Cases Of Invasive Candidiasis Research Articles

Candida Non-albicans and Non-auris Causing Invasive Candidiasis in a Fourth-Level Hospital in Colombia: Epidemiology, Antifungal Susceptibility, and Genetic Diversity.

Increasingly common and associated with healthcare settings, Candida infections are very important, since some species of this genus can develop antifungal resistance. We contribute data on the epidemiology, antifungal susceptibility, and genetic diversity of Candida non-albicans and non-auris affecting critically ill patients in a fourth-level hospital in Colombia. Ninety-seven isolates causing invasive infections, identified by conventional methods over 18 months, were studied. Data from patients affected by these yeasts, including sex, age, comorbidities, treatment, and outcome, were analysed. The antifungal susceptibility of the isolates was determined, and the ribosomal DNA was sequenced. Candida parapsilosis, Candida tropicalis, Candida glabrata, Candida dubliniensis, and Candida guilliermondii caused 48.5% of all cases of invasive candidiasis. The species were mainly recovered from blood (50%). Patients were mostly men (53.4%), between 18 days and 93 years old, hospitalized in the ICU (70.7%). Overall mortality was 46.6%, but patients in the ICU, using antibiotics, with diabetes mellitus, or with C. glabrata infections were more likely to die. Resistant isolates were identified in C. parapsilosis, C. tropicalis, and C. glabrata. This study provides epidemiological data for the surveillance of emerging Candida species, highlighting their clinical impact, as well as the emergence of antifungal resistance and clonal dispersal.

A cluster of Candida parapsilosis displaying fluconazole-trailing in a neonatal intensive care unit successfully contained by multiple infection-control interventions.

This study aimed to investigate and contain a cluster of invasive candidiasis cases caused by fluconazole-resistant Candida parapsilosis (FRC) in a neonatal intensive care unit. Active surveillance was initiated. Direct observations of hand-hygiene compliance (HHC) among staff were conducted before and after the implementation of hand-hygiene (HH) education. Thirty-five environmental cultures were obtained. Phylogenetic analysis of FRC was performed using Fourier-transform infrared spectroscopy and microsatellite genotyping. A total of 14 patients (mean birth weight = 860 g, gestational age = 25 weeks) infected with FRC were identified using the fully automated analyzer, including 5 with clinical infection (three with catheter-related bloodstream infection, one with cutaneous infection, and one with fatal peritonitis) and 9 with colonization. The HHC rate in nurses before performing a sterile or aseptic procedure significantly improved after the HH education (P < .05). Sinks near the patients were contaminated with FRC. All FRC strains were confirmed to be susceptible to fluconazole using the CLSI method, and the microdilution procedure indicated a trailing effect. Phylogenetic analysis showed that all the fluconazole-trailing isolates from patients were clustered together and had the same genotype. Sinks were successfully decontaminated using accelerated hydrogen peroxide and drainage pipes were replaced. Ultraviolet-C decontamination was applied in the milk preparation room. No new cases were detected after the education and disinfection interventions. Sinks are an important reservoir of C. parapsilosis. Active surveillance, environmental hygiene, and constant staff education on maintaining a high level of HHC are necessary to limit the spread of C. parapsilosis.

A Quality Improvement Project Aimed at Standardizing the Prescribing of Fluconazole Prophylaxis in a Level IV Neonatal Intensive Care Unit.

Invasive candidiasis has a high morbidity and mortality among premature neonates. Antifungal prophylaxis with fluconazole significantly lowers the risk of invasive fungal infection in this population. We noted the use of fluconazole prophylaxis in our level IV neonatal intensive care unit (NICU) was variable and sought to standardize prescribing of prophylactic fluconazole. We formed a multidisciplinary team to develop an evidence-based protocol using literature and expert consensus to guide appropriate use of fluconazole prophylaxis in our level IV NICU. After determining baseline fluconazole prophylaxis prescribing before protocol implementation, we used plan-do-study-act (PDSA) cycles to introduce protocolized prescribing and incorporate it into daily practice. A 6-month intervention phase was followed by a 2-year control phase, in which monthly audits were performed to evaluate protocol adherence. Results were displayed in a statistical process control chart. Before protocol implementation, fluconazole prophylaxis prescribing adhered to the protocol in 81% of patients. During the first PDSA cycle, adherence increased significantly to 94.5% (86/91 patients), which further increased to 98.7% (74/75 patients) during the second PDSA cycle and remained at 96% (120/125 patients) during the control phase (P < 0.0001). A multidisciplinary group-designed protocol was successful in standardizing fluconazole prophylaxis prescribing for infants in the level IV NICU. Adherence to protocol was high following implementation and was sustained for the duration of the project. There were no cases of invasive candidiasis noted.

A microplate‐based Response Surface Methodology model for growth optimization and biofilm formation on polystyrene polymeric material in a Candida albicans and Escherichia coli co‐culture

AbstractBiofilm formation is one of the crucial factors for virulence in Candida albicans, Escherichia coli and their polymicrobial biofilm formed on medical prosthetics. In this study, high biofilm forming C. albicans M207 from a case of invasive candidiasis and a standard strain of bacterial culture E. coli ATCC 39936 were used for initial screening and media optimization using One Variable at a time (OVAT) and Response Surface Methodology (RSM) models, respectively, in polystyrene microtiter plates for in vitro biofilm studies. Sucrose and peptone significantly affected biofilm formation when screened by OVAT. Media optimization by Central Composite Design (CCD) showed that pH significantly affected biofilm formation for all the cultures which was further validated at critical parameters. Biofilm was quantified by growth OD measurements, MTT and CV assays in the presence and absence of FBS precoating and compared with standard Trypticase Soy Broth (TSB) media which did not show any significant difference. This high throughput polystyrene microtiter plate assay for preliminary screening of nutritional components using OVAT and media optimization using RSM model is being reported for the first time for biofilm formation by C. albicans and E. coli in a single and dual species environment. This study is essential for functional analysis of in‐vitro growth and biofilm formation by these two pathogenic strains on polymeric hospital equipments and to develop suitable control measures to inhibit biofilm formation by C. albicans and E. coli single species and their co‐culture.

Diagnosis and Treatment of Invasive Candidiasis.

Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used. Principles and methods of treatment are discussed in this review. The emergence of pan-drug-resistant C. auris strains indicates an insufficient choice of available medications. Further surveillance, alongside the development of diagnostic and therapeutic methods, is essential.

Let's talk about sex characteristics-As a risk factor for invasive fungal diseases.

Biological sex, which comprises differences in host sex hormone homeostasis and immune responses, can have a substantial impact on the epidemiology of infectious diseases. Comprehensive data on sex distributions in invasive fungal diseases (IFDs) are lacking. In this review, we performed a literature search of in vitro/animal studies, clinical studies, systematic reviews and meta-analyses of invasive fungal infections. Females represented 51.2% of invasive candidiasis cases, mostly matching the proportions of females among the general population in the United States and Europe (>51%). In contrast, other IFDs were overrepresented in males, including invasive aspergillosis (51% males), mucormycosis (60%), cryptococcosis (74%), coccidioidomycosis (70%), histoplasmosis (61%) and blastomycosis (66%). Behavioural variations, as well as differences related to biological sex, may only in part explain these findings. Further investigations concerning the association between biological sex/gender and the pathogenesis of IFDs are warranted.

Invasive candidiasis in Africa, what is the current picture?

Invasive candidiasis is a serious, progressive, and potentially deadly infection that can affect the brain, heart, bones, eyes, and other parts of the body. It is associated with risk factors such as the use of indwelling medical devices, prolonged hospital stay, and broad-spectrum antibiotics use. It is especially seen in immunocompromised individuals such as patients with prolonged hospital stay, gastrointestinal surgery, haematological malignancies, and respiratory diseases. We have conducted a systematic search of literature using a select group of databases and appropriate search words and found that in Africa, there are 18293 documented/reported cases of invasive candidiasis in the last few decades (1976-2021) and 16636(91%) were cases of candidaemia. South Africa had the highest number of reported cases-15002(82%), which may be due to underreporting of cases in other countries. HIV positive persons with invasive candidiasis in Africa accounted for 1 052(5.8%). Candida albicans was the most frequently isolated species 6 328(32.6%), followed by Candida parapsilosis 5 910(30.4%), and Candida auris 1 505(7.8%). Due to the affordability and availability of blood culture, it was used for diagnosis in most of the studies examined, while a few studies combined other techniques and just three studies from two countries used serological tests. Echinocandins are recommended as first-line therapy but are only available in 12 countries and are highly priced. The use of fluconazole, because of its availability and relatively inexpensive nature, has led to increased resistance of Candida species to the drug.

Rotenone enhances antifungal activity of novel pyrazoles against Candida spp.

Mycoses annually affect about 2 million individuals worldwide, especially in tropical countries. Candida spp., one of the main etiologic agents of these mycoses, and in particular Candida albicans has been the most isolated pathogen in patients with severe clinical cases of invasive candidiasis and candidemia, causing frequent infections or opportunistic and chronic systemic forms. However, the emergence of non-albicans infections has become a public health concern worldwide. In discovering har.mless molecules, the pyrazoles have attracted many scientists because their great synthetic versatility and extensive therapeutic properties such as antibacterials, antivirals, antimalarials, and anti-inflammatories, anti-leishmaniasis, and antifungals. They are part of Azole compounds used for decades for antifungal treatment. The azole action mechanism is related to ergosterol synthesis inhibition by blocking the target enzymes, known as Erg11p, leading to fungistatic action. We evaluated the antifungal potential of 12 pyrazole derivatives. Compound 1d caused prominent action against Candida glabrata. Thus, we employed Rotenone as a mitochondrial complex I inhibitor. Rotenone helped to enhance the effect of the novel pyrazole derivatives tested against Candida spp, decreasing MICs value from a range of 250–500 to <3.1 ​μg/mL. Pyrazoles had a reduced cytotoxicity effect on in vivo cell culture than ketoconazole. Although ROS production might be a possible mechanism, it remained unclear. Thus, new studies must elucidate this synergistic action.

Invasive Candidiasis with Cavitary Lung Lesion in a Post-Covid-19 Diabetic Patient- A Case Report

There have been reported several complications after corona virus disease-2019 (COVID-19). Superinfections, especially secondary fungal diseases are now on rise in post-COVID-19 patients. Candida usually reflects airway colonization and true Candida pneumonia is rare, but can occur after hematologic dissemination from other body sites, such as the skin, gastrointestinal and genitourinary tract. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and increased susceptibility to fungal infections. We describe a case of invasive candidiasis in a 72-year-old post-COVID-19 diabetic male, who presented with cough, fever and cavitary lesion in lung seen on contrast-enhanced computed tomography (CECT) Chest. The patient’s sputum and blood cultures were positive for Candida.

Invasive candidiasis in a Brazilian neonatal intensive care unit

Abstract Objectives: to describe the epidemiology of invasive candidiasis in a neonatal intensive care unit. Methods: cross-sectional study that included all neonates with invasive candidiasis confirmed by blood culture from April 2015 to June 2018. Demographic, clinical and microbiological data were analyzed, comparing neonates with extreme low birth weight (ELBW) with neonates ≥ 1000g birth weight, considering a p &lt;0.05 as statistically significant. Results: there were 38 cases of invasive candidiasis, resulting in an overall incidence of 2.5%. Twelve (32%) were ELBW neonates and 26 (68%) neonates ≥ 1000g birth weight, an incidence of 4.4% and 2.0%, respectively. Abdominal surgery was more frequent among neonates with birth weight ≥ 1000g compared to ELBW neonates (85% vs. 17%; p &lt;0.01), as well as the median in days of antibiotics use (18 vs. 10.5; p = 0.04). The median in days of mechanical ventilation was more frequent among ELBW neonates (10 vs. 5.5; p = 0.04). The majority of Candida species were non-albicans (64%). Fatality rate was 32%. Conclusions: the incidence of invasive candidiasis among neonates with birth weight ≥ 1000g was higher than that found in the literature. This group has a higher proportion of gastrointestinal malformations that require surgery. Thus, fluconazole prophylaxis may be necessary for a broader group of neonates.

A predictive nomogram for mortality of cancer patients with invasive candidiasis: a 10-year study in a cancer center of North China

BackgroundInvasive candidiasis is the most common fungal disease among hospitalized patients and continues to be a major cause of mortality. Risk factors for mortality have been studied previously but rarely developed into a predictive nomogram, especially for cancer patients. We constructed a nomogram for mortality prediction based on a retrospective review of 10 years of data for cancer patients with invasive candidiasis.MethodsClinical data for cancer patients with invasive candidiasis during the period of 2010–2019 were studied; the cases were randomly divided into training and validation cohorts. Variables in the training cohort were subjected to a predictive nomogram based on multivariate logistic regression analysis and a stepwise algorithm. We assessed the performance of the nomogram through the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) in both the training and validation cohorts.ResultsA total of 207 cases of invasive candidiasis were examined, and the crude 30-day mortality was 28.0%. Candida albicans (48.3%) was the predominant species responsible for infection, followed by the Candida glabrata complex (24.2%) and Candida tropicalis (10.1%). The training and validation cohorts contained 147 and 60 cases, respectively. The predictive nomogram consisted of bloodstream infections, intensive care unit (ICU) admitted > 3 days, no prior surgery, metastasis and no source control. The AUCs of the training and validation cohorts were 0.895 (95% confidence interval [CI], 0.846–0.945) and 0.862 (95% CI, 0.770–0.955), respectively. The net benefit of the model performed better than “treatment for all” in DCA and was also better for opting low-risk patients out of treatment than “treatment for none” in opt-out DCA.ConclusionCancer patients with invasive candidiasis exhibit high crude mortality. The predictive nomogram established in this study can provide a probability of mortality for a given patient, which will be beneficial for therapeutic strategies and outcome improvement.

Cell Rupture and Morphogenesis Control of the Dimorphic Yeast Candida albicans by Nanostructured Surfaces.

Nanostructured surfaces control microbial biofilm formation by killing mechanically via surface architecture. However, the interactions between nanostructured surfaces (NSS) and cellular fungi have not been thoroughly investigated and the application of NSS as a means of controlling fungal biofilms is uncertain. Cellular yeast such as Candida albicans are structurally and biologically distinct from prokaryotic microbes and therefore are predicted to react differently to nanostructured surfaces. The dimorphic opportunistic fungal pathogen, C. albicans, is responsible for most cases of invasive candidiasis and is a serious health concern due to the rapid increase of drug resistance strains. In this paper, we show that the nanostructured surfaces from a cicada wing alter C. albicans’ viability, biofilm formation, adhesion, and morphogenesis through physical contact. However, the fungal cell response to the NSS suggests that nanoscale mechanical interactions impact C. albicans differently than prokaryotic microbes. This study informs on the use of nanoscale architecture for the control of eukaryotic biofilm formation and illustrates some potential caveats with the application of NSS as an antimicrobial means.

General hospital outbreak of invasive candidiasis due to azole-resistant Candida parapsilosis associated with an Erg11 Y132F mutation.

An increasing number of outbreaks due to resistant non-albicans Candida species have been reported worldwide. Between 2014 and 2016, Candida isolates causing invasive candidiasis were recovered in a Mexican hospital. Isolates were identified to species level and antifungal susceptibility was determined. In the time period studied, 74 invasive candidiasis cases were identified, with 38% (28/74) caused by Candida parapsilosis, out of which 54% (15/28) were fluconazole resistant. The ERG11 gene was sequenced for 12 recoverable fluconazole-resistant C. parapsilosis isolates and SNPs identified. The 12 isolates had one common silent point mutation in ERG11 (T591C) and seven isolates had an additional (A395T) mutation, which corresponded to Y132F. Four of the isolates carrying this mutation were closely related within the same cluster by microsatellite typing. This is the first report of an invasive candidiasis outbreak in Mexico due to azole-resistant C. parapsilosis associated with the Y132F substitution.

Comparative analysis of antifungal susceptibility testing methods for echinocandins in candidemia isolates

Background: The alarming rise in antifungal resistance during therapy, increased use of antifungals and the recognition of innate resistance in some fungal species has led to greater demand for antifungal susceptibility testing (AFST). Candida spp. are the most prevalent invasive fungal infections. Also, each species has its unique virulence potential, epidemiology and antifungal susceptibility patterns. One of the novel species, Candida auris (first described in 2009) has emerged as a cause of rapidly spreading nosocomial outbreaks, further it has reduced susceptibility to the major classes of antifungal agents. Our objective is to analyse various methods of AFST for testing MIC (Minimum inhibitory concentration) of echinocandins in candidemia isolates. Methods and materials: This study was conducted at Medanta-The Medicity, Haryana, India. We performed three methods of AFST on each of the 100 clinical bloodstream Candida isolates which were identified by Matrix Assisted Laser Desorption Ionization-Time of Fight Mass Spectrometry (MALDI-TOF MS) (Bruker Daltonics). The methods performed for detecting MIC of antifungal agents included VITEK 2 (bioMérieux), Etest (bioMérieux) and CLSI (Clinical and Laboratory Standards Institute) Broth Microdilution (BMD) following the M27-A3 guidelines. The echinocandins tested were caspofungin and micafungin. Results: Nonalbicans Candida (70/100) were more frequently isolated as compared to Candida albicans (30/100). The nonalbicans detected were Candida auris (28/70) followed by Candida tropicalis (24/100) and others. The MIC range of Caspofungin with VITEK 2, CLSI BMD and Estrip respectively for Candida albicans and Candida tropicalis (similar) ≤0.25–0.5, 0.03–0.125, 0.06–0.08; for Candida auris ≤0.25–0.5, 0.5–1, 0.5–1. Similarly, the MIC range of micafungin with VITEK 2, CLSI BMD and Estrip respectively for Candida albicans and Candida tropicalis ≤0.06–0.5, 0.03–0.06, 0.064–0.125; for Candida auris 0.12, 0.06–0.125, 0.064–0.125. The results suggest that the CLSI BMD and Estrip give similar results while Vitek 2 deviates, but the variation is not statistically significant. Conclusion: The clinical laboratories should have a clear approach about which method of AFST is feasible, reliable and cost effective to their setting. Identification of Candida to the species level and AFST helps in prompt management of difficult-to-treat cases of invasive candidiasis. Furthermore, epidemiological studies should also be done periodically to determine the antifungal resistance rates for individual centres.

Clinical case of invasive candidiasis in phthisiatrician’s practice

The paper presents a case of generalized candidomycosis in a 67-year old woman. Literature data regarding the cases of respiratory mycoses and candida sepsis are summarized. This case is interesting from the point of view of difficulty of differential diagnosis in patients with respiratory mycosis and tuberculosis, choice of adequate treatment.

Breakthrough invasive candidiasis in pediatric patient with Ewing’s sarcoma: dinical case report and literature review

We presented clinical case of invasive candidiasis in 13 years old girl with Ewing's sarcoma during intensive treatment with combined chemotherapy according EWING 2008 protocol. The most significant risk factors were recurrent chemotherapy induced neutropenia gr IV, multifocal Candida colonization, prolonged central venous catheter use, combined antibiotic therapy in the previous >10 days, parenteral nutrition. In spite of provided prophylaxis and antifungal therapy patient died because of progression of invasive candidiasis. We analyzed literature data on frequency of invasive candidiasis in children with Ewing's sarcoma and cases of breakthrough candidiasis in pediatric malignancies.

A Rare Case of Candida Pericarditis Associated with Esophagopericardial Fistula

Patient: Male, 43Final Diagnosis: Candida albicans pericarditisSymptoms: Chest painMedication: —Clinical Procedure: —Specialty: CardiologyObjective:Rare diseaseBackground:Candida albicans is the principal human fungal opportunistic organism commonly detected in the gastrointestinal and genitourinary systems. Five species of candida (Glabrata, Tropicalis, Albicans, Parapsilosis, and Kruzei) are responsible for most cases of invasive candidiasis or candidemia, which is a growing public health concern due to the increasing complexity of patients, leading to a high fatality rate.Case Report:We report an extremely rare case of candida pericarditis due to esophagopericardial fistula in a young, heavy, alcoholic adult diagnosed by culture of the drained pericardial fluid, which showed a growth of Candida albicans.Conclusions:We highlight the first case of candida pericarditis in immunocompetent adult successfully treated by pericardiocentesis and oral fluconazole.

Invasive candidiasis in children after hematopoietic stem cell transplantation

Invasive fungal disease due to Candida spp. – Invasive candidiasis/candidaemia, is a life-threatening complication in immunosuppressed patients. The publications on epidemiology of invasive candidiasis (IC) in children after hematopoietic stem cell transplantation (HSCT) is limited. The purpose of the study was to study the epidemiology of IC in children after HSCT for the 7 years in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation. In 2009–2016 yy have been performed 754 HSCT in children: 494 allogeneic and 260 autologous. The study was approved by the Independent Ethics Committee of the Raisa Gorbacheva Memorial Research Institute of Children's Oncology, Hematology and Transplantation. A retrospective study included 22 cases of invasive candidiasis in after HSCT. EORTC/MSG 2008 criteria were used for the diagnosis of proven invasive candidiasis as well as to evaluate response to therapy. Incidence of IC was 2.9%: allo-HSCT – 3% (n = 15), auto-HSCT – 2,7% (n = 7). The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The etiology: Candida parapsilosis – 50%, Candida albicans – 27%, Candida krusei – 14%, Candida tropicalis – 5%, Candida dubliniensis – 4%. The most frequent underlying diseases was acute leukemia – 45% (n = 10). The median age was 8 y.o. (3 month–18 years). The median day of onset of IC after allo-HSCT was 63 days (4–243), auto-HSCT – 12 days (3–20). Febrile fever was the main clinical symptom; septic syndrome develops in 32% cases. Antifungal therapy was with echinocandins – 23%, lipid ampho B – 27%, triazole (fluconazole, voriconazole) – 32%, without therapy (due to early mortality) – 18%. Overall survival (OS) at 30 days from diagnosis invasive candidiasis was 50%. The central venous catheter (CVC) removal was the only factor significantly improved OS (70% vs 33%, p = 0,035). Incidence of Invasive candidiasis in children after hematopoietic stem cell transplantation was 2.9%. The main etiology agent was Candida parapsilosis. Invasive candidiasis infections most often affect leukemia patients, after allo-HSCT developed later than auto-HSCT. Overall survival at 30 days from the diagnosis was 50%. Removing of CVC improved overall survival in children with invasive candida infections after HSCT

Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.

The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice "humanized" with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011, https://doi.org/10.3201/eid1701.P11101), and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress.

Searching for a change: The need for increased support for public health and research on fungal diseases

Fungal diseases have been continually neglected over the years despite their alarming impact on human health. Recent estimates [1] suggest a global annual occurrence of approximately 3,000,000 cases of chronic pulmonary aspergillosis, more than 200,000 cases of cryptococcal meningitis, 700,000 cases of invasive candidiasis, 500,000 cases of Pneumocystis jirovecii pneumonia, 250,000 cases of invasive aspergillosis, 100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma, and 1,000,000 cases of fungal keratitis. It is estimated that fungal infections kill more than 1.5 million people every year [2]. Morbidity due to fungal infections is also significant. Chromoblastomycosis and eumycetoma, for instance, cause debilitating diseases affecting subcutaneous tissues, skin, and underlying bones [3,4]. Importantly, the epidemiology of fungal diseases is dynamic and hard to predict. Recently, the multidrug-resistant pathogen Candida auris has emerged as a serious threat to human health, with some infections resistant to all main classes of antifungal medications [5]. Known diseases also raise new concerns. The city of Rio de Janeiro, Brazil, currently faces the largest epidemic of sporotrichosis in history [6]. Paracoccidioidomycosis is still one of the most important systemic mycoses in Latin America and the leading fungal cause of mortality in non-immunosuppressed individuals in Brazil [3,7]. Mortality and morbidity due to fungal diseases mostly affect individuals living under socioeconomic restrictions [8,9]. Reliable and cost-effective diagnostic tools are available for a very limited number of mycoses, and therapeutic options are restricted to a few classes of poorly effective, toxic, and expensive pharmaceutical agents [10]. There are no licensed antifungal vaccines [12]. The last antifungals approved for clinical use were the echinocandins in 2002 [11]. According to the Global Fund for Fungal Infections (GAFFI), several key antifungals also are not available or not even registered in multiple regions where fungal diseases are most lethal [2]. These serious gaps in diagnostic, therapeutic, and preventive tools for fungal infections are a dangerous combination that results in high costs and low efficacy of clinical approaches [13]. To minimize the number of deaths caused by fungal diseases, novel therapeutic, diagnostic, and preventive tools must be developed, and the diagnostic tests and antifungal agents that are available must be rationally deployed.