Abstract Background Beta-lactam allergy (BLA) is associated with increased broad-spectrum antibiotic (Br-ABX) use, worse clinical outcomes, and higher costs. Our hospital-wide BLA protocol (BLA-P) was launched in 7/2021 with following categories: intolerance, low-risk (urticaria only >5 years ago, mild rash, remote childhood reaction with limited details), and high-risk (angioedema, anaphylaxis, severe rashes). Delabeling was done directly based on antibiotic history/interview alone (direct-delabeling), or via graded challenge for low-risk patients. We evaluated the delabeling rate and its impact on Br-ABX usage. Methods Hospitalized patients ≥ 18 years old with listed BLA during 10/2021-12/2022 were eligible. Exclusion criteria were critically ill, surgical, hospice or comfort care, or non-verbal patients. Assessment was counted each time a pharmacist evaluated BLA; multiple assessments could occur in case of prolonged hospital stay or multiple admissions. Interventions were categorized as no further action (due to high-risk allergy, patient refusal for any update, clinical status), updated allergy label, or delabeled. Missed assessments were reported due to logistical issues. Br-ABX usage was compared in the delabeled patients: the empiric antibiotic use 90 days post-intervention versus pre-intervention using McNemar test (SPSS). Results A total of 700 assessments in 631 unique patients with BLA were identified (Figure 1). 556 assessments in 489 unique patients (median age 63 years, 41% male, 46% hematological cancer) met inclusion criteria. In this cohort, the assessments revealed 8% intolerance, 54% low-risk, 17% high-risk and 21% unknown allergy. Interventions resulted in no further action 7%, updated label 72%, and delabeling 21%. 65% of the delabeling was done via direct-delabeling and 35% via graded challenge (Figure 1). Passing rate with graded challenge was 97%. The use of aztreonam and meropenem decreased significantly in delabeled patients compared to pre-delabeling while cefepime and piperacillin-tazobactam usage increased (Table 1). Conclusion Implementation of BLA-P led to 21% delabeling, which resulted in increased use of preferred Br-ABX and a significant decrease in meropenem and aztreonam use. Disclosures Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria Randy Taplitz, MD, Karius: Advisor/Consultant|Merck: Advisor/Consultant|SNIPR biome: Advisor/Consultant

Patients living with HIV are now living longer due to increased access to antiretroviral therapy (ART) and a decrease in AIDS-defining cancer (ADC). However, increasing age and previous chemotherapy exposure for ADC (e.g, anthracyclines, and topoisomerase inhibitors) are factors that may increase the risk in developing therapy-related myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and highlight an unmet need. There are no established guidelines for the treatment of AML in patients with HIV and the literature is limited to treatment outcomes and experience. In addition, cladribine, a purine analogue used in AML has a package insert warning to avoid administration with concurrent agents that undergo phosphorylation, which include HIV ART backbones (e.g, NRTI – nucleoside reverse transcriptase inhibitors). Whether concurrent NRTI based ART is deliverable with AML induction chemotherapy has not been reported previously. In our single center experience of seven HIV-AML patients, all patients continued concurrent ART with induction chemotherapy. In six evaluable patients, three (50%) of patients went into complete remission. Five (71.4%) patients were able to proceed to allogenic transplant (HCT). Median OS was 16.6 months, with patients who received HCT having longer median OS compared to those who were unable to proceed to HCT (49.6 months vs. 3.4 months). Interestingly, none of the patients who received AML regimens that included fludarabine were able to obtain a response. On the contrary, four patients who received AML regimens that utilized cytarabine given over a prolonged period of time (e.g. 7+3, liposomal daunorubicin/cytarabine) achieved a CR rate of 75%. Concurrent HIV ART and AML induction chemotherapy is deliverable, although much remains to be investigated on potential drug interactions between purine analogue based chemotherapy and HIV ART.

Abstract Background HSV reactivation (HSVr) is frequent in HM and SOM patients while oropharyngeal/ mucocutaneous infections (OP-MCI) and especially HSV pneumonitis (HSVP) are uncommon. BALF-HSV-PCR can identify shedding or disease, however, may result in inappropriate high dose antiviral usage in non-HSVP situations. We report a cohort of patients with positive BALF-HSV-PCR, its impact on antiviral usage and role of IDC on antiviral use. Methods Retrospective chart review of BALF-HSV-PCR positive patients who had IDC between 1/1/2018 and 8/31/2022. Exclusion criteria: No chest imaging (CT scan or chest X-ray imaging within ±7 days of positive test) and no malignancy. Data collection: demographics, laboratory and clinical findings, and antiviral medication dosing before and after each positive BALF-HSV-PCR preceding the IDC. Clinical diagnosis and treatment of HSVP versus non-HSVP was based on IDC. Kruskal-Wallis tests was used for continuous variables and Fisher’s exact test for categorical variables, and p-values reported were 2-sided at significance level of 0.05.Table 3.Impact of BALF HSV PCR and IDC on Antiviral use. PPX=prophylaxis, Y=yes, N=No; ACV=acyclovir Results One-hundred-nine patients met inclusion criteria. Nineteen (17.4%) had HSVP, 90 (82.6%) non-HSVP. In non-HSVP; 83 (92%) had oropharyngeal shedding (HM >SOM), 6 (6%) OP-MCI and 1 (1%) immunotherapy related pneumonitis (IrP). Tables 1-3 provide details on demographics and baseline characteristics, antiviral use, and statistical analysis. HSV shedding/ disease (HSVP and OP-MCI) was more common in HM patients. All HSVP patients received high dose antiviral agents. Of ninety patients determined as non-HSVP, 42% were overtreated with antivirals with a positive test that preceded IDC. Positive PCR led to change in antiviral dose (p < 0.05) with highly significant impact on the dose of acyclovir used (prophylaxis vs. OP-MCI vs. HSPV doses) (p< 0.0001). IDC led to modification of HSVP dosing to either prophylaxis or complete discontinuation in 84.2% of patients (p=0.008). Conclusion BALF-HSV-PCR positive test without HSVP led to overtreatment in both HM and SOM patients that is preventable by IDC, underscoring its value in antiviral stewardship. Diagnostic stewardship can further limit inappropriate use of antivirals. Disclosures Randy Taplitz, MD, Karius: Advisor/Consultant|Merck: Advisor/Consultant|SNIPR biome: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria

Patients living with HIV are now living longer due to increased access to antiretroviral therapy (ART) and a decrease in acquired immunodeficiency syndrome-defining cancer (ADC). However, increasing age and previous chemotherapy exposure for ADC (e.g., anthracyclines and topoisomerase inhibitors) are factors that may increase the risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (AML) and highlight an unmet need. There are no established guidelines for the treatment of AML in patients with HIV and the literature is limited to treatment outcomes and experience. In addition, cladribine, a purine analog used in AML, has a package insert warning to avoid administration with concurrent agents that undergo phosphorylation, which include HIV ART backbones (e.g., nucleoside reverse transcriptase inhibitors [NRTI]). Whether concurrent NRTI-based ART is deliverable with AML induction chemotherapy has not been reported previously. In our single-center experience of seven HIV-AML patients, all patients continued concurrent ART with induction chemotherapy. In 6 evaluable patients, three (50%) of patients went into complete remission (CR). Five (71.4%) patients were able to proceed to allogenic hematopoietic stem cell transplantation (HCT). Median OS was 16.6 months, with patients who received HCT having longer median OS compared to those who were unable to proceed to HCT (49.6 months vs. 3.4 months). Interestingly, none of the patients who received AML regimens that included fludarabine were able to obtain a response. On the contrary, 4 patients who received AML regimens that utilized cytarabine given over a prolonged period of time (e.g., 7 + 3, liposomal daunorubicin/cytarabine) achieved a CR rate of 75%. Concurrent HIV ART and AML induction chemotherapy is deliverable, although much remains to be investigated on potential drug interactions between purine analog-based chemotherapy and HIV ART.

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3–12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4+ T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty®-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations.

Abstract Introduction In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild‐to‐moderate COVID‐19 at high risk for disease progression. Methods We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. Results Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab‐imdevimab. Four (11%) patients were hospitalized due to COVID‐19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID‐19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS‐CoV‐2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7–138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12–42). We observed a significant difference in hospitalization among patients who received a HCT versus non‐HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01). Conclusions This study demonstrates that SARS‐CoV‐2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients.

Background COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. Methods This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18-54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m(2) or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1.0 x 10(7) plaque-forming units (PFU; low dose), 1.0 x 10(8) PFU (medium dose), and 2.5 x 10(8) PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466. Findings Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p<0.0001 vs placebo for each comparison). Four times or more increase in SARS-CoV-2 neutralising antibodies within 56 days was measured in nine of 17 participants in the low-dose COH04S1 group, all eight participants in the medium-dose COH04S1 group, and eight of nine participants in the high-dose COH04S1 group (p=0.0035 combined dose levels vs placebo). Post-prime and post-boost four times increase in spike-specific or nucleocapsid-specific T cells secreting interferon-gamma was measured in 48 (98%; 95% CI 89-100) of 49 participants who received at least one dose of COH04S1 and provided a sample for immunological analysis. Interpretation COH04S1 was well tolerated and induced spike-specific and nucleocapsid-specific antibody and T-cell responses. Future evaluation of this COVID-19 vaccine candidate as a primary or boost vaccination is warranted. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here, we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by reverse transcriptase polymerase chain reaction on day = 1 of matched unrelated donor (SARS-CoV-2 immunoglobulin G negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient's nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2-specific T cells, starting early after transplant was unexpected, and in combination with the clinical strategy, may have contributed to the favorable outcome. Additionally, it is plausible that preexisting cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.

Abstract Background Pneumonia is the most common infectious cause of morbidity and excess mortality complicating hematopoietic cell transplantation (HCT) and treatment of hematologic malignancy. Standard bronchoscopic and noninvasive microbiologic testing identify causative pathogens in less than half of cases. The Karius Test, a plasma next-generation sequencing assay of microbial cell-free DNA, may improve diagnostic yield in these patients. Methods Patients with active hematologic malignancy or recent HCT undergoing bronchoscopy for suspected pneumonia were prospectively enrolled in this observational study conducted at 10 United States medical centers. A panel of expert clinicians blinded to Karius Test results reviewed a standardized panel of microbiologic and molecular testing from bronchoalveolar lavage and blood samples for bacterial and fungal testing, nasopharyngeal swab for respiratory viral testing, imaging results, clinical documentation, and any additional microbiologic or molecular testing collected per usual standard of care to adjudicate a probable cause of pneumonia. The panel then adjudicated whether a probable cause of pneumonia or other clinically relevant infection was identified by the Karius Test. Results Between January 3, 2020 and February 4, 2022, 257 patients were enrolled. A planned interim analysis of the first 69 sequentially enrolled patients in the per protocol population was conducted. An adjudicated probable cause of pneumonia was identified by standard care in 18/69 (26%) patients. The Karius Test identified an adjudicated probable cause of pneumonia in 10/51 (20%) patients when no cause of pneumonia was identified by standard care testing. The combination of standard care and the Karius Test together identified a probable cause of pneumonia in 28/69 (41%) patients. At least one additional pathogen adjudicated as a probable cause of pneumonia was identified by the Karius Test in 6/18 (33%) of patients with positive standard care testing. Conclusion The Karius Test notably increased the probability of identifying a pathogenic cause of pneumonia among immunocompromised patients undergoing bronchoscopy. The additive diagnostic value of the Karius Test may significantly enhance management of this common condition. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support Radha Duttagupta, PhD, Karius Inc: Stocks/Bonds Sanjeet S. Dadwal, MD, FACP, FIDSA, AlloVir: Advisor/Consultant|AlloVir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope: Advisor/Consultant|Aseptiscope: Stocks/Bonds|Astellas: Speaker's Bureau|Cidara: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Speaker's Bureau|Takeda: Speaker's Bureau Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Ghady Haidar, MD, Karius, Allovir, and AstraZeneca: Grant/Research Support Alfred Luk, MD, Karius: Grant/Research Support Jamie Todd, MD, Altavant Sciences: Advisor/Consultant|AstraZeneca: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|CareDx: Grant/Research Support|Cellarity: Advisor/Consultant|Natera: Advisor/Consultant Genovefa Papanicolaou, MD, AlloVir: Board Member|AlloVir: Serve as member of DSMC|Amplyx: Board Member|Amplyx: Serve as member of DSMC|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Investigator for Merck|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Board Member|Octapharma: Serve as EAC member|Partners RX: Advisor/Consultant|SymBio: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Takeda: Investigator for Takeda|Vera: Board Member|Vera: Serve as member of DSMC Elena Nemirovich-Danchenko, MD PhD, Karius: Stocks/Bonds Mona Mughar, BS, Karius: Stocks/Bonds Sudeb Dalai, MD, Karius: Stocks/Bonds Sudeb Dalai, MD, Karius: Stocks/Bonds Yuen Cho, MS, CLS(CA-DPH), Karius: Stocks/Bonds Asim A. Ahmed, MD, Karius: Employee|Karius: Stocks/Bonds Desiree Hollemon, MSN, MPH, Karius: Stocks/Bonds David K. Hong, MD, Janssen Pharmaceutical Companies of Johnson & Johnson: Employee|Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Marla Lay Vaughn, BS, MT(ASCP), Karius: Employee|Karius: Stocks/Bonds Tim Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Zivjena Vucetic, MD, Karius: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Rina Romano, BS, Karius Inc: Stocks/Bonds|Karius Inc: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Thomas L. Holland, MD, Aridis: Advisor/Consultant|Lysovant: Advisor/Consultant.

s / Transplant Cell Ther 28 3S (2021) S1–S509 S359

Invasive aspergillosis (IA) is a serious fungal infection that primarily affects patients with prolonged and profound neutropenia, and compromised cell-mediated immunity. Aspergillosis of the oesophagus and gastrointestinal tract is uncommon but seen in advanced cases of disseminated IA. However, it is difficult to diagnose antemortem due to the poor specificity of the symptoms and the absence of characteristic imaging findings. Therefore, the reported cases of gastrointestinal aspergillosis have been associated with high morbidity and mortality, and frequently diagnosed postmortem. Here we present a successful outcome in a patient with relapsed and refractory multiple myeloma who had presented with febrile neutropenia, cough and dysphagia, and was diagnosed with disseminated IA comprising of pulmonary and oesophageal involvement. This case highlights the need for a high index of suspicion and the importance of invasive procedures for histopathology and molecular diagnostics to ensure an early diagnosis and therapeutic intervention.

Histoplasmosis-associated hemophagocytic lymphohistiocytosis is a rate but lethal disease in immunocompromised hosts. Unusual clinical presentations make diagnosing invasive fungal infection even more challenging. Here we present a case of hemophagocytic lymphohistiocytosis secondary to progressive disseminated histoplasmosis presenting as cellulitis in a patient with systemic lupus erythematous. A high index of suspicion combined with histopathology and molecular diagnostic techniques are important to establish an accurate and timely diagnosis of opportunistic infections in immunocompromised patients.

PURPOSE:Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. METHODS:We performed a retrospective study (range 01/2008 - 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses. RESULTS:Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p < 0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (> 5 mg/day) at 1-year follow-up. CONCLUSIONS:Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival.

Abstract Background Pneumocystis jirovecii, an ubiquitous fungus, can lead to opportunistic pneumonia (PJP) in patients with hematological malignancies (HM) and hematopoietic cell transplantation (HCT) with mild to severe presentation. Unlike patients with HIV, diagnosis of PJP pneumonia is often challenging in patients with HM/HCT possibly related to lower fungal burden versus atypical presentation. The gold standard for diagnosis of PJP from bronchoalveolar lavage fluid (BALF) is cytology, followed by direct fluorescent antigen (DFA), however, in the context of lower fungal burden, quantitative polymerase chain reaction (PCR) is increasingly used. PCR DNA load cut-off for diagnosis of PJP is not established. The objective of this study is to assess the correlation between three tests (cytology, DFA and PCR) and diagnosis of PJP (colonization, possible, probable or proven infection). Methods In this retrospective study at City of Hope, HM/HCT patients with BALF performed to investigate pneumonia who tested positive for any of the 3 tests were included. The study period is from July 2014 to July 2020. All patients had a clinical and radiographic diagnosis of pneumonia. Results Eighty-five patients were identified to have at least one positive diagnostic test for PJP. Twenty (23.5%) patients had a PCR with less than 84 copies/mL, and colonization was suspected in these patients. Of the remaining 65 patients, 46 had all 3 tests done. Twenty seven (58.7%) patients only had positive PCR ranging from 106 to 588,000 copies/mL with negative DFA and cytology. Twelve (26.1%) patients had either DFA or cytology positive with a positive PCR, and in 6 patients (13%) all 3 tests were positive. All of these 18 patients had clinical presentation and radiographic findings consistent with PJP. Quantitative or qualitative serum beta-D-glucan (BDG) level was available in 28 patients and 17 had a positive test with a level >80 pg/ml. Conclusion PJP PCR is a very sensitive test that can lead to early detection of PJP pneumonia in HM/HCT with lower sensitivity of DFA/cytology unless the fungal burden is high. However, the optimal cut off PCR value associated with disease needs to be clinically validated in our patient population and a concurrent serum BDG level can increase diagnostic yield. Disclosures All Authors: No reported disclosures

Prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) prevents Pneumocystis jirovecii pneumonia and nocardiosis in immunocompromised patients but sometimes is avoided because of purported allergies or side effects. Of 25 immunocompromised patients receiving alternative prophylaxis in whom nocardiosis developed, 16 subsequently tolerated TMP/SMX treatment. Clinicians should consider TMP/SMX allergy evaluation and rechallenging to assess patient tolerance.

Abstract Background In patients (pts) with cancer, the risk of Pneumocystis jirovecii pneumonia (PJP) is a function of dose and duration of corticosteroids (CS), underlying immunodeficiency, and immunosuppressive drugs. Trimethoprim/sulfamethoxazole (TMP/SMX) and atovaquone (ATO) are effective prophylaxis (ppx) agents against PJP. Guidelines recommend PJP ppx for pts on > 20 mg /day of prednisone or its equivalent for ≥ 1 month. A best practice alert (BPA) to identify pts receiving CS may assist with improving PJP ppx prescribing in cancer pts. Methods PJP BPA was created to identify pts on CS (excluding hydrocortisone) with no active prescription for TMP/SMX or ATO ppx in EMR. Dapsone and pentamidine excluded since not preferred agents at our institution. PJP case: positive PJP polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) > 84 copies or positive PJP direct fluorescent antibody (DFA) or cytology with clinical and radiographic suspicion. PJP PCR from BAL < 84 copies/ml with negative DFA and cytology excluded. Preventable PJP (P-PJP): pts after CS > = 30 days without PJP ppx. Non-preventable PJP (NP-PJP) : pts after CS < 30 consecutive days, or on PJP ppx (non-compliance, failure), or day +1 to +30 post hematopoietic cell transplant (HCT). Pre-intervention (pre-i) PJP pts 3/1/2018 to 7/31/19 (17 months), post-intervention (post-i) PJP pts 8/1/19 to 2/1/20 (18 months) evaluated to assess BPA impact on PJP inpatient (inpt) admissions. Results In the post-i, the BPA fired 3,588 times in 1,302 pts. Pre-i: 20 P-PJP, 13 NP-PJP out of 33 pts. Post-i: 6 P-PJP, 25 NP-PJP out of 31 pts. The BPA fired in 4/31 PJP pts in the post-i period: 2/6 of P-PJP, 2/25 NP-PJP. The number of P-PJP decreased from 20 to 6 in the post-i period (p=0.0097). Conclusion Implementation of a decision support tool significantly decreased the number of P-PJP. The BPA was limited by identifying pts after CS were prescribed after the initial visit leading to periods of CS use without ppx and inability to calculate CS dosing and length of prescription. BPA provided passive education in the outpatient setting and future opportunities include refining the EMR to better identify pts at risk for developing PJP. Disclosures All Authors: No reported disclosures