BACKGROUND:Cytomegalovirus (CMV) is an opportunistic pathogen that causes infection in certain immunocompromised hosts, but the risk of clinically significant CMV infection in patients with multiple myeloma (MM) is not well understood. PATIENTS AND METHODS:We conducted a prospective observational study of CMV reactivation in CMV seropositive patients with MM who were receiving anti-CD38 and B-cell maturation antigen (BCMA) targeted therapies to characterize the rate of viral reactivation and clinically significant infection. We monitored CMV PCR biweekly for 12 weeks in patients with newly diagnosed and relapsed MM receiving these agents. The primary endpoint was CMVPCR ≥500 IU/mL; secondary endpoints included any detectable CMV viremia, CMV end-organ disease, and overall survival. An Anderson-Gill Cox model for recurrent events was used to model detectable CMV viremia at each visit, and a swimmer plot was used to present biweekly follow-up data for patients with CMV detection. RESULTS:We included 40 patients, including 15 patients with newly diagnosed MM and 25 patients with relapsed MM. Three participants (7.5%) developed CMV viremia ≥ 500 IU/mL during follow-up, and 24 additional patients had CMV detection below that threshold. One patient received preemptive treatment with valganciclovir for asymptomatic viremia, but there was no symptomatic CMV infection, end-organ disease or mortality during study follow-up. In multivariate analysis, lagged lymphopenia (low absolute lymphocyte count at preceding visit), prior CMV infection, relapsed disease (compared to newly diagnosed MM), and younger age were associated with a higher risk of CMV detection. CONCLUSION:Low-level CMV detection occurs frequently in patients with MM receiving agents targeting CD38 and BCMA, but viremia is usually self-limited, and in our study cohort, there was no symptomatic CMV infection despite relatively high rates of CMV detection.

Abstract Background The landscape of multiple myeloma (MM) treatment has shifted over the past decade, leading to increased cumulative immunosuppression as patients live longer and receive treatment for multiple relapses. Newer MM therapies, including anti-CD38 and BCMA directed agents, impact cell-mediated immunity. We hypothesized that patients receiving such therapies are at risk of CMV infection and we launched a prospective pilot study to assess CMV incidence in this population.Table 1:Characteristics of CMV reactivation among patients with multiple myeloma Methods Eligible patients included seropositive adults with MM undergoing treatment with anti-CD38 or anti-BCMA therapies. Plasma CMV PCR was monitored every 14 days (+/- 7 days) for three months (Cobas 6800 System, limit of quantification 34.5 IU/mL). The primary endpoint was CMV viral load >500 IU/mL. Treating providers were blinded to results unless CMV PCR was sent outside of the study for clinical reasons.Figure 1:Proportion with CMV > 500 IU/mL during follow-up period Results Twenty-two patients had data available at the time of interim analysis. Eleven (50%) patients received anti-CD38 containing regimens (10 daratumumab, 1 isatuximab), 5 (23%) received anti-BCMA bispecific antibody, and 6 (27%) received BCMA-targeted CAR-T. Eight (36%) patients had newly diagnosed MM and 14 (64%) had relapsed disease. Among relapsed patients, median prior lines of chemotherapy was 4 (range 1-13). Nine (41%) patients had prior autologous stem cell transplant. Fourteen (64%) patients had detectable CMV DNA, but CMV viral load remained < 34.5 IU/mL in the majority (8/14, 57%). Only three (13.6%) patients had CMV viral load >500 IU/mL, including one asymptomatic CAR-T cell recipient who received valganciclovir. Median duration of DNA-emia was 2 weeks (range 1-15). There was a trend toward more DNA-emia in subjects with newly diagnosed compared to relapsed MM (88% vs 29%, HR 2.58 [95% CI 0.86-7.79], p=0.0758). Previous history of CMV infection was also associated with CMV reactivation during the study (HR 5.54 [95% CI 1.36 - 22.48], p=0.0063). There were no patients with end-organ CMV disease and no mortality during the study.Figure 2:Proportion with any CMV DNA detection during follow-up period Conclusion Low-level CMV reactivation occurs frequently in patients with MM receiving anti-CD38 and BCMA therapies, but clinically significant CMV infection remains uncommon. Future studies should also evaluate the impact of subclinical CMV DNA-emia on oncologic outcomes.Figure 3:Proportion with any CMV DNA detection, stratified by prior MM treatment Disclosures Emily Baneman, MD, Merck: Grant/Research Support Samantha E. Jacobs, MD, MS, Ansun Biopharma: Advisor/Consultant|Eurofins, Viracor, LLC.: Grant/Research Support

Abstract Background Hematopoietic cell transplant (HCT) recipients and patients with acute leukemia are at high risk of Gram-negative bacteremia during neutropenia. Fluoroquinolone (FQ) prophylaxis is used to prevent bacterial infections during neutropenia, but the impact of colonization with FQ-resistant Enterobacterales (FQRE) on its effectiveness is unclear. Methods Adult patients undergoing HCT or receiving induction chemotherapy for acute leukemia were enrolled at 10 U.S. centers from 2021 to 2023. Patients received FQ prophylaxis during neutropenia. Perianal swabs were collected within 4 days of initiating chemotherapy or during the week before HCT, and underwent selective broth enrichment culture for FQRE. Isolates underwent antimicrobial susceptibility testing by disk diffusion. Risk factors for FQRE colonization were identified and infections prior to neutrophil recovery were compared between FQRE-colonized and non-colonized patients. Results Among 784 patients (376 allogeneic HCT recipients, 291 autologous HCT recipients, and 117 receiving chemotherapy for acute leukemia), 81 (10.3%) were colonized with FQRE. Risk factors for FQRE colonization were non-White race, prior HCT, receipt of a β-lactam or any antibacterial agent within last 3 months, and having prior detection of FQRE or a 3rd-generation cephalosporin-resistant Enterobacterales (Table 1). Of the 87 colonizing FQRE isolates (Escherichia coli: n=71; Klebsiella pneumoniae: n=12), 33% were susceptible to trimethoprim-sulfamethoxazole, 53% to amoxicillin-clavulanate, and 66% to cefpodoxime (Figure 1). FQRE-colonized patients had increased risk of bloodstream infections (BSIs) due to any Gram-negative bacteria (28.4% vs. 3.6%; p< 0.001) and FQRE (23.5% vs. 1.6%; p< 0.001) compared to non-colonized patients (Figure 2). They also had an increased risk of infections other than BSIs (12.3% vs. 4.0%; p=0.003) and intensive care unit admissions (12.3% vs. 4.2%; p=0.005) prior to neutrophil recovery, but similar 90-day mortality (4.9% vs. 4.0%, p=0.6). Conclusion Screening for FQRE colonization identifies patients at high risk of Gram-negative bacteremia following FQ prophylaxis. Alternate infection prevention strategies are needed in FQRE-colonized patients. Disclosures Catherine Liu, MD, Pfizer: Grant/Research Support Sarah B. Doernberg, MD, MAS, Basilea Pharmaceutica: Grant/Research Support|F2G Limited: Grant/Research Support|Genentech: Advisor/Consultant|Gilead Biosciences: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Regeneron, Inc: Grant/Research Support|Shinogi: Grant/Research Support Scott D. Rowley, MD, COTA: Stocks/Bonds (Private Company)|Genetic Testing Cooperative: Stocks/Bonds (Private Company)|SirPant Immunotherapeutics: Advisor/Consultant 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 David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support Samantha E. Jacobs, MD, MS, Ansun Biopharma: Advisor/Consultant|Eurofins, Viracor, LLC.: Grant/Research Support Thomas J. Walsh, MD, PhD (Hon), FIDSA, FAAM, FECMM, Abbott Laboratories: Advisor/Consultant|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|Cape Cod Associates: Advisor/Consultant|F2G: Advisor/Consultant|F2G: Grant/Research Support|Omeros: Advisor/Consultant|Omeros: Grant/Research Support|Partner Therapeutics: Advisor/Consultant|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Statera: Advisor/Consultant|T2 Biosystems: Advisor/Consultant|T2 Biosystems: Grant/Research Support Henry Chambers, MD, Merck: Stocks/Bonds (Private Company)|Moderna: Stocks/Bonds (Private Company) Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) Lars Westblade, PhD, Accelerate Diagnostics, Inc: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Element Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Roche Molecular Systems, Inc.: Advisor/Consultant|Roche Molecular Systems, Inc.: Grant/Research Support|Selux Diagnostics, Inc.: Grant/Research Support|Shionogi, Inc: Advisor/Consultant|Talis Biomedical: Advisor/Consultant Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support

We implemented a policy to discontinue empiric antibiotics after 48 hours of defervescence in neutropenic fever with no identified clinical/microbiologic infection. Among patients with acute myeloid leukemia or hematopoietic stem cell transplant, early de-escalation was not associated with increased subsequent infection, decompensation, or mortality, supporting its safety and feasibility.

BACKGROUND:Although infections are a leading cause of morbidity and mortality among patients with multiple myeloma (MM), the epidemiology of invasive fungal disease (IFD) is less well characterized in this population than in other hematologic malignancies. METHODS:We conducted a nested 3:1 case-control study of IFD at a large MM referral center to identify risk factors for IFD in this population. RESULTS:In a cohort of 2960 patients, we identified 32 episodes of IFD among 31 patients between 01/2011 and 06/2019. There was a median of 3.6 years from MM diagnosis to IFD, and patients had a median of four lines of chemotherapy (range 1-12) before IFD. Seventeen (53%) had previous autologous hematopoietic cell transplants. At the time of IFD, 23 (72%) had progressive disease status. Fifteen (47%) and 13 (41%) had severe neutropenia and lymphopenia, respectively, and 18 (56%) had hypogammaglobulinemia. Microbiologic etiologies included Aspergillus (n = 18), Candida (n = 6), Cryptococcus (n = 3), Mucorales (n = 3), Histoplasma (n = 1), and undetermined organism (n = 1). In the case-control analysis, progressive disease status (OR 1.35, p = 0.02) and neutropenia (OR 17.5, p = 0.02) were significant risk factors for IFD. In addition, ≥3 prior lines of chemotherapy trended toward statistical significance (OR 5.6, p = 0.07). CONCLUSION:This is the largest detailed description of IFD epidemiology in MM patients and the largest controlled analysis of risk factors in this population. Overall, the risk of IFD was low.

Background Immunocompromised patients who do not respond to vaccination are at increased risk of SARS-CoV-2 infections, including hospitalization and death. Tixagevimab/cilgavimab is a monoclonal antibody combination that has been shown to reduce the risk of SARS-CoV-2 infection. We aimed to assess the incidence and outcomes of COVID-19 among severely immunocompromised patients who received tixagevimab/cilgavimab for pre-exposure prophylaxis (PrEP) during the period when the Omicron variant was the dominant circulating variant. Methods We conducted a retrospective cohort study of vaccinated, severely immunocompromised adults who received at least 1 dose of tixagevimab/cilgavimab for SARS-CoV-2 PrEP. The study specifically evaluated those who did not mount an immune response to vaccination, as indicated by a negative anti–spike immunoglobulin G. Results Seventy-one patients (20.3%) developed breakthrough COVID-19 after tixagevimab/cilgavimab administration. Among patients who developed breakthrough infection with COVID-19, 70 (98.6%) had mild disease and were treated as outpatients. Conclusion Our study suggests that tixagevimab/cilgavimab may be efficacious for vaccinated severely immunocompromised patients. Developing a universal vaccine and other long-acting monoclonal antibodies for PrEP in immunocompromised patients against all SARS-CoV-2 variants, as well as potential emerging coronaviruses, holds promise for combating future outbreaks.

Abstract Background Cancer patients with neutropenic fever are frequently continued on broad-spectrum empiric antimicrobial therapy (EAT) until neutrophil recovery, but recent randomized trials demonstrate that EAT de-escalation prior to neutrophil recovery is safe in certain subgroups. We evaluated outcomes of EAT de-escalation based on clinical criteria in patients with neutropenic fever at our institution. Methods We retrospectively reviewed charts of 49 patients with acute myeloid leukemia (AML) or hematologic stem cell transplantation (HSCT) and neutropenic fever following revisions to Standard of Practice (SOP) institutional guidelines (hereafter “SOP” group) allowing for antibiotic de-escalation using a clinical approach in comparison to a historic cohort of 60 patients. The revised SOP recommended antibiotic de-escalation to levofloxacin prophylaxis in patients who received ≥ 72 hours of EAT, were afebrile and clinically stable for 48 hours, and did not have a clinically or microbiologically documented infection. The primary endpoint was the EAT duration. Secondary end points included incidence of recurrent fever, infections, vasopressor support and/or intensive care unit (ICU) stay, and in-hospital mortality. Results Baseline characteristics were similar between both groups, with differences including a larger proportion of males in the SOP group compared to the control group (59% vs. 35%) and the primary underlying malignancy of multiple myeloma in the SOP group compared to AML in the control group. The median duration of EAT prior to de-escalation was shorter in the SOP group compared to the historic cohort (5.0 [IQR 4.0, 6.0] vs. 7.0 days [IQR 5.0, 10.2], p< 0001). There was no difference in incidence of recurrent fever (20% vs. 30%, p=0.3) or secondary infection (10% vs. 12%, p=0.8). Incidence of vasopressor support and/or ICU stay(10% vs. 3.3%, p=0.2) and in-hospital mortality (2.0% vs. 3.3 %, p >0.9) were also similar between both groups. Conclusion Our study indicates that our new institutional guidelines successfully lead to reduced broad spectrum antimicrobial exposure without increased infections, ICU stays, or mortality. Thus, de-escalation of EAT based on clinical criteria is safe in this high risk patient population. Disclosures Douglas Tremblay, MD, AbbVie: Advisor/Consultant|Astellas: Grant/Research Support|Cogent Biosciences: Advisor/Consultant|Cogent Biosciences: Grant/Research Support|Gilead: Grant/Research Support|GSK: Advisor/Consultant|Novartis: Advisor/Consultant|Sierra Oncology: Advisor/Consultant|Sobi: Advisor/Consultant|Sobi: Grant/Research Support|Sobi: Patent for use of pacritinib and azacitidine in CMML|Sumitomo: Grant/Research Support Samantha E. Jacobs, MD, MS, Ansun Biopharma: Advisor/Consultant|Eurofins, Viracor, LLC.: Grant/Research Support

Background:Mycobacterium kansasii is typically associated with pulmonary disease and is an uncommon cause of disseminated infection and thus can be challenging to diagnose and treat. Case Summary:We present a 59-year-old female with a history of renal cell carcinoma (RCC) and T-cell large granular lymphocytic leukemia (T-LGLL) who developed disseminated Mycobacterium kansasii infection. Targeted next-generation sequencing (tNGS) facilitated the rapid detection of M. kansasii from formalin-fixed, paraffin-embedded (FFPE) tissue, aiding in clinical decision-making prior to culture confirmation. Conclusion:The case highlights the diagnostic challenges posed by overlapping clinical features and chronic granulomatous inflammation in immunocompromised patients, as well as the utility of amplicon-based sequencing in expediting diagnostic turnaround and guiding therapeutic interventions.

Oral immunotherapy (OIT) is an emerging treatment option for food allergy. Limited data exists on cashew OIT outcomes. An IRB-approved retrospective chart review of patients under age 3 years undergoing OIT to cashew was conducted. OIT involved an initial low dose oral food challenge (OFC) to cashew flour (approximately 10-30mg of cashew protein) with incremental dose escalation until patients reached a maintenance dose with cashew flour, butter, or whole cashews. Thirty-nine cashew-allergic patients underwent OIT. Of the 25 participants who reached a maintenance dose of 800mg-2000mg of cashew protein, 10 pursued full-dose cashew OFC after daily ingestion for at least 6 months. Of those 10, 100% tolerated 3000mg of cashew protein (approximately 10 cashews). Eight of these 10 patients underwent sustained unresponsiveness OFCs after at least 4-6 weeks of cashew avoidance. Seven tolerated 3000mg of cashew protein on the first attempt, while 1 initially reacted after 2 cashews but passed on their second attempt. Of the 14 patients who did not reach maintenance dosing, 3 remain in the build-up phase, 2 discontinued secondary to reactions, and 9 were lost to follow-up during the build-up phase. Four of 39 patients required epinephrine during desensitization. All but 1 of 4 reactions occurred with augmentation factors known to lower reaction thresholds; 2 occurred during the build-up phase and 2 while on maintenance. OIT, when adhered to, might be a safe and effective way to achieve desensitization and sustained unresponsiveness to cashew in pediatric patients when started before age 3.

AbstractBackgroundCytomegalovirus‐specific T‐cell‐mediated immunity (CMV‐CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo‐HCT), but to date, there is no validated measure of CMV immunity for this population.MethodsIn this prospective, observational, pilot study, CMV T‐cell responses were evaluated monthly and at onset of graft‐versus‐host disease (GVHD) or CMV infection in CMV‐seropositive allo‐HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T‐Cell Immunity Panel (CMV‐TCIP). The primary endpoint was the time to first positive CMV‐TCIP, defined as percentage of interferon‐γ‐producing CD4+ or CD8+ CMV‐specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.ResultsTwenty‐eight allo‐HCT recipients were enrolled. The median time to first positive CMV‐TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV‐CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV‐CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low‐level CMV reactivation, the sensitivity and negative predictive value of CMV‐TCIP were 90% and 87.5%, respectively, for CD4+ CMV‐TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV‐TCIP.ConclusionsThere was significant variability in time to CMV‐CMI recovery post‐HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV‐CMI may protect against CS‐CMVi, but immunity may be lost with GVHD diagnosis and treatment. image

https://tidbitapp.io/tidbits/trypanosoma-cruzi-reactivation-post-chimeric-antigen-receptor-t-cell-therapy/update.

In immunocompromised hosts, it may be more difficult to recognize infection as typical signs and symptoms are not present. Therefore routine monitoring for de novo infection or reactivation of a latent infection is extremely important. In this chapter, we will review strategies for monitoring cytomegalovirus, Epstein–Barr virus, hepatitis B virus, BK virus, adenovirus, and human herpesvirus 6 in immunocompromised hosts, focusing on solid organ transplant and hematopoietic cell transplant recipients. We will also review monitoring strategies for increased risk organ transplant donors and recipients.

The global burden of invasive fungal disease is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower and less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most invasive fungal diseases due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarized findings from animal models of CAF and assessed laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.

(R,R′)-4′-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of MNF in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by focusing first on internalization of the fluorescent ligand Tocrifluor 1117 (T1117). Initial results indicated that cell pretreatment with GPR55 agonists, including the atypical cannabinoid O-1602 and l-α-lysophosphatidylinositol, dose-dependently reduced the rate of cellular T1117 uptake, a process that was sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2 phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a coordinated negative regulation of AM251 and O-1602 inducible processes, including changes in cellular morphology and cell migration using scratch wound healing assay. This study shows for the first time that MNF impairs GPR55-mediated signaling and, therefore, may have therapeutic potential in the management of cancer.

Intravascular diseases due to Candida species, including endocarditis and cardiac device-associated infections, are rare yet devastating manifestations of invasive candidiasis affecting an already vulnerable population. Despite their significant associated morbidity and mortality, limited prospective data exist to inform the optimal diagnostic and therapeutic approaches to these entities. Herein, we review the existing literature pertaining to the epidemiology, diagnosis, and management of infectious endocarditis, rhythm management device infections, and circulatory support device infections caused by Candida species and suggest areas for future research.

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.

Abstract Background Substantial progress in the treatment of multiple myeloma (MM) has led to improved patient outcomes and prolonged survival of patients. These therapeutic advances have resulted in increased cumulative immunosuppression leading to increased susceptibility to opportunistic infections including CMV infection. The significance of CMV infection in MM patients is not well understood. We sought to describe the clinical characteristics and outcomes of patients with MM who develop CMV infection. Methods Retrospective chart review of MM patients at Mount Sinai Hospital in NY who had CMV DNA PCR sent. The Mount Sinai Multiple Myeloma Database was utilized to identify patients who developed CMV viremia. Demographic, clinical and laboratory data were abstracted from electronic medical records. IRB approval was obtained. Statistical Analysis Factors associated with 30-day mortality by univariate analysis were evaluated using Fischer’s exact and Wilcoxon rank-sum test. Results Demographics 414 MM patients had CMV PCR sent at least once. Forty-six cases of CMV infection were identified. CMV Infection Characteristics Forty-six patients were found to have CMV viremia, defined as PCR >500 IU/mL. Twenty-two (47%) had symptomatic infection. One patient had CMV pneumonitis and in 7/46 (15%) patients, CMV end-organ disease was suspected. Twenty (43%) patients had progressive disease status, 73% had prior history of autologous stem cell transplant and 85% had received steroids within 30 days of CMV infection. Twenty-nine (63%) patients had concurrent infections within 30 days of CMV infection, including bloodstream infection (n=16), bacterial pneumonia (n=9), respiratory viral infection (n=6), infectious colitis (n=5), and fungal infection (n=3). Outcomes 9/46 (19%) patients died within 30 days of CMV infection and 12/46 (26%) required ICU admission during that hospitalization. In univariate analysis of risk factors associated with mortality, higher weekly steroid dose approached statistical significance (p=0.06) and peak CMV PCR >1000 IU/mL (p.008) was associated with lower mortality. Conclusion CMV infection is associated with morbidity and mortality in MM patients. Prospective studies are needed to better assess the clinical significance of CMV reactivation in this population. Disclosures Emily Baneman, MD, Merck: Grant/Research Support.

Introduction: Patients with acute myeloid leukemia (AML) have a high risk of infection during induction therapy due to the severity and duration of chemotherapy-induced neutropenia. As a result, the American Society of Clinical Oncology and the Infectious Diseases Society of America recommend fluoroquinolone prophylaxis in this patient population during induction therapy. The initial studies supporting the current guidelines showed decreased risk of neutropenic fever and systemic bacterial infections with fluoroquinolone prophylaxis but no mortality benefit. Notably, the use of fluoroquinolone prophylaxis is associated with colonization and infection with multidrug-resistant organisms, and these studies were conducted in areas with low rates of fluoroquinolone resistance. At our institution, the rates of fluoroquinolone resistance among the 3 most common causes of Gram-negative bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) ranged from 17% to 45% among inpatients during the study period. We aimed to evaluate the efficacy of fluoroquinolone prophylaxis in a population with high rates of fluoroquinolone resistance. Methods: We performed a retrospective chart review of newly diagnosed adult AML patients who received induction therapy at Mount Sinai Hospital in New York, NY, from 6/1/2012 to 12/31/2016. Patients were excluded if they received antibiotics for >4 days in the 1 week prior to induction therapy, developed a clinically or microbiologically documented infection (CDI or MDI) in the 2 weeks prior to induction therapy, did not develop neutropenia (defined as neutrophil count < 500 cells/μL), or developed fever on the first day of neutropenia. Patients were followed for 6 months after initiation of induction therapy. The primary outcome was development of neutropenic fever. The secondary outcomes were development of infections, infection with multidrug-resistant organisms, and mortality. We used a time-varying (Simon-Makuch) statistical approach to categorize patients into the prophylaxis group or no prophylaxis group. We adjusted each outcome for gender, age at diagnosis, type of AML (de novo vs. secondary), and type of induction therapy. Results: Of the 95 included patients, 77 received primary fluoroquinolone prophylaxis and 18 did not receive any bacterial prophylaxis. There was no difference in median age, gender, or type of induction therapy between the prophylaxis and no prophylaxis groups (Table 1). Although more patients in the prophylaxis group had de novo disease (61% vs. 33%, p=0.003) and received inpatient induction therapy (88% vs. 56%, p=0.003), there was no difference in duration of neutropenia (28 vs. 23 days, p=0.349). There was no statistically significant difference in risk of febrile neutropenia (multivariable HR 1.41 [0.70 - 2.84], p=0.339) or mortality (multivariable HR 0.72 [0.35-1.48], p=0.371), with or without adjustment for baseline confounders. During the induction period and 6-month follow up, there was no difference in rates of bacteremia, invasive fungal infections, Clostridium difficile infections, CDI, MDI, or infection with fluoroquinolone-resistant or multidrug-resistant organisms (Table 2). Conclusions: Use of primary fluoroquinolone prophylaxis during AML induction therapy did not impact rates of neutropenic fever, infections, and antimicrobial resistance during induction and 6 month follow up. Similar to prior studies, fluoroquinolone prophylaxis also did not improve overall survival. This suggests that primary fluoroquinolone prophylaxis in this high-risk population provides neither benefit nor harm. Larger randomized controlled clinical trials are needed to further investigate this topic. Disclosures Jacobs: Ansun Biopharma, Inc.: Consultancy.