Search

Background Invasive fungal diseases (IFD) have been described in patients (pts) with severe coronavirus disease 2019 (COVID), albeit with geographic variability in rates. Methods We performed a retrospective study to determine rates of & risk factors for IFD occurring within 30 days (d) of COVID diagnosis (dx) in adults requiring critical care for severe COVID between 5/11/20 & 2/7/21. Mortality was assessed at 90 d following COVID dx and at 84 d after IFD dx, if applicable. ECMM/ISHAM criteria were used for COVID-associated pulmonary aspergillosis (CAPA) and EORTC/MSGERC criteria were used for other IFD and treatment response. Results 218 pts were included; median age was 62 (19 – 91) & 63% were men. Underlying conditions included solid organ transplant (Tx) (16; 7%), allogenic stem cell Tx (3; 1%), malignancy (21; 10%), & exposure to either high-dose steroids (HDS) (11; 5%) or T- or B-cell suppressants (29; 13%) within 90 d prior to COVID dx. 209 (96%) pts had respiratory failure & 127 (58%) required mechanical ventilation. 15 (7%) required extracorporeal membrane oxygenation. COVID treatment consisted of corticosteroids in 205 (96%) & tocilizumab in 10 (5%). 12 (6%) pts developed IFD. 6 pts had CAPA (2 probable, 4 possible); 50% were men, median age 64.5 (48 – 83). Mean time to CAPA dx from COVID dx was 17 d (± 14d). All pts had received corticosteroids for COVID but only 1 pt received > 30d of HDS by the time of IFD dx. Mortality at 84 d from CAPA dx was 67%. 5 (2%) pts had central venous catheter associated candidemia; 80% were men & median age 61 (55 – 77). Mean time from COVID to candidemia dx was 29 d (±12 d). All pts with Candida infection had received steroids for COVID. Mortality at 84 d from candidemia dx was 60%. A 35-year-old man with prolonged exposure to HDS had Paecilomyces pneumonia; he was alive at 84 d after IFD dx. No cases of mucormycosis were identified. All-cause mortality in the entire cohort was 38% at 90 d after COVID dx. Mortality among pts who developed IFD was 58% at the same time point. Conclusion Rates of IFD in pts with severe COVID were low and most pts with IFD after COVID had CAPA or catheter-associated candidemia. All but one pt with CAPA had no risk factors for IFD. In pts with severe COVID, mortality was higher among pts who developed IFD than those who did not. Disclosures Marisa H. Miceli, MD, Astellas: Advisor/Consultant|F2G: Grant/Research Support|Miravista: Advisor/Consultant|PSI: Advisor/Consultant|Scynaxis: Advisor/Consultant|Scynaxis: Grant/Research Support.

Pulmonary aspergillosis has been reported at high rates in patients with coronavirus disease 2019 (COVID-19) and is associated with high morbidity and mortality. We retrospectively assessed all patients admitted to an intensive care unit during the early COVID-19 surge (3/17/20–5/10/20) at our medical center in the midwestern USA for the presence of COVID-19-associated pulmonary aspergillosis (CAPA). Patients were not routinely screened for CAPA; diagnostic work-up for fungal infections was pursued when clinically indicated. Among 256 patients admitted to the ICU with severe COVID-19, 188 (73%) were intubated and 62 (24%) ultimately expired within 30 days of admission to the ICU. Only three patients (1%) were found to have CAPA; diagnosis was made by tracheal aspirate cultures in two cases and by bronchoalveolar lavage fluid Aspergillus galactomannan in one case. None of the patients who developed CAPA had classic risk factors for invasive fungal infection. The occurrence of CAPA was much lower than that reported at other centers, likely reflecting the local epidemiology.

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%), antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Isavuconazole is a broad-spectrum azole that is FDA-approved for the treatment of aspergillosis and mucormycosis; data on the use of isavuconazole for the treatment and prevention of other invasive fungal infections are limited. Here, we report a patient with pulmonary cryptococcosis treated with isavuconazole who experienced progression to disseminated infection with Cryptococcus while on isavuconazole. Caution is advised when using isavuconazole in situations where there is a paucity of data to recommend its use.

This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. There is an increasing awareness of histoplasmosis in Central and South America in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and deaths from histoplasmosis in this region may outnumber deaths from tuberculosis. Diagnosis in this region is hampered by lack of rapid diagnostic tests. Growth of H. capsulatum in culture is definitive, but takes weeks. In areas in which antigen testing is available, this has become an important rapid diagnostic tool, and methods combining antigen and antibody testing appear to improve diagnostic accuracy for acute pulmonary and central nervous system histoplasmosis. Pulmonary histoplasmosis, although usually self-limited, rarely can lead to life-threatening complications. Uncommon, but serious and sometimes fatal complications of disseminated histoplasmosis include Addison’s disease, meningitis, culture-negative endocarditis, and hemophagocytic lymphohistiocytosis. The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. Complications of both pulmonary and disseminated histoplasmosis remain challenging.

Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected.Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load 1000 international units (IU)/ml at LET initiation, two experienced 1 log rise in viral load by week 12, and no deaths were attributed to CMV. Ten patients had viral load 1000 IU/ml at LET initiation, and six of 10 (60%) had a CMV viral load 1000 IU/ml at completion of therapy or last known value. LET was discontinued in two patients for an adverse event.Patients treated with LET with viral load 1000 IU/ml had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed.

We conducted a retrospective review of the infectious complications and outcomes over a 2-year follow-up period of adult patients who received a second allogeneic hematopoietic cell transplant (2nd allo-HCT) during a five-year period at two cancer centers in Michigan. Sixty patients, of whom 44 (73%) had acute leukemia or myelodysplastic syndrome, were studied. The majority (n = 37,62%) received a 2nd allo-HCT because of relapsed leukemia. Infection episodes after the 2nd allo-HCT totaled 112. Bacteria were identified in 76 episodes, the majority of which occurred pre-engraftment. The most common infecting organisms were Enterococcus species and Clostridioides difficile. Viral infections, predominantly cytomegalovirus, accounted for 59 infection episodes and occurred mostly in pre-engraftment and early post-engraftment periods. There were 16 proven/probable fungal infections, of which 9 were invasive aspergillosis or candidiasis. Mortality was 45% (n = 27) at one year and 65% (n = 39) at 2 years after transplant, and 16 deaths (41%) were due to infection. Of those 16 infection deaths, 8 were bacterial, 4 fungal, 2 both bacterial and fungal, and 2 viral. Failure to engraft neutrophils or platelets was significantly associated with decreased survival, p 0.0001 and p 0.001, respectively. Infections are common after a 2nd allo-HCT and are associated with a high mortality rate.

We evaluated the performance of the (1,3)-β-d-glucan (BDG) assay on bronchoalveolar lavage fluid (BALF) as a possible aid to the diagnosis of Pneumocystis jirovecii pneumonia. BALF samples from 18 patients with well-characterized proven, probable, and possible Pneumocystis pneumonia and 18 well-matched controls were tested. We found that the best test performance was observed with a cut-off value of 128 pg/mL; receiver operating characteristic/area under the curve (ROC/AUC) was 0.70 (95% CI 0.52–0.87). Sensitivity and specificity were 78% and 56%, respectively; positive predictive value was 64%, and negative predictive value was 71%. The low specificity that we noted limits the utility of BALF BDG as a diagnostic tool for Pneumocystis pneumonia.

Background Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. Methods Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. Results Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064. Conclusions Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

Detection of (1,3)-beta-d-glucan (BDG), a component of the cell wall of many fungi, was studied in bronchoalveolar lavage fluid (BALF) as a possible aid for the diagnosis of proven/probable invasive pulmonary aspergillosis (IPA). BDG was measured on stored BALF from 13 patients with EORTC/MSGERC defined proven/probable IPA and 26 matched control patients without IPA. The median BALF BDG was 80 pg/mL (range

We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML). We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12 weeks after initiation of appropriate antifungal therapy. Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12 weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04. Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

BACKGROUND The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. We evaluated the performance characteristics of a newly formatted Aspergillus lateral flow test, AspLFD, in bronchoalveolar lavage (BAL) fluid from patients with classic risk factors for IPA. METHODS Prospectively banked BAL samples from 14 patients with proven or probable IPA defined by EORTC/MSG criteria and 28 BAL samples from age-matched high-risk patients without IPA were tested with AspLFD according to manufacturer's directions. Results were read by two independent observers, and test performance was calculated. RESULTS Age, gender and underlying risk factors, except for neutropenia and haematological malignancy, were similar between IPA cases and controls. Seven patients (50%) in the IPA group received a mould-active agent within 5 days prior to bronchoscopy compared with only three patients (11%) in the control group, P = .004. Of 14 patients with proven/probable IPA, AspLFD was positive in 3 and negative in 9; two tests yielded invalid results. All 28 control patients had a negative AspLFD test. AspLFD showed low sensitivity (25%, 95% CI: 5.5% to 57.2%), but high specificity (100%. (95% CI: 87.7% to 100%). CONCLUSIONS A positive AspLFD test in BAL fluid of patients with classic risk factors for IPA could be useful to support the diagnosis of proven/probable IPA because of its high specificity. However, as a stand-alone test for IPA, the use of AspLFD is limited by low sensitivity.

Background Despite the use of antifungal prophylaxis, IFD remains a serious complication of AML causing extensive morbidity and mortality. This study seeks to clarify our experience with breakthrough infections in patients with AML. Methods This retrospective study included all adult patients undergoing induction chemotherapy for a new diagnosis of AML from June 2014 – Dec 2019 at the University of Michigan Hospital. Chart review determined co-morbidities, chemotherapy regimens, allogeneic hematopoietic cell transplant (HCT), antifungal prophylaxis, development of IFD, and outcomes. Patients were followed for 1 year from first induction chemotherapy. EORTC-MSGERC definitions for proven, probable, and possible IFD were used, as were MSGERC-ECMM definitions for breakthrough IFD. Results Of 251 patients, mean age was 61.8±14 years, 55% were men, and 73 (29%) underwent allogeneic HCT, 52 of whom developed GVHD. Thirty-one patients developed 33 IFD (12.3%): 4 proven, 12 probable, and 17 possible IFD. Four IFD occurred in patients with GVHD post-HCT; all were treated with high dose steroids and one received an anti-TNF agent. Of the 16 proven and probable IFD, 8 were breakthrough IFD. Mucormycosis occurred in 2 patients on voriconazole; fusariosis occurred in 3 patients taking fluconazole (2), or posaconazole (1). Aspergillosis occurred in 2 patients taking isavuconazole (1) or fluconazole (1), and pneumocystosis occurred in a patient receiving inhaled pentamidine. There were 8 non-breakthrough IFD, including 2 pneumocystosis, 4 aspergillosis, and 2 candidiasis. Risk for IFD increased with subsequent episodes of induction chemotherapy, p=.04. Six of 8 patients with breakthrough IFD and 5 of 8 without breakthrough IFD died within 12 weeks of IFD diagnosis. Excluding the 15 patients who had only possible IFD, 69% (11/16) patients with proven/probable IFD died compared with 35% (77/220) patients without IFD, p=.01. Conclusion Patients with AML remain at risk for fatal IFD despite the use of antifungal prophylaxis. Failure of prophylaxis in our patients who developed breakthrough IFD was associated with a shift towards less common fungi. Disclosures All Authors: No reported disclosures

Background Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. Methods All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. Results Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. Conclusions Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.

Infections with the endemic fungus Blastomyces dermatitidis are uncommonly reported in hematopoietic cell transplant recipients. We present a case of pulmonary blastomycosis in a patient who had an allogeneic hematopoietic cell transplant 10 months previously and who responded rapidly to tre

A 30-year-old woman with history of diabetes mellitus type 1 and a kidney/pancreas transplant 2 years earlier presented with 24 h of nausea and non-bloody, non-bilious vomiting. She had sharp right upper quadrant and epigastric pain that worsened after eating. She reported decreased urinary output, fatigue, and malaise. She denied having fevers or chills. Two weeks prior to presentation, she had intermittent rhinorrhea and sinus congestion that had recently resolved.

A 58-year-old man had a history of chronic lymphocytic leukemia. Seven weeks after an allogeneic hematopoietic stem cell transplant, he presented with loss of vision in his left eye, impaired depth perception, and gait imbalance. Before the transplant, he had developed mild impairment of visual acuity.

Background A major challenge in patients with AL receiving chemotherapy is to decrease the risk of IFI during the prolonged neutropenic period. Even with antifungal prophylaxis, the incidence of breakthrough IFI can be as high as 14%. Our objectives were to determine the incidence of all IFI and breakthrough IFI, to define risk factors associated with IFI, and to assess outcomes. Methods Single-center retrospective cohort analysis of all adult patients admitted to the University of Michigan for AL from January 1, 2010 to December 31, 2013. Chart review determined co-morbidities, chemotherapy regimens, antifungal prophylaxis, occurrence of IFI as determined by EORTC/MSG criteria, and outcomes. Chi-square, Fischer’s, ANOVA, and binary logistic regression tests were performed when appropriate. Results Of 363 patients, all but 4 had acute myeloid leukemia (AML); 124 had a stem cell transplant (SCT). A total of 103 (28%) had proven (n = 13), probable (n = 22), or possible (n = 68) IFI. Considering only those 35 patients who had proven or probable IFI, the only risk factor for development of IFI by logistic regression analysis was IFLAG chemotherapy (P = .006). Mold infections occurred in 27 patients: Aspergillus (19), Mucorales (5), both Aspergillus and Mucorales (1), Alternaria (1), and Scedosporium (1). Additionally, 5 patients had invasive candidiasis and 3 had Pneumocystis. Eighteen of 35 patients (51%) had breakthrough IFI while on posaconazole suspension (6), fluconazole (5), micafungin (5) or voriconazole (2). Factors significantly associated with breakthrough IFI were SCT (P = .04), neutrophils Conclusion Patients receiving chemotherapy for AL remain at risk for IFI despite the the use of antifungal prophylaxis. In our study, prophylaxis with posaconazole suspension was found to be an independent risk factor for breakthrough IFI. Mortality was high among patients with breakthrough IFI. Disclosures All authors: No reported disclosures.

Background Early diagnosis of IPA is challenging and has a direct impact on mortality. Several diagnostic modalities have been developed with variable performance. AspID is a new multiplex Aspergillus qRT-PCR assay and AspLFD is a rapid test that targets the Aspergillus specific antigen JF5; both tests were developed by OLM Diagnostics. We evaluated the performance characteristics of AspID used alone and in combination with AspLFD on BAL fluid of patients at high risk for IPA. Methods Samples had been prospectively banked in our BAL repository. Forty-two samples, 14 from patients with proven/probable IPA by EORTC/MSG criteria and 28 from control patients without IPA, were tested with AspID and AspLFD. For AspID, DNA extraction and qRT-PCR were performed per manufacturer instructions. For AspLFD, 100 μL of sample was applied to the device. AspID and AspLFD results were each read by three different blinded observers. Only patient with a valid result for both tests were included in the analysis. Sensitivity, specificity, and accuracy of AspID alone and in combination with AspLFD were calculated. Results Of the 42 samples, 22 were excluded because the AspID internal extraction control showed the assay to be invalid and one sample was excluded because the AspLFD internal control line was not visible. Thus, 19 patients were analyzed, eight with IPA and 11 without IPA. Among eight IPA cases, seven were positive by AspID and one was negative; two tested positive by AspLFD and six were negative. Of the 11 control patients without IPA, four were positive by AspID and seven were negative; all 11 were negative by AspLFD. AspID sensitivity was significantly higher than that of AspLFD (87.5% vs. 25%, P = .0001), but specificity of AspLFD was superior to that of AspID (100% vs. 64%, P = 0.049). Accuracy was 74% for AspID and 68% for AspLFD. When deciding whether doing both tests was beneficial for diagnosis, union analysis showed the sensitivity to be 87.5% and the specificity to be 64%. Accuracy was not improved and remained at 74%. Conclusion AspID had higher sensitivity than AspLFD and AspLFD had higher specificity than AspID. Using both tests in combination did not improve the ability to diagnose IPA in patients with classic risk factors. Disclosures All authors: No reported disclosures.

Background UCBT can be performed in pt with hematologic malignancies who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic stem cell transplant. Delayed engraftment can increase the risk for infections, but characteristics of specific infections & outcomes have not been well characterized in adults undergoing UCBT. Methods All adults who underwent UCBT between January 1, 2006 and January 1, 2016 at our two centers were included. Infectious episodes within 6 months before and up to 2 years after UCBT were reviewed. Results Fifty-seven patients underwent UCBT. Mean age was 43 ± 14 years, and 34 patients were women. Thrity-nine (60%) had acute leukemia. Only 47 patients had neutrophil engraftment. One hundred and seventy-nine infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. HHV-6 occurred in 28 episodes, 24 of which were viremia alone, and was most common within 30 days of UCBT. One patient died of HHV-6 encephalitis. CMV caused 32 infectious episodes, 24 of which were viremia only, was most common from Days 30–100, and caused no deaths. BK viruria occurred in 18 episodes. Bacteria were responsible for 82 (46%) infections; most common were bacteremias due to Staphylococcus, van-R Enterococcus and Enterobacteriaceae. Three patients had mycobacterial infections, two of which were fatal. Of 11 invasive fungal infections (IFI), nine were invasive aspergillosis, of which four were fatal. Overall mortality was 56% in the first year, including 13 deaths from infection. Eleven of these 13 infections occurred in the first 100 days post-UCBT and seven of them in the first 30 days. Patients who died within 100 days were significantly more likely to have had IFI (P = 0.04) or infection with VRE (P = 0.03) or Enterobacteriaceae (P = 0.03) within 30 days after UCBT. Among the 10 patients who never had neutrophil engraftment, nine died within 100 days post-UCBT, six from infection. Conclusion Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected, most likely because of increased screening and prophylaxis for CMV infections. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT. Disclosures All authors: No reported disclosures.

Background LTx patients (pt) are at increased risk for IFI. Systemic AP is widely used, but the optimal strategy remains unclear. Our LTx program changed from universal to targeted AP in July 2016; we compared outcomes between the 2 strategies. Methods All adult pt who underwent LTx at U. Michigan from July 1, 2014 to December 31, 2017 were studied for 18 mo post-LTx. Universal AP consisted of itraconazole (itra) ± inhaled liposomal amphotericin-B (iAmB) for 6 months. Pt received targeted AP with voriconazole for 3 months if they had a history of pre-LTx Aspergillus colonization or invasive pulmonary aspergillosis (IPA); 14 days of a yeast-active azole was given if donor or recipient had Candida colonization at the time of LTx. All other pt received no AP. Demographics, LTx characteristics, occurrence of proven/probable IFI defined by EORTC/MSG criteria, and mortality data were recorded. Results Of 105 LTx patients, 73 (70%) were men and 84 (80%) received a double LTx. The most common indication for LTx was idiopathic pulmonary fibrosis (38, 36%). Of 59 pt receiving universal AP, 36 (61%) received itra, and 23 (39%) received itra+iAmB; outcomes did not differ between these 2 regimens. Of 46 patients in the targeted AP cohort, 10 (22%) received antifungals based on predefined criteria. Overall, 19 proven/probable IFI occurred: 14 IPA, 3 invasive Candida infections, 1 Cryptococcus pneumonia, and 1 mold wound infection. IFI occurred in 5 patients (8%) in universal AP group vs. 13 patients (28%) in targeted AP group, P = .008. All but 1 IFI in the targeted AP group occurred among pt for whom antifungals were not recommended or given. IPA occurred in 4 patients (7%) in universal AP group and 9 patients (20%) in targeted AP group, P = 0.05; Candida infections occurred only among patients in the targeted AP cohort. Time to IFI was similar between the 2 AP strategies with the majority occurring Conclusion When compared with universal AP, targeted AP strategy was associated with a significant increase in IFI post-LTx. Universal AP for 6 months appears to be more effective than our targeted AP strategy for prevention of IFI post-LTx. Disclosures Marisa H. Miceli, MD, FIDSA, Astellas: Advisory Board, Research Grant; Scynexis: Research Grant.

Group A streptococcal bloodstream infection is the most common presentation of invasive group A streptococcal disease. We sought to determine the impact of immunosuppression on severity of disease and clinical outcomes.This retrospective review of 148 patients with at least one positive blood culture for Streptococcus pyogenes from 1/2003 to 3/2013 compared immunocompromised patients with those with no immunocompromise in regards to development of severe complications and mortality.Twenty-five patients (17%) were immunocompromised; 123 were not. Skin and soft tissue infection occurred in 60% of immunocompromised vs. 38% of non-immunocompromised patients, p = .04. Necrotizing fasciitis and septic shock were significantly more common in immunocompromised patients, p .0001 and .028, respectively. Mortality at 30 days was 32% in immunocompromised patients vs. 16% in non-immunocompromised patients, p = .05.Patients who are immunocompromised are more likely to develop necrotizing fasciitis and septic shock as complications of group A streptococcal bacteremia and have a higher mortality rate than patients who are not immunocompromised.

Background IPA causes high morbidity and mortality in immunocompromised patients, but diagnosis remains challenging. A newly formatted AspLFD targets specific Aspergillus antigen JF5, but reported results for this test are variable. We evaluated the performance characteristics of this new AspLFD in BAL fluid of patients with IPA. Methods Samples tested were from patients with classic risk factors for IPA defined by EORTC/MSG criteria and that had been prospectively banked in our BAL repository. Each case of IPA identified was matched to two high-risk control patientst without IPA or other invasive fungal infection. Samples were thawed, vortexed, centrifuged, and 100 μL of supernatant was applied to the AspLFD. Results were interpreted at 15 minutes as +, ++, +++, or negative by three independent, blinded observers. Test characteristics, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Samples from 14 patients with proven/probable IPA by EORTC/MSG criteria and 28 control patients without IPA were tested. Median age was 58 (range 22–87); 28 were men. Age and gender distribution were similar between cases and controls. Among IPA cases, 9 were on T cell depleting agents, 4 on high-dose steroids, and 3 had prolonged neutropenia. Among non-IPA controls, risk factors were T-cell depleting agents (17), high-dose steroids (11), and stem cell transplant (2). Of the 14 patients with IPA, AspLFD was positive in 3, negative in 9; in 2, the internal control line did not display and these were considered invalid. Of 6 patients receiving an azole, three had a positive AspLFD test. AspLFD was negative for all 28 BAL in the non-IPA group. AspLFD showed low sensitivity (25%) and high specificity (100%); PPV was 100% and NPV was 75%. Accuracy of the test was 77.5%. Conclusion A positive AspLFD test in BAL of patients with classic risk factors for IPA could be useful for ruling in proven/probable IPA because of its high specificity. However, the use of AspLFD as a screening test for IPA is limited by its poor sensitivity. Disclosures All authors: No reported disclosures.

In hospitalized patients with urinary tract infection or asymptomatic bacteriuria, urinary pathogens frequently contaminate skin, high-touch environmental surfaces, and urinary catheters. Contamination is more common in patients with a urinary catheter in place and with gram-positive pathogens. Patients' skin and environmental surfaces may provide an important source for transmission of urinary pathogens.

A morphometric analysis of mouse sperm and of their nuclei was undertaken to investigate their respective post-testicular maturation. Sperm were collected from the testis, caput and cauda epididymidis, and their corresponding nuclei were isolated. Results indicate that the post-testicular maturation of sperm is distinct from that of nuclei. The size of intact sperm heads increases in the caput followed by a subsequent decrease in the cauda. In contrast, sperm nuclei decrease progressively in size. In general, a greater magnitude and number of alterations in intact heads and nuclei occur while in transit from the testis to the caput than during passage to the cauda epididymis. These results suggest that the period immediately following their release from the testis is crucial to the complete morphological maturation of sperm heads and nuclei. © 1993 Wiley-Liss, Inc.