. Open table in a new tab IQR, interquartile range. A single REGN-COV2 infusion of casirivimab 1200 mg and imdevimab 1200 mg was tolerated by our kidney transplant recipients. We did not encounter any cases of hypersensitivity reactions. During infusion, 1 adverse event occurred where a recipient complained of burning sensation in the hands, which resolved following a dose of acetaminophen. Of the 14 treated recipients, 1 individual, aged 61 years, was hospitalized 6 days after infusion for worsening symptoms and de novo supplementation oxygen requirement. This patient received dexamethasone, remdesivir, and tocilizumab, and required up to 15 L oxygen. On the day of discharge, oxygen requirement was weaned down to 2 L oxygen via nasal cannula for ambulation. The patient continued to improve and no longer need oxygen supplement 2 weeks after discharge. A second recipient, aged 79 years, was admitted after testing positive for COVID-19 and received the REGN-COV2 infusion from the emergency department. His risk factors for progression include advanced age, significant coronary disease, and hypertension. He required 2 L oxygen supplementation via nasal cannula, remdesivir, and dexamethasone. He was discharged 12 days after admission without oxygen supplementation. We did not observe any cases of allograft rejection during the 30-day follow-up period. There was no mortality during the minimum 30-day follow-up period. In a phase 3 study enrolling 4057 COVID-19 outpatients with 1 or more risk factors for developing severe disease, treatment with REGN-COV2 significantly reduced hospitalization or all-cause mortality, lowered viral load, and promptly resolved COVID-19–related symptoms.7Weinreich DM, Sivapalasingam S, Norton T, et al. REGEN-COV antibody cocktail clinical outcomes study in COVID-19 outpatients. Preprint. medRxiv 21257469. doi: https://doi.org/10.1101/2021.05.19.21257469Google Scholar A recent report showed that the use of REGN-COV2 in solid organ transplant patients with mild to moderate COVID-19 infection resulted in no progression of symptoms or the need for hospitalization.8Dhand A. Lobo S.A. Wolfe K. et al.Casirivimab-imdevimab for treatment of COVID-19 in solid organ transplant recipients: an early experience.Transplantation. 2021; 105: e68-e69Crossref PubMed Scopus (41) Google Scholar In contrast, 2 of the 14 individuals at our center were hospitalized for additional management. Our analysis is limited by its small sample size to draw conclusions about efficacy but our findings demonstrate that it was safe for kidney transplant recipients with mild to moderate COVID-19 infections to receive REGN-COV2 therapy. Because our study lacked a control group, we examined our internal data for risk of hospitalization after COVID-19 diagnosis.9Craig-Shaprio R. Salinas T. Lubetzky M. et al.COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.Am J Transplant. 2021; 21: 1576-1585Crossref PubMed Scopus (61) Google Scholar At our center, we observed a 65% hospitalization rate for COVID-19–positive kidney transplant patients when the REGN-COV2 infusions were not yet available.9Craig-Shaprio R. Salinas T. Lubetzky M. et al.COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.Am J Transplant. 2021; 21: 1576-1585Crossref PubMed Scopus (61) Google Scholar We found that 31% of our hospitalized patients did not require respiratory support—it may be possible that these patients could have avoided hospitalization completely with REGN-COV2 administration.9Craig-Shaprio R. Salinas T. Lubetzky M. et al.COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.Am J Transplant. 2021; 21: 1576-1585Crossref PubMed Scopus (61) Google Scholar Although we did not test our patients for presence of endogenous antibodies, further study on whether transplant patients benefit from REGN-COV2 in the presence of endogenous antibodies may be warranted. We posit that neutralizing antibody therapy with REGN-COV2 will continue to be useful in our transplant population regardless of vaccination status. More than 50% of renal transplant recipients do not develop antispike antibodies after the 2-dose standard vaccination schedule of Moderna or Pfizer-BioNTech.3Husain S.A. Tsapepas D. Paget K.F. et al.Postvaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplant recipients.Kidney Int Rep. 2021; 6: 1699-1700Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Alternatively, the half-life of REGN-COV2 may extend for several months.5Weinreich D.M. Sivapalasingam S. Norton T. et al.REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19.N Engl J Med. 2021; 384: 238-251Crossref PubMed Scopus (1095) Google Scholar,7Weinreich DM, Sivapalasingam S, Norton T, et al. REGEN-COV antibody cocktail clinical outcomes study in COVID-19 outpatients. Preprint. medRxiv 21257469. doi: https://doi.org/10.1101/2021.05.19.21257469Google Scholar In kidney transplant recipients who are unable to obtain or have impaired antibody response to vaccinations, timely administration of REGN-COV2 in COVID-19–positive kidney transplant recipients may prevent progression to severe illness. In conclusion, infusion of neutralizing antibody therapy with REGN-COV2 was well tolerated in kidney transplant recipients with mild to moderate COVID-19 infection at our center. None of the treated recipients required mechanical respiratory support nor escalation of care to the intensive care unit. As COVID-19 continues to persist in many communities, a strategy of deploying REGN-COV2 infusion as therapy or prophylaxis in kidney transplant recipients warrants further investigation. All the authors declared no competing interests.

Abstract Background Exposure to Infectious Diseases (ID) education is highly variable in post-graduate medical training. We report our experience with a required one-week ID consult rotation for Internal Medicine (IM) interns with a focus on antimicrobial stewardship education. Methods Since 2018 all IM interns at our institution have participated in a required one-week ID consult rotation. Antimicrobial stewardship is a core feature of this rotation, with educational resources on antibiotic spectrum and decision-making, and interdisciplinary rounding with ID pharmacists. Between March 2020 and May 2021 we piloted an 11-item pre-rotation and post-rotation quiz with distinct but paired questions on key stewardship topics. The quiz was administered anonymously in SurveyMonkey. Mean pre/post rotation scores were compared using a paired T-test and the McNemar test of paired proportions was used to compare the pre/post change in percentage of correct responses for each topic. Results Among 47 interns who completed the rotation, 16 interns completed both pre- and post-rotation quizzes (response rate=34%). Mean scores on the pre-rotation quiz were 60%, compared to 77% on the post-rotation quiz (p=0.01), indicating significant improvement at the end of the rotation (Figure 1). Among 11 residents who scored below 65% on their pre-rotation quiz, all achieved an increased score on their post-rotation quiz (mean pre-test of 49% to mean post-test 79%). Table 1 displays the question topics and pre/post test change in percentage correct. The most difficult pre-test topics were ‘Recognition of AmpC-Expressing Organisms’ and ‘Antibiotics with activity against Pseudomonas aeruginosa,’ which improved, from 31% to 81% correct (p=0.03) and 50% to 100% correct (p=0.01), respectively. Figure 1. Mean score of interns on pre-rotation vs post-rotation antimicrobial stewardship quiz from March 2020 to May 2021 (n=16; p=0.01). Table 1. Question topics and change in percentage correct on pre-rotation and post-rotation quizzes. Conclusion A required one-week ID consult rotation for IM interns improved antimicrobial stewardship knowledge. Our experience may serve as a model for other institutions interested in increasing IM housestaff exposure to ID and antimicrobial stewardship. Disclosures Kristen Marks, MD, Gilead Sciences (Grant/Research Support)

Background: In recent years, several rapid molecular diagnostic tests (RMDTs) for infectious diseases diagnostics, such as bloodstream infections (BSIs), have become available for clinical use. The extent to which RMDTs have been adopted and how the results of these tests have been incorporated into clinical care are currently unknown. Methods: We surveyed members of the Society for Healthcare Epidemiology of America Research Network to characterize utilization of RMDT in hospitals and antimicrobial stewardship program (ASP) involvement in result communication and interpretation. The survey was administered using Qualtrics software, and data were analyzed using Stata and Excel software. Results: Overall, 57 responses were received (response rate, 59%), and 72% were from academic hospitals; 50 hospitals (88%) used at least 1 RMDT for BSI (Fig. 1). The factors most commonly reported to have been important in the decision to adopt RMDT were improvements in antimicrobial usage (82%), clinical outcomes (74%), and laboratory efficiency (52%). Among 7 hospitals that did not use RMDT for BSI, the most common reason was cost of new technology. In 50 hospitals with RMDT for BSI, 54% provided written guidelines for optimization or de-escalation of antimicrobials based upon RMDT results. In 40 hospitals (80%), microbiology laboratories directly notified a healthcare worker of the RMDT results: 70% provided results to a physician, nurse practitioner, or physician assistant; 48% to the ASP team; and 33% to a nurse. Furthermore, 11 hospitals (22%) had neither guidelines nor ASP intervention. In addition, 24 hospitals (48%) reported performing postimplementation evaluation of RMDT impact. Reported findings included reduction in time to antibiotic de-escalation (75%), reduction in length of stay (25%), improved laboratory efficiency (20%), and reduction in mortality and overall costs (12%). Among the 47 hospitals with both RMDT and ASP, 79% reported that the ASP team routinely reviewed blood culture RMDT results, and 53.2% used clinical decision support software to do so. Finally, 53 hospitals (93%) used 1 or more RMDT for non–bloodstream infections (Fig. 1). Fewer than half of hospitals provided written guidelines to assist clinicians in interpreting these RMDT results. Conclusions: RMDTs have been widely adopted by participating hospitals and are associated with positive self-reported clinical, logistic, and financial outcomes. However, nearly 1 in 4 hospitals did not have guidelines or ASP interventions to assist clinicians with optimization of antimicrobial prescribing based on RMDT results for BSI. Also, most hospitals did not have guidelines for RMDT results for non-BSI. These findings suggest that opportunities exist to further enhance the potential benefits of RMDT.Funding: NoneDisclosures: None

A survey of acute-care hospitals found that rapid molecular diagnostic tests (RMDTs) have been widely adopted. Although many hospitals use their antimicrobial stewardship team and/or guidelines to help clinicians interpret results and optimize treatment, opportunities to more fully achieve the potential benefits of RMDTs remain.

PURPOSE:To investigate the antimycotic activity of amphotericin B deoxycholate that has been previously frozen for 28 days before supplementation of Optisol-GS.METHODS:Triplicate Optisol-GS samples were inoculated with 10 colony-forming units (CFU) of Candida albicans. Each set of triplicate cultures was supplemented with 2.5 μg/mL of amphotericin B that was either freshly resuspended and never frozen, frozen overnight at -20°C and thawed, or frozen at -20°C for 4 weeks and thawed. The cultures were stored at 4°C, with aliquots taken at 0, 6, 24, and 72 hours for quantification. The efficacy of each preparation of amphotericin B in reducing C. albicans growth was assessed at these time points.RESULTS:Six hours after antifungal supplementation, there was a 1.33 log10 CFU reduction with freshly resuspended amphotericin B, compared with a 1.31 log10 reduction with amphotericin B that was frozen overnight (P = 0.20) and a 1.18 log10 reduction with amphotericin B that was frozen for 4 weeks (P = 0.05). After 72 hours, there was a 2.72 log10 CFU reduction with freshly resuspended amphotericin B, a 2.64 log10 CFU reduction with amphotericin B that was frozen overnight (P = 0.45), and a 2.18 log10 CFU reduction with amphotericin B that was frozen for 4 weeks (P = 0.05).CONCLUSIONS:Previously frozen amphotericin B remains highly effective against C. albicans. Optisol-GS supplemented with 2.5 μg/mL amphotericin B that was frozen for 4 weeks at -20°C resulted in >90% CFU reduction by 6 hours and >99% reduction by 72 hours.

Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy. Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies. Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.

Background: Approximately 20%-50% of antimicrobial use in hospitals is inappropriate. Limited data exist on the effect of frontline provider engagement on antimicrobial stewardship outcomes. Methods: A three-arm pre-post quality improvement study was conducted on three adult internal medicine teaching services at an urban academic hospital. Data from September through December 2016 were compared to historic data from corresponding months in 2015. Intervention arms were (1) Educational bundle (Ed-only); (2) Educational bundle plus antimicrobial stewardship rounds twice weekly with an infectious disease-trained clinical pharmacist (Ed+IDPharmDx2); and (3) Educational bundle plus internal medicine-trained clinical pharmacist embedded into daily attending rounds (Ed+IMPharmDx5). Results: Total antibiotic use decreased by 16.8% (p < 0.001), 6.8% (p= 0.08), and 33.0% (p < 0.001) on Ed-only, Ed+IDPharmDx2, and Ed+IMPharmDx5 teams, respectively. Broad-spectrum antibiotic use decreased by 26.2% (p < 0.001), 7.8% (p= 0.09), and 32.4% (p < 0.001) on the Ed-only, Ed-FIDPharmaa, and Ed+IMPharmDx5 teams, respectively. Duration of inpatient antibiotic therapy decreased from 4 to 3 days on the Ed+IMPharmDx5 team (p = 0.01). Length of stay for patients who received any antibiotic decreased from 9 to 7 days on the Ed-only team (p < 0.001) and from 9 to 6 days on the Ed+IMPharmDx5 team (p < 0.001). There was no significant change in 30-day readmission to the same facility, transfer to ICU, or in-hospital mortality for any team. Conclusion: Multidisciplinary, frontline provider-driven approaches to antimicrobial stewardship may contribute to reduced antibiotic use and length of hospital stay.

OBJECTIVETo assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.DESIGNCross-sectional survey.SETTINGOnline survey.PARTICIPANTSA convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.INTERVENTIONThe following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.RESULTSIn total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.CONCLUSIONSBarriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.Infect Control Hosp Epidemiol 2018;39:316–322

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Background: Misuse of antibiotics can lead to the development of antibiotic resistance, which adversely affects morbidity, mortality, length of stay, and cost. To combat the threat of antimicrobial resistance, The Joint Commission and the Centers for Medicare & Medicaid Services have initiated or proposed requirements for hospitals to have antimicrobial stewardship programs (ASPs), but implementation remains challenging. A key-informant interview study was conducted to describe the characteristics and innovative strategies of leading ASPs. Methods: Semistructured interviews were conducted with 12 program leaders at four ASPs in the United States, chosen by purposive sampling on the basis of national reputation, scholarship, and geography. Questions focused on ASP implementation, program structure, strengths, weaknesses, lessons learned, and future directions. Content analysis was used to identify dominant themes. Results: Three major themes were identified. The first was evolution of ASPs from a top-down structure to a more diffuse approach involving unit-based pharmacists, multidisciplinary staff, and shared responsibility for antimicrobial prescribing under the ASPs' leadership. The second theme was integration of information technology (IT) systems, which enabled realtime interventions to optimize antimicrobial therapy and patient management. The third was barriers to technology integration, including limited resources for data analysis and poor interoperability between software systems. Conclusion: The study provides valuable insights on program implementation at a sample of leading ASPs across the United States. These ASPs used expansion of personnel to amplify the ASP's impact and integrated IT resources into daily work flow to improve efficiency. These findings can be used to guide implementation at other hospitals and aid in future policy development.

Abstract Background Hospitalists are critical partners in antimicrobial stewardship program (ASP) efforts to improve antimicrobial use, but limited data exists on the effectiveness of ASP-hospitalist collaboration. We performed a hospitalist-led quality improvement project with pharmacy collaboration to improve antimicrobial prescribing practices on general internal medicine teaching services at an urban academic medical center. Methods We conducted a 3-arm intervention study on internal medicine teaching services from September-December 2016. Three services received an educational (Ed) intervention consisting of an antibiotic rationale checklist, a templated progress note to promote trainee critical thinking about antibiotic management, and a pocket card with institutional guidelines. In addition, 1 team received twice weekly stewardship rounds with an infectious disease clinical pharmacist (Ed+ID-PharmDx2) while another team received 5x week stewardship rounds with a generalist clinical pharmacist (Ed+PharmDx5). The primary outcome was broad-spectrum antibiotic use calculated as days of therapy (DOT) per 1000 patient days compared with historical data from the corresponding months. Secondary outcomes included duration of inpatient therapy, antibiotic costs, length of stay, 30-day readmission, ICU transfer and in-hospital mortality. Results Broad-spectrum antibiotic use significantly decreased by 26% (415 vs. 306 DOT/1000 patient days) and 32% (425 vs. 287 DOT per 1000 patient days) on the Ed and Ed+PharmDx5 teams, respectively (P <0.01). Broad-spectrum use on the ED+ID-PharmDx2 team decreased by 9% but was not statistically significant. There was a significant improvement in median length of stay among patients receiving antibiotics for Ed only (-1.5 days; P < 0.001) and Ed+PharmDx5 (-1 day; P < 0.001) and no significant change in 30 day readmissions, ICU transfer and in-hospital mortality for any team. Direct antibiotic costs were reduced by $80,000 during the study period. Conclusion A hospitalist-led initiative to improve inpatient antimicrobial prescribing led to reductions in broad-spectrum antimicrobial use and reduced length of stay. ASPs should target hospitalists and pharmacists as partners in programmatic efforts to improve inpatient antimicrobial prescribing. Disclosures All authors: No reported disclosures.

Abstract Background Guidelines for candidemia (CAND) treatment recommend initial echinocandin (ECHINO) therapy with transition to fluconazole (FLUC) after 5–7 days in patients with clinical stability, FLUC-susceptibility, and negative cultures; however, optimal timing for transition is unknown. In the era of rapid diagnostics and antimicrobial stewardship programs (ASP), studies are needed to evaluate the impact of earlier transition in CAND due to routinely FLUC-susceptible species. Methods Retrospective study of adult patients at NewYork-Presbyterian Hospital from 2012 to 2014. Inclusion criteria included ≥1 blood culture with C. albicans, C. tropicalis or C. parapsilosis, ≥1 dose ECHINO initial therapy, ≥3 days total treatment, and no prior episode of CAND within 30 days. Patients with polymicrobial bloodstream infection excluded. Patients de-escalated from ECHINO at ≤3 days (short-course; SC-ECH) were compared with those who received ≥4 days of ECHINO (long course; LC-ECH). The primary outcome was 14-day complete response (CR), defined as survival with clinical improvement and sterilization of blood cultures. Secondary outcomes included day 7 microbiological success (MicroS) and 28-day survival (SURV). Results 76 patients included: 21 in SC-ECH, 55 in LC-ECH groups. C. albicans (58%) most common species. Majority were male (59%) with median age 64 years (IQR 49–74), 62% were in ICU at time of CAND, 50% had recent surgery. No significant baseline differences between SC-ECH and LC-ECH groups, including in PITT bacteremia score ≥4 (43% vs. 42%; P = 0.4) or median APACHE (20 vs. 20; P = 0.684). There was no difference between SC-ECH vs. LC-ECH in CR (52% vs. 49%; P = 1.0), early MicroS (81% vs. 87%; P = 0.484), or SURV (62% vs. 73%; P = 0.523). On multivariable analysis with duration of ECHINO therapy forced into the model, only PITT bacteremia score <4 remained an independent predictor of CR (OR 6.1, 95% CI 2.1, 17.9; P = 0.001). Conclusion In adult patients with CAND due to routinely FLUC-susceptible species, early de-escalation from ECHINO was associated with similar outcomes, including day 7 MicroS. Early de-escalation based on early species identification has the potential to be a target for ASPs to optimize antifungal therapy without compromising clinical outcomes. Disclosures All authors: No reported disclosures.