Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis. LAY SUMMARY: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

OBJECTIVES: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. PATIENTS AND METHODS: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. RESULTS: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01). CONCLUSIONS: Coinfections are frequent in IA patients and are associated with higher mortality.

A retrospective analysis of mortality in captive Magellanic penguins (Spheniscus magellanicus) in the United States, 2008-2018.

Mortality data for Magellanic penguins (Spheniscus magellanicus) housed in zoos and aquariums in the United States has not previously been published. Necropsy and histopathology records were examined for Magellanic penguins housed at 12 Association of Zoos and Aquariums institutions from 2008 through 2018. If birds lived through the first year, the mean longevity was found to be 18.9 years of age (standard deviation: 7.9). Prefledge chicks and geriatric penguins experienced the highest mortality rates. Aspergillosis was a major cause of death in this species. There was no significant difference in mortality between males and females. Based on these data, recommendations for the husbandry and veterinary care of captive Magellanic penguins can be made.

Influenza-Associated Aspergillosis: Nationwide Trends, Predictors and Outcomes From 2005 to 2014.

BACKGROUND: Influenza-associated aspergillosis (IAA) has been increasingly reported in the literature in recent years, but contemporary large-scale data on the morbidity and mortality burden of IAA are lacking. RESEARCH QUESTION: The goal of this study was to estimate the predictors, associations, and outcomes of IAA in the United States. STUDY DESIGN AND METHODS: This retrospective cohort study was performed by using the National (Nationwide) Inpatient Sample database from 2005 to 2014 to identify influenza and IAA hospitalizations. Baseline variables and outcomes were compared between influenza hospitalizations without IAA and those with IAA. These variables were then used to perform an adjusted analysis for obtaining predictors and associations of the diagnosis and in-hospital mortality of IAA. RESULTS: Of the 477,556 hospitalizations identified with the principal diagnosis of influenza, IAA was identified in 823 (0.17%) hospitalizations. The IAA cohort consisted more commonly of 45- to 65-year-olds in urban teaching hospitals with substance abuse. Yearly trends revealed that both influenza and IAA hospitalizations have increased over time, with a peak observed in 2009, the year of the influenza A(H1N1) pandemic. Mortality was higher (20.58% vs 1.36%), average length of stay was longer (17.94 vs 4.05 days), and mean cost per hospitalization was higher ($194,932 vs $24,286) in the IAA cohort compared with the influenza cohort without IAA (P < .005). Solid-organ transplantation, hematologic malignancies, and use of invasive mechanical ventilation were associated with higher odds of IAA, among other factors. Use of invasive mechanical ventilation (adjusted OR, 13.43; P < .005), longer length of stay (adjusted OR, 5.47; P < .005), utilization of extracorporeal membrane oxygenation (adjusted OR, 4.99; P = .014), and the group aged 45 to 64 years (adjusted OR, 3.03; P = .012) were associated with higher in-hospital mortality in the IAA cohort. INTERPRETATION: Although IAA is a rare complication of influenza hospitalizations, it is associated with increased all-cause mortality, more extended hospital stays, and higher hospital charges compared with influenza without IAA.

Aspergillosis in albatrosses.

Aspergillosis is a respiratory fungal disease of importance in captive marine birds. The aim of this study was to describe the occurrence of aspergillosis in Thalassarche melanophris during rehabilitation events and to identify the etiological agent. All the albatrosses that were received for rehabilitation and died within a 2-year period were included in the study. The proportionate mortality rate caused by aspergillosis was 21.4% (3/14). One of the etiological agents was Aspergillus flavus/oryzae lineage, and the other was A. fumigatus sensu stricto. Our study suggests that aspergillosis can act as a limiting factor in the rehabilitation of albatrosses.

Intracranial aspergillosis amongst immunocompetent patients: An experience with combined surgical and medical management of 18 patients.

OBJECTIVE: Fungal infections of central nervous system (CNS) commonly affect immunocompromised patients, however, recently such cases have been reported even amongst immunocompetent patients. PATIENTS & METHODS: In this study, we retrospectively analyzed outcome of 18 immunocompetent patients with histopathologically proven intracranial Aspergillosis undergoing combined surgical and medical management. RESULTS: The age of patients ranged from 5-65 years. Fourteen out of 18 patients had well defined lesions while 4 had diffuse disease. Paranasal sinuses were involved in 8 & cavernous sinus in 3 patients. Six patients had hydrocephalus. Four patients developed infarcts during their clinical course. Surgical interventions included gross (n = 4) or subtotal excision (n = 8), decompressive craniectomy & biopsy of lesion (n = 4), biopsy only (n = 2) and ventriculoperitoneal shunt placement (n = 6). All patients received postoperative antifungal therapy. The duration of follow up ranged from 10-60 months. Overall mortality was 44.4%. Mortality amongst patients undergoing gross total and subtotal excision was 25% & 50% respectively. Patients undergoing DC had a mortality of 25%. Both patients undergoing only biopsy died. Hydrocephalus was associated with a very high mortality (83.3%). Amongst surviving patients (n = 10), 6 patients became disease free & rest 4 had stable disease at last follow up. CONCLUSIONS: Intracranial aspergillosis is associated with high morbidity & mortality even amongst immunocompetent patients. An aggressive multidisciplinary management is thus needed to improve outcome. Our study shows that a combination of surgical excision or decompressive craniectomy and antifungal therapy can be helpful in improving prognosis of these patients.

Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients.

BACKGROUND: Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported. OBJECTIVES: To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA. METHODS: We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks. RESULTS: We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99). CONCLUSIONS: A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.

Contrasts between mucormycosis and aspergillosis in oncohematological patients.

In retrospective multicenter study from years 2007-2017, we evaluated 59 oncohematological patients with mucormycosis and 541 with invasive aspergillosis (IA). Mucormycosis developed more often in children and adolescents (P = .001), as well as after the emergence of graft versus host disease (P = .0001). Patients with mucormycosis had more severe neutropenia (88% vs 82%), the median duration was 30 versus 14 days (P = .0001) and lymphocytopenia (77% vs 65%), with a median duration (25 vs 14 days, P = .001) as compared to patients with IA. The lung infection was less frequent in patients with mucormycosis than in IA patients (73% vs 97%, P = .02), but more frequent was involvement of 2 or more organs (42% vs 8%, P = .001) and involvement of paranasal sinuses (15% vs 6%, P = .04). Typical clinical features of mucormycosis were localized pain syndrome (53% vs 5%, P = .0001), hemoptysis (32% vs 6%, P = .001), pleural effusion on lung CT scan (53% vs 7%, P = .003), lesions with destruction (38% vs 8%, P = .0001), and a "reverse halo" sign (17% vs 3%). The overall 12-week survival was significantly lower in patients with mucormycosis than for IA patients (49% vs 81%, P = .0001). In both groups unfavorable prognosis factors were ≥2 organs involvement (P = .0009), and concomitant bacterial or viral infection (P = .001, P = .008, respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (P = .006).

A novel monoclonal antibody against enolase antigen of Aspergillus fumigatus protects experimental aspergillosis in mice.

Aspergillus fumigatus is one of the most common opportunistic fungal pathogens responsible for a variety of diseases in human, from allergic bronchopulmonary aspergillosis to chronic pulmonary aspergillosis, mostly in immunocompromized patients. In this study, one monoclonal antibody MAb R-5 (IgM) raised against enolase cell surface protein of A. fumigatus exhibited significant inhibition of spore germination in A. fumigatus (88.3%), Aspergillus flavus (57.4%) and Aspergillus niger (30.6%). The MAb R-5 also showed in vitro fungicidal activity against these species as follows: A. fumigatus (24.1%), A. flavus (13.3%) and A. niger (8.8%). These findings were supported by the indirect immunofluorescence microscopy, where the antibody showed binding with germinated spores and hyphae of A. fumigatus as well as A. flavus and A. niger.In vivo protective effect of MAb R-5 was evaluated in BALB/c mice challenged intravenously with A. fumigatus spores, where a significant reduction in CFU (85.9%) was observed in kidney tissue. The mean survival time of mice treated with MAb R-5 (18.5 days) was also enhanced compared to control (6.5 days). These results indicate that MAb R-5 could be valuable in diagnosis as well as in the treatment of broad range of Aspergillus infections.

Emerging threat of triazole-resistant Aspergillus fumigatus.

Invasive aspergillosis is a leading cause of morbidity and mortality among immunocompromised populations and is predicted to cause more than 200 000 life-threatening infections each year. Aspergillus fumigatus is the most prevalent pathogen isolated from patients with invasive aspergillosis, accounting for more than 60% of all cases. Currently, the only antifungal agents available with consistent activity against A. fumigatus are the mould-active triazoles and amphotericin B, of which the triazoles commonly represent both front-line and salvage therapeutic options. Unfortunately, the treatment of infections caused by A. fumigatus has recently been further complicated by the global emergence of triazole resistance among both clinical and environmental isolates. Mutations in the A. fumigatus sterol-demethylase gene cyp51A, overexpression of cyp51A and overexpression of efflux pump genes are all known to contribute to resistance, yet much of the triazole resistance among A. fumigatus still remains unexplained. Also lacking is clinical experience with therapeutic options for the treatment of triazole-resistant A. fumigatus infections and mortality associated with these infections remains unacceptably high. Thus, further research is greatly needed to both better understand the emerging threat of triazole-resistant A. fumigatus and to develop novel therapeutic strategies to combat these resistant infections.

Inpatient Mortality After Endoscopic Sinus Surgery for Invasive Fungal Rhinosinusitis.

OBJECTIVES:: Invasive fungal rhinosinusitis is a rare, life-threatening condition that affects the paranasal sinuses. The standard of care after diagnosis includes surgical debridement and aggressive medical management. Despite treatment, mortality remains unacceptably high. Most data are derived from small cohort experiences, with limited identification of mortality risk factors in the acute setting. The authors used a large national database to better understand clinical factors associated with inpatient mortality for this challenging condition. METHODS:: Using the 2000-2014 National (Nationwide) Inpatient Sample database, the authors identified 979 adult patients with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of mucormycosis or aspergillosis and a procedure code of sinus surgery. Multivariate imputation by chained equation was performed to account for missing data, followed by multivariate logistic regression to identify predictors of inpatient mortality. RESULTS:: In total, 979 adult patients were identified, with a median age of 57 years. The inpatient mortality rate was 15.8%. The most prevalent comorbidity was hematologic disorders (42.9%). Mucormycosis versus aspergillosis was associated with increased odds of inpatient mortality (odds ratio, 2.95; 95% confidence interval, 2.00-4.34; P < .001). The odds of inpatient mortality were significantly increased between patients with hematologic disorders and those without (odds ratio, 1.92; 95% confidence interval, 1.08-3.39; P = .024). Diabetes (odds ratio, 0.53; 95% confidence interval, 0.34 - 0.80; P = .003) was associated with the lowest odds of inpatient mortality. CONCLUSIONS:: This represents the first population-based study evaluating the factors associated with inpatient mortality. These findings support prior observations demonstrating that the underlying immune dysfunction and type of fungal infection are important predictors of early mortality.

The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis.

BACKGROUND: Pathologic diagnosis remains the gold standard for final diagnosis of acute invasive fungal sinusitis (AIFS); however, other less invasive tests could suggest the presence of AIFS in at-risk populations where early diagnosis is crucial. Serum galactomannan Aspergillus antigen has been shown to correlate with a diagnosis of invasive pulmonary aspergillosis; however, it has not adequately been evaluated in regard to AIFS. The objective of this study is to evaluate the statistical relevance of galactomannan in predicting diagnosis of AIFS. METHODS: This study was a retrospective review of pathologic records using Co-Path from 2006 to 2017, incorporating 2 separate searches with designated criteria identifying patients who received pathologic evaluation for invasive fungal sinusitis. Electronic medical records were subsequently reviewed. After exclusions isolating at-risk populations and removing duplications, 78 cases were reviewed using the indicated search criteria. Of these, 38 met further criteria of having had both pathologic evaluation and galactomannan analysis. Statistical variables were assessed, as well as all-cause mortality. Peak and closest galactomannan levels were evaluated. RESULTS: Overall, galactomannan had a sensitivity of 44.8% (95% confidence interval [CI], 26.5% to 64.3%), specificity of 100% (95% CI, 66.4% to 100%), positive predictive value of 100% (95% CI, 74.3% to 100%), and negative predictive value of 36% (95% CI, 18.0% to 57.5%). No significant association was observed in galactomannan status and mortality in this patient population. CONCLUSION: Positive serum galactomannan can be an indication of AIFS in patients with a high clinical suspicion. In our study, a positive galactomannan always correlated with a positive pathologic diagnosis. However, given its low sensitivity, one must use caution in relying on galactomannan as a screening tool in diagnosis of AIFS.

Outcomes by MIC Values for Patients Treated with Isavuconazole or Voriconazole for Invasive Aspergillosis in the Phase 3 SECURE and VITAL Trials.

This pooled analysis evaluated the relationship of isavuconazole and voriconazole MICs of Aspergillus pathogens at baseline with all-cause mortality and clinical outcomes following treatment with either drug in the SECURE and VITAL trials. Isavuconazole and voriconazole may have had reduced efficacy against pathogens with drug MICs of ≥16 µg/ml, but there was no relationship with clinical outcomes in cases where the MIC was <16 µg/ml for either drug.

Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.

BACKGROUND: Early antifungal therapy for invasive aspergillosis (IA) has been associated with improved outcome. Traditionally, of empiric antifungal therapy has been used for clinically suspected IA. We compared outcomes of patients with hematologic malignancy and IA who were treated with voriconazole using the diagnostic driven DDA (DDA-Vori) that includes galactomannan testing vs. empiric therapy with a non-voriconazole-containing regimen (EMP-non-Vori) or empiric therapy with voriconazole (EMP-Vori). METHODS: We retrospectively reviewed the medical records of 342 hematologic malignancy patients diagnosed with proven, or probable IA between July 1993 and February 2016 at our medical center who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all-cause mortality, and IA-attributable mortality. RESULTS: By multivariate analysis, factors predictive of a favorable response included localized/sinus IA vs. disseminated/pulmonary IA (p <  0.0001), not receiving white blood cell transfusion (p <  0.01), and DDA-Vori vs. EMP-non-Vori (p < 0.0001). In contrast, predictors of mortality within 6 weeks of initiating IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (p < 0.01), not undergoing stem cell transplantation within 1 year before IA (p = 0.01), and EMP-non-Vori vs. DDA-Vori (p < 0.001). CONCLUSIONS: DDA-Vori was associated with better outcome (response and survival) compared with EMP-non-Vori and with equivalent outcome to EMP-Vori in hematologic malignancy patients. These outcomes associated with the implementation of DDA could lead to a reduction in the unnecessary costs and adverse events associated with the widespread use of empiric therapy.

Increased Mortality Among Renal Transplant Patients With Invasive Pulmonary Aspergillus Infection.

INTRODUCTION: Renal transplantation is the most effective and preferred definite treatment option in patients with end-stage renal disease. Due to long-term immunesuppressive treatment, renal transplant recipients become vulnerable to opportunistic infections, especially to fungal infections. METHOD: This was a single-center, retrospective observational study of 438 patients who underwent renal transplantation between 2010 and 2016. RESULTS: Thirty-eight renal transplant recipients who had lower respiratory tract infection with median age of 41.5 years were evaluated for invasive pulmonary aspergillus (IPA). Of these, 52.6% were female and 84.2% had living donors. Eleven of 38 lower respiratory patients were found to have IPA infection, 5 with proven infection. Compared to patients who did not have fungal pulmonary infection, patients with invasive aspergillus were older and had high fever, galactomannan levels, and leukocyte counts. Mortality was also higher in those patients. Having fever at the baseline and IPA infection was significantly associated with mortality in univariate analysis and remained related in multivariate model after adjustment for age, gender, and fever. CONCLUSION: Invasive pulmonary aspergillus infection is highly associated with increased mortality rates in renal transplant patients. Fungal pulmonary infections in immune-suppressed patients should be diagnosed and treated immediately in order to avoid the life-threatening complications and may greatly improve prognosis.

Invasive aspergillosis in patients with systemic lupus erythematosus: a retrospective study on clinical characteristics and risk factors for mortality.

Objective The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE). Methods Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed. Results Four patients (19.0%) had definite and 17 had probable (81.0%) IA. Seven patients (33.3%) survived and 14 died (66.7%). Concurrently, there were 19 pneumonias (90.5%), 17 cases of other infections (81.0%), eight bacteremia (38.1%), nine cytomegalovirus (CMV, 42.7%) and six Candida (28.6%) infections. In all 55 blood cultures, 38 (69.1%) yielded gram-negative bacilli, of which carbapenem-resistant A. baumannii accounted for eight (21.1%); 17 (30.9%) yielded gram-positive cocci, of which methicillin-resistant S. aureus accounted for six (35.3%); and vancomycin-resistant Enterococcus accounted for four (23.5%). Daily steroid dose ≥ 20 mg (hazard ratio (HR) 2.00), recent pulse steroid therapy (HR 2.80), azathioprine (HR 2.00), rituximab (HR 2.00), plasmapheresis (HR 2.00), acute respiratory distress syndrome (HR 2.00), concurrent infections (HR 5.667) and CMV viremia (HR 1.75) were higher in the fatality group. All p values were less than 0.05. Septic shock ( n = 7, 50% in the fatality group) is the most common cause of mortality. Conclusions High daily steroid dosing, recent pulse steroid therapy, azathioprine, rituximab, concurrent infections, and CMV viremia were mortality risk factors for IA in SLE.

Toxic epidermal necrolysis data from the CELESTE multinational registry. Part I: Epidemiology and general microbiological characteristics.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare, life-threatening autoimmune disease predominantly manifested in the skin and mucous membranes. Today, infectious complications have the dominant share in mortality of TEN patients. Due to the nature of the therapy and administration of immunosuppressive medications, a wide range of potentially pathogenic microorganisms, which cause infectious complications in different compartments in these patients, is not surprising. MATERIAL AND METHODOLOGY: This is a multicentric study, which included all patients with TEN hospitalized between 2000-2015 in specialized centres in the Czech Republic and Slovakia. The total catchment area was over 12.5 million inhabitants. The actual implementation of the project was carried out using data obtained from the registry CELESTE (Central European LyEll Syndrome: Therapeutic Evaluation), when specific parameters relating to epidemiological indicators and infectious complications in patients with TEN were evaluated in the form of a retrospective analysis. RESULTS: In total, 39 patients with TEN were included in the study (12 patients died, mortality was 31%), who were hospitalized in the monitored period. The median age of patients in the group was 63 years (the range was 4-83 years, the mean was 51 years), the median of the exfoliated area was 70% TBSA (total body surface area) (range 30-100%, mean 67%). SCORTEN was calculated for 38 patients on the day of admission. Its median in all patients was 3 (range 1-6; mean 3). Any kind of infectious complication in the study group was recorded in 33 patients in total (85%). In total, 30 patients (77%) were infected with gram-positive cocci, 27 patients (69%) with gram-negative rods, and yeast cells or fibrous sponge were cultivated in 12 patients (31%). A total of 32 patients (82%) were found to have infectious complications in the exfoliated area, 15 patients (39%) had lower respiratory tract infections, 18 patients (46%) urinary tract infections and 15 patients (39%) an infection in the bloodstream. The most common potentially pathogenic microorganism isolated in our study group was coagulase neg. Staphylococcus, which caused infectious complications in 24 patients. Enterococcus faecalis/faecium (19 patients), Pseudomonas aeruginosa (17 patients), Staphylococcus aureus (11 patients) and Escherichia coli (11 patients) were other most frequently isolated micro-organisms. CONCLUSION: The published data were obtained from the unique registry of TEN patients in Central Europe. In the first part, we have succeeded in defining the basic epidemiological indicators in the group of patients anonymously included in this registry. The study clearly confirms that infectious complications currently play an essential role in TEN patients, often limiting the chances of survival. The study also shows a high prevalence of these complications in the period after 15days from the start of hospitalization, when most patients already have completely regenerated skin cover.

Epidemiology and Outcomes of Hospitalizations With Invasive Aspergillosis in the United States, 2009-2013.

Background: Though invasive aspergillosis (IA) complicates care of up to 13% of patients with immunocompromise, little is known about its morbidity and mortality burden in the United States. Methods: We analyzed the Health Care Utilization Project's data from the Agency for Healthcare Research and Quality for 2009-2013. Among subjects with high-risk conditions for IA, IA was identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). Using propensity score matching, we calculated the IA-associated excess mortality and 30-day readmission rates, length of stay, and costs. Results: Of the 66634683 discharged patients meeting study inclusion criteria, 154888 (0.2%) had a diagnosis of IA. The most common high-risk conditions were major surgery (50.1%) in the non-IA and critical illness (41.0%) in the IA group. After propensity score matching, both mortality (odds ratio, 1.43; 95% confidence interval, 1.36-1.51) and 30-day readmission (1.39; 1.34-1.45) rates were higher in the IA group. IA was associated with 6.0 (95% confidence interval, 5.7-6.4) excess days in the hospital and $15542 ($13869-$17215) in excess costs per hospitalization. Conclusions: Although rare even among high-risk groups, IA is associated with increased hospital mortality and 30-day readmission rates, excess duration of hospitalization, and costs. Given nearly 40000 annual admissions for IA in the United States, the aggregate IA-attributable excess costs may reach $600 million annually.

The burden of Invasive Aspergillosis in patients with haematological malignancy: A meta-analysis and systematic review.

INTRODUCTION: Successful treatment of haematological malignancies is frequently complicated by Invasive Aspergillosis (IA), a life-threatening fungal infection that occurs in at least 10% of haemato-oncological patients. Case fatality rates (CFR) may fluctuate over time, depending on host pathogen interactions as well as on treatment and quality of patient care. We conducted a systematic review and metaanalysis of current - i.e. 2008-revised EORTC-MSG criteria era - incidence and case fatality rates (CFR) of IA in patients with haematological malignancy. METHODS: A systematic search according to PRISMA guidelines was performed to identify all literature reporting populations with a haematological malignancy and the incidence of IA, defined according to the EORTC/MSG 2008 criteria. Pooled cumulative incidences and CFR within 100 days were estimated using a random effects model for predefined patient populations and stratified by use of prophylaxis. RESULTS: The systematic literature search yielded 1285 publications of which n = 49 met the inclusion criteria. Overall, 16.815 patients were involved of which 1056 (6.3%) developed IA. IA risk ranged from 4% (during remission-induction, with prophylaxis) to 11% (during remission-induction, without prophylaxis). Antifungal prophylaxis was associated with a lower rate of IA, especially in the pre-HSCT population. The pooled CFR within 100 days was 29% (95% CI: 20-38%). DISCUSSION: This study confirms that IA is a relevant threat in the treatment of haematological cancer despite the universal use of antifungal prophylaxis. These outcomes inform scientists and other stakeholders about the current burden of IA and may be used to direct, implement and improve antifungal stewardship programs.