A fatal neonatal case of fungemia due to Exophiala dermatitidis-case report and literature review.

BACKGROUND: Systemic infections caused by the black yeast-like fungus Exophiala dermatitidis are rare, but are associated with high mortality especially in immunocompromised patients. We report the first case of E. dermatitidis fungemia in a premature extremely low birth weight (ELBW) neonate who succumbed despite antifungal therapy with liposomal amphotericin (AMB) and fluconazole. A systematic review of all fungemia cases due to E. dermatitidis was also conducted aiming for a better understanding of the risk factors, treatment strategies and outcomes. CASE PRESENTATION: A male, ELBW premature neonate, soon after his birth, developed bradycardia, apnoea and ultimately necrotizing enterocolitis with intestinal perforation requiring surgical intervention. Meanwhile, he had also multiple risk factors for developing bloodstream infection, such as intubation, mechanical ventilation, central venous catheter (CVC), parenteral nutrition, empirical and prolonged antibiotic use. His blood cultures were positive, firstly for Acinetobacter junii and then for Klebsiella pneumoniae together with E. dermatitidis while on fluconazole prophylaxis and antibiotic empiric therapy. Despite the treatment with broad spectrum antibiotics, liposomal AMB and fluconazole, the newborn succumbed. A literature review identified another 12 E. dermatitidis bloodstream infections, mainly in patients with hematologic malignancies and solid organ transplant recipients (61%), with overall mortality 38% despite CVC removal and antifungal therapy. CONCLUSIONS: Due to the rarity of E. dermatitidis infections, little is known about the characteristics of this yeast, the identification methods and the optimal therapy. Identification by common biochemical tests was problematic requiring molecular identification. Resolution of neonatal fungemia is difficult despite proper antifungal therapy especially in cases with multiple and severe risk factors like the present one. Therapeutic intervention may include CVC removal and treatment for at least 3 weeks with an azole (itraconazole or fluconazole after susceptibility testing) or AMB monotherapy but not echinocandins or AMB plus azole combination therapy.

Filamentous Fungal Keratitis in Greece: A 16-Year Nationwide Multicenter Survey.

In a multicenter, prospective study of filamentous fungal keratitis in Greece, predisposing factors, etiology, treatment practices, and outcome, were determined. Corneal scrapings were collected from patients with clinical suspicion of fungal keratitis, and demographic and clinical data were recorded. Fungal identification was based on morphology, molecular methods, and matrix assisted laser desorption ionization time-of-flight mass-spectrometry. A total of 35 cases were identified in a 16-year study period. Female to male ratio was 1:1.7 and median age 48 years. Corneal injury by plant material, and soft contact lens use were the main risk factors (42.8% and 31.4%, respectively). Trauma was the leading risk factor for men (68.1%), contact lens use (61.5%) for women. Fusarium species were isolated more frequently (n = 21, 61.8%). F. solani was mostly associated with trauma, F. verticillioides and F. proliferatum with soft contact lens use. Other fungi were: Purpureocillium lilacinum (14.7%), Alternaria (11.8%), Aspergillus (8.8%), and Phoma foliaceiphila, Beauveria bassiana and Curvularia spicifera, one case each. Amphotericin B and voriconazole MIC50s against Fusarium were 2 mg/L and 4 mg/L respectively. Antifungal therapy consisted mainly of voriconazole locally or both locally and systemically, alone or in combination with liposomal AmB. Cure/improvement rate with antifungal therapy alone was 52%, keratoplasty was required in 40% of cases, and enucleation in 8%. In conclusion, filamentous fungal keratitis in Greece is rare, but with considerable morbidity. A large proportion of cases resulted in keratoplasty despite appropriate antifungal treatment.

Immune Mechanisms of Filamentous Fungal Keratitis.

Filamentous fungal keratitis is a particularly serious eye infection that often results in ulceration, corneal perforation, and blindness. The cornea acts as a natural barrier against harmful agents due to the close connection of its epithelial cells. In addition, on its surface, there is a large number of substances with anti-inflammatory and bactericidal properties, such as secretory IgA and mucin glycoproteins, and antimicrobial peptides (AMPs), such as human ß-defensin 2 (HBD-2) and LL-37, which are especially increased in filamentous fungal keratitis. The interaction between pathogenic fungi and the host's immune mechanisms is a complex process: pathogen-associated molecular pattern (PAMP) molecules (chitin, ß-glucan, and mannan) found in the fungal cell wall are recognized by pattern recognition receptors (PRRs) (toll-like receptors {TLRs}, C-type lectin receptors {CLRs}, nucleotide-binding oligomerization domain-like receptors {NLRs}, and scavenger receptors {SR}) found in host defense cells, triggering the secretion of various types of cytokines, such as interleukins (IL), tumor necrosis factors (TNFs), and chemokines, which recruit macrophages and neutrophils to migrate to the site of infection and activate inflammatory responses. In addition, the interaction of hyphae and corneal epithelial cells can activate cluster of differentiation (CD) 4+ T cells, CD8+ T cells, and B cells and induce secretion of T-helper (Th)-type cytokines 2 (IL-4 and IL-13) and IgG.

The History of the Greek Refugee Hospital of the Interwar Period in a General Hospital of Nikaia "Agios Panteleimon".

The Asia Minor Catastrophe caused the uprooting of thousands of Greeks from Asia Minor and their arrival in Greece. Especially in the areas around Piraeus, there was a large settlement of refugee populations. During that period, a small hospital was created, the "American Women's Hospital," by an initiative of the "American Women's Union," with the aim of treating and caring for suffering refugees. Within a decade, the hospital expanded and became a general hospital. In 1934, after the departure of the "American Women's Service" from Greece, it was renamed "Refugee Hospital of Nea Kokkinia," and then a year later (1935), it was renamed again to "Protypo Laiko Iatreio" (Model Public Clinic). In 1939, the construction of a larger hospital in Nea Kokkinia began. During World War II, the hospital managed to respond to the difficult conditions of the period and was renamed "General Hospital of Piraeus, Saporta Warehouse Building." After the war, in 1953, it was renamed to General Hospital of Piraeus "Queen Frederika." In 1986, it was renamed to Regional General Hospital of Nikaia "Damon Vassileiou" in honor of the Professor of Medicine of the University of Athens Damon Vassileiou who was one of the greatest Greek doctors. In 2001, it was renamed again to its current name General Hospital of Nikaia "Agios Panteleimon," becoming one of the largest hospitals in the Balkans.

In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study.

Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation.

Fungemia due to Moesziomyces aphidis (Pseudozyma aphidis) in a premature neonate. Challenges in species identification and antifungal susceptibility testing of rare yeasts.

Premature neonates are at particularly increased risk to develop invasive infections with excessive case fatality due to their low birth weight, enteral malabsorbtion, insufficient microbial defenses and underdeveloped anatomic barriers. We present a case of Moesziomyces aphidis (syn. Pseudozyma aphidis) fungemia in a newborn with severe morbidity and prolonged hospital stay. Phenotypic tests failed to identify the isolate whereas commercial antifungal susceptibility tests failed to detect resistance to fluconazole. To the best of our knowledge, this is the first case of M. aphidis fungemia in a premature neonate in whom complete clinical resolution occurred after liposomal amphotericin B administration. Our case is the third Pseudozyma spp. infection described in Europe. Twenty-one cases have been described globally. Common risk factors were central venus catheter (80%), previous antibiotic treatment (80%), hematologic malignancies (27%) and solid tumors (20%) with 3 cases reported in neonates. The most commonly used antifungal therapy was amphotericin B followed by oral voriconazole or itraconazole. Our report highlights the clinical importance of rare yeasts species in neonates, emphasizes the roles of prematurity and lower birth weight as major risk factors for invasive infections with high morbidity. Reliable identification and susceptibility testing of these rare yeasts is a key issue for an adequate therapy and better outcome.

Successful therapy of Candida pulcherrima fungemia in a premature newborn with liposomal amphotericin B and micafungin.

New Candida species may cause bloodstream infections challenging current therapeutic approaches because of unpredictable susceptibility and virulence. In the present report, we describe a fungemia case due to Candida pulcherrima in a premature neonate. After full in vitro diagnostic workup, the neonate was successfully treated with liposomal amphotericin B and micafungin achieving rapid fungal eradication from blood.