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The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred days and 23% (95% CI 20-26%) by one year. There was a higher incidence of viremia associated with cord blood transplant (p = .04). No other patient, donor or transplant characteristics were identified that predicted for viremia. In 47 patients (80%), viremia remained well below 200,000 copies/mL and resolved. Twelve patients developed high level viremia. Treatment with antivirals and in some cases adoptive cell therapy, was often ineffective and only two survived. Low lymphocyte count at initial detection of adenovirus viremia was the best predictor of uncontrolled disease.

Background Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. Methods We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. Results Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum β-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P Conclusions Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.

Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877., Immunocompromised adults with severe parainfluenza received nebulized DAS181 or placebo for up to 10 days. The primary endpoint was not met, but a subgroup of severely immunocompromised patients experienced a faster return to room air by day 28 (P = .012).

Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD) are common and potentially fatal complications after allogeneic transplantation with mismatched donors and T-cell depletion. Haplo-cord transplantation combines a mismatched UCB graft with third-party cells. Conditioning involves thymoglobulin. EBV reactivation and PTLD were common in initial patients. As of March 2017, we administered a prophylactic dose of rituximab 375 mg/m

Background The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear. Methods To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method. Results We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing. Conclusion The characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention. Disclosures All Authors: No reported disclosures

Infectious diarrhea following hematopoietic cell transplantation (HCT) significantly contributes to morbidity and mortality. Most HCT recipients experience diarrhea in the post-transplantation period, and infectious pathogens are frequently detected during diarrheal episodes. However, little is known about how frequently these patients are colonized with gastrointestinal (GI) pathogens before their transplantation and whether colonization predicts future diarrheal illness. We sought to determine how frequently HCT recipients are colonized with GI pathogens before HCT and the degree to which pre-HCT colonization predicts post-transplantation infectious diarrheal illness. We conducted a prospective cohort study of allogeneic and autologous HCT recipients at a single center between December 2016 and January 2019. Stool samples were collected during the week before HCT, and formed samples were evaluated for the presence of 22 diarrheal pathogens using the BioFire FilmArray GI panel. We determined the frequency with which participants were colonized with each pathogen and identified factors associated with colonization. We then determined how frequently pretransplantation colonization led to post-transplantation diarrheal infections due to the colonizing pathogen and whether colonization was associated with increased number of days of post-transplantation diarrhea during the transplant hospitalization. We enrolled 112 asymptomatic patients (allogeneic, 61%; autologous, 39%) who had a formed stool specimen before HCT, of whom 41 (37%) had a GI pathogen detected. The most commonly detected organisms were Clostridioides difficile (n = 21; 19%), Yersinia enterocolitica (n = 9; 8%), enteropathogenic Escherichia coli (EPEC) (n = 6; 6%), and norovirus (n = 5; 4%). Female sex and previous C. difficile infection were associated with C. difficile colonization, and having non-Hodgkin lymphoma was associated with being colonized with a diarrheal pathogen other than C. difficile. Thirteen of 21 patients (62%) with pretransplantation C. difficile colonization developed a clinical C. difficile infection post-transplantation, and 8 of 10 patients (80%) colonized with EPEC or enteroaggregative E. coli developed post-transplantation infections due to their colonizing pathogen. Pretransplantation C. difficile colonization was also associated with an increased duration of post-transplantation diarrhea (P = .048). Conversely, none of the 9 patients with pretransplantation Yersinia enterocolitica colonization developed a post-transplantation Y. enterocolitica infection. Patients admitted for HCT are frequently colonized with a diverse range of GI pathogens. Colonization with C. difficile colonization and diarrheagenic E. coli is frequently associated with post-transplantation diarrheal infections caused by these organisms, but the clinical significance of colonization with other GI pathogens is not clear.

With a rising incidence of COVID-19-associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and adaptive immune cells in disease progression and absolute changes of lymphocyte and myeloid cells in severe versus mild cases or healthy controls. Intubation and death were coupled with selected natural killer cell KIR receptor usage and IgM+ B cells and associated with profound CD4 and CD8 T cell exhaustion. Pseudo-temporal reconstruction of the hierarchy of disease progression revealed dynamic time changes in the global population recapitulating individual patients and the development of an eight-marker classifier of disease severity. Estimating the effect of clinical progression on the immune response and early assessment of disease progression risks may allow implementation of tailored therapies.

Background Seasonal influenza causes significant morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. In this population, influenza virus can replicate for prolonged periods, despite neuraminidase inhibitor treatment, leading to resistance and treatment failure. Baloxavir targets the influenza polymerase and may be an effective treatment option in these patients. Methods We used baloxavir to treat five allogeneic SCT recipients that were still symptomatic and shedding influenza virus after completing one or more treatment courses of oseltamivir and characterized the viral isolates before and during treatment. Results Two patients were infected with influenza A/H1pdm09 carrying a neuraminidase variant (H275Y) linked to oseltamivir resistance. Both these two patients were successfully treated with baloxavir. Of the three patients infected with wild-type influenza virus, two cleared the virus after baloxavir treatment, while the third patient developed the polymerase I38T variant linked to baloxavir resistance. Conclusions Our data suggest that baloxavir treatment can be effective in treating neuraminidase inhibitor-resistant influenza in profoundly immunocompromised patients. Randomized clinical trials are needed to define the role of baloxavir alone and combined with oseltamivir for the treatment of influenza in SCT recipients and other immunocompromised populations.

IntroductionMycobacterial spindle cell pseudotumour (MSP) is a rare disease characterised by tumour-like local proliferation of spindle-shaped histiocytes containing acid-fast positive mycobacteria. The aim of this literature review is to describe the clinical parameters and treatment outcomes of patients with MSP.MethodsA literature search was conducted using the search terms related to mycobacteria and spindle cell tumours. A previously unreported stem cell transplant recipient from our institution diagnosed with MSP was also included. Demographics, comorbidities, site of infection, treatment and clinical outcomes were analysed.ResultsFifty-one patients were analysed. Twenty-six (51%) had HIV infection.Mycobacterium aviumcomplex was the most frequent organism isolated in 24 (47.1%) followed byMycobacterium tuberculosiscomplex in eight (16%) cases. Lymph nodes were the most common site of infection (45.1%). Twenty (39.2%) patients received antimycobacterial agents, 12 (23.5%) underwent surgical resection and six (11.8%) received antimycobacterial agents plus surgery. Treatment was successful in 24 (47.1%) patients and failed in 15 (29.4%); 13 of these 15 patients died. Antimycobacterial therapy was significantly associated with successful outcome compared with surgical resection or no treatment (PConclusionMSP is a rare condition associated primarily with immunodeficiencies. Antimycobacterial therapy is significantly associated withsuccessfuloutcome.

BackgroundDiarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed polymerase chain reaction (PCR) assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated.MethodsOur center replaced stool cultures and other conventional microbiologic methods with the FilmArray Gastrointestinal Panel (GI PCR) in June 2016. We reviewed all adult patients who received an HCT from June 2014–May 2015 (pre–GI PCR, n = 163) and from June 2016–May 2017 (post–GI PCR, n = 182) and followed them for 1 year after transplantation. Clostridioides difficile infection was diagnosed by an independent PCR test in both cohorts.ResultsThe proportion of patients with ≥1 identified infectious diarrheal pathogen increased from 25% to 37% after implementation of GI PCR (P = .01). Eight patients (5%) in the pre–GI PCR cohort tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post–GI PCR cohort (P < .001). The most common non–C. difficile diarrheal pathogens in the post–GI PCR cohort were enteropathogenic Escherichia coli (n = 14, 8%), norovirus (n = 14, 8%), and Yersinia enterocolitica (n = 7, 4%). The percentage of diarrheal episodes with an identified infectious etiology increased from 14% to 23% (P = .001). Median total costs of stool testing per patient did not increase (pre: $473; post: $425; P = .25).ConclusionsInfectious etiologies of diarrhea were identified in a higher proportion of HCT recipients after replacing conventional stool testing with a multiplexed PCR assay, without an increase in testing costs.

Background: As one of the most prevalent pathogens in the environment, influenza affects millions of patients annually and contributed to tens of thousands of deaths in the United States during 2018-2019 alone. Immune deficiency is one of the most significant risk factors for adverse outcomes in adults with influenza, and similarly infectious complications are one of the most common causes of death in hematopoietic stem cell transplant (HSCT) recipients. However, data on outcomes or risk factors for progression in influenza infections specifically in HSCT recipients are limited. Methods: We reviewed patient demographics, oncology and transplant history from HSCT recipients with polymerase chain reaction (PCR)-confirmed influenza over 5 influenza seasons (from 2013-2014 through 2018-2019). Influenza subtype (A H1, H3, and B), laboratory studies at diagnosis, treatments, vaccination status, and outcomes for each influenza infection were recorded and analyzed. Results: A total of 143 infection events were collected and analyzed for symptoms and outcomes. Influenza infections of each subtype occurred in each season, although a different strain predominated each season. The most common symptoms at presentation were cough (65.3%) and fever (55.2%). Symptoms at presentation and outcomes were not significantly different amongst Influenza type A H1, A H3 and type B infections (p>0.05). In total, 22 (15.4%) infections presented as lower respiratory tract infections (LRTIs) and 7 additional infections progressed to LRTIs (all LRTI: 29; 20.1%). 63 (44.1%) infected patients required hospital admission, 15 (10.5%) required transfer to the intensive care unit (ICU) and 8 (5.6%) were intubated. 6 patients (4.2%) died by 30 days after the initial positive test, and 23 (16.1%) died by 180 days. LRTI was significantly associated with hospital admission (p0.05) or intubation (p>0.05). No other factors were significantly associated with LRTI, including vaccination status or treatment with antivirals (p>0.05). Logistic regression analysis of selected factors found that patients receiving steroids were significantly associated with LRTI (OR 2.58: 95% CI 1.00-6.63; p=0.047) (Table 1). There was, however, no statistically significant association detected between active graft-versus-host disease and LRTI (OR 1.25: 95% CI 0.35-4.06; p=0.721). We also found that treatment with oseltamivir within 2 days of symptom onset was not significantly associated with LRTI (OR 1.42: 95% CI 0.59-3.49; p=0.431). Persistent shedding (positive tests longer than 21 days from initial positive test) was also not associated with adverse outcomes (p>0.05). Conclusion: This study suggests that the use of chronic steroids in treatment for graft-versus-host disease in HSCT patients may increase the risk for adverse outcomes in influenza infections. Disclosures No relevant conflicts of interest to declare.

Background Limited data are available for risk assessment and outcome of COVID-19 in patients with hematologic malignancies (HM). We present a single center study of COVID-19 pneumonia in a cohort of 31 patients with HM. Methods Data were abstracted from electronic medical records for patients admitted to NYPH between 3/5/20 and 4/17/20 and entered into a REDCap database. Results Twenty (64.5%) were male; median age was 71 years. There were 8 patients with Multiple Myeloma (MM), 8 with Chronic Lymphocytic Leukemia (CLL), 6 (19.4%) had AML, 5 (16.1%) NHL, 2 (3.2%) ALL; CML, MDS and Polycythemia Vera occurred in 1 patient each. Twenty-four (77.4%) had active HM; 6 (19.4%) were in remission; and 1 relapsed. Nineteen patients (61.3%) received recent chemotherapy and 11 (35.5%) immunosuppressive therapies. There were 7 (22.6%) hematopoietic stem cell transplant (HSCT) recipients (4 allogeneic and 3 autologous). Comorbidities were evenly distributed among all malignancies: 18 (58.1%) had hypertension, 9 (38.7%) obesity, 7 (22.6%) diabetes mellitus, and 11 (35.5%) were former smokers. The most common symptoms included cough (90.3%), fever (83.9%) and dyspnea (61.3%); 7 (22.6%) had nausea and vomiting; 7 (22.6%) had diarrhea. On presentation, hypoxia (O2 sat ≤94% on room air) occurred in 64.5%; median ALC was 330/ml; 23 (74.2%) had ALC< 1000/ml; median CRP was 15.9 mg/dl (2.5–40.4), ferritin 1162 ng/ml (264 - > 16500), and D-dimers 456 ng/ml (< 150–2418). Thirteen patients (41.9%) required ICU admission and were intubated; among those 9 (69.2%) had either MM or CLL. Co-infections were uncommon; two patients developed HSV1 pneumonitis and one of these also had CMV pneumonitis. Twenty-eight (90.3%) were treated with hydroxychloroquine, 5 (16.1%) remdesivir, 2 (6.5%) tocilizumab, 1 (3.2%) sarilumab, and 4 (12.9%) with methylprednisolone 0.5mg/kg Q12h. Seventeen patients (54.8%) recovered and were discharged, 12 (38.7%) died; 2 (6.5%) were still hospitalized but left the ICU. Conclusion In our cohort, there were predominantly more patients with MM and CLL and 56% of these were intubated; larger cohort studies will further define the risk and outcome for COVID-19 in patients with HM. Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Grant/Research Support)Merck (Grant/Research Support)Shionogi Inc. (Consultant)

Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Unlike other respiratory viruses, little is known about the clinical significance of human coronavirus infection (HCoV) in this population. We retrospectively identified all HSCT recipients who were transplanted between May 2013 and June 2017 at our institution and characterized the cumulative incidence of post-transplant HCoV infection. Of 678 patients who underwent HSCT during the study period, 112 (17%) developed HCoV infection, making HCoV the fourth most common respiratory viral infection. Thirty-four (30%) HCoV-infected patients progressed to proven or probable lower respiratory tract infection (LRTI). Age ≥50, graft-versus-host disease, corticosteroids, hypoalbuminemia, and inpatient status at the time of infection were independently associated with progression to LRTI. Twenty-seven (59%) patients who underwent repeat NP swab had persistent viral shedding for ≥21 days, with a median duration of 4 weeks of viral shedding. We conclude that HCoV is common and clinically significant in HSCT recipients, with nearly one-third of patients progressing to proven or probable LRTI. Evaluating for LRTI risk factors found in this study may identify patients who require closer surveillance and aggressive supportive care when infected with HCoV.

BACKGROUND: Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. METHODS: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. RESULTS: We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. CONCLUSIONS: HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used. Methods We performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology. Results 1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively. Conclusion PJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid. Disclosures All authors: No reported disclosures.

Background Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. Objectives This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. Study design From April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. Results One hundred and ten HM patients presented with HRV URTI (n = 78) and HRV LRTI (n = 32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0–9.2; p = 0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. Conclusions HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.

Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT.

Background PIV infections are an important cause of morbidity and mortality in IC patients. DAS181, a sialidase fusion protein, has demonstrated activity in preclinical and clinical studies. Methods Adult IC patients diagnosed with PIV LRTI on chest imaging and required SO ≥ 2 L/minute were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5 mL/day) or matching placebo for up to 10 days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45. Results From 2014 to 2016, 110 patients were randomized and received study drug (74 DAS181 and 36 placebo). Median age was 57 years (range, 18–85). The majority were hematopoietic cell transplant (HCT) recipients (74), followed by hematological malignancy/solid tumor patients on chemotherapy (29), and lung transplant recipients (7). Day 45 CSS was achieved by 39.2% of DAS181-treated patients compared with 31.4% of placebo (P = 0.29), while the proportion among non-MV patients was 45.0% vs. 31.0% (difference −14.0%, P = 0.15), respectively. Time to CSS in the non-MV stratum was shorter in DAS181-treated patients (figure). Median change in nasopharyngeal PIV viral load by Day 10 and median hospitalization days were −1.44 vs. −0.68 log10 (P = 0.51) and 13.5 vs. 21 days (P = 0.10) for DAS181 and placebo, respectively. Mean absolute increase from baseline FEV1% predicted was 16.82 for DAS181 vs. 2.02 for placebo (P = 0.001). Post-hoc analysis on the probability to return to room air (RTRA) suggested that DAS181 reduced SO need in the non-MV stratum after Day 21 (P = 0.09). HCT recipients within 360 days from transplant had a 40.8% treatment effect on RTRA at Day 28 (P = 0.04) and 36.7% on mortality at Day 45 when compared with placebo (P = 0.06). The rate of adverse events was similar in both treatment groups. Day 45 all-cause mortality was comparable in both groups (32.4% DAS181 vs. 31.4% placebo). Conclusion DAS181 was well tolerated and showed a signal for clinical efficacy in IC patients with PIV LRTI. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned. Disclosures R. F. Chemaly, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research grant. R. Moss, Ansun Biopharma: Employee, Salary. F. M. Marty, Ansun Biopharma: Investigator, Research grant. C. R. Wolfe, Ansun Biopharma: Investigator, Research grant. S. J. Lawrence, Ansun Biopharma: Investigator, Research grant. S. Dadwal, Ansun Biopharma: Investigator, Research grant. R. Soave, Ansun Biopharma: Investigator, Research grant. J. Hwang, Ansun Biopharma: Employee, Salary. S. Hawley, Ansun Biopharma: Employee, Salary. R. Routh, Ansun Biopharma: Employee, Salary. J. Ho, Ansun Biopharma: Employee, Salary. G. Wang, Ansun Biopharma: Employee, Salary. N. Chang, Ansun Biopharma: Employee, Salary. M. Boeckh, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research support.

Background Diarrhea is common among hematopoietic stem cell transplant (HSCT) recipients, but the etiology is rarely identified. Multiplexed PCR may increase the detection of diarrheal pathogens, but its role has not been evaluated in this population. Methods In June 2016, the FilmArray™ Gastrointestinal panel (GI PCR) was implemented at NewYork-Presbyterian Hospital/Weill Cornell Medical Center to diagnose infectious diarrhea, replacing stool culture and other conventional Methods. We reviewed all adult patients who received a HSCT at our center from June 2014–May 2015 (pre-GI PCR) and June 2016–March 2017 (post-GI PCR). Clostridium difficile infection was diagnosed by PCR for toxin B gene in both cohorts. Patients were followed for 1 year post-transplant. We compared the percentage of patients with an identified diarrheal pathogen, yield of testing per diarrheal episode, and number and cost of stool tests between cohorts. Results We identified 163 HSCT recipients in the pre-GI PCR cohort and 146 in the post-GI PCR cohort. Patients had a median of two diarrheal episodes during 1-year follow-up in both cohorts. The proportion of patients with at least one identified infectious etiology of diarrhea increased from 21.5 to 34.3% after implementation of GI PCR (P = 0.01). Only two patients (1.2%) in the pre-GI PCR cohort tested positive for a pathogen other than C. difficile, vs. 35 patients (24.0%) in the post-GI PCR cohort (P < 0.001). Post-GI PCR, patients were most likely to have the following pathogens: C. difficile (n = 23, 15.8%), diarrheagenic Escherichia coli (n = 20, 13.7%), and norovirus (n = 10, 6.8%). The percentage of diarrheal episodes for which an infectious etiology was identified increased from 11.7% (41/351) to 20.9% (74/354; P = 0.001) in the post-GI PCR period. The median number of stool tests performed per year per patient decreased from 12 (interquartile range [IQR] 7–20) to 5 (IQR 3–11; P < 0.001). Median costs of stool testing per patient during follow-up did not differ: (pre: $473, IQR $243–851) vs. (post: $425, IQR 249–956; P = 0.23). Conclusion After introduction of GI PCR, infectious etiologies of diarrhea were identified in a higher proportion of HSCT recipients compared with traditional stool testing, without an increase in testing costs. Disclosures L. Westblade, BioFire Diagnostics, LLC.: Research Contractor, Grant recipient. C. Crawford, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee; Redhill: Speaker’s Bureau, Speaker honorarium. M. Satlin, Biomerieux: Grant Investigator, Grant recipient.

Background PIV infections are an important cause of morbidity and mortality in HCT recipients. DAS181, a sialidase fusion protein, has demonstrated activity in pre-clinical and clinical studies. Methods Adult immunocompromised patients (IC), including HCT recipients, diagnosed with PIV LRTI on chest imaging and required SO ≥ 2L/min were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5mL/day) or matching placebo for up to 10 consecutive days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45. An exploratory end point of proportion to return to room air (RTRA) was analyzed. Results Out of the 110 patients randomized, 64 HCT recipients received study drug (43 DAS181 and 21 placebo). Median age was 53 years (range, 19-77), half were male (50%), white (84%), and had received an allogeneic HCT (86%). A post-hoc analysis of the HCT recipients on SO showed that day 45 CSS was achieved by 46.5% of DAS181-treated patients compared to 33.3% of placebo (p = 0.23). In addition, when compared to placebo, HCT recipients on SO who received DAS181 within 1 year from transplant were more likely to achieve CSS at day 45 (48.4% vs. 12.5%; p = 0.071), were more likely to RTRA at day 28 and day 45 (53.3% vs. 12.5%; p = 0.04 and 60% vs. 25%; p = 0.086, respectively), more likely to be discharged from the hospital by day 45 (64.5% vs. 12.5%; p = 0.011), and had a trend for lower mortality at day 45 (25.8% vs. 62.5%, p = 0.064). The rate of adverse events was similar in both treatment groups. Conclusion DAS181 was well tolerated and a post-hoc analysis in HCT recipients with PIV LRTI on SO within 1 year of transplant, DAS181 was effective (RTRA) and showed a trend towards lower mortality by day 45. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned.

Acanthamoeba is the most common cause of granulomatous amebic encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under-recognized cause of encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure.

Summary Objectives To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. Methods We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. Results CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior β-lactam/β-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08). Conclusions CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE-active agents and improve outcomes in this vulnerable population.

After a cluster of fatal toxoplasmosis among stem cell transplant recipients at 2 hospitals, surveillance with polymerase chain reaction (PCR) (blood) was instituted. Rate of reactivation among seropositive recipients was 2.2 and 16%. Parasitemia was successfully managed with preemptive treatment. For seropositive recipients unable to take prophylaxis, toxoplasma PCR surveillance should be routinely performed.

Background The aim of this study is to describe the clinical manifestations, molecular mechanisms, and treatment outcomes of patients with echinocandin-resistant Candida tropicalis (C. tropicalis) bloodstream infections (BSI). Methods A PubMed search was conducted using the search terms related to C. tropicalis BSI and echinocandin resistance. Two previously unreported cases from our institution diagnosed with C. tropicalisBSI that developed resistance to echinocandins were also included. Demographics, comorbidities, treatment, clinical outcomes, and molecular mechanisms were analyzed. Results Seven patients with echinocandin-resistant C. tropicalis BSI were identified, including 5 previously reported cases and two from our institution. Median age was 58.7 ± 20.4 years; 3 (43%) patients were males. Three (43%) had acute myelogenous leukemia, 3 (43%) had acute lymphoblastic leukemia, and 1 (14%) had urothelial cancer. All patients were immunocompromised having received chemotherapy in the last six months and 3 (43%) were hematopoietic stem cell transplant recipients. Five (71%) had breakthrough of echinocandin resistance while receiving an echinocandin; one (14%) received caspofungin in the past 3 months and only one (14%) had no reported echinocandin exposure in the past 3 months. DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance was performed in 4 cases, including our two index cases. Homozygous T-to-C mutations in two alleles of FKS1gene was detected in 2 cases, and a heterozygous mutation was detected in the other 2 cases, which resulted in a deduced serine-to-proline amino acid change at position 654 (S654P). Six patients (86%) survived after being treated with an antifungal agent other than an echinocandin. Treatment was changed to liposomal amphotericin B in two cases, and one each to voriconazole, fluconazole, voriconazole plus liposomal amphotericin B, and caspofungin plus voriconazole. The one patient who died received intravenous voriconazole. Conclusion Echinocandin resistance emerged in neutropenic patients with C. tropicalis fungemia through a characteristic mutational hot-spot amino acid change in the target FKS1 gene. Although alternative antifungal agents may be successfully used as salvage therapy, the outcome may still be fatal. Disclosures D. Perlin, Pfizer: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Astrellas: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Merck: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Cidara: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Synexis: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. F2G: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Myconostica: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Amplyx: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Matinas: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. GAFFI: Scientific Advisor, Advisor. Bill and Melinda Gates Foundation: Scientific Advisor, Advisor

Background Fluoroquinolone (FQ) prophylaxis is widely used to prevent bloodstream infections (BSIs) in neutropenic patients undergoing hematopoietic stem cell transplantation (HCT). In order to assess whether increasing FQ resistance threatens the effectiveness of FQ prophylaxis, we screened HCT recipients for colonization with FQ-resistant Enterobacteriaceae (FQRE) and assessed the impact of colonization on the risk of BSI. Methods We collected stool samples on admission for HCT and weekly until neutrophil engraftment from patients at NewYork-Presbyterian Hospital/Weill Cornell Medical Center from November 2016 to March 2018. Patients received FQ prophylaxis during neutropenia. Perianal swabs were used when stool was unavailable. Stool and swab samples were plated onto MacConkey agar with 1 μg/mL ciprofloxacin, and colonies were identified and underwent antimicrobial susceptibility testing. We determined the prevalence of colonization with FQRE on admission for HCT, the risk of acquiring FQRE, and compared the risk of BSI during the transplant admission in colonized and noncolonized patients. Results We evaluated 178 HCT recipients and found that 35 (20%) had pre-transplant FQRE colonization (allogeneic: 20/89, 22%; autologous: 15/89, 17%). Thirty FQRE (86%) were Escherichia coli, 5 (14%) were Klebsiella pneumoniae, and 13 (37%) were extended-spectrum β-lactamase producers. Five (14%) of the 35 patients with pre-transplant FQRE colonization developed BSI due to an Enterobacteriaceae, and all bloodstream isolates had identical susceptibility profiles to the colonizing FQRE. In contrast, only one (1%) of 143 patients without pre-transplant FQRE colonization developed Enterobacteriaceae BSI (P = 0.001). Patients with pre-transplant FQRE colonization also had higher rates of any Gram-negative BSI (20% vs. 1%, P < 0.001), but did not have increased risk of Gram-positive BSI (6% vs. 11%, P = 0.5). Of 123 patients without initial FQRE colonization who had follow-up samples collected, 10 (8%) acquired FQRE during post-HCT neutropenia. Conclusion FQRE colonization is common on admission for HCT and is associated with decreased effectiveness of levofloxacin prophylaxis in preventing Gram-negative BSI during post-transplant neutropenia. Disclosures M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Achaogen: Consultant, Consulting fee. R. Malherbe, Hardy Diagnostics: Employee, Salary. S. G. Jenkins, Merck: Grant Investigator, Grant recipient. L. F. Westblade, Accelerate Diagnostics: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee.

Background Seasonal influenza causes significant morbidity and mortality on HSCT recipient. The 2017–2018 influenza has been characterized in the United States by prolonged high rates of both influenza A (IAV) and B (IBV) and low vaccine effectiveness. The aim of this study was to assess the impact of both IAV and IBV during 2017–2018 influenza season on a cohort of stem cell transplant (SCT) recipients at Weill Cornell- NYP. Methods We reviewed charts of HSCT recipients that were diagnosed with influenza by PCR on nasopharyngeal swabs. Demographics, clinical and microbiological data, and outcomes were collected. The study was approved by Weill Cornell Institutional review board. Results From September 2017 to March 2018, 30 stem cell transplant recipient at NYP were diagnosed with influenza. IAV cases peaked in January (11 cases) while IBV infected-patients were equally distributed from December to March. Infected subject were more likely to be male (n = 20, 66.6%) with mean age of 57 ± 12 (IAV) vs. 59 + 11 (IBV). Nine patients had received auto SCT and 21 patient allo SCT. Most commons symptoms were cough (present in all patients), fever (28/30), nausea, dyspnea. Patient received oseltamivir (for 5 or 10 days) in 28/30 cases, with one patient developing resistance under treatment. Interestingly both IAV and IBV caused lower respiratory tract infection (LRTI, 7 cases) with severe pneumonia (IAV 1 cases, IBV 2 cases) and intubation. In two severe cases IV was detected in the BAL. 13 subjects (56%) with a URTI and 4 (43%) subjects with LRTI had not received the influenza vaccine for the season. Prolonged shedding of influenza on oseltamivir treatment was documented in 7 patients. Conclusion Both IAV and IBV are serious threat in SCT population. Vaccination and oseltamivir are useful tools. Resistance testing should be considered in subjects with prolonged disease. Disclosures S. G. Jenkins, Merck: Grant Investigator, Grant recipient. M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support. Allergan: Grant Investigator, Grant recipient. Merck: Grant Investigator, Grant recipient. Biomerieux: Grant Investigator, Grant recipient. Achaogen: Consultant, Consulting fee. L. F. Westblade, Accelerate Diagnostics: Grant Investigator, Grant recipient. Biomerieux: Grant Investigator, Grant recipient. Allergan: Grant Investigator, Grant recipient. Merck: Grant Investigator, Grant recipient.

Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy.

An innovative program developed to work with families in which substance use during pregnancy leads to Child Protective Services involvement is introduced in this article. The Vulnerable Infants Program of Rhode Island (VIP-RI) was established to facilitate permanency planning for substance-exposed infants by focusing on the interface of social service systems with one another and with the families affected by perinatal substance use. Permanent placement within the time frame mandated by federal legislation places increased pressures on parents and the social service systems designed to provide them with assistance. The Vulnerable Infants Program of Rhode Island promotes collaboration, coordination, and communication among social service systems engaged with families of substance-exposed infants. The Vulnerable Infants Program of Rhode Island works to increase the efficacy of social service systems in order to optimize the resources that are available to a family in their attempts at reunification with their infant. Case examples illustrate the complexities of the families of substance-exposed infants, the breadth of social service systems that become involved with these families, and the vastly different placement outcomes that substance-exposed infants may experience.

Background Hematopoietic stem cell transplants (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Although the epidemiology of many respiratory viruses has been well characterized in this population, little is known about the epidemiology of human coronavirus (HoCV) infection. Methods We identified HSCT recipients with symptoms of a respiratory tract infection who tested positive for HoCV by nasopharyngeal (NP) swab from January 2013 to December 2016 at our hospital. NP swabs were analyzed by the FilmArray® Respiratory Panel, which detects 17 respiratory viruses, including 4 coronavirus serotypes. We reviewed the demographics, transplant type, comorbidities, smoking status, respiratory symptoms, co-pathogens, and radiographic findings of infected patients. We then assessed the incidence of developing a lower respiratory tract infection (LRTI), defined as new pulmonary infiltrates or detection of HoCV in bronchoalveolar lavage fluid, within 30 days of initial diagnosis. Results We identified 58 HSCT recipients who tested positive for HoCV. The median patient age was 54 years, 29 (50%) were men, and 24 (41%) were current or prior smokers. Fifty (86%) patients had received an allogeneic HSCT and 8 (14%) had received an autologous HSCT. The coronavirus serotypes were: OC43 (n = 19, 33%), NL63 (n = 18, 31%), HKU1 (n = 16, 28%), and 229E (n = 5, 9%). The median time from transplant until detection of HoCV infection was 135 days (IQR=256). Seventeen (29%) patients were lymphopenic at the time of diagnosis and 17 (29%) were receiving corticosteroids. The most common initial symptoms were cough (n = 41, 71%), rhinorrhea (n = 31, 53%), and dyspnea (n = 17, 29%), and 19 (33%) and 16 (28%) patients had fever and hypoxia, respectively. Seventeen patients (29%) developed a LRTI within 30 days of diagnosis and 43% harbored a co-pathogen in the blood or respiratory tract. Three patients (5%) were intubated for respiratory failure and 1 (2%) died within 30 days. Conclusion HoCV infection is common in HSCT recipients and is caused by multiple serotypes. Nearly one-third of patients have fever and hypoxia upon initial diagnosis or progress to LRTI. Further research is needed to identify risk factors for HoCV LRTI in this population. Disclosures All authors: No reported disclosures.

Summary With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g−1 dl−1 increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

As antimicrobial resistance increases, understanding the current epidemiology of bloodstream infections (BSIs) in hematopoietic stem cell transplant (HSCT) recipients is essential to guide empirical antimicrobial therapy. We therefore reviewed microbial etiologies, timing and outcomes of BSIs in patients who were transplanted from September 2007 to December 2011. Vancomycin-resistant enterococci (VRE) were the most common pathogens in allogeneic HSCT recipients and the fourth most common after autologous transplant. VRE did not cause any of 101 BSIs in neutropenic patients who were not receiving antibacterials, but caused 32 (55%) of 58 BSIs in neutropenic patients receiving a broad-spectrum β-lactam agent (p < 0.001). Rates of septic shock and 7-day mortality were 5% and 0% for streptococcal bacteremia, 12% and 18% for VRE bacteremia, and 20% and 14% for Gram-negative bacteremia. In conclusion, VRE bacteremia was the most common BSI in allogeneic HSCT recipients, occurred primarily in neutropenic patients receiving broad-spectrum β-lactams and was associated with poor outcomes.

We conducted a survey to determine the prevalence of known and theoretical exposure risks for cryptosporidiosis among selected New York City residents. Subjects were recruited from outpatients attending either a practice for persons with HIV infection (n=160), or other medical practices (n=153), at The New York Hospital–Cornell Medical Center. Despite a greater concern for waterborne infection, 82% of HIV-infected subjects reported consuming municipal tap water compared to 69% of subjects from other medical clinics (OR 2·1, 95% CI 1·2–3·6, P=0·006). Although 18% and 31% of subjects, respectively, denied any tap water consumption at home or work, all but one from each cohort responded positively to having at least one possible alternate source of tap water ingestion such as using tap water to brush teeth or drinking tap water offered in a restaurant. 78% and 76% of subjects, respectively, had at least one potential risk for exposure other than municipal water consumption, such as swimming in pools or contact with animals. Our findings indicate that it is possible to stratify the population into subsets by the amount of tap water consumed. This suggests that an observational epidemiologic study of the risk of contracting cryptosporidiosis from everyday tap water consumption is feasible.

A prospective study of 137 human immunodeficiency virus (HIV)-infected outpatients was conducted at a New York City clinic to determine the seroprevalence of anticryptosporidial antibody, and the prevalence of cryptosporidial infection. In addition, the potential risk factors for cryptosporidial infection in an HIV-infected population in an urban environment were also investigated. A seroprevalence of 20.3% was found for anti- Cryptosporidium antibody within the urban HIV-positive population studied. This prevalence is within the range that has been established for immunocompetent populations in the United States and in Europe. It indicates that a significant proportion of the population has had cryptospordial infection in the past. Longitudinal studies are needed to establish whether cryptosporidiosis is a reactivation of past infection in the immunocompromised host. Stool samples were examined for ova and parasites and acid-fast stained for detection of cryptosporidial oocysts. Previously unrecognized cryptosporidial infection was found in 3.6% of the study population. This prevalence is similar to that reported for an HIV-infected inner city population in Los Angeles. The numbers obtained in this study may be an underestimate of the true prevalence of cryptosporidial infection, because serial stool samples were not examined and because there is evidence that the commonly used acid-fast method for identification of Cryptosporidium in stool is insensitive. There was no correlation between risk factors for cryptosporidial infection and either stool or seropositivity.

Diarrhea is a common problem for AIDS patients, and is chronic and debilitating. A thorough evaluation will reveal a pathogen in the majority of patients, and the organisms most frequently identified in AIDS patients with chronic diarrhea are Cryptosporidium, microsporidia, and Mycobacterium avium complex. Bacterial pathogens are more common in AIDS patients than in the general population and may present in different ways from infections in immunocompetent hosts. Other pathogens, including Cryptosporidium and microsporidia, are difficult to diagnose and have no effective therapy. Moreover, enteric viruses and HIV itself may contribute to the diarrhea. In addition to microbes, other factors such as medication, immune dysregulation, automatic dysfunction, and nutritional supplementation play a substantial role in diarrhea of AIDS patients.

We retrospectively examined the hospital course of 12 patients with exacerbated inflammatory bowel disease (IBD), who also had stool specimens positive for Blastocystis hominis to determine the effect of B. hominis on their disease. Bloody bowel movements were common with ulcerative colitis patients and watery diarrhea with Crohn's disease; other findings included abdominal pain, fever, nausea, and vomiting. All patients responded favorably to medical therapy. Three responded to treatment with corticosteroids alone, and one patient improved with bowel rest without medications. Five patients failed to improve on metronidazole; four of them responded to a subsequent course of corticosteroids, whereas the fifth patient became asymptomatic after erythromycin treatment for concomitant Campylobacter jejuni. Finally, three patients responded to treatment with metronidazole alone, which is known to eradicate B. hominis but may also have a beneficial effect on IBD. In no case did corticosteroid treatment worsen the condition. Our findings indicate that B. hominis is not a significant pathogen in IBD and treatment must be directed toward the underlying illness.

Cryptosporidium sp. and Isospora belli are coccidian protozoan parasites that were long recognized as pathogens for many animal species. The medical community became acquainted with these organisms with the advent of AIDS. Both parasites are associated with persistent, debilitating enteritis and, in the case of Cryptosporidium, biliary tract involvement in patients with AIDS. For the immunocompetent host, infection with these two pathogens usually results in self-limited diarrhea. Cryptosporidiosis appears to occur more often than isosporiasis, but the true prevalence of both infections for various populations of humans is unknown. Clinically, cryptosporidiosis is indistinguishable from isosporiasis. Diagnosis is based on finding the acid-fast (red staining oocyst in stained fecal specimens). There is no known effective therapy for cryptosporidiosis, whereas patients with isosporiasis respond promptly to treatment with trimethoprim-sulfamethoxazole. Patients with AIDS and isosporiasis have a high relapse rate after achieving complete remission and therefore need to be maintained on suppressive therapy. Much more needs to be learned about these two fascinating, "newly recognized" parasites.

Recent guidelines have suggested PCR screening for toxoplasmosis in high risk patients.6 Use of PCR as a standard part of fever work up in seropositive allogeneic stem cell transplant recipients has also been recommended.5 Pseudo-Outbreak of Fulminant Toxoplasmosis in Hematopoietic Stem Cell Transplant [HSCT] Recipients Flonza Isa, MD, Mini Kamboj, MD, Kohta Saito, MD, Koen Van Besien, MD, Sergio A. Giralt, MD, Audrey N. Schuetz, MD, Steven Salvatore, MD, Genovefa Papanicolaou, MD, and Rosemary Soave, MD New York Presbyterian Hospital [NYPH]/Weill Cornell and Memorial-Sloan Kettering Cancer Center [MSKCC], New York, NY

In addition to the net state of immunosuppression, the risk of infection after transplantation is largely determined by the transplant recipient's epidemiologic exposures. Potential sources of infection in the transplant recipient include the environment and the recipient's endogenous flora. This article presents aspects of prevention of infection after solid-organ transplantation such as avoidance of epidemiologic exposures, antibacterial prophylaxis, prophylaxis for tuberculin-positive transplant recipients, and prophylaxis against infections with Pneumocystis carinii and Toxoplasma gondii.

Although the histopathologic changes associated with Cyclospora cayetanensis infection have been previously described, the histopathology and the appearance of various life cycle stages have not been correlated with severity, stage, and duration of clinical disease. We report a prospective clinical investigation of disease characteristics and histopathologic findings in three otherwise healthy, immunocompetent patients with symptomatic C. cayetanensis infection, the duration of which ranged from 6 to 60 days. Varying degrees of gross and microscopic gastrointestinal inflammation were seen before treatment. An electron-dense phospholipid membrane/myelin-like material was variably present both before and after treatment. The greatest amount of myelin-like material was seen in the patient with prolonged disease. The results of our study suggest that inflammatory changes associated with C. cayetanensis infection may persist beyond parasite eradication. It is intriguing to speculate that the myelin-like material is a marker for persistent inflammation, but further study and confirmation are needed.