Search

Limited data exist on the spatial distribution of the colonic bacteria in humans. We collected the colonic biopsies from five segments of 27 polyp-free adults and collected feces from 13 of them. We sequenced the V4 region of the bacterial 16S rRNA gene using the MiSeq platform. The sequencing data were assigned to the amplicon sequence variant (ASV) using SILVA. Biodiversity and the relative abundance of the ASV were compared across the colonic segments and between the rectal and fecal samples. Bacterial functional capacity was assessed using Tax4fun. Each individual had a unique bacterial community composition (Weighted Bray–Curtis P value = 0.001). There were no significant differences in richness, evenness, community composition, and the taxonomic structure across the colon segments in all the samples. Firmicutes (47%), Bacteroidetes (39%), and Proteobacteria (6%) were the major phyla in all segments, followed by Verrucomicrobia, Fusobacteria, Desulfobacterota, and Actinobacteria. There were 15 genera with relative abundance > 1%, including Bacteroides, Faecalibacterium, Escherichia/Shigella, Sutterella, Akkermansia, Parabacteroides, Prevotella, Lachnoclostridium, Alistipes, Fusobacterium, Erysipelatoclostridium, and four Lachnospiraceae family members. Intra-individually, the community compositional dissimilarity was the greatest between the cecum and the rectum. There were significant differences in biodiversity and the taxonomic structure between the rectal and fecal bacteria. The bacterial community composition and structure were homogeneous across the large intestine in adults. The inter-individual variability of the bacteria was greater than inter-segment variability. The rectal and fecal bacteria differed in the community composition and structure.

To characterize the spatial variation of the mucosa-associated adherent mycobiota along the large intestine in individuals with a normal-colon, we performed eukaryotic rRNA operon’s internal transcribed spacer-2 sequencing to profile fungal community composition and structure in 70 mucosal biopsies taken from the cecum, ascending, transverse, descending colon, and rectum of 14 polyp-free individuals. The bacteriome of these samples was previously characterized by sequencing the V4 region of the 16S rRNA gene. We identified 64 amplicon sequence variants (ASVs) with the relative abundance no less than 0.05% from these colonic mucosa samples. Each individual has a unique community composition of the gut mycobiome (P = 0.001 for beta diversity). Alpha-diversity and beta-diversity did not differ significantly across the colon segments. The most common phyla (relative abundance) were Ascomycota (45.4%) and Basidiomycota (45.3%). The most common genera were Malassezia (28.2%) and Candida (13.4%). Malassezia was found in 13 of 14 individuals. Other fungi genera were sporadically found in the large intestine. The most common species were Malassezia restricta (22.7%), Candida albicans (11.9%), Malasseziales sp. (8.80%), unclassified fungi (7.80%), and Penicillium paneum (5.70%). Malasseziaceae was co-abundant with Enterobacteriaceae and co-exclusive with Barnesiellaceae, Rikenellaceae, and Acidaminococcaceae. Malassezia was widely colonized whereas other fungal genera were sporadically colonized in the large intestine. The physiologic and pathogenic functions of fungi in human gastrointestinal tract including Malasseziaceae that may interact with several bacterial families remain to be fully elucidated.

To prevent rejection, liver transplant providers largely base their management decisions on their clinical impression and pharmacokinetics. Clinical impression relies on assessing graft function, liver enzymes, and biopsy. High immunosuppressive drug levels, although minimizing rejection, are related to significant side effects such as nephrotoxicity and metabolic syndrome, contributing to long-term morbidity and mortality. Similarly, levels that are lower than necessary can decrease the rate of side effects with a potential toll on rejection and graft survival. Herein, the authors present an update on immunosuppressive drug level monitoring and manipulation strategies according to different scenarios and time from transplant. They also provide a brief overview of next level immunosuppression monitoring strategies that aim to properly balance rejection rates with drug side effect profiles.

Apart from the classic knowledge that ethanol mediates its hepatotoxicity through its metabolism to acetaldehyde, a well-known hepatotoxic molecule, recent research has elucidated several key mechanisms that potentiate ethanol's damage to the liver parenchyma, such as generation of free radicals, activation of Kupffer cells, and alterations to the human bacterial and fungal microbiome. Genetic studies have suggested the role of PNPLA3 and TM6SF2 gene mutations in the progression of alcoholic liver disease.

Limited data exist on the spatial distribution of the colonic bacteria in humans. We collected the colonic biopsies from five segments of 27 polyp-free adults and collected feces from 13 of them. We sequenced the V4 region of the bacterial 16S rRNA gene using the MiSeq platform. The sequencing data were assigned to the amplicon sequence variant (ASV) using SILVA. Biodiversity and the relative abundance of the ASV were compared across the colonic segments and between the rectal and fecal samples. Bacterial functional capacity was assessed using Tax4fun. Each individual had a unique bacterial community composition (Weighted Bray-Curtis P value = 0.001). There were no significant differences in richness, evenness, community composition, and the taxonomic structure across the colon segments in all the samples. Firmicutes (47%), Bacteroidetes (39%), and Proteobacteria (6%) were the major phyla in all segments, followed by Verrucomicrobia, Fusobacteria, Desulfobacterota, and Actinobacteria. There were 15 genera with relative abundance 1%, including Bacteroides, Faecalibacterium, Escherichia/Shigella, Sutterella, Akkermansia, Parabacteroides, Prevotella, Lachnoclostridium, Alistipes, Fusobacterium, Erysipelatoclostridium, and four Lachnospiraceae family members. Intra-individually, the community compositional dissimilarity was the greatest between the cecum and the rectum. There were significant differences in biodiversity and the taxonomic structure between the rectal and fecal bacteria. The bacterial community composition and structure were homogeneous across the large intestine in adults. The inter-individual variability of the bacteria was greater than inter-segment variability. The rectal and fecal bacteria differed in the community composition and structure.

Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls.

Background Studies have demonstrated an association between anti-TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether specific medication types affect protective HBsAb titers. Our aim was to analyze this association. Methods This is a retrospective cohort study. Inclusion criteria: age ≥18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), previous HBV vaccination series and/or ≥1 positive HBsAb, and record of IBD therapy in 6 months before titer level. Patients were stratified based upon medication exposures: anti-TNF, immunomodulator, combination anti-TNF and immunomodulatory, and a reference arm. Titer levels following vaccination and specific medication types given in the 6 months before titer were recorded. Seroprotection was defined as HBsAb ≥10 IU/l and ≥100 IU/l. Results The study cohort (N = 391) was 70.8% white, 51.4% female and 64.2% had CD and 35.8% had UC. The mean age was 45.8 years. A significantly lower percentage of patients exposed to anti-TNF, immunomodulator or dual therapy had titers ≥10 (P < 0.01). Regarding specific medications, only patients exposed to infliximab (P < 0.01) were less likely to have titer levels ≥10, after controlling for other medication exposures, age at titer level, and interval time between vaccination/titer level. This was not found for patients exposed to adalimumab, methotrexate, 6-mercaptopurine, or azathioprine. Conclusions Patients exposed to infliximab were significantly less likely to have protective HBsAb titer levels following vaccination, a trend not seen in patients on adalimumab. Efforts to vaccinate IBD patients against HBV before use of immunomodulators and anti-TNFs, infliximab specifically, and screen periodically thereafter must be reinforced.

Apart from the classic knowledge that ethanol mediates its hepatotoxicity through its metabolism to acetaldehyde, a well-known hepatotoxic molecule, recent research has elucidated several key mechanisms that potentiate ethanol's damage to the liver parenchyma, such as generation of free radicals, activation of Kupffer cells, and alterations to the human bacterial and fungal microbiome. Genetic studies have suggested the role of PNPLA3 and TM6SF2 gene mutations in the progression of alcoholic liver disease.

Background and objectives: Autophagy is a physiologic mechanism, which utilizes the self-digestion of cell organelles to promote cellular homeostasis, such as in the setting of dysfunctional cellular components, cellular stress or energy-deprived states. In vitro studies have pointed toward the key role of autophagy in colorectal cancer. However, in vivo studies from human colorectal cancer tissues are lacking. Methods: We collected tissue samples from six patients with colon cancer who received curative surgery at Baylor College of Medicine. We also obtained normal colonic mucosa biopsy from five unrelated polyp-free individuals who were matched to cases individually by age, sex, ethnicity, and colon segment. Total RNA was successfully extracted from fresh frozen tissue biopsies of five tumor tissues and five unrelated normal tissues. We tested the expression levels of 84 genes in a predefined autophagy pathway using the RT2 Profiler PCR array. We compared differences using Student’s t-test. The false-discovery rate was used for multiple testing adjustment. We also used the TCGA dataset to validate our findings. Results: We observed significant differential expression between colon cancer tissue and normal colon mucosa for 29 genes in the autophagy pathway (p < 0.05). After multiple testing adjustment, the expression of 17 genes was significantly down-regulated, with fold-change greater than 2 in colon cancer; these included ATG4A, ATG4C, ATG4D, and CTSS (q < 0.10). The down-regulation was observed in both early and late stage colon cancer. We observed the same down-regulation of multiple autophagy-related genes using the TCGA data. The ATG9B gene was the only statistically non-significantly up-regulated gene after multiple testing adjustment. Conclusions: This pilot study showed the down-regulation of multiple autophagy pathway genes in human colon cancer, corroborating the increasing clinical relevance of autophagy in human colorectal carcinogenesis. This preliminary finding should be validated in larger studies.

An 87-year-old man presented with a 3-week history of nausea, emesis, anorexia, and weight loss. Upper endoscopy identified three pigmented lesions, and melanoma was confirmed on biopsy.

Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention.

One carbon (1C) metabolism nutrients influence epigenetic regulation and they are supplied by diet and synthesized by gut microbiota. We examined the association between dietary consumption of methyl donors (methionine, betaine and choline) and B vitamins (folate, B2, B6, and B12) and the community composition and structure of the colonic mucosa-associated gut microbiota determined by 16S rRNA gene sequencing in 97 colonic biopsies of 35 men. We used the food frequency questionnaire to assess daily consumption of nutrients, and the UPARSE and SILVA databases for operational taxonomic unit classification. The difference in bacterial diversity and taxonomic relative abundance were compared between low versus high consumption of these nutrients. False discover rate (FDR) adjusted p value &lt, 0.05 indicated statistical significance. The bacterial richness and composition differed significantly by the consumption of folate and B vitamins (p &lt, 0.001). Compared with higher consumption, a lower consumption of these nutrients was associated with a lower abundance of Akkermansia (folate), Roseburia (vitamin B2), and Faecalibacterium (vitamins B2, B6, and B12) but a higher abundance of Erysipelatoclostridium (vitamin B2) (FDR p values &lt, 0.05). The community composition and structure of the colonic bacteria differed significantly by dietary consumption of folate and B vitamins.

Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested.

Pathogenic fungi are capable of switching between different phenotypes, each of which has a different biological advantage. In the most prevalent human fungal pathogen, Candida albicans , phenotypic transitions not only improve its adaptation to a continuously changing host microenvironment but also regulate sexual mating. In this report, we show that Candida tropicalis , another important human opportunistic pathogen, undergoes reversible and heritable phenotypic switching, referred to as the “white-opaque” transition. Here we show that N -acetylglucosamine (GlcNAc), an inducer of white-to-opaque switching in C. albicans , promotes opaque-cell formation and mating and also inhibits filamentation in a number of natural C. tropicalis strains. Our results suggest that host chemical signals may facilitate this phenotypic switching and mating of C. tropicalis , which had been previously thought to reproduce asexually. Overexpression of the C. tropicalis WOR1 gene in C. albicans induces opaque-cell formation. Additionally, an intermediate phase between white and opaque was observed in C. tropicalis , indicating that the switching could be tristable.

OBJECTIVE To assess whether statin therapy decreases the incidence of cultures positive for Candida species among high-risk hospitalized patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS We performed a retrospective cohort study analyzing the records of all patients with type 2 DM who were admitted to Massachusetts General Hospital for lower gastrointestinal tract surgery between January 1, 2001, and May 1, 2008. We defined statin exposure as the filling of at least 1 prescription of statins during the 6 months before hospitalization or during the current hospital stay. The primary outcome was a culture positive for Candida species during hospitalization. Clinical information on a wide range of covariates was collected. Logistic regression analysis was used to adjust for possible confounders. RESULTS Of the 1019 patients who were eligible for the study, 493 (48%) were receiving statins. A total of 139 patients (14%) had at least 1 culture positive for Candida species during hospitalization. An adjusted multivariate model based on a backward stepwise elimination procedure showed that statin therapy significantly decreased the incidence of cultures positive for Candida species (odds ratio, 0.60; 95% confidence interval [CI], 0.38-0.96; P =.03) with a statistically significant prolonged time to event compared with no statin therapy (adjusted hazard ratio, 0.62; 95% CI, 0.44-0.88; P =.01). The benefit of statins was more prominent in patients with type 2 DM who had greater comorbidities (Charlson Comorbidity Index ≥2) (adjusted odds ratio, 0.47; 95% CI, 0.27-0.79; P =.01). CONCLUSION Among patients with type 2 DM who underwent gastrointestinal surgery, use of statins correlated with a decreased incidence of cultures positive for Candida species.

Fluconazole is the first line of therapy for the management of candidiasis. However, fluconazole-resistant strains pose an emerging challenge in everyday clinical practice. In this study, we sought to determine whether cumulative length of hospital stay (CLOS) is a predictive factor for the acquisition of non-susceptible Candida strains to fluconazole. Thirty-three critically ill emergency surgery patients with 56 Candida isolates were enrolled in this prospective study. We divided our isolates according to their minimum inhibitory concentration (MIC) to fluconazole using 8 mcg/ml as a cutoff. We then compared the two groups with respect to basic demographics, antifungal agents prescribed, number of wide-spectrum antibiotics, duration of central venous catheter placement, elapsed time to positive culture, duration of prior hospital stay, and length of hospital stay. Non-susceptible fluconazole samples belonged to patients with a significantly longer prior hospital stay and a longer CLOS (P = 0.02 and 0.01, respectively). The difference between the 2 groups regarding non-albicans strains was statistically significant (P

Background: Data on Candida infection among critically ill trauma patients are limited and not recently updated. Here we study the epidemiology and economic impact of Candida and examine potential risk factors for Candida infection in this population. Methods: In this 5-year retrospective study, all severely injured patients with ³4 days of intensive care unit stay were included, with the primary outcome being Candida infection. We identified 3 distinct patient groups: 1) The Candida infection, 2) The Candida colonization and 3) the Candida-free group. All comparisons between groups with p-values ≤0.2 from the univariate analysis were entered into stepwise logistic regression to identify independent risk factors for candidiasis. Results: 374 patients were included. Upon comparisons between groups, candidiasis patients received significantly more blood transfusions (p=0.013), antibiotics (p=0.005), and total parenteral nutrition (TPN) (p=0.004), had a longer duration of mechanical ventilation (MV) (p=0.008...

A multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of Cryptococcus neoformans mutants to identify previously unknown virulence factors. The primary screen was performed using a Caenorhabditis elegans-C. neoformans infection assay. The hits among these strains were reconfirmed as less virulent than the wild type in the insect Galleria mellonella-C. neoformans infection assay. After this 2-stage screen, and to prioritize hits, we performed serial evaluations of the selected strains, using the C. elegans model. All hit strains identified through these studies were validated in a murine model of systemic cryptococcosis. Twelve strains were identified through a stepwise screening assay. Among them, 4 (CSN1201, SRE1, RDI1, and YLR243W) were previously discovered, providing proof of principle for this approach, while the role of the remaining 8 genes (CKS101, CNC5600, YOL003C, CND1850, MLH3, HAP502, MSL5, and CNA2580) were not previously described in cryptococcal virulence. The multi-host approach is an efficient method of studying the pathogenesis of C. neoformans. We used diverse model hosts, C. elegans, G. mellonella, and mice, with physiological differences and identified 12 genes associated with mammalian infection. Our approach may be suitable for large pathogenesis screens.

Background Ventilator associated pneumonia (VAP) is a serious infection among patients in the intensive care unit (ICU). Methods We reviewed the medical charts of all patients admitted to the adult intensive care units of the Massachusetts General Hospital that went on to develop VAP during a five year period. Results 200 patients were included in the study of which 50 (25%) were infected with a multidrug resistant pathogen. Increased age, dialysis and late onset (≥5 days from admission) VAP were associated with increased incidence of resistance. Multidrug resistant bacteria (MDRB) isolation was associated with a significant increase in median length of ICU stay (19 vs. 16 days, p = 0.02) and prolonged duration of mechanical ventilation (18 vs. 14 days, p = 0.03), but did not impact overall mortality (HR 1.12, 95% CI 0.51–2.46, p = 0.77). However, age (HR 1.04 95% CI 1.01–1.07, p = 0.003) was an independent risk factor for mortality and age ≥65 years was associated with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections (OR 2.83, 95% CI 1.27–6.32, p = 0.01). Conclusions MDRB-related VAP is associated with prolonged ICU stay and mechanical ventilation. Interestingly, age ≥ 65 years is associated with MRSA VAP.

Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34+ cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 106 cells/kg increase in CD34+ cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P

Central nervous system (CNS) aspergillosis is a highly fatal infection. We review the clinical presentation, diagnosis, and outcome of this infection and present a case series of 14 consecutive patients with CNS aspergillosis admitted to Massachusetts General Hospital (MGH) from 2000 to 2011. We also review 123 cases reported in the literature during that time. We included only proven CNS aspergillosis cases conforming to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal infections. In the MGH case series, neutropenia, hematologic malignancies, autoimmune diseases requiring steroid treatment, and solid organ transplantation were the predominant comorbid conditions. Notably, all MGH patients were immunosuppressed, and more than half (n = 8) had a history of previous brain injury, unrelated to their index hospitalization. For most MGH patients (11 of 14), the lung was the primary focus of aspergillosis, while 2 had paranasal sinus involvement, and 1 had primary Aspergillus discitis. Among reported cases, paranasal sinuses (27.6%) and the lung (26.8%) were the primary foci of infection, whereas 22% of those cases had no obvious primary organ involvement. Although a selection bias should be considered, especially among published cases, our findings suggest that patients who underwent neurosurgery had improved survival, with MGH and literature patients having 25% and 28.6% mortality, respectively, compared to 100% and 60.4%, respectively, among patients who received only medical treatment. Although this was not the case among MGH patients, CNS aspergillosis can affect patients without significant immune suppression, as indicated by the high number of reported immunocompetent cases. In conclusion, mortality among CNS aspergillosis patients remains high, and the infection may be more common among patients with previous brain pathology. When indicated, neurosurgical procedures may improve prognosis.

Despite recent improvements in the diagnosis and treatment of cryptococcosis, cryptococcal meningitis is responsible for > 600,000 deaths/year worldwide. The aim of this work is to provide an update on the developments in its epidemiology and management. Understanding the pathogenesis of Cryptococcus has improved, and new insights for the virulence of the fungus and the host response have enabled scientists to design new ways to confront this infection. Additionally, invertebrate model hosts have greatly facilitated the research in this field. Importantly, the epidemiology of Cryptococcus gattii has continued to evolve, and the emergence of this highly virulent species in immunocompetent populations, especially in Northwestern America and British Columbia, warrants increased awareness because delayed diagnosis and inappropriate antifungal therapy is associated with high mortality. Diagnosis remains a challenge, but new techniques for early and inexpensive identification of the pathogen are under development. Management can vary, based on the patient population (HIV-seropositive, organ transplant recipients or non-transplant/non-HIV). In most patients, amphotericin B with flucytosine continues to be the most appropriate induction therapy. However, in organ transplant recipients the use of liposomal amphotericin B improves mortality compared with deoxycholate amphotericin B. Also, the combination of amphotericin B with fluconazole seems to be a reasonable alternative, while fluconazole with flucytosine is superior to fluconazole monotherapy.

Currently accepted fungal diagnostic techniques, such as culture, biopsy, and serology, lack rapidity and efficiency. Newer diagnostic methods, such as polymerase chain reaction (PCR)-based assays, have the potential to improve fungal diagnostics in a faster, more sensitive, and specific manner. Preliminary data indicate that, when PCR-based fungal diagnostic assays guide antifungal therapy, they may lower patient mortality and decrease unnecessary antifungal treatment, improving treatment-associated costs and avoiding toxicity. Moreover, newer PCR techniques can identify antifungal resistance DNA loci, but the clinical correlation between those loci and clinical failure has to be studied further. In addition, future studies need to focus on the implementation of PCR techniques in clinical decision making and on combining them with other diagnostic tests. A consensus on the standardization of PCR techniques, along with validation from large prospective studies, is necessary to allow widespread adoption of these assays.

Candida is a significant pathogen among critically ill patients. However, candidiasis among non-trauma emergency surgery (NTES) patients has not been previously investigated. Herein we describe the incidence of both colonization and infection from Candida and risk factors for invasive disease in this population.For this retrospective single center study we included all NTES patients with ICU stay ≥4 days from May 1(st), 2002 to April 30(th), 2007. Patients were divided into 3 non-overlapping groups: 1) patients with Candida-infection, 2) patients with Candida colonization and 3) patients with negative Candida cultures. Groups were compared by univariate and multivariate analyses to identify significant risk factors for invasive candidiasis.Of all 289 eligible patients, 63 (21.7%) fulfilled the criteria for Candida infection and 110 (38%) were included in the Candida colonization group. Interestingly, from the 63 patients with invasive candidiasis, 25 (39.7%) were infected by a non-albicans species. Upon multivariate analyses, ventilator-associated pneumonia (VAP) (Odds Ratio [OR]: 2.34; 95%, Confidence Interval [CI]: 1.213-4.533, p = 0.0112), bacteremia (OR: 4.778; 95%CI: 1.519-15.029, p = 0.0075) and surgical complications (OR: 3.903; 95%CI: 1.335-11.412, p = 0.0129) were independent risk factors for the development of Candida infection. Candida infection and colonization were both found to correlate with approximately $40,000-100,000 mean additional costs). Interestingly, candidemia was associated with 63% all-cause mortality. For all other forms of candidiasis, mortality was not significantly different among groups.We found that Candida infection is alarmingly high among NTES patients with prolonged intensive care unit (ICU) stay. Surgical complications and bacterial infections (VAP and bacteraemia) were significantly correlated with the development of candidiasis. Candidiasis reached a rate of 21.7/100 discharges, which is significantly higher than most established high-risk populations for candidiasis. Future studies should review the need for antifungal prophylaxis on this population.

Abstract 4134 Invasive fungal infections/disease (IFI/IFD) are a major cause of morbidity and mortality after hematopoietic stem cell transplants (HCT), but their incidence and risk factors are not well defined. We performed a retrospective review of 270 consecutive adults (152 M/118 F), median age 53 (18–75) years, with hematologic malignancy receiving allogeneic HCT at Massachusetts General Hospital between 2000 to 2010 to determine the incidence, risk factors and outcomes of patients that developed IFD. All patients received antifungal prophylaxis from the start of conditioning until Day +100; 90% received fluconazole 400 mg daily. We defined IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, defining proven cases as evidence of fungal elements in a sterile tissue, and probable as presence of fungal elements in non sterile tissue or positive Galactomannan antigen or β-D-Glucan test in patients with clinical features suggestive of IFI. Diagnoses were Acute Myeloid Leukemia (34%), Non Hodgkin's Lymphoma (24%), Myelodysplastic syndrome (15%), Acute Lymphoblastic Leukemia (8%), Chronic Lymphocytic Leukemia (5%), Myeloproliferative disorders, Hodgkin Lymphoma and Multiple Myeloma (4% each), and others (2%). 15% had a prior autologous transplant. Conditioning included reduced intensity (64%) or myeloablative (36%) regimens. Donor source was fully HLA matched (MRD) in 60%, matched unrelated (MUD) in 20%, Haploidentical in 12% and Cord Blood in 8%. 41% received ATG based aGVHD prophylaxis vs non ATG based in 59%. 11% were diabetic, while 6% had a history of IFD prior to transplant. 55% received systemic steroids for GVHD and 34% received TPN during transplant course. Median follow up was 28 (1.0–141.0) months. 49 distinct episodes of IFI were observed in 40 subjects (15%). Aspergillus spp (47%) was most frequently encountered, followed by Candida spp (43%). Mucor was isolated in 1 case. Among the Candida spp, the majority (52%) were non albicans- Candida glabrata (8) vs 1 each of Candida krusei, Candida tropicalis and Candida parapsilosis. Most frequently infected site was the lungs (69%), followed by the blood stream and paranasal sinuses (14% each), and GI tract (4%). Spleen (hepatosplenic candidiasis), kidneys and brain were affected in 1 patient each. In 6%, involvement of both the lungs and sinuses was observed. The estimated probability of early IFD (within 100 days post transplant) was 7%. Patients and transplant factors, including age, diagnosis, prior autologous transplant, type of conditioning regimen, type of aGVHD prophylaxis, donor type, CD34+ cell dose infused, history of diabetes or prior IFD, systemic use of steroids for GVHD and TPN administration, were examined to determine risk factors for developing IFD. In multivariable analysis, haploidentical donor transplants (HR 3.48, 95% CI 1.35–8.99, p=0.01) and the development of Grade III and IV aGVHD (HR 3.32, 95% CI 1.23–9.01, p=0.02) were risk factors for the development of IFD. Conversely, higher CD34+ cell dose infused was associated with a lower risk of IFD (HR 0.80, 95% CI 0.68–0.94, p=0.01, per 1×10⋀6 cells/kg increase). The overall mortality (OM) of patients with IFD was 41%. A higher non-relapse mortality (NRM) was observed for patients with IFD as compared to patients without IFD, 55% vs 18% (HR 3.76, 95% CI 2.03–6.97, p Disclosures: Mylonakis: T2 Biosystems: Research Funding; Astellas inc : Research Funding.