The role of pacas of captivity as a potential reservoir of zoonotic fungi in Acre, Western Amazon, Brazil / O papel de pacas de cativeiro como potencial reservatório de fungos zoonóticos no Acre, Amazônia Ocidental, Brasil

Wild animals can be natural reservoirs of different microorganisms, essential for monitoring these pathogens for the generation of knowledge and creation of tools aimed at programs for the prevention and control of infectious diseases, including zoonoses. The objective was to report the fungal diversity in the skin of pacas in captivity in Acre, Western Amazon, Brazil. Twenty-six animals were evaluated, from which skin samples were collected by superficial scraping, hair avulsion, and sterile plastic brush. The samples were seeded on Mycosel agar, and the phenotypic characteristics of the colonies were analyzed. In 80.8% of the samples, different fungi were isolated, from the genera Candida, Microsporum,and Trichophyton, among others. This is the first description of the identification of fungi in the skin of pacas and suggests that these animals can be considered essential reservoirs of saprophytic or pathogenic microorganisms with zoonotic potential in the Western Amazon.(AU)

Animais silvestres podem ser reservatórios naturais de diferentes microrganismos, sendo fundamental o monitoramento destes patógenos para a geração de conhecimento e criação de ferramentas direcionadas a programas de prevenção e controle de enfermidades infecciosas, incluindo as zoonoses. Assim, objetivou-se relatar a diversidade fúngica da pele de pacas criadas em cativeiro no Acre, Amazônia Ocidental, Brasil. Foram avaliados 26 animais, dos quais amostras cutâneas foram colhidas por raspagem superficial, avulsão pilosa e escova plástica estéril. As amostras foram semeadas em ágar Mycosel e as características fenotípicas das colônias foram analisadas. Em 80,8% das amostras houve isolamento de diferentes fungos, dos gêneros Candida, Microsporum e Trichophyton, dentre outros. Esta é a primeira descrição da identificação de fungos na pele de pacas e sugere que estes animais podem ser considerados importantes reservatórios de microrganismos saprófitas ou patogênicos, de potencial zoonótico, na Amazônia Ocidental.(AU)

Interactions of Both Pathogenic and Nonpathogenic CUG Clade Candida Species with Macrophages Share a Conserved Transcriptional Landscape.

Candida species are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including Candida albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Innate immune cells such as macrophages are crucial for controlling infection, and C. albicans responds to phagocytosis by a coordinated induction of pathways involved in catabolism of nonglucose carbon sources, termed alternative carbon metabolism, which together are essential for virulence. However, the interactions of other CUG clade species with macrophages have not been characterized. Here, we analyzed transcriptional responses to macrophage phagocytosis by six Candida species across a range of virulence and clinical importance. We define a core induced response common to pathogenic and nonpathogenic species alike, heavily weighted to alternative carbon metabolism. One prominent pathogen, Candida parapsilosis, showed species-specific expansion of phagocytosis-responsive genes, particularly metabolite transporters. C. albicans and Candida tropicalis, the other prominent pathogens, also had species-specific responses, but these were largely comprised of functionally uncharacterized genes. Transcriptional analysis of macrophages also demonstrated highly correlated proinflammatory transcriptional responses to different Candida species that were largely independent of fungal viability, suggesting that this response is driven by recognition of conserved cell wall components. This study significantly broadens our understanding of host interactions in CUG clade species, demonstrating that although metabolic plasticity is crucial for virulence in Candida, it alone is not sufficient to confer pathogenicity. Instead, we identify sets of mostly uncharacterized genes that may explain the evolution of pathogenicity. IMPORTANCE Candidiasis is a major fungal infection by Candida species, causing life-threatening invasive disease in immunocompromised patients. C. albicans, which is adapted to commensalism of human mucosae, is the most common cause. While several other species cause infection, most are less prevalent or less virulent. As innate immune cells are the primary defense against Candida infection, we compared the transcriptional responses of C. albicans and related species to phagocytosis by macrophages, to understand the basis of variation in pathogenesis. This response, including the metabolic remodeling required for virulence in C. albicans, was strikingly conserved across the virulence spectrum. Macrophage responses to different species were also highly similar. This study indicates that important elements of host-pathogen interactions in C. albicans are not driven by adaptation to the mammalian host and improves our understanding of pathogenicity in opportunistic fungal species that are understudied but collectively impose a significant threat of their own.

Increased diversity, fungal burden, and virulence of oral Candida spp. in patients undergoing anti-tuberculosis treatment.

Some studies have demonstrated a high prevalence of Candida species in patients with tuberculosis (TB). This is most likely due to long-term antimicrobial therapy. To date, no longitudinal studies addressed the effects of anti-TB treatment on the fungal burden and virulence of Candida spp. This study investigated the prevalence and virulence of Candida spp. in the oral cavity of 30 TB patients at different stages of treatment through a cohort study. These results were compared with those of 60 systemically healthy individuals in a cross-sectional study. Oral rinse samples from TB patients were collected before 45 and after 120 days of treatment. In the control group, the biological samples were collected only once. Candida spp. were identified by restriction fragment length polymorphism (RFLP) assays, and the following virulence factors were studied: phospholipase C and proteinase production, as well as Candida spp. biofilm and hyphae formation. The clinical diagnosis of TB and its treatment time were associated with the greater fungal burden (p < 0.0001), presence of non-albicans Candida (NAC) species (p = 0.0003), and increased virulence factors when compared with the Candida spp. isolated from systemically healthy individuals. The results showed that anti-TB treatment time was responsible for the increased fungal burden and isolation of NAC in TB patients (p = 0.0233). The increased prevalence, quantification, and virulence of Candida spp. isolated from the oral cavity of TB patients highlight the greater risk of oral lesions and cases of systemic dissemination in these patients.

An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness.

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an "infection-vulnerable" gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.

Hedera rhombea inhibits the biofilm formation of Candida, thereby increases the susceptibility to antifungal agent, and reduces infection.

Candida is an opportunistic pathogen and a common cause of fungal infections worldwide. Anti-fungal use against Candida infections has resulted in the appearance of resistant strains. The limited choice of anti-fungal therapy means alternative strategies are needed to control fungal infectious diseases. The aim of this study was to evaluate the inhibition of Candida biofilm formation by Hedera rhombea (Korean name: songak) extract. Biofilm formation was assessed using the crystal violet assay which showed a dose dependent reduction in the presence of extract with the biofilm formation inhibitory concentration of C. albicans (IC50 = 12.5µg/ml), C. tropicalis var. tropicalis (IC50 = 25µg/ml), C. parapsilosis var. parapsilosis (IC50 = 6.25µg/ml), C. glabrata (IC50 = 6.25µg/ml), C. tropicalis (IC50 = 12.5µg/ml), and C. parapsilosis (IC50 = 12.5µg/ml) without directly reducing Candida growth. Treatment with 6.25µg/mL of extract increased the antifungal susceptibility to miconazole from 32% decreasing of fungal growth to 98.8% of that based on the fungal growth assay. Treatment of extract dose-dependently reduced the dimorphic transition of Candida based on the dimorphic transition assay and treatment of 3.125µg/mL of extract completely blocked the adherence of Candida to the HaCaT cells. To know the molecular mechanisms of biofilm formation inhibition by extract, qRT-PCR analysis was done, and the extract was found to dose dependently reduce the expression of hyphal-associated genes (ALS3, ECE1, HWP1, PGA50, and PBR1), extracellular matrix genes (GSC1, ZAP1, ADH5, and CSH1), Ras1-cAMP-PKA pathway genes (CYR1, EFG1, and RAS1), Cph2-Tec1 pathway gene (TEC1) and MAP kinases pathway gene (HST7). In this study, Hedera rhombea extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is good screen for developing the antifungal adjuvant and Hedera rhombea extract should be a good candidate against biofilm-related fungal infection.

Trained Innate Immunity Induced by Vaccination with Low-Virulence Candida Species Mediates Protection against Several Forms of Fungal Sepsis via Ly6G+ Gr-1+ Leukocytes.

We recently discovered a novel form of trained innate immunity (TII) induced by low-virulence Candida species (i.e., Candida dubliniensis) that protects against lethal fungal/bacterial infection. Mice vaccinated by intraperitoneal (i.p.) inoculation are protected against lethal sepsis following Candida albicans/Staphylococcus aureus (Ca/Sa) intra-abdominal infection (IAI) or Ca bloodstream infection (BSI). The protection against IAI is mediated by long-lived Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs) and not by prototypical trained macrophages. This study aimed to determine if a similar TII mechanism (Gr-1+ cell-mediated suppression of sepsis) is protective against BSI and whether this TII can also be induced following intravenous (i.v.) vaccination. For this, mice were vaccinated with low-virulence Candida strains (i.p. or i.v.), followed by lethal challenge (Ca/Sa i.p. or Ca i.v.) 14 days later, and observed for sepsis (hypothermia, sepsis scoring, and serum cytokines), organ fungal burden, and mortality. Similar parameters were monitored following depletion of macrophages or Gr-1+ leukocytes during lethal challenge. The results showed that mice vaccinated i.p. or i.v. were protected against lethal Ca/Sa IAI or Ca BSI. In all cases, protection was mediated by Ly6G+ Gr-1+ putative granulocytic MDSCs (G-MDSCs), with no role for macrophages, and correlated with reduced sepsis parameters. Protection also correlated with reduced fungal burden in spleen and brain but not liver or kidney. These results suggest that Ly6G+ G-MDSC-mediated TII is induced by either the i.p. and i.v. route of inoculation and protects against IAI or BSI forms of systemic candidiasis, with survival correlating with amelioration of sepsis and reduced organ-specific fungal burden. IMPORTANCE Trained innate immunity (TII) is induced following immunization with live attenuated microbes and represents a clinically important strategy to enhance innate defenses. TII was initially demonstrated following intravenous inoculation with low-virulence Candida albicans, with protection against a subsequent lethal C. albicans intravenous bloodstream infection (BSI) mediated by monocytes with enhanced cytokine responses. We expanded this by describing a novel form of TII induced by intraperitoneal inoculation with low-virulence Candida that protects against lethal sepsis induced by polymicrobial intra-abdominal infection (IAI) via Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs). In this study, we addressed these two scenarios and confirmed an exclusive role for Ly6G+ Gr-1+ leukocytes in mediating TII against either IAI or BSI via either route of inoculation, with protection associated with suppression of sepsis. These studies highlight the previously unrecognized importance of Ly6G+ MDSCs as central mediators of a novel form of TII termed trained tolerogenic immunity.

Oral Candidal Load and Oral Health Status in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Case-Cohort Study.

OBJECTIVE: The objective of this study was to determine the candidal load of the patients with Chronic Obstructive Pulmonary Disease (COPD) and evaluate the oral health status of subjects with COPD. Material and Methods. N = 112 COPD subjects and N = 100 control subjects were included in the study. The selection of COPD cases was confirmed based on the set criteria from the American College of Physicians. The oral health status was assessed as per WHO criteria to determine the score of decayed, missing, and filled teeth (DMFT), significant caries index (SiC), community periodontal index and treatment needs (CPITN), and oral hygiene index-simplified (OHI-S). Gram staining was performed to identify Candida using the whole saliva. Quantitative evaluation of the candidal load was carried out using Sabouraud Dextrose Agar (SDA). Chrome agar was used to differentiate between the commensal carriages. A statistical analysis paired t-test and 95% confidence interval (CI) for proportions was carried out using STATA software. RESULTS: Candidal growth was found in 21.42% (n = 24) of COPD cases and 1.1% (n = 11) of control cases (p < 0.05) (95% CI 0.45, 0.59). The DMFT score was 8.26 in COPD subjects and 4.6 in controls, the SiC score was 16.42 in COPD subjects and 10.25 in controls, and the CPITN score for both COPD and control cases was score 2. CONCLUSION: In conclusion, there was a higher candidal load among subjects suffering from COPD. Theophylline medication can be a risk factor for increased candidal load in COPD patients.

Study of Titanium-Silver Monolayer and Multilayer Films for Protective Applications in Biomedical Devices.

The search for coatings that extend the useful life of biomedical devices has been of great interest, and titanium has been of great relevance due to its innocuousness and low reactivity. This study contributes to the investigation of Ti/Ag films in different configurations (monolayer and multilayer) deposited by magnetron sputtering. The sessile droplet technique was applied to study wettability; greater film penetrability was obtained when Ag is the external layer, conferring high efficiency in cell adhesion. The morphological properties were characterized by SEM, which showed porous nuclei on the surface in the Ag coating and crystals embedded in the Ti film. The structural properties were studied by XRD, revealing the presence of TiO2 in the anatase crystalline phase in a proportion of 49.9% and the formation of a silver cubic network centered on the faces. Tafel polarization curves demonstrated improvements in the corrosion current densities of Ag/Ti/Ag/Ti/Ag/Ti/Ag/Ti and Ti/Ag compared to the Ag coating, with values of 0.1749, 0.4802, and 2.044 nA.m-2, respectively. Antimicrobial activity was evaluated against the bacteria Pseudomonas aeruginosa and Bacillus subtilis and the yeasts Candida krusei and Candida albicans, revealing that the Ti/Ag and Ag/Ti/Ag/Ti/Ag/Ti/Ag/Ti coatings exhibit promise in biomedical material applications.

The Inhibition of Non-albicans Candida Species and Uncommon Yeast Pathogens by Selected Essential Oils and Their Major Compounds.

The epidemiology of yeast infections and resistance to available antifungal drugs are rapidly increasing, and non-albicans Candida species and rare yeast species are increasingly emerging as major opportunistic pathogens. In order to identify new strategies to counter the threat of antimicrobial resistant microorganisms, essential oils (EOs) have become an important potential in the treatment of fungal infections. EOs and their bioactive pure compounds have been found to exhibit a wide range of remarkable biological activities. We investigated the in vitro antifungal activity of nine commercial EOs such as Thymus vulgaris (thyme red), Origanum vulgare (oregano), Lavandula vera (lavender), Pinus sylvestris (pine), Foeniculum vulgare (fennel), Melissa officinalis (lemon balm), Salvia officinalis (sage), Eugenia caryophyllata (clove) and Pelargonium asperum (geranium), and some of their main components (α-pinene, carvacrol, citronellal, eugenol, γ-terpinene, linalool, linalylacetate, terpinen-4-ol, thymol) against non-albicans Candida strains and uncommon yeasts. The EOs were analyzed by GC-MS, and their antifungal properties were evaluated by minimum inhibitory concentration and minimum fungicidal concentration parameters, in accordance with CLSI guidelines, with some modifications for EOs. Pine exhibited strong antifungal activity against the selected non-albicans Candida isolates and uncommon yeasts. In addition, lemon balm EOs and α-pinene exhibited strong antifungal activity against the selected non-albicans Candida yeasts. Thymol inhibited the growth of all uncommon yeasts. These data showed a promising potential application of EOs as natural adjuvant for management of infections by emerging non-albicans Candida species and uncommon pathogenic yeasts.

Nucleus-Independent Chemical Shift (NICS) as a Criterion for the Design of New Antifungal Benzofuranones.

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL-1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL-1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation.

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.

Development of a Highly Sensitive ß-Glucan Detection System Using Scanning Single-Molecule Counting Method.

To overcome the limitations of the Limulus amebocyte lysate (LAL) assay method for the diagnosis of invasive fungal infection, we applied a reaction system combining recombinant ß-glucan binding proteins and a scanning single-molecule counting (SSMC) method. A novel (1→3)-ß-D-glucan recognition protein (S-BGRP) and a (1→6)-ß-glucanase mutant protein were prepared and tested for the binding of (1→6)-branched (1→3)-ß-D-glucan from fungi. S-BGRP and (1→6)-ß-glucanase mutant proteins reacted with ß-glucan from Candida and Aspergillus spp. Although LAL cross-reacted with plant-derived ß-glucans, the new detection system using the SSMC method showed low sensitivity to plant (1→3)-ß-D-glucan, which significantly improved the appearance of false positives, a recognized problem with the LAL method. Measurement of ß-glucan levels by the SSMC method using recombinant ß-glucan-binding proteins may be useful for the diagnosis of fungal infections. This study shows that this detection system could be a new alternative diagnostic method to the LAL method.

Fungal species in endodontic infections: A systematic review and meta-analysis.

Fungal infections are common on oral mucosae, but their role in other oral sites is ill defined. Over the last few decades, numerous studies have reported the presence of fungi, particularly Candida species in endodontic infections, albeit in relatively small numbers in comparison to its predominant anaerobic bacteriome. Here, we review the fungal biome of primary and secondary endodontic infections, with particular reference to the prevalence and behavior of Candida species. Meta-analysis of the available data from a total of 39 studies fitting the inclusion criteria, indicate the overall weighted mean prevalence (WMP) of fungal species in endodontic infections to be 9.11% (from a cumulative total of 2003 samples), with 9.0% in primary (n = 1341), and 9.3% in secondary infections (n = 662). Nevertheless, WMP for fungi in primary and secondary infections which were 6.3% and 7.5% for culture-based studies, increased to 12.5% and 16.0% in molecular studies, respectively. The most prevalent fungal species was Candida spp. The high heterogeneity in the reported fungal prevalence suggests the need for standardized sampling, and speciation methods. The advent of the new molecular biological analytical platforms, such as the next generation sequencing (NGS), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF), that enables identification and quantitation of a broad spectrum of hitherto unknown organisms in endodontic infections should radically alter our understanding of the endodontic mycobiome in the future. Candida spp. appear to be co-pathogens with bacteria in approximately one in ten patients with endodontic infections. Hence, clinicians should comprehend the importance and the role of fungi in endodontic infections and be cognizant of the need to eradicate both bacteria and fungi for successful therapy.

LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris.

The emergent fungal pathogen Candida auris exhibits high resistance to antifungal drugs and environmental stresses, impeding treatment and decontamination1-3. The fungal factors mediating this stress tolerance are largely unknown. In the present study, we performed piggyBac, transposon-mediated, genome-wide mutagenesis and genetic screening in C. auris, and identified a mutant that grew constitutively in the filamentous form. Mapping the transposon insertion site revealed the disruption of a long non-coding RNA, named DINOR for DNA damage-inducible non-coding RNA. Deletion of DINOR caused DNA damage and an upregulation of genes involved in morphogenesis, DNA damage and DNA replication. The DNA checkpoint kinase Rad53 was hyperphosphorylated in dinorΔ mutants, and deletion of RAD53 abolished DNA damage-induced filamentation. DNA-alkylating agents, which cause similar filamentous growth, induced DINOR expression, suggesting a role for DINOR in maintaining genome integrity. Upregulation of DINOR also occurred during exposure to the antifungal drugs caspofungin and amphotericin B, macrophages, H2O2 and sodium dodecylsulfate, indicating that DINOR orchestrates multiple stress responses. Consistently, dinorΔ mutants displayed increased sensitivity to these stresses and were attenuated for virulence in mice. Moreover, genome-wide genetic interaction studies revealed links between the function of DINOR and TOR signalling, an evolutionarily conserved pathway that regulates the stress response. Identification of the mechanism(s) by which DINOR regulates stress responses in C. auris may provide future opportunities for the development of therapeutics.

Unsaturated fatty acid salts remove biofilms on dentures.

Candidiasis-causing Candida sp. forms biofilms with various oral bacteria in the dentures of the elderly, making it harder to kill and remove the microorganism due to the extracellular polymeric substances. We found that biofilms on dentures can effectively be removed by immersion in an unsaturated fatty acid salt solution. Using optical coherence tomography to observe the progression of biofilm removal by the fatty acid salt solution, we were able to determine that the removal was accompanied by the production of gaps at the interface between the biofilm and denture resin. Furthermore, microstructural electron microscopy observations and time-of-flight secondary ion mass spectrometry elucidated the site of action, revealing that localization of the fatty acid salt at the biofilm/denture-resin interface is an important factor.

Characteristics, Risk Factors and Predictors for Candidemia in the Pediatric Intensive Care Unit at the University Hospital Centre Zagreb in Croatia: A 9-Year Retrospective Study.

BACKGROUND: Candidemia is one of the leading causes of bloodstream infections in the pediatric intensive care unit (PICU). The aim of this study was to define characteristics and risk factors for candidemia in the PICU setting and propose a predictive model to identify the patients at risk. METHODS: This was a retrospective matched case-control study in the PICU during a 9-year period. Patients with candidemia were studied and matched with control patients without candidemia. Univariate analysis was performed for potential risk factors and multivariate analysis was conducted to determine the prediction score for candidemia. RESULTS: Forty-two cases of candidemia were matched with 84 control patients. Candida parapsilosis was the most common (71.4%) species. Risk factors independently associated with candidemia were: the use of >2 antibiotics in a maximum period of 4 weeks before the candidemia (odds ratio [OR]: 10.59; 95% confidence interval [CI]: 2.05-54.83), a previous bacterial infection in a maximum period of 4 weeks before the candidemia (OR: 5.56; 95% CI: 1.44-21.5) and the duration of PICU stay of >10 days (OR: 4.22; 95% CI: 1.02-17.41). The proposed predictive scoring system has a sensitivity of 95.24%, specificity of 76.12%, OR 64.0, 95% CI 14.2-288.6, the positive predictive value of 66.67% and the negative predictive value of 96.97%. CONCLUSIONS: Previously reported risk factors for candidemia have been confirmed and some new have been detected. The presented scoring system can help identify patients who would benefit from prophylactic antifungal therapy.

Spectrum and Antifungal Resistance of Candidemia in Neonates With Early- and Late-Onset Sepsis in Pakistan.

BACKGROUND: Neonatal candidemia leads to high morbidity and mortality in developing countries. We studied the trends, spectrum and antifungal resistance in neonatal candidemia isolates from the year 2014 to 2019. METHODS: This was a cross-sectional study conducted at the Aga Khan University, Pakistan. Neonates with positive blood cultures with Candida species were retrospectively identified from the laboratory database (2014-2018) and prospectively in 2019 where clinical information was also collected as part of routine laboratory reporting. RESULTS: We identified 669 neonates with Candida species in blood cultures. Three hundred forty-six neonates had early-onset disease (EOD age ≤7 days) and 323 had late-onset disease (LOD age >7 days). Non-albicans Candida species (86.7%) were predominant versus C. albicans (13.3%; P-value 0.024) with Candida tropicalis being most common in both EOD and LOD. Candida pelliculosa and Candida guilliermondii were associated with EOD and C. albicans with LOD. Isolation of fluconazole nonsusceptible non-albicans Candida species was significantly higher in early-onset (5.9%) versus late-onset (2%) neonatal candidemia (P-value 0.005; crude odds ratio [COR] 2.73, 95% CI: 1.34-5.53). LOD in neonates was more likely associated with the use of vancomycin (COR 3.89, 95% CI: 1.39-10.89). EOD was more likely seen in patients with vaginal delivery (COR 4.16, 95% CI: 1.42-12.23) and in neonates with respiratory distress leading to intensive care unit admission (COR 3.31, 95% CI: 1.05-10.42). CONCLUSIONS: Non-albicans Candida species were increasingly isolated from neonates with candidemia during recent years from Pakistan. Amphotericin remains first-line option for neonatal candidemia in our setting as fluconazole nonsusceptible Candida species are commonly isolated.

Candidemia in intensive care units over nine years at a large Italian university hospital: Comparison with other wards.

PURPOSE: Candidemia is an alarming problem in critically ill patients including those admitted in intensive care units (ICUs). We aimed to describe the clinical and microbiological characteristics of bloodstream infections (BSIs) due to Candida spp. in patients admitted to ICUs of an italian tertiary referral university hospital over nine years. METHODS: A retrospective observational study of all cases of candidemia in adult patients was carried out from January 1, 2010 to December 31, 2018 at a 980-bedded University Hospital in Ancona, Italy, counting five ICUs. The incidence, demographics, clinical and microbiologic characteristics, therapeutic approaches and outcomes of ICU-patients with candidemia were collected. Non-ICU patients with candidemia hospitalized during the same time period were considered for comparison purposes. Early (7 days from the occurrence of the episode of Candida BSI) and late (30 days) mortality rates were calculated. RESULTS: During the study period, 188/505 (36%) episodes of candidemia occurred in ICU patients. Cumulative incidence was 9.9/1000 ICU admission and it showed to be stable over time. Candida albicans accounted for 52% of the cases, followed by C. parapsilosis (24%), and C. glabrata (14%). There was not a significant difference in species distribution between ICU and non-ICU patients. With the exception of isolates of C. tropicalis which showed to be fluconazole resistant in 25% of the cases, resistance to antifungals was not of concern in our patients. Early and late mortality rates, were 19% and 41% respectively, the latter being significantly higher than that observed in non-ICU patients. At multivariate analysis, factors associated with increased risk of death were septic shock, acute kidney failure, pulmonary embolism and lack of antifungal therapy. The type of antifungal therapy did not influence the outcome. Mortality did not increased significantly over time. CONCLUSION: Neither cumulative incidence nor crude mortality of candidemia in ICU patients increased over time at our institution. However, mortality rate remained high and significantly associated with specific host-related factors in the majority of cases.

Candidemia and Invasive Candidiasis.

Invasive candidiasis (IC) is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 6 of which cause most cases globally. Candidemia is probably the most commonly recognized syndrome associated with IC; however, Candida can cause invasive infection of any organ, especially visceral organs, vasculature, bones and joints, the eyes and central nervous system. Targeted prevention and empirical therapy are important interventions for patients at high risk for IC, and the current approach should be based on a combination of clinical risk factors and non-culture-based diagnostics, when available.