Invasive fungal infections secondary to traumatic injury

Invasive fungal infection (IFI) is a rare but serious complication of traumatic injury. The purpose of this article is to review the epidemiology, natural history, mycology, risk factors, diagnosis, treatment, and outcomes associated with post-traumatic IFI in military and civilian populations. The epidemiology of post-traumatic IFI is poorly characterized, but incidence appears to be rising. Patients often suffer from severe injuries and require extensive medical interventions. Fungi belonging to the order Mucorales are responsible for most post-traumatic IFI in both civilian and military populations. Risk factors differ between these cohorts but include specific injury patterns and comorbidities. Diagnosis of post-traumatic IFI typically follows positive laboratory results in the appropriate clinical context. The gold standard of treatment is surgical debridement in addition to systemic antifungal therapy. Patients with post-traumatic IFI may be at greater risk of amputation, delays in wound healing, hospital complications, and death as compared to trauma patients who do not develop IFI. More research is needed to understand the factors surrounding the development and management of post-traumatic IFI to reduce the significant morbidity and mortality associated with this disease

Creation and assessment of a clinical predictive calculator and mortality associated with Candida krusei bloodstream infections

Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics. </jats:sec

End-stage liver disease Is a strong predictor of early mortality in cryptococcosis

Background. Cryptococcosis in the setting of end-stage liver disease (ESLD) has been associated with high mortality. We sought to compare the outcome of cryptococcal disease in patients with ESLD to that of human immunodeficiency virus (HIV)-positive patients and to those patients without HIV or ESLD. Methods. We assembled a retrospective cohort of 232 consecutive cases of cryptococcosis in our institution, from 2002 to 2014, inclusively. We analyzed the cases for comorbidities, type of infection, and survival. Data were analyzed with t tests, Fishers Exact test, and Kaplan-Meyer analysis. Results. Twenty-five (10.8%) patients with cryptococcal infection had concomitant ESLD; of these, 5 (20%) presented with peritonitis. Most (17 of 25, 68%) did not have any other cause of immunocompromise that has been more classically associated with cryptococcosis. Patients with ESLD had a significantly higher mortality than HIV-positive patients and HIV-negative patients without ESLD (HIVNE) (80% vs 13.6% and 22.7%, respectively; P < .001). In addition, fatal outcome in ESLD patients occurred more rapidly than in HIVNE patients, with a median survival of 6 days (vs 17), despite a comparable time to diagnosis (6.2 vs 6.6 days). Conclusions. Cryptococcosis is an important morbidity in patients with ESLD. Patients with ESLD who are infected with Cryptococcus have a high and rapid mortality. This suggests that a high level of vigilance for cryptococcal infection should be kept in patients with ESLD

AIDS-defining illnesses at initial diagnosis of HIV in a large Guatemalan cohort

AbstractBackgroundAnecdotal evidence suggests that a high proportion of patients diagnosed with HIV in Guatemala present with AIDS. There remain limited data on the epidemiology of AIDS-defining illnesses (ADIs) in Central America.MethodsWe conducted a retrospective cohort study of all patients living with HIV at the largest HIV clinic in Guatemala. Charts were analyzed for clinical and demographic data. Presence of an ADI was assessed by US Centers for Disease Control definitions; patients who presented with an ADI were compared with those without ADI using descriptive statistics.ResultsOf 3686 patients living with HIV, 931 (25.3%) had an ADI at HIV diagnosis, 748 (80.3%) of whom had CD4 counts lower than 200 cells/mm3. Those with ADIs were more likely to be male (67.5% vs 54.6%; P &amp;lt; .0001) and heterosexual (89.4% vs 85.0%; P = .005). The most common ADIs were Mycobacterium tuberculosis (55.0%), Pneumocystis jirovecii pneumonia (13.7%), esophageal candidiasis (13.4%), and histoplasmosis (11.4%). Histoplasmosis and HIV wasting syndrome were both more common among rural patients.ConclusionsIn this large Guatemalan cohort of patients currently living with HIV, a significant portion presented with an ADI. These data inform the most common ADIs diagnosed among survivors, show that histoplasmosis is more commonly diagnosed in rural patients, and suggest that HIV wasting syndrome may reflect missed histoplasmosis diagnoses.</jats:sec

Assessment of Lichens' Metabolic and Degradation Products at Dornava Manor

Five major types of lichen were discovered in the investigated specimens from Dornava Manor. All these lichens and/or their combinations are considered common lichenous overgrowth for the region and its climate. For all of the positively identified lichen species, it is common that they are found on a wide variety of calciferous or base-rich substrata, incl. mortar, brick, roofing tiles, walls, also in large urban areas (are not particularly disturbed by pollution/eutrophication), therefore preferring neutral to basic environment. They are well adapted to sunlight (from scarce direct solar irradiation to sites with very high direct solar irradiation) and can tolerate low water accessibility. In some of the lichens parietin, an orange organic pigment, was found, indicating the sun exposed areas. Additionally, carotenoids and pulvinic acid derivatives were identified, from which the metabolic pathway of lichens can be determined. These products can also represent biomarkers that can be linked to the survival strategies of lichen communities in stressed environmental habitats. For many of the investigated samples the lichens' degradation products like oxalates were identified, mainly calcium oxalate Weddellite, while the ammonium oxalate Oxammite is also possible.Research Institute, Conservation Centre, Institute for the Protection of the Cultural Heritage of Slovenia, Poljanska 40, 1000 Ljubljana, Slovenia

T cells from patients with Candida sepsis display a suppressive immunophenotype

BACKGROUND: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. METHODS: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. RESULTS: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). CONCLUSIONS: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users

MSG-15: Super-bioavailability itraconazole versus conventional itraconazole in the treatment of endemic mycoses-A multicenter, open-label, randomized comparative trial

BACKGROUND: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). METHODS: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. RESULTS: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by CONCLUSIONS: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. CLINICAL TRIALS REGISTRATION: NCT03572049

Noninvasive testing and surrogate markers in invasive fungal diseases

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities