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Objectives: The aims of this study were to evaluate the demographic characteristics, risk factors, mortality rates, and laboratory findings of infants with fungal sepsis in the Neonatal Intensive Care Unit (NICU). Methods: This retrospective multicenter study included patients in NICU with Candida spp isolated in blood cultures between November 01, 2019, and September 01, 2022. The patients were evaluated in two groups as Group 1 infants with Candida albicans and Group 2 infants with Candida non-albicans positive blood cultures. Results: Candida infection was detected in blood cultures in 57 of 3450 patients admitted to the NICU. A total of 57 infants included in the study. Candida infection was determined 1.6% of infants in the study population, and 57% of them were extremely pre-term infants. There was no significant difference between the two groups in terms of laboratory data. Normal vaginal birth was determined at a higher rate in Group 1. In Group 2, length of hospital stay, duration of total parenteral nutrition (TPN), and mechanical ventilation (MV) were determined to be longer. The mortality due to Candida fungemia was determined as 35%, and of these patients, 65% had an additional medical condition. Conclusion: In accordance with the literature, this study showed that prolonged MV and longer TPN increased the incidence of fungal sepsis. Therefore, to decrease the fungal sepsis rate of NICU, shortening the hospital stay and effective screening programs are recommended.

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BACKGROUND: Systemic candidiasis is an important nosocomial infection in neonatal intensive care units. The objective of this study was to identify the change in the profile of neonatal candidiasis in a tertiary neonatal intensive care unit (NICU) in eastern India in recent times. METHODS: It was a retrospective review of case records from 2014 to 2019 from a tertiary NICU of eastern India. Data of the fungal sepsis, demographic details, risk factors of fungal sepsis and mortality were collected from 103 neonates. RESULTS: One hundred and three neonates had blood culture positive for fungal species of which 91 (88.3%) infants weighed ≥1500 g and 66 (64%) infants were term. There was significant higher incidence of candidiasis among outborn (Relative risk of outborn 18.84, 95% CI 10.74-33.05). Prolonged antibiotic usage (>14 days), meropenem usage (>5 days), central catheterization (>5 days), invasive mechanical ventilation (>5 days), surgical intervention were found in 64 (62.1%), 46 (44.6%), 31(30.0%), 40 (38.8%) and 39 (37.8%) infants. Non albicans candida (NAC) was isolated as the predominant species (82/103, 79.6%). Resistance to both of fluconazole and amphotericin B were found in 19 (18.4%) babies. Presence of NAC infection and resistance to both amphotericin B and fluconazole were independent predictors of candida associated mortality in NICU. CONCLUSION: Neonatal candidiasis is found among outborn infants with higher birth weight and gestational age. NAC species are predominant organisms with resistance to common antifungal drugs.

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Purpose: Magnetic separation of microbes can be an effective tool for pathogen identification and diagnostic applications to reduce the time needed for sample preparation. After peptide functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with an appropriate interface, they can be used for the separation of sepsis-associated yeasts like Candida albicans. Due to their magnetic properties, the magnetic extraction of the particles in the presence of an external magnetic field ensures the accumulation of the targeted yeast. Materials and Methods: In this study, we used SPIONs coated with 3-aminopropyltriethoxysilane (APTES) and functionalized with a peptide originating from GP340 (SPION-APTES-Pep). For the first time, we investigate whether this system is suitable for the separation and enrichment of Candida albicans, we investigated its physicochemical properties and by thermogravimetric analysis we determined the amount of peptide on the SPIONs. Further, the toxicological profile was evaluated by recording cell cycle and DNA degradation. The separation efficiency was investigated using Candida albicans in different experimental settings, and regrowth experiments were carried out to show the use of SPION-APTES-Pep as a sample preparation method for the identification of fungal infections. Conclusion: SPION-APTES-Pep can magnetically remove more than 80% of the microorganism and with a high selective host-pathogen distinction Candida albicans from water-based media and about 55% in blood after 8 minutes processing without compromising effects on the cell cycle of human blood cells. Moreover, the separated fungal cells could be regrown without any restrictions.

Asunto(s)

Candida albicans , Nanopartículas Magnéticas de Óxido de Hierro , Proteínas y Péptidos Salivales , Humanos , Candida albicans/aislamiento & purificación , Fenómenos Magnéticos

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We aimed to analyze infections in children undergoing hematopoietic stem cell transplantation (HSCT) until engraftment. The spectrum and risk factors associated will help plan interventions to reduce mortality. We performed a retrospective analysis on the infections, associated risk factors, and mortality until engraftment in children up to 18 years of age undergoing HSCT from January 2017 to August 2020. A total of 399 children were included, with a male: female ratio of 1.9:1, with matched related donor HSCT in 36.6%, a matched unrelated donor in 18.3%, and haploidentical HSCT in 38.1% of children. Culture positive bacteremia was documented in 22.1% transplants with gram-negative bacteria (GNB) isolated in 71/88 (80%). Among the GNB, the predominant organism was Klebsiella pneumonia in 38 (53%), E.coli in 16 (22%), Pseudomonas in 9 (12%). Carbapenem resistance was documented in 24/71 (33%). The incidence of possible, probable, and proven fungal infections in the cohort was 63 (15%), 28 (7%), and 6 (1.5%), respectively. Mortality up to engraftment due to sepsis in our cohort is 3.3% (n = 13). There was a significant association between mortality and a perianal focus (30.8%, p value 0.029) and the presence of carbapenem resistance (38%, p value 0.002). Mortality among those who developed proven fungal infections was significantly higher than those with bacteremia (p value 0.004). Our study has identified fungal sepsis and carbapenem-resistant GNB sepsis as high-risk groups for mortality. Risk directed interventions in these groups would help ensure survival and optimal outcomes.

RESUMEN

Fungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. Candida albicans (C.albicans) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we performed single-cell RNA sequencing (scRNA-Seq) using the 10x Genomics platform to analyze the changes in murine adrenal transcriptome following systemic C.albicans infection. A total of 16 021 cells were categorized into 18 transcriptionally distinct clusters, representing adrenocortical cells, endothelial cells, various immune cells, mesenchymal cells, smooth muscle cells, adrenal capsule, chromaffin cells, neurons and glials. As the main cell component in the adrenal gland responsible for steroidogenesis, the adrenocortical cells dramatically diminished and were further grouped into 10 subclusters, which differently distributed in the infected and uninfected samples. Pseudo-time analysis revealed transitions of the adrenocortical cells from the initial normal states to active or dysfunctional states following systemic C.albicans infection via two trajectory paths. Endothelial cells in the highly vascularized organ of adrenal gland further proliferated following infection, with the upregulation of genes positively regulating angiogenesis and downregulation of protective genes of endothelial cells. Immune cells were also excessively infiltrated in adrenal glands of C.albicans-infected mice. Macrophages dominated the immune microenvironments in murine adrenal glands both before and after C.albicans infection, mediating the crosstalk among the steroid-producing cells, endothelial cells and immune cells within the adrenal gland. NLR family, pyrin domain containing 3 (NLRP3, encoded by Nlrp3) and complement receptor 3 (CR3, encoded by Itgam) were found to be significantly upregulated on the adrenal macrophages upon systemic C.albicans infection and might play critical roles in mediating the myeloid response. Meanwhile, the number and strength of the interactions between the infiltrating immune cells and adrenal resident cells were unveiled by cell-cell communication analysis to be dramatically increased after systemic C.albicans infection, indicating that the immune-adrenal crosstalk might contribute to the compromised functions of adrenal cells. Overall, our comprehensive picture of the murine adrenal gland microenvironment in systemic C.albicans infection provides deeper insights into the immune-adrenal cell communications during fungal sepsis.

Asunto(s)

Candidiasis , Sepsis , Ratones , Animales , Candida albicans , Proteína con Dominio Pirina 3 de la Familia NLR , Células Endoteliales , Glándulas Suprarrenales , Antígeno de Macrófago-1

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Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a "sweet spot" for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.

Asunto(s)

Micosis , Neoplasias , Animales , Antifúngicos/uso terapéutico , Inmunoterapia , Factores Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Micosis/tratamiento farmacológico , Microambiente Tumoral

RESUMEN

OBJECTIVE: Recent data imply that strengthening host immunity by checkpoint inhibition improves outcome in invasive fungal infections (IFI), particularly in candidiasis. METHODS: To assess T-cell exhaustion in this context, we compared peripheral blood mononuclear cells (PBMCs) and serum samples of patients with invasive Candida albicans infection (IC, n = 21) to PBMCs or tumor-infiltrating lymphocytes (TILs) from cancer patients (n = 14) and PBMCs of healthy controls (n = 20). Type and differentiation of lymphocytes and expression of 29 immune-regulatory molecules were analyzed by flow cytometry. C. albicans specific responses were assessed by FluoroSpot (n = 8) and antibody measurement (n = 14). RESULTS: Fractions and phenotypes of lymphocyte subsets in PBMCs of IC patients were similar compared to PBMCs of controls, while they were different in TILs. PBMCs of patients with IC showed increased expression of immune-checkpoint molecules. The pattern of upregulated molecules was similar to TILs, but not present in PBMCs of control cancer patients. Fractions of T-cells expressing PD-1 and TIGIT were higher in IC patients that died. FluoroSpot analysis showed a Candida-specific IFN-y or IL-2 response in 5/8 patients, enhanced by addition of nivolumab in vitro. CONCLUSIONS: Together with preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment. TRIAL REGISTRATION: NCT04533087; retrospectively registered on August 31, 2020.

Asunto(s)

Candidiasis Invasiva , Receptor de Muerte Celular Programada 1 , Linfocitos T CD8-positivos , Candidiasis Invasiva/tratamiento farmacológico , Humanos , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/metabolismo , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T

RESUMEN

Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8+ T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear. Here, a lethal fungal sepsis model induced by candidemia was created and we found a decreased CD8+ T-cell count and exaggerated apoptosis. Simultaneously, expression of light chain (LC)3B in CD8+ T cells increased, along with increased autophagosomes and accumulation of p62 in infected mice. We regulated the activity of the mammalian target of rapamycin (mTOR) pathway using T-cell-specific mTOR/ TSC1 deletion mice. We observed increased number of autophagosomes and expression of LC3B in CD8+T cells after T-cell-specific mTOR knockout, while accumulation of p62 was not ameliorated, and there was no increase in the number of autolysosomes. Apoptosis rate and expression of BIM, a pro-apoptotic gene, decreased in CD8+ T cells in mTOR-deletion mice but increased in TSC1-deletion mice. Our results showed increased CD8+ T-cell death in spleen of lethal fungal sepsis mice, and decreased expression of mTOR ameliorated CD8+ T-cell survival. mTOR may be a possible target to reverse CD8+ T-cell immune dysfunction in lethal fungal sepsis.

Asunto(s)

Linfocitos T CD8-positivos/inmunología , Candidemia/inmunología , Supervivencia Celular/inmunología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Linfocitos T CD8-positivos/metabolismo , Candida albicans/inmunología , Candidemia/sangre , Candidemia/microbiología , Candidemia/mortalidad , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Transgénicos , Serina-Treonina Quinasas TOR/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/metabolismo

RESUMEN

BACKGROUND: Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis (C. parapsilosis) bloodstream infection (BSI) in view of its reduced sensitivity to fluconazole. METHODS: The clinical characteristics of 58 C. parapsilosis BSI newborns who received treatment between June 2014 to December 2018 in the Shanghai Children's Hospital were retrospectively analyzed. Based on the initial antifungal drugs, these patients were divided into fluconazole group (n=30) and voriconazole group (n=21). After 7-10-day treatment, the antifungal drugs were replaced if blood culture still showed positive. The clinical characteristics and therapeutic effects were compared between two groups. RESULTS: There were no significant differences in the clinical characteristics between two groups (P>0.05). The median time to a negative culture in the voriconazole group was 7 [interquartile range (IQR), 6-10] days, which was significantly shorter than in the fluconazole group [9 (IQR, 7-18.5) days; P=0.034]. The overall median time to a negative culture was 8 days. After 8-day antifungal therapy, in the voriconazole group and fluconazole group, negative culture was observed in 16 and 12 patients, respectively; the positive culture was noted in 5 and 16 patients, respectively; the effective rate was 76.1% and 40%, respectively, showing marked difference (χ2=6.535, P=0.011). None died in the voriconazole group, but 4 died in the fluconazole group. The median time of treatment for fungal sepsis in the voriconazole group was 22 (IQR, 20-26) days, which was significantly shorter than in the fluconazole group [32 (IQR, 23.5-40) days; P=0.000]. CONCLUSIONS: The initial clinical manifestations of C. parapsilosis BSI vary among individuals, and voriconazole is superior to fluconazole in the treatment of C. parapsilosis BSI.

RESUMEN

The mammalian target of rapamycin (mTOR) pathway can mediate T-cell survival; however, the role of this pathway in T-cell survival during fungal sepsis is unclear. Here, we investigated the role of the mTOR pathway in CD4+ T-cell survival in a mouse model of rapidly progressive lethal sepsis induced by severe invasive candidiasis and explored the possible mechanism. The decrease in CD4+ T-cell survival following fungal sepsis was ameliorated in mice with a T-cell-specific mTOR deletion, whereas it was exacerbated in mice with a T-cell-specific tuberous sclerosis complex (TSC)1 deletion. To explore the mechanism further, we measured expression of autophagy proteins light chain 3B and p62/sequestosome 1 in CD4+ T cells. Both proteins were increased in T-cell-specific mTOR knockout mice but lower in T-cell-specific TSC1 knockout mice. Transmission electron microscopy revealed that T-cell-specific mTOR knockout mice had more autophagosomes than wild-type mice following fungal sepsis. CD4+ T-cell mTOR knockout decreased CD4+ T-cell apoptosis in fungal sepsis. Most notably, the T-cell-specific mTOR deletion mice had an increased survival rate after fungal sepsis. These results suggest that the mTOR pathway plays a vital role in CD4+ T-cell survival during fungal sepsis, partly through the autophagy-apoptosis pathway.

Asunto(s)

Apoptosis , Linfocitos T CD4-Positivos/patología , Candidiasis/inmunología , Sepsis/inmunología , Sepsis/microbiología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/inmunología , Animales , Autofagia , Linfocitos T CD4-Positivos/inmunología , Supervivencia Celular/inmunología , Eliminación de Gen , Masculino , Ratones , Ratones Noqueados , Transducción de Señal , Esclerosis Tuberosa/genética

RESUMEN

Invasive Candida infections (ICI) have been associated with neurodevelopmental impairment or death in human pre-term neonates. Candidiasis in nonhuman primates is seen mostly in immunosuppressed animals, and ICI is not commonly reported. Here, we report a case of Candida albicans-associated ICI in a pre-term neonatal rhesus macaque.

Asunto(s)

Candidiasis Invasiva/veterinaria , Macaca mulatta , Enfermedades de los Monos/microbiología , Sepsis/veterinaria , Animales , Candidiasis Invasiva/microbiología , Masculino , Sepsis/microbiología

RESUMEN

Individual susceptibility differences to fungal infection following invasive and/or immunosuppressive medical interventions are an important clinical issue. In order to explore immune response-related factors that may be linked to fungal infection susceptibility, we have compared the response of inbred C57BL/6J and outbred CD1 mouse strains to different experimental models of fungal sepsis. The challenge of animals with the zymosan-induced generalised inflammation model revealed poorer survival rates in C57BL/6J, consistent with lower Th1 cytokine interferon (IFN)-γ serum levels, compared with CD1 mice. Likewise, ex vivo exposure of C57BL/6J splenocytes to zymosan but also bacterial lipopolisaccharide or lipoteichoic acid, resulted in lower IFN-γ secretion compared with CD1 mice. C57BL/6J susceptibility could be reverted by rescue infusion of relative low IFN-γ doses (0.2 µg/kg) either alone or in combination with the ß-glucan-binding CD5 protein (0.7 mg/kg) leading to improved post zymosan-induced generalised inflammation survival. Similarly, low survival rates to systemic Candida albicans infection (2.86 × 104  CFU/gr) were ameliorated by low-dose IFN-γ infusion in C57BL/6J but not CD1 mice. Our results highlight the importance of strain choice in experimental fungal infection models and provide a susceptibility rationale for more specific antifungal immunotherapy designs.

Asunto(s)

Candidiasis/inmunología , Susceptibilidad a Enfermedades/inmunología , Interferón gamma/uso terapéutico , Micosis/inmunología , Sepsis/inmunología , Animales , Animales no Consanguíneos , Proteínas de la Membrana Bacteriana Externa/inmunología , Antígenos CD5/administración & dosificación , Candida albicans/inmunología , Candida albicans/patogenicidad , Candidiasis/tratamiento farmacológico , Citocinas/sangre , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades/microbiología , Interferón gamma/administración & dosificación , Interferón gamma/sangre , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Micosis/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Sepsis/mortalidad , Especificidad de la Especie , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Ácidos Teicoicos/toxicidad , Zimosan/toxicidad

RESUMEN

ß-(1,3)-d-glucan (BDG) is used to rule out invasive fungal disease (IFD) but its usefulness in cystic fibrosis (CF) has not been evaluated. We measured serum BDG in CF patients with no clinical suspicion of IFD. Samples from 46 adult CF patients during a stable period and during pulmonary exacerbation were tested. The association of BDG with clinical variables was analyzed. Three hundred and three non-CF patients with suspected IFD were used as comparators. Both samples were negative in 52% of CF patients, whereas 67% of comparators had only negative results (P=0.08). CF patients with pancreatic insufficiency and CF-related diabetes had fewer negative results (P<0.05 for both). Negative results were more common in older CF patients (P<0.05). Use of antibiotics, presence of fungi in sputum and CF liver disease did not impact BDG levels. In conclusion, patients with CF experience significant BDG antigenaemia in the absence of IFD.

Asunto(s)

Fibrosis Quística/sangre , Fibrosis Quística/microbiología , Micosis/sangre , beta-Glucanos/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis/microbiología , Suero/metabolismo , Adulto Joven

RESUMEN

To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27-0.67; p = 0.0002; I2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46-0.88; p = 0.006; I2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44-1.78; p = 0.72; I2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27-0.68; p = 0.0002; I2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38-1.08; p = 0.10; I2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.

Asunto(s)

Candidiasis/tratamiento farmacológico , Suplementos Dietéticos , Sepsis Neonatal/prevención & control , Probióticos/uso terapéutico , Humanos , Recién Nacido , Recien Nacido Prematuro , Sepsis Neonatal/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

Summary Objective: To describe thyroid alterations in term newborns (TNB) with fungal sepsis during NICU hospitalization. Method: The study included six TNB that during the clinical and laboratory manifestations of sepsis with positive cultures for fungus showed changes in thyroid hormones, called low T3 syndrome and low T3-T4 syndrome. TNB that could present hormonal changes caused by disease as those born to mothers with thyroid disease, or who had perinatal asphyxia and major surgeries were excluded. Results: Of six TNB with fungal sepsis, five had positive culture for Candida albicans and one had positive culture for Candida tropicalis. Low T3 syndrome was observed in two TNB (50%), while T3-T4 syndrome was observed in other two (100%). The four children progressed to septic shock. Conclusion: Fungal sepsis is becoming more common among newborns admitted to NICU. Thyroid insufficiency could be a marker of disease severity with possible need for hormone supplementation.

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Resumo Objetivo: descrever as alterações tireoidianas em recém-nascidos de termo (RNT) que apresentaram sepse fúngica durante internação na UTI neonatal. Método: foram incluídos seis RNT que, durante as manifestações clínicas e laboratoriais de sepse, com culturas positivas para fungo, apresentaram alterações dos hormônios tireoidianos, denominadas síndrome do T3 baixo e síndrome do T3 e T4 baixo. Foram excluídos RNT que apresentaram alteração hormonal por doença, como RNT filhos de mães com doença tireoidiana, asfixia perinatal e cirurgias de grande porte. Resultados: dos seis RNT com sepse fúngica, cinco apresentavam cultura positiva para Candida albicans e um para C. tropicalis. A síndrome do T3 baixo foi observada em duas crianças (50%) e a do T3 e T4 baixo em dois RN (100%). As quatro crianças evoluíram com choque séptico. Conclusão: a sepse fúngica é cada vez mais frequente nos recém-nascidos internados em UTI neonatal. A insuficiência tireoidiana pode vir a ser marcadora de gravidade da doença, e a suplementação hormonal pode ser necessária.

Asunto(s)

Humanos , Masculino , Femenino , Recién Nacido , Síndromes del Eutiroideo Enfermo/microbiología , Sepsis/sangre , Candidemia/sangre , Enfermedades del Recién Nacido/sangre , Candida albicans/aislamiento & purificación , Cuidado Intensivo Neonatal , Sepsis/microbiología , Candida tropicalis/aislamiento & purificación , Candidemia/microbiología , Enfermedades del Recién Nacido/microbiología

RESUMEN

Zygomycosis is a rare invasive opportunistic fungal infection that occurs in the setting of hematologic malignancies, chemotherapy-induced neutropenia, and immunosuppressive therapies. We report the first case of disseminated appendiceal zygomycosis due to Absidia spp. in a neutropenic patient who initially presented as acute appendicitis. A 63-year-old woman with acute myeloid leukemia presented as acute appendicitis while receiving induction chemotherapy and ultimately succumbed to overwhelming disseminated zygomycosis. Initial symptoms included loose stools and right lower abdominal pain unresponsive to broad-spectrum antibiotics. Clinical examination and cross-sectional imaging suggested acute appendicitis. The final diagnosis was established by histological evaluations of the ileocecectomy specimen, which showed angioinvasive fungal organisms within the necrotic appendiceal wall with characteristics typical of zygomycetes. Fungal cultures demonstrated Absidia spp. The patient was treated with amphotericin B but expired in the setting of fungal sepsis. A diagnosis of a fungal infection, including zygomycosis, should be considered in all chemotherapy-induced neutropenic patients who present with symptoms of acute appendicitis. A high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may reduce the high mortality and morbidity associated with zygomycosis of the gastrointestinal tract.

RESUMEN

OBJECTIVE: To evaluate the effect of fluconazole prophylaxis on invasive fungal infection (IFI) in very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU). METHODS: VLBW infants receiving antibiotics for more than 3 days were randomized to receive either fluconazole (6 mg/kg) or placebo, every other day for 7 days followed by everyday till day 28 or discharge whichever was earlier. The primary outcome was IFI, and secondary outcome was fungal attributable mortality and all-cause mortality. RESULTS: The incidence of IFI was significantly lower (21%) in the fluconazole group compared to the control group (43.2%, 95%CI 0.09-0.37, p < 0.05). The ARR (absolute risk reduction) was 22.2% and the NNT (number needed to treat) was 5. Fungal attributable mortality was also lower in the fluconazole group (2.6% versus 18.9%, 95%CI 0.003-0.52, p < 0.05). CONCLUSION: In VLBW neonates on the NICU, use of fluconazole prophylaxis decreases IFI and fungal attributable mortality.

Asunto(s)

Antifúngicos/uso terapéutico , Candidiasis/prevención & control , Fluconazol/uso terapéutico , Recién Nacido de muy Bajo Peso , Sepsis/prevención & control , Candidiasis/epidemiología , Femenino , Humanos , India/epidemiología , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/microbiología , Enfermedades del Prematuro/prevención & control , Unidades de Cuidado Intensivo Neonatal , Masculino , Sepsis/microbiología

RESUMEN

Sepsis and necrotizing enterocolitis (NEC) cause significant morbidity and mortality in the newborn. Their ill effects persist in spite of appropriate and effective antibiotic therapy. Lactoferrin as an adjunct to antibiotics in the treatment of sepsis or NEC in the newborn may improve the clinical outcomes by enhancing the host defense and modulating the inflammatory response. This review focuses on the various aspects of lactoferrin use in the newborn.

Asunto(s)

Enfermedades del Prematuro/tratamiento farmacológico , Lactoferrina/uso terapéutico , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Antivirales/uso terapéutico , Desarrollo Infantil/efectos de los fármacos , Enterocolitis Necrotizante/tratamiento farmacológico , Madurez de los Órganos Fetales/efectos de los fármacos , Humanos , Factores Inmunológicos/uso terapéutico , Recién Nacido , Enfermedades del Prematuro/inmunología , Sepsis/tratamiento farmacológico

RESUMEN

BACKGROUND: Candida albicans is the predominant isolate in many neonatal fungal bloodstream infections (BSIs), so fluconazole is used as empiric antifungal therapy. AIM: To determine the predominant organisms, antifungal sensitivity patterns, clinical and demographic risk factors and crude mortality rate in neonatal fungal BSI cases. SUBJECTS AND METHODS: This is a review of all neonatal fungal BSI cases between January 2007 and December 2011. RESULTS: Fifty-nine patients were included in the study. Candida parapsilosis (54.2%) was isolated in majority of the cases, followed by C. albicans (27.1%). Fluconazole resistance was present in 16 of 32 cases of C. parapsilosis versus 1 of 16 cases of C. albicans (P = 0.003). Mortality rate was 45.8%. Surgical problems were present in 55.9%. Death was significantly associated with lower birth weight (P = 0.046) and necrotizing enterocolitis (P = 0.034). CONCLUSIONS: The increase in neonatal fungal BSI and resistant organisms highlights the need to review use of routine empiric fluconazole and to implement preventive measures.

Asunto(s)

Antifúngicos/uso terapéutico , Candida/aislamiento & purificación , Candidemia/diagnóstico , Candidiasis/diagnóstico , Antifúngicos/farmacología , Peso al Nacer , Candida/clasificación , Candida/efectos de los fármacos , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Candidemia/microbiología , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Candidiasis/mortalidad , Farmacorresistencia Fúngica , Femenino , Fluconazol/farmacología , Fluconazol/uso terapéutico , Humanos , Incidencia , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Factores de Riesgo , Factores Socioeconómicos , Sudáfrica/epidemiología , Resultado del Tratamiento , Triazoles/farmacología , Triazoles/uso terapéutico , Voriconazol

RESUMEN

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/microbiología , Ascitis Quilosa/complicaciones , Ascitis Quilosa/microbiología , Penicillium/metabolismo , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Alquinos , Anfotericina B/farmacología , Antirretrovirales/uso terapéutico , Antifúngicos/farmacología , Benzoxazinas/uso terapéutico , Ascitis Quilosa/tratamiento farmacológico , Ciclopropanos , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Penicillium/efectos de los fármacos , Pirimidinas/farmacología , Sepsis/tratamiento farmacológico , Triazoles/farmacología , Voriconazol