We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response.

Histoplasma capsulatum causes pneumonia and multisystemic disease in humans. Musculoskeletal involvement in histoplasmosis is most often tenosynovitis and rarely septic arthritis. Even more uncommon is the involvement of prosthetic joints. Here, we report a series of 3 cases of prosthetic joint failures caused by infection due to H capsulatum. Together with a review of 4 previously reported cases, we summarize host characteristics, clinical presentation, surgical approaches, antifungal management, and outcomes of this rare orthopedic joint infection.

Abstract Background The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. Methods This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. Results Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). Conclusions Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

The World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO 2017) included updated criteria for diagnosis and classification of post-transplant lymphoproliferative disorders (PTLDs). This study evaluated the clinicopathologic spectrum using WHO 2017 criteria and adult PTLD patients’ outcomes over 30 years between 1987 and 2017 at Mayo Clinic (Rochester, MN). Patients were retrospectively reviewed for clinical features, outcomes, and diagnostic pathology material and classified based on WHO 2017 criteria. A total of 227 patients were diagnosed with PTLD, with a median time from transplant to PTLD of 45 months. PTLD occurred >1 year after transplant in 149 (66%) patients. Monomorphic PTLD was the most common subtype (173, 76%), with diffuse large B cell lymphoma as the commonest morphology (n = 137). Epstein-Barr virus was positive in 61% of total cases and 90% of PTLD that developed within 1 year from transplant. The median event-free survival (EFS) and overall survival for the entire cohort were 21 months (95% confidence interval [CI]: 9–35) and 82 months (95% CI: 39–115), respectively. The EFS or overall survival was not impacted by Epstein-Barr virus status but differed based on WHO subtypes and year of diagnosis. Management changed over time with increased use of rituximab or chemotherapy + immunosuppression reduction as initial therapy. When compared to the matched general population and de novo diffuse large B cell lymphoma, patients not achieving EFS 24 status (no progression/treatment or death within 24 mo of diagnosis) had a worse standardized mortality ratio 16.75 (95% CI: 13.91–20) versus SMR 1.72 (95% CI: 1.26–2.28) in those who achieved EFS24. Cause of death was mostly attributed to non-lymphoma–related causes in those achieving EFS 24.

Neutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation.

The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections. We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD. We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn’s disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically. We identified 49 patients (median age 44 years; range 19–76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary disease alone 0.375 ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%). Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

Abstract Background Tumor necrosis factor (TNF)-α antagonist therapy has revolutionized the practice of management of inflammatory bowel disease (IBD); however, these medications carry a boxed warning from the Food and Drug Administration for risk of serious infection. We aimed to study the invasive fungal infection, histoplasmosis, in the setting of TNF-α antagonist therapy. Methods We performed a retrospective review of patients with IBD receiving TNF-α antagonist therapy who developed histoplasmosis during the time period January 2001–May 2018 at the Mayo Clinic, Rochester, MN. The medical records of patients were reviewed for demographics, medications, symptoms, diagnosis, treatment, and outcomes including mortality. IBD was diagnosed by biopsy, radiographic, or endoscopic evidence of disease. Results We identified 49 patients (age range 19–74; median 44 years) with a confirmed diagnosis of histoplasmosis while receiving a TNF-α antagonist. 73.5% of cases were classified as disseminated. Median time from starting TNF-α antagonist to histoplasmosis diagnosis was 2.1 years. Liposomal amphotericin B was given in 17 cases as the initial treatment. Itraconazole was given to all 49 patients. Initial treatment was split evenly between inpatient (49%) and outpatient (51%) locations with 6 patients (12%) requiring ICU-level care. Median length of stay was 9.5 days. The total length of treatment for all antifungals was 38.4 weeks, with 20.4% of patients developing documented antifungal side effects. TNF-α antagonist was continued in 9 patients (18.4%) and another 10 patients resumed TNF-α antagonist. Half of those who resumed TNF-α antagonists were on antifungal therapy. There was one histoplasmosis recurrence while off TNF-α antagonist, and three deaths (6%). Conclusion Histoplasmosis outcomes in IBD patients on TNF-α antagonists were mostly favorable; however, approximately half required hospitalization. Many patients were young with few co-morbidities, and over one-third were able to continue or resume TNF-α antagonists without documented recurrence of histoplasmosis. Practitioners should be vigilant for histoplasmosis infections in this patient population who reside in histoplasma-endemic regions. Disclosures All authors: No reported disclosures.

The D-index assesses neutropenia dynamics. Prolonged neutropenia is a major risk for invasive fungal infection (IFI); we hypothesized that D-index is predictive of IFI risk. We retrospectively reviewed 789 adults who underwent allogeneic hematopoietic transplant (HSCT) from 1/1/2005 to 9/30/2015. Medical records were reviewed from transplant (D0) through Day 100. The D-index was calculated as area over the neutrophil curve until engraftment. 714 patients were included for analysis. Sixteen (2%) developed probable (11) or proven (5) IFI. Median time to IFI was 40 days (range 8–98) after HSCT. Groups with and without IFI did not differ significantly in duration of mild or profound neutropenia. Median D-index of those with IFI was 4293 days neutrophil/µl compared to 3590 days neutrophil/µl for those without IFI (P = 0.17). Patients who were neutropenic on D0 showed higher rates of IFI than those who were not (10/123 [8%] vs 6/591 [1%]; P < 0.001). Only 2% developed IFI, likely due to mold-active antifungal prophylaxis. The D-index was not significantly higher in those with IFI. Duration of profound neutropenia and neutropenia at D0 may be better markers for IFI among HSCT recipients during the first 30 and 100 days after transplant.

Abstract Background Diffuse large B cell lymphoma post-transplant lymphoproliferative disorder (DLBCL-PTLD) represents a fatal complication after a solid organ transplant (SOT). Approximately 50% of DLBCL-PTLD can be related to Epstein Barr Virus (EBV) infection. However, the EBV status is not taken into account in the DLBCL-PTLD categorization, although increasing evidence suggests its critical role in biological, clinical and prognostic aspects of the disease. In this single center retrospective study, we compared clinical and histological features, as well as outcomes of DLBCL-PTLDs by EBV status. Methods This study focused on patients with SOT who were diagnosed with DLBCL-PTLD at Mayo Clinic (Rochester, MN). Patients were identified through the Mayo Clinic Lymphoma Data base and the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), between 1989 and 2017. The histology was re-reviewed (RLK) and classified according to the WHO Classification or Tumours of Haematopoietic and Lymphoid Tissues 2017. Cell of origin (COO) was performed by Hans algorithm. EBV RNA in situ hybridization (EBER) was performed. Cox proportional hazards models were used to assess the association of clinical factors in overall survival (OS). Results 148 DLBCL-PTLD were identified. The median age at SOT and at the time of PTLD diagnosis were 50 years (range: 15-71) and 56 years (range: 18-82), respectively. The median time to PTLD diagnosis from SOT was 38 months (range: 1-499). The types of SOT included renal (44%), liver (36%), cardiac (9%), renal/pancreas (5%), pancreas (8%), lung (7%) and multiorgan (4%). 62% were stage III-IV, 30% had elevated LDH and 67% had an IPI >1. 88% of patients presented with extranodal disease, and 16% had involvement of the grafted organ. Eighty-three (56%) cases were EBV positive. The COO information was available on 35 cases. The non-GCB subtype was identified in 24 cases and GCB subtype in 11 cases. The initial treatment was as follows: reduction in immunosuppression (12%), immunosuppression reduction with rituximab (26%), rituximab alone (5%), chemotherapy with or without rituximab (35%). Patients with EBV positive PTLD were more likely to have grafted organ involvement (20% vs. 8%, p=0.047) and late PTLD (occurring after 12 months from SOT - 60% vs. 8%, p<0.001) than patients with EBV negative PTLD. There was no association between EBV status and age, sex, stage, LDH, and extranodal site involvement. At a median follow-up of 80 months (range 9-269), 83 patients (56%) had died. The 5-year survival rate from PTLD diagnosis was 56% (95% CI: 48-65%). The median OS was 85 months (95% CI: 37-148). There was no difference in OS in patients with EBV positive PTLD (median OS=84.7 months, HR=1.21, 95% CI: 0.77-1.92) versus patients with EBV negative DLBCL-PTLD (median OS=85.4 months, p=0.41). Conclusion Our study assessed the impact of EBV status on the presentation and clinical outcome of DLBCL-PTLD in a 148-patient single-institution cohort. 56% of cases were EBV positive. EBV positivity was associated with grafted organ involvement and late PTLD diagnosis. Patients with EBV-negative and EBV-positive disease had similar survival from PTLD diagnosis. Disclosures Maurer: Celgene: Research Funding; Morphosys: Research Funding; Nanostring: Research Funding. Cerhan:Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.

Left ventricular assist devices (LVAD)-associated infections are associated with fivefold higher 1-year mortality. Published literature is insufficient to inform clinicians regarding optimal management of bloodstream infection (BSI) in patients LVAD recipients. In particular, it is unclear which episodes of BSI may result in occult hematogenous seeding of the device surfaces, and therefore should be managed with chronic suppressive therapy (CAS). We aim to describe BSI, CAS, and breakthrough BSI in our LVAD population. We retrospectively reviewed 332 episodes of all LVAD infections at Mayo Clinic from 2007 to 2015. We categorized BSI as LVAD related/associated and LVAD nonrelated as defined by established criteria in the cardiac device literature. Our primary outcome was to describe breakthrough BSI in LVAD related and nonrelated infections in patients receiving CAS and those who were not. We identified 68 episodes of bacteremia in our LVAD population. Of these, 55 were proven BSI (see Fig 1). In our study cohort, 45/55 (82%) were male and median patient age was 62 years. A majority of LVAD implants were destination therapy 34/55 (62%) and 35/55(64%) had a central line in place at the time of BSI. Twenty patients had non-VAD-related BSI and nine of these (9/20, 45%) patients were placed on CAS with two of these (2/9, 22%) had subsequent breakthrough BSI, whereas 11/20 (55%) were not placed on CAS with no breakthrough infections seen (Figure 1). Our preliminary data suggest that routine use of CAS for non-VAD-related BSI is not necessary as only a minority go on to have breakthrough BSI. Limiting unnecessary use of antibiotics will have significant implications for stewardship and preventing emergence of resistance. L. M. Baddour, UpToDate: Collaborator, Royalty payment. M. R. Sohail, TyRx Inc: Investigator, Research support; Medtronic Inc: Investigator, Research support; Medtronic Inc: Consultant, Speaker honorarium; Spectranetics: Consultant, Speaker honorarium; Boston Scientific Corp: Consultant, Speaker honorarium.

Background: PTLD is the most common malignancy, other than non-melanoma skin cancer, complicating solid organ transplantation (SOT) and has been one of the most commonly observed fatal consequences in SOT. The clinical presentations, management strategies, histologies, causes of death and outcomes are diverse (Dierickx D, Habermann TM. N Engl J Med 2018;378:549-62). The 2017 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues has redefined the categories as non-destructive PTLDs (plasmacytic hyperplasia, infectious mononucleosis, and florid follicular hyperplasia), polymorphic PTLD, monomorphic PTLD: B-cell neoplasms (diffuse large B-cell lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, plasma cell myeloma, plasmacytoma, and other) and T-cell neoplasms (peripheral T-cell lymphoma NOS, hepatosplenic T-cell lymphoma, other), and classic Hodgkin lymphoma (CHL) PTLD. We report the outcomes and long-term follow-up of patients from a single institution based on these categories whose pathology was retrospectively reviewed and reclassified based on the WHO 2017 classification.

Table 1.Urinary sucrose excretion (µmol), L/M and

Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms.

Clinical and microbiological characteristics of patients with Bacteroides prosthetic joint infection (PJI) have not been well described in the literature. The aim of this retrospective cohort study was to assess the outcome of patients with Bacteroides PJI and to review risk factors associated with failure of therapy. Between 1/1969 and 12/2012, 20 episodes of Bacteroides PJI in 17 patients were identified at our institution. The mean age of the patients in this cohort at the time of diagnosis was 55.6 years; 59% (n=10) had knee involvement. Twenty four percent (n=4) had diabetes mellitus, and 24% had a history of either gastrointestinal (GI) or genitourinary (GU) pathology prior to the diagnosis of PJI. Thirty five percent (n=6) were immunosuppressed. The initial medical/surgical strategy was resection arthroplasty (n=9, 50%) or debridement and implant retention (n=5, 28%). Thirty seven percent (n=7) were treated with metronidazole. Eighty percent (n=4) of patients that failed therapy had undergone debridement and retention of their prosthesis, as compared to none of those treated with resection arthroplasty. Seventy percent (n=14) of patient episodes were infection free at their last date of follow up. In conclusion, a significant proportion of patients with Bacteroides PJI are immunosuppressed and have an underlying GI or GU tract pathology. Retention and debridement of the prosthesis is associated with a higher risk of treatment failure.

BACKGROUND:Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited.METHOD:The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17 000 OTRs. Analyses were undertaken to determine predictors of infection and mortality.RESULTS:A total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra-abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All-cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non-white race and female gender were more commonly associated with non-albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species.CONCLUSION:These data highlight the common and distinct features of IC in OTRs.

The outcome of patients with prosthetic joint infection (PS PJI) has not been well studied. The aim of this retrospective cohort study was to assess the outcome of patients with PJI and to review risk factors associated with failure of therapy. Between 1/1969 and 12/2012, 102 episodes of PS PJI in 91 patients were identified. : The mean age at the time of diagnosis was 67.4 years; forty three percent had knee involvement. Over 40 percent had either diabetes mellitus or a history of gastrointestinal or genitourinary surgery. Nearly half (48 out of 102 episodes) received aminoglycoside monotherapy, while 25% received an anti-pseudomonal cephalosporin. The 2-year cumulative survival free from failure was 69% (95% CI, 56%-82%). Patients treated with resection arthroplasty, two-stage exchange, and debridement with implant retention had a 2-year cumulative survival free from failure of 80% (95% CI, 66%-95%), 83% (95% CI, 60%-100%), and 26% (95% CI, 23%-29%) respectively (P=0.0001). PS PJI's are associated with a high failure rate. Patients treated with debridement and implant retention had a worse outcome.

Background: The outcome of patients with Pseudomonas prosthetic joint infection (PS PJI) has not been well studied. The aim of this retrospective cohort study was to assess the outcome of patients with Pseudomonas PJI and to review risk factors associated with failure of therapy. Methods: Between 1/1969 and 12/2012, 102 episodes of PS PJI in 91 patients were identified. Results: The mean age at the time of diagnosis was 67.4 years; forty three percent had knee involvement. Over 40 percent had either diabetes mellitus or a history of gastrointestinal or genitourinary surgery. Nearly half (48 out of 102 episodes) received aminoglycoside monotherapy, while 25% received an anti-pseudomonal cephalosporin. The 2-year cumulative survival free from failure was 69% (95% CI, 56%-82%). Patients treated with resection arthroplasty, two-stage exchange, and debridement with implant retention had a 2-year cumulative survival free from failure of 80% (95% CI, 66%-95%), 83% (95% CI, 60%-100%), and 26% (95% CI, 23%-29%) respectively (P=0.0001). Conclusions: PS PJI's are associated with a high failure rate. Patients treated with debridement and implant retention had a worse outcome.