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A 38-years-old female with an aortic valve replacement presented to an outside hospital (OSH) with fevers and malaise. Blood cultures revealed VRE which was resistant to linezolid, resistant to ampicillin, non-susceptible to daptomycin (MIC of 8 mcg/mL), and exhibited susceptibility to gentamicin. The patient was therefore initiated on intravenous (IV) daptomycin 6 mg/kg q24h and gentamicin IV 1 mg/kg q8h. However, after 14 days of therapy with daptomycin and gentamicin, the patient was transferred to our institution for the management of cardiogenic shock and hypoxemic respiratory failure. Given the concern for treatment failure, her antimicrobial regimen was changed to IV chloramphenicol 12.5 mg/kg every 6 hours with IV daptomycin 10 mg/kg every 48 hours given an estimated creatinine clearance of 30 mL/minutes. In vitro susceptibilities for chloramphenicol were performed which confirmed susceptibility. A transesophageal echocardiogram revealed a possible abscess at the left coronary cusp and aortic valve dehiscence. The patient underwent aortic valve replacement with aortic root reconstruction. The aortic valve culture grew VRE susceptible to linezolid but resistant to ampicillin and doxycycline. The patient was deemed clinically cured after 42 days of combination therapy with daptomycin and chloramphenicol. After 6 years of follow-up, the patient has not had a recurrent VRE infection. To our knowledge, this is the first case of endocarditis secondary to VRE that was successfully managed with the combination of daptomycin and chloramphenicol.

Background Sotrovimab, a monoclonal antibody with efficacy against SARS-CoV-2 including certain Omicron variants, has been used in treatment of mild-moderate COVID-19. Limited data exists regarding its use in pregnant women. Methods Electronic medical record review of pregnant COVID-19 patients treated with sotrovimab from 12/30/21-1/31/22 (Yale New Haven Health Hospital System [YNHHS]) was performed. Included were pregnant individuals ≥ 12 years, weighing ≥ 40 kg, with positive SARS-CoV-2 test (within 10 days). Those receiving care outside YNHHS or receiving other SARS-CoV-2 treatment were excluded. We assessed demographics, medical history, and Monoclonal Antibody Screening Score (MASS). Clinical outcomes assessed included emergency department (ED) visit < 24 hours, hospitalization, ICU admission, and/or death within 29 days of sotrovimab. Pregnancy and neonatal outcomes were assessed until 8/15/22. Results Among 22 subjects, median age was 32 years and body mass index was 27 kg/m2. Sixty-three percent were Caucasian, 9% Hispanic, 14% African-American, and 9% Asian. Nine percent had diabetes and sickle cell disease. Five percent had well-controlled HIV. Eighteen percent, 46%, and 36% received sotrovimab in trimester 1, 2, and 3, respectively. No infusion/allergic reactions occurred. MASS values were < 4. Only 12/22 (55%) received complete primary vaccination (46% mRNA-1273; 46% BNT162b2; 8% JNJ-78436735); none received a booster. There were no ICU admissions nor deaths. One subject was hospitalized for post-partum pyelonephritis; another had an ED visit for post-partum vaginal bleeding. Median gestational age at birth was 38.9 weeks. Nine percent had premature labor and premature rupture of membranes, respectively. Median infant birth weight was 3220 g. One neonate required an ICU stay due to prenatally diagnosed omphalocele (before sotrovimab) in a mother with congenital defect history. There were no abortions, fetal loss, or other birth/neurodevelopmental defects. Conclusion Pregnant COVID-19 patients receiving sotrovimab at our center tolerated it well with good clinical outcomes. Pregnancy and neonatal complications did not appear sotrovimab-related. Though a limited sample, our data helps elucidate the safety and tolerability of sotrovimab in pregnant women. Disclosures All Authors: No reported disclosures.

Background Rapid microbiology diagnostic results paired with immediate ASP intervention have been shown to decrease time to OAT and improve patient outcomes. For Gram positive (GP) BSI, studies have primarily focused on Staphylococci. However, the value of using rapid diagnostics for GPC in chains is not well studied. With the use of BioFire® FilmArray® Blood Culture Identification 2 (BCID2) to identify GPC in chains, we aimed to compare the time to OAT between pre- and post- implementation. Methods In May 2021, our institution implemented the use of BCID2 for GPC in chains, which detects 5 types of GPC in chains to the species level and the van A/B gene. Positive results were communicated in real time 24/7 to ASP who provided recommendations on OAT to the treatment team. A retrospective chart review compared the pre-implementation cohort (Jan - Sept 2019) to the post-implementation cohort (May 2021 - Jan 2022). The following patients were excluded from analysis: < 18 years of age, presence of polymicrobial infection or Streptococci with unidentified species by BCID2, discharged or deceased before rapid diagnostic result, on comfort measures or left against medical advice within 72 hours of result. The primary study endpoint was time to OAT which was defined as time from positive Gram stain to OAT. Secondary outcomes included percentage of ASP recommendations accepted, length of stay (LOS), and 30-day mortality. Results A total of 199 patients met inclusion criteria, 117 pre-cohort vs. 82 post-cohort. Baseline demographics were similar in both groups with the exception of the post-cohort having a numerically higher Charlson Comorbidity Index (Table 1). The most common sources of the bacteremias were intra-abdominal, skin and soft tissue, and endovascular (Table 2). The primary endpoint, average time to OAT, was 35 hours in the pre-cohort and 18 hours in the post-cohort with a difference of 16.8 hours (95% CI 9.8 – 23.8; p < 0.0001) (Table 3). ASP recommendations were accepted 91% of the time. The median LOS was 9 days (IQR 6 - 21) in the pre-cohort vs. 13 days (IQR 7-32) in the post-cohort (p = 0.07). The 30-day mortality rate was numerically lower in the pre-cohort (6.1% vs. 10.3%; p = 0.79). Conclusion For BSI due to GPC in chains, rapid diagnostics via BCID2 paired with 24/7 ASP led to markedly decreased time to OAT. Disclosures David Peaper, MD, Tangen Biosciences: Stocks/Bonds.

Background The optimal metronidazole dose for the treatment of Bacteroides spp. has not been defined. The purpose of this study was to evaluate the utility of a twice (BID), rather than thrice (TID) daily metronidazole dosing strategy among patients with bacteremia due to Bacteroides spp. Methods Adult, hospitalized patients with bacteremia secondary to Bacteroides spp. between October 2010 and June 2021 were assessed across 11 hospitals. The primary endpoint was clinical failure which was a composite of all-cause 30-day mortality, escalation of antimicrobial therapy, 30-day readmission or recurrence due to an anaerobic infection, positive repeat blood cultures for Bacteroides spp., or failure to resolve leukocytosis or fever. Results 208 patients were included; 68 received metronidazole 500mg BID and 140 patients received metronidazole 500mg TID (Figure). Patient age, Charlson comorbidity index, and Pitt Bacteremia score were similar among patients receiving BID vs TID dosing (Table 1). On balance, patients who received BID dosing were more likely to receive oral metronidazole and had shorter lengths of hospitalization prior to bacteremia. Overall, there was no significant difference between rates of clinical failure or other outcomes between patients who received BID versus TID metronidazole dosing (Table 2). In the multivariate model, neither the use of TID dosing (OR = 0.74; 95% CI = 0.33–1.65; P=0.457), time to treatment initiation (OR = 1; 95% CI = 0.81–1.22; P=0.968), days of initial non-metronidazole anaerobic therapy (OR = 0.91; 95% CI = 0.59–1.34; P=0.646), pre-infection length of stay (OR = 1.02; 95% CI = 0.99–1.05; P=0.106), admission prior to 2016 (OR = 1.09; 95% CI = 0.49–2.39; P=0.829), or initial oral metronidazole use (OR = 0.45; 95% CI = 0.18–1.03; P=0.066) were significantly associated with clinical failure. Figure 1:Inclusion and exclusion Non-metronidazole anaerobic coverage consisted of a beta-lactam/beta-lactamase inhibitor, cefoxitin, or a carbapenem Table 1:Demographics and baseline characteristicsTable 2:Clinical outcomes*Patients were considered to have escalated antimicrobial therapy if, in the setting of ongoing signs of infections, antimicrobial therapy was either broadened or the frequency of metronidazole was increased from twice daily to thrice daily. Conclusion In the largest study to date of patients with Bacteroides spp. bacteremia treated with metronidazole, there was no significant difference between BID and TID metronidazole dosing strategies. In the absence of a clear benefit, metronidazole 500mg BID is a reasonable dosing strategy in lieu 500mg TID for infections due to Bacteroides spp. Disclosures Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.

Background There is a paucity of data to support the efficacy and safety of placing vancomycin powder into and around the joint in total hip arthroplasty (THA), total knee arthroplasty (TKA), and shoulder arthroplasty (SA). Methods This was a retrospective chart review of patients undergoing THA, TKA, or SA who received intrawound (IW) vancomycin powder placed into and around the joint with a vancomycin impregnated bone cement spacer (VIBCS) compared to patients who received a VIBCS alone (usual care). Results There were 24 patients who met inclusion criteria. Of the 14 patients who received IW vancomycin, the median dose (Range) was 5g (4-10). While there were no statistically significant differences in baseline demographics, those who received IW vancomycin were more likely to experience vancomycin induced nephrotoxicity (VIN) compared to those who received usual care (42.9% vs. 0%, P=0.02) (Table 1). Conclusion Our experience with IW vancomycin at a median dose of 5g in combination with VIBCS was associated with an increased risk of nephrotoxicity in our patients. Therefore, re-evaluation of the use of IW vancomycin at these doses is warranted. Disclosures All Authors: No reported disclosures.

A 38-years-old female with an aortic valve replacement presented to an outside hospital (OSH) with fevers and malaise. Blood cultures revealed VRE which was resistant to linezolid, resistant to ampicillin, non-susceptible to daptomycin (MIC of 8 mcg/mL), and exhibited susceptibility to gentamicin. The patient was therefore initiated on intravenous (IV) daptomycin 6 mg/kg q24h and gentamicin IV 1 mg/kg q8h. However, after 14 days of therapy with daptomycin and gentamicin, the patient was transferred to our institution for the management of cardiogenic shock and hypoxemic respiratory failure. Given the concern for treatment failure, her antimicrobial regimen was changed to IV chloramphenicol 12.5 mg/kg every 6 hours with IV daptomycin 10 mg/kg every 48 hours given an estimated creatinine clearance of 30 mL/minutes. In vitro susceptibilities for chloramphenicol were performed which confirmed susceptibility. A transesophageal echocardiogram revealed a possible abscess at the left coronary cusp and aortic valve dehiscence. The patient underwent aortic valve replacement with aortic root reconstruction. The aortic valve culture grew VRE susceptible to linezolid but resistant to ampicillin and doxycycline. The patient was deemed clinically cured after 42 days of combination therapy with daptomycin and chloramphenicol. After 6 years of follow-up, the patient has not had a recurrent VRE infection. To our knowledge, this is the first case of endocarditis secondary to VRE that was successfully managed with the combination of daptomycin and chloramphenicol.

BackgroundThrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain.Research QuestionHow does in-hospital mortality compare with intermediate-versus prophylactic-dose anticoagulation, and separately with in-hospital aspirin versus no antiplatelet therapy, in treatment of COVID-19?Study Design and MethodsUsing data from 2785 hospitalized adult COVID-19 patients, we established two separate, nested cohorts of patients (1) who received intermediate- or prophylactic-dose anticoagulation (“anticoagulation cohort”, N = 1624), or (2) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy (“aspirin cohort”, N = 1956). Propensity score matching utilizing various markers of illness severity and other patient-specific covariates yielded treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death.ResultsAmong propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate-compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]).InterpretationIn this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.Summary conflict of interest statementsNo conflict of interest exists for any author on this manuscript.

Objective:Methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs are utilized to guide the discontinuation of empiric MRSA therapy. In multiple studies, MRSA nasal swabs have been shown to have a negative predictive value (NPV) of ~99% in non-oncology patients with pneumonia and other infections. We evaluated the performance characteristics of a negative MRSA nasal swab in the acute myeloid leukemia (AML) populaion to determine its NPV.Design:Retrospective chart review.Patients:This study included adult AML patients with a suspected infection and a MRSA nasal swab collected between 2013 and 2018.Methods:MRSA nasal swab and culture-documented infections were identified to determine the sensitivity, specificity, NPV, and positive predictive value of the MRSA nasal swabs.Results:In total, 194 patients were identified, and 484 discrete encounters were analyzed. Overall, 468 (97%) encounters had a negative MRSA nasal swab upon admission with no cultured documented MRSA infection during their hospitalization. However, 3 encounters (0.6%) had a negative MRSA nasal swab with a subsequent cultured documented MRSA infection during their admission. Identified infections were bacteremia (n = 2) and confirmed pneumonia (n = 1). MRSA nasal swab had a sensitivity of 62% (95% CI, 0.24–0.91), specificity of 98% (95% CI, 0.96–0.99), positive predictive value of 38% (95% CI, 0.21–0.6), and NPV of 99% (95% CI, 0.98–1).Conclusions:A negative MRSA nasal swab has a 99% NPV for subsequent MRSA infections in AML patients with no prior history of MRSA colonization or infection. Based on these findings, a negative MRSA nasal swab can help guide de-escalation of empiric MRSA antibiotic therapy.

Solid organ transplant recipients are at increased risk of COVID-19-associated morbidity and mortality.We describe a nosocomial outbreak investigation on an immunocompromised inpatient unit.Patients positive for SARS-CoV-2 were identified. An epidemiologic investigation was assisted with whole genome sequencing of positive samples.Two patients were identified as potential index cases; one presented with diarrhea and was initially not isolated, and the other developed hypoxemia on hospital day 18 before testing positive. Following identification of a SARS-CoV-2 cluster, the unit was closed and all patients and staff received surveillance testing revealing eight additional positive patients and staff members. Whole genome sequencing confirmed an outbreak. Enhanced infection prevention practices mitigated further spread. Asymptomatic patients with COVID-19 were successfully treated with bamlanivimab.Preventing SARS-CoV-2 outbreaks in transplant units poses unique challenges as patients may have atypical presentations of COVID-19. Immunocompromised patients who test positive for SARS-CoV-2 while asymptomatic may benefit from monoclonal antibody therapy to prevent disease progression. All hospital staff members working with immunocompromised patients should be promptly encouraged to follow infection prevention behaviors and receive SARS-CoV-2 vaccination.SARS-CoV-2 outbreaks on immunocompromised units can be mitigated through prompt identification of cases and robust infection prevention practices.

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74)

Objectives. Successful treatment for Nocardia thailandica is not well elucidated in the literature. To the best of our knowledge, N. thailandica has not yet been described in the medical literature to cause central nervous system (CNS) infection from brain abscess. We report the case of an immunocompromised patient who underwent successful treatment to treat his brain abscess caused by N. thailandica. Methods. After failing medical therapy, the patient underwent a craniotomy, and tissue was sent for culture. Upon identification by 16S rDNA sequencing, the organism causing infection was identified to be N. thailandica. Results. Based on susceptibilities, the patient was treated with IV ceftriaxone 2 grams daily for five months. The patient demonstrated clinical and radiological improvement which persisted to 7 months after initiation of therapy. Conclusions. To the best of our knowledge, this is the first documented case of a brain abscess due to N. thailandica which was successfully treated. Due to the location of the infection, ceftriaxone was chosen because of optimal CNS penetration. Ceftriaxone monotherapy demonstrated clinical and radiographic treatment success resulting in the successful treatment of this infection.

We describe the case of a 54-year-old male receiving intermittent hemodialysis (iHD) who was found to have Pseudomonas aeruginosa bacteremia secondary to osteomyelitis of the calcaneus bone. The patient was clinically cured without recurrence using a ceftolozane/tazobactam (CTZ) dosing strategy of 100/50 mg every 8 hours (standard dosing) and 1000/500 mg thrice weekly following iHD. Utilizing a susceptibility breakpoint of ≤4 µg/mL for P. aeruginosa, the T > MIC for standard dosing and the 1000/500-mg thrice-weekly following iHD regimen were calculated to be 92.7% and 94.1%, respectively. Ceftolozane total body clearance for the standard q 8 h dosing and the 1000/500-mg thrice-weekly following iHD regimen were calculated to be 0.196 L/h and 0.199 L/h, respectively. To our knowledge, this is the first report to illustrate the administration of CTZ at a dose of 1000/500 mg thrice weekly following iHD.

As medication experts, clinical pharmacists play an active and dynamic role in a medication shortage response. Supplementing existing guidelines with an actionable framework of discrete activities to support effective medication shortage responses can expand the scope of pharmacy practice and improve patient care. Dissemination of best practices and illustrative, networked examples from health systems can support the adoption of innovative solutions. In this descriptive report, we document the translation of published shortage mitigation guidelines into system success through broad pharmacist engagement and the adaption and implementation of targeted strategies. The profound, wide‐reaching medication shortages that accompanied the coronavirus disease 2019 (COVID‐19) pandemic are used to highlight coordinated but distinct practices and how they have been combined to expand the influence of the pharmacy enterprise.

Background The renal transplant population is at increased risk of Nocardiosis due to impaired T-cell mediated immunity with immunosuppression. Pneumocystis jirovecii (PJP) prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX) provides coverage against Nocardia spp. unlike alternative agents such as atovaquone (ATQ), aerosolized pentamidine (AP), and dapsone. During the COVID-19 pandemic, patients receiving AP were transitioned to ATQ to avoid the use of nebulized medication. This, in turn, led to decreased use of TMP/SMX as patients on oral ATQ were not reassessed for the use of TMP/SMX as would have occurred while on AP. Additionally, an increased incidence of Nocardia infections was observed during this time. The objective of this study was to determine the association between the incidence of Nocardia infections and number of TMP/SMX prophylaxis-days in pre- versus COVID-19 cohorts. Methods This was a single center retrospective chart review of all renal transplant recipients between September 2018 – August 2019 (pre-COVID-19 cohort) and April 2020 – March 2021 (COVID-19 cohort). Patients were included if they were at least 18 years of age and a recipient of a cadaveric or living donor kidney transplant. Exclusion criteria included multi-organ transplant, pediatric patients, and repeat transplants. The primary outcome was incidence of Nocardiosis within the first 6 months post-transplant in the pre- and COVID-19 cohorts. Results A total of 218 patients were included (Table 1). Induction therapy and initial immunosuppression did not differ significantly between groups, nor did rates of rejection within 180 days of transplant (Table 2). Although the pre-COVID-19 cohort had a higher rate of neutropenia, there was no difference in median absolute lymphocyte count between the two groups. The COVID-19 cohort had a decreased percentage of TMP/SMX prophylaxis-days (59.2% vs. 72.5%, p < 0.0001) and an increased incidence of Nocardia infections in the first 6 months post-transplant (4% vs. 0%, p=0.0292). All 4 cases of Nocardia infections occurred in patients receiving ATQ. Conclusion The increased incidence of Nocardiosis was associated with a decreased use of TMP/SMX for PJP prophylaxis which may have been an unintended consequence of increased use of ATQ in lieu of AP during COVID-19. Disclosures All Authors: No reported disclosures

This was a multicenter, retrospective study of patients with anaerobic bacteremia comparing metronidazole 500 mg every 8 h versus 500 mg every 12 h. Of 782 patients reviewed, 85 met inclusion criteria. There was no significant difference in mortality, length of stay, or escalation of therapy between dosing strategies.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir., Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of

Introduction: Venous thromboembolism and in-situ small vessel thrombosis are increased in hospitalized patients with COVID-19 in several patient cohorts. Endotheliopathy and activation of both platelets and coagulation predict critical illness and death. For these reasons the use of anti-platelet agents and increased-intensity anticoagulation in the care of hospitalized patients with COVID-19 is under intense study in several clinical trials. We sought to examine the impact of aspirin and anticoagulation on hospitalization outcomes. Methods: We examined outcomes in a large multi-site cohort of consecutive, hospitalized, COVID-19 laboratory confirmed patients under a risk-stratified treatment algorithm from March 13 through June 18, with a focus on efficacy of aspirin and/or increased-intensity anticoagulation. Out of 4150 identified hospitalized patients with COVID-19, we created 3 study cohorts. The overall cohort (2785 patients) excluded pediatric patients, those with incomplete electronic data, and those with multiple admissions. The aspirin (1956 patients) and anticoagulation (1623 patients) cohorts were nested within the overall cohort; the former excluded patients on any home anti-platelet therapy or those who received non-aspirin anti-platelet therapy in the hospital, while the latter excluded patients who did not receive prophylactic or intermediate dose anticoagulation in the hospital. The primary outcome was in-hospital death. Secondary outcomes were time-to-death with a competing risk (time-to-hospital-discharge), escalation to ICU, length-of-stay and use of mechanical ventilation. Variables examined included age, gender, BMI, race, Rothman Index (RI), D-dimer (DD) and patient co-morbidities including cardiovascular disease, chronic kidney disease, and prior VTE. The aspirin and anticoagulation cohorts underwent propensity score (PS) matching utilizing variables found to be significant in multivariable regression modeling in the overall cohort with 638 and 386 patients, respectively. Results: Univariate followed by multivariable regression modeling in the 2785 patient overall cohort established a novel role for RI, and independent roles for age, BMI, and maximum DD, in predicting severity of illness. In all cohorts the 50th and lower percentile of admission RI was predictive of mortality in multivariable modeling (i.e. aspirin: 3rd and 4th admission RI quartiles with HR = 0.18 for both, p Conclusion: We show in a large cohort of consecutively hospitalized patients with COVID-19 treated under a risk-stratified algorithm the prognostic utility of the admission RI in assessing outcomes in hospitalized patients with COVID-19 and a potential benefit of aspirin therapy on in-hospital death from COVID-19. A potential albeit marginal benefit of intermediate dose anticoagulation over prophylactic dose anticoagulation merits further study with results of clinical trials awaited. Figure Disclosures Neuberg: Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Celgene: Research Funding.

Introduction: There is an urgent need for safe and efficacious antiviral drugs to improve outcomes for COVID-19 patients. Understanding SARS-CoV-2 virology can elucidate potential drug targets for ...

Background Tocilizumab, an IL-6 receptor antagonist, can be used to treat cytokine release syndrome (CRS), with observed improvements in a coronavirus disease 2019 (COVID-19) case series. Research Question The goal of this study was to determine if tocilizumab benefits patients hospitalized with COVID-19. Study Design and Methods This observational study of consecutive COVID-19 patients hospitalized between March 10, 2020, and March 31, 2020, and followed up through April 21, 2020, was conducted by chart review. Patients were treated with tocilizumab using an algorithm that targeted CRS. Survival and mechanical ventilation (MV) outcomes were reported for 14 days and stratified according to disease severity designated at admission (severe, ≥ 3 L supplemental oxygen to maintain oxygen saturation > 93%). For tocilizumab-treated patients, pre/post analyses of clinical response, biomarkers, and safety outcomes were assessed. Post hoc survival analyses were conducted for race/ethnicity. Results Among the 239 patients, median age was 64 years; 36% and 19% were black and Hispanic, respectively. Hospital census increased exponentially, yet MV census did not. Severe disease was associated with lower survival (78% vs 93%; P < .001), greater proportion requiring MV (44% vs 5%; P < .001), and longer median MV days (5.5 vs 1.0; P = .003). Tocilizumab-treated patients (n = 153 [64%]) comprised 90% of those with severe disease; 44% of patients with nonsevere disease received tocilizumab for evolving CRS. Tocilizumab-treated patients with severe disease had higher admission levels of high-sensitivity C-reactive protein (120 vs 71 mg/L; P < .001) and received tocilizumab sooner (2 vs 3 days; P < .001), but their survival was similar to that of patients with nonsevere disease (83% vs 91%; P = .11). For tocilizumab-treated patients requiring MV, survival was 75% (95% CI, 64-89). Following tocilizumab treatment, few adverse events occurred, and oxygenation and inflammatory biomarkers (eg, high-sensitivity C-reactive protein, IL-6) improved; however, D-dimer and soluble IL-2 receptor (also termed CD25) levels increased significantly. Survival in black and Hispanic patients, after controlling for age, was significantly higher than in white patients (log-rank test, P = .002). Interpretation A treatment algorithm that included tocilizumab to target CRS may influence MV and survival outcomes. In tocilizumab-treated patients, oxygenation and inflammatory biomarkers improved, with higher than expected survival. Randomized trials must confirm these findings.

Background: Antimicrobial use during end-of-life care of older adults with advanced cancer is prevalent. Factors influencing the decision to prescribe antimicrobials during end-of-life care are not well defined. Aim: To evaluate factors influencing medicine subspecialists to prescribe intravenous and oral antimicrobials during end-of-life care of older adults with advanced cancer to guide an educational intervention. Design: 18-item single-center cross-sectional survey. Setting/participants: Inpatient medicine subspecialists in 2018. Results: Of 186 subspecialists surveyed, 67 (36%) responded. Most considered withholding antimicrobials at the time of clinical deterioration during hospitalization ( n = 54/67, 81%), viewed the initiation of additional intravenous antimicrobials as escalation of care ( n = 44/67, 66%), and believed decision-making should involve patients or surrogates and providers ( n = 64/67, 96%). Fifty-one percent ( n = 30/59) of respondents who conducted advance care planning did not discuss antimicrobials. Barriers to discussing end-of-life antimicrobials included the potential to overwhelm patients or families, challenges of withdrawing antimicrobials, and insufficient training. Conclusions: Although the initiation of additional intravenous antimicrobials was viewed as escalation of care, antimicrobials were not routinely discussed during advance care planning. Educational interventions that promote recognition of antimicrobial-associated adverse events, incorporate antimicrobial use into advance care plans, and offer communication simulation training around the role of antimicrobials during end-of-life care are warranted.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.

Objectives To date, clinical trials evaluating baloxavir have excluded patients hospitalized with influenza infection and therefore this study sought to evaluate the efficacy of baloxavir in inpatients with influenza A. Methods This study was a multicentre, retrospective chart review of adult patients admitted to the hospital within the Yale New Haven Health System who received oseltamivir or baloxavir for the treatment of influenza A. Patients were screened for inclusion between January 2018 and April 2018 in the oseltamivir group, while patients in the baloxavir group were screened for inclusion between January 2019 and April 2019. Influenza A diagnosis was confirmed by RT–PCR using a nasopharyngeal swab specimen. Results Of the 2392 patients assessed, 790 met the inclusion criteria. There were 359 patients who received baloxavir and 431 patients who received oseltamivir. Patients who received baloxavir were younger compared with those who received oseltamivir [median = 69 (IQR = 57–81) years versus 77 (IQR = 62–86) years; P Conclusions The results of this study support the use of baloxavir for the treatment of influenza A in hospitalized patients with the potential benefit of a faster time to resolution of hypoxia.

Purpose Transgender patients face considerable healthcare disparities. Improved means of recognizing transgender patients and understanding their medical needs is important to provide optimal care. The electronic medical record (EMR) of our health system allows for differentiation of gender identity, legal sex, and sex at birth. With EMR recognition of transgender patients, a recommendation for estimating creatinine clearance (CLcr) and ideal body weight (IBW) was needed to standardize medication dosing. Summary The literature was reviewed for evidence on the effect of gender-affirming hormone therapy on serum creatinine concentration and lean body mass. Findings informed a recommendation for drug dosing based on CLcr and IBW in transgender patients. Four studies that reported the effect of hormone therapy on biometric laboratory values were found. Three studies reported that values of transgender patients more closely resembled the standard values of their gender identity vs sex at birth after hormone therapy; 1 study reported a range of values that more closely resembled those associated with sex at birth while still overlapping with values associated with gender identity. Consequently, it was recommended that pharmacists dose medications based on CLcr and IBW calculations consistent with gender identity after a patient has been on hormone therapy for 6 months or longer. Conclusion Providing optimal care to transgender patients includes considering the effect of gender-affirming hormone therapy on overall physiology. Consistently using the appropriate CLcr and IBW calculations for each patient ensures safe and effective care. Additional studies are needed to confirm the effect of hormone therapy on renal clearance and lean body mass.

Background Voriconazole is an azole antifungal utilized for prophylaxis and treatment of invasive fungal infections in hematologic patients. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic 4 mcg/mL levels. A voriconazole dose modification guideline was introduced in July 2014 based on a retrospective analysis. Objective The primary objective was to evaluate the voriconazole dose modification guideline. Secondary objectives were to identify patient-specific characteristics that contribute to inadequate levels, adverse effects, and breakthrough invasive fungal infections. Methods This prospective study included 128 patients with 250 admissions who received voriconazole from July 2014 to February 2016. Eligible adult patients receiving voriconazole for prophylaxis or treatment with at least one trough level, drawn appropriately, were included. Demographics, adverse effects, and breakthrough invasive fungal infections were documented. Results Voriconazole use was categorized as: new start, new start with loading dose, or continuation of home therapy. The median initial levels were 1.5, 3.5, and 1.7 mcg/mL with 62% (73/119), 55% (6/11), and 60% (72/120) within the therapeutic range, respectively. Using the voriconazole dose modification guideline, 80% were within goal by the second dose adjustment. Age ≤ 30 and BMI ≤ 25 kg/m2 had higher rates of subtherapeutic levels in the new start cohorts ( p = 0.024 and p = 0.009). Approximately 7.6% of patients experienced an adverse effect with neurologic/psychological being the most common. A total of 8.5% of patients had a possible, probable or proven breakthrough invasive fungal infections while on voriconazole. Conclusion Using the voriconazole dose modification guideline, the number of patients that reached therapeutic range improved from 36% to 80% by the second dose adjustment ( p = 0.007). This voriconazole dose modification guideline can be utilized to help dose and adjust voriconazole in order to achieve therapeutic levels.

Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

Background Oral antimicrobial therapy for Enterobacteriales bloodstream infection (EB-BSI) is advantageous to reduce the risk of central line complications, cost of care, and length of stay. Fluoroquinolones (FQ) given their high bioavailability have been utilized as the standard for stepdown therapy (SDT) for EB-BSI. Given the recent increased warnings around FQ use including Clostridioides difficile infection (CDI) and the increasing FQ resistance alternative oral options for treatment are warranted. Recent literature has suggested beta-lactams (BLM) may be an option for EB-BSI. To enhance the antimicrobial stewardship goal of reducing FQ use, our team began recommending de-escalation to a BLM for EB-BSI and the objective of this study is to evaluate the outcomes of this approach. Methods This study was a retrospective chart review of patients with EB-BSI due to ceftriaxone sensitive monomicrobial E. coli, Klebsiella spp., or P. mirabilis who received a BLM or a FQ as SDT. Patients were excluded if < 18 years of age; pregnant; ANC < 1000 cells/µL; had endocarditis, a bone/joint, or a CNS infection; discharged to hospice or expired prior to discharge; anaphylactic BLM allergy; or prior kidney transplant. SDT was defined as a switch to a definitive oral antibiotic after empiric IV therapy. The primary outcome was clinical cure defined as completion of therapy without signs of infection (increase in WBC > 2000 cells/mL if WBC was ≥ 12,000 cells/mL, fever (>38°C), or change in antibiotic due to failure). Secondary outcomes included 30 day re-admission rates, reinfection rate defined as positive culture within 30 days of completion of therapy, antibiotic associated adverse events defined as side effects leading to discontinuation and/or CDI within 90 days from start of treatment. Results A total of 159 patients were included in the study (Figure 1). The BLM patients had a higher median age (78 vs 72, p=0.008), higher median PITT bacteremia score (2 vs 1, p=0.037), were less likely to be immunosuppressed (9% vs 25%, p=0.045), and had shorter median duration of therapy (13 vs 14, p=0.034). There was no difference in the primary or secondary outcomes (Table 2). Conclusion BLM may enhance stewardship efforts as a FQ sparing option for treatment of EB-BSI; however, prospective studies in this area are warranted. Disclosures All Authors: No reported disclosures

Objective Vancomycin, a commonly used antimicrobial, has a narrow therapeutic index; therefore, Therapeutic Drug Monitoring (TDM) is required. Although the Electronic Medical Record (EMR) may improve patient care, without appropriate optimization, it can contribute to incorrectly drawn vancomycin levels. For medication administration, nurses utilize the Medication Administration Record (MAR) for medication administration documentation and medication workflow guidance. Therefore, we hypothesized creating a MAR level order which would be incorporated into this already established medication workflow may improve the rate of correctly drawn vancomycin levels. Materials and Methods This was a multicenter, retrospective, pre-and post-intervention study which evaluated the effect of a Medication Administration Record (MAR) level order within the EMR on the correct timing of vancomycin level collection. Vancomycin levels were classified into pre-and post-intervention groups. The primary endpoint was the rate of incorrectly drawn levels, defined as a level being drawn early, a level being drawn late, a level drawn while infusing, or a missed level. Results A total of 1353 vancomycin levels were assessed, and 628 levels met inclusion criteria. Of the levels eligible for inclusion, 331 were in the pre-intervention period and 297 were in the post-intervention period. Levels in the post-intervention group utilizing the vancomycin MAR level order were less likely to be missed or drawn at an incorrect time (11.1 % vs 36 %, P Conclusion Utilization of a vancomycin MAR level order was associated with a significant decrease in incorrectly drawn vancomycin levels.

Norovirus enteritis can cause intractable diarrhea in solid organ transplant (SOT) recipients, for which there are no established treatments. We reviewed medical records of 9 SOT recipients at our center who received orally administered human immunoglobulin for norovirus enteritis, and it appeared to be an effective treatment modality.

A 55-year-old female with a past medical history of cocaine use and hypertension was admitted for intracranial hemorrhage requiring right decompressive craniotomy with duraplasty. Due to persistent fevers, a head CT scan obtained on day 28 of hospitalization identified a low-density subgaleal fluid collection overlying the duraplasty. Aspiration of this collection was sent for culture which grew 2+ Enterobacter cloacae complex susceptible to sulfamethoxazole-trimethoprim (SMX-TMP), gentamicin, ciprofloxacin, and ertapenem. Based on these results, the patient was transitioned from empiric vancomycin and ceftazidime to SMX-TMP and metronidazole. Despite treatment with SMX-TMP and metronidazole, aspirated subgaleal collection cultures remained positive for E. cloacae. Intrathecal gentamicin was therefore added; however, repeat subgaleal culture collections remained persistently positive. Given the persistently positive subgaleal culture collections, the patient was transitioned from SMX-TMP and metronidazole to ertapenem. After transition to ertapenem, subgaleal cultures were sterilized and the patient’s infection was resolved. This report suggests ertapenem may be a viable option for central nervous system infections; however, further study is needed.

A retrospective study was conducted to evaluate the value of the antimicrobial stewardship team (AST) combined with infectious diseases consultation (IDC) on management and outcomes of Staphylococcus aureus bacteremia (SAB) in a tertiary-care academic center. Involvement of AST or IDC was associated with reduced mortality of SAB.

Mucormycosis is a life threatening infection caused by fungi in the order Mucorales. Mucormycosis can affect any organ system with rhino-orbital-cerebral and pulmonary infections being the most predominant infection types. Gastrointestinal mucormycosis is rare and accounts for only 4–7% of all cases. Here, we present a case of invasive gastrointestinal mucormycosis in an immunocompromised host treated with systemic and topical anti-mold therapy.

Background Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data. Methods The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions. Results Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities. Conclusion De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections. Disclosures All Authors: No reported disclosures