Obstructive hydrocephalus and intracerebral mass secondary to Epicoccum nigrum

Here we report a case of a 14-week-old girl with a history of intrauterine drug exposure and hypoxic ischemic encephalopathy secondary to cardiac arrest requiring prolonged resuscitation at birth presented with irritability and a bulging anterior fontanelle. After neurosurgical resection, pathologic examination showed fungal hyphae, an

Coculture of Staphylococcus aureus with Pseudomonas aeruginosa Drives S. aureus towards Fermentative Metabolism and Reduced Viability in a Cystic Fibrosis Model

The airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood. Staphylococcus aureus is the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading to Pseudomonas aeruginosa community predominance in ∼50% of adults. We developed a robust dual-bacterial in vitro coculture system of P. aeruginosa and S. aureus on monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show that P. aeruginosa drives the S. aureus expression profile from that of aerobic respiration to fermentation. This shift is dependent on the production of both 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) and siderophores by P. aeruginosa. Furthermore, S. aureus-produced lactate is a carbon source that P. aeruginosa preferentially consumes over medium-supplied glucose. We find that initially S. aureus and P. aeruginosa coexist; however, over extended coculture P. aeruginosa reduces S. aureus viability, also in an HQNO- and P. aeruginosa siderophore-dependent manner. Interestingly, S. aureus small-colony-variant (SCV) genetic mutant strains, which have defects in their electron transport chain, experience reduced killing by P. aeruginosa compared to their wild-type parent strains; thus, SCVs may provide a mechanism for persistence of S. aureus in the presence of P. aeruginosa. We propose that the mechanism of P. aeruginosa-mediated killing of S. aureus is multifactorial, requiring HQNO and P. aeruginosa siderophores as well as additional genetic, environmental, and nutritional factors

Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis

Abstract Background Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required. Results We characterized the fungi and bacteria in expectorated sputa from six CF subjects. Samples were collected upon admission for systemic antibacterial therapy and upon the completion of treatment and analyzed using a pyrosequencing-based analysis of fungal internal transcribed spacer 1 (ITS1) and bacterial 16S rDNA sequences. A mixture of Candida species and Malassezia dominated the mycobiome in all samples (74%–99% of fungal reads). There was not a striking trend correlating fungal and bacterial richness, and richness showed a decline after antibiotic therapy particularly for the bacteria. The fungal communities within a sputum sample resembled other samples from that subject despite the aggressive antibacterial therapy. Quantitative PCR analysis of fungal 18S rDNA sequences to assess fungal burden showed variation in fungal density in sputum before and after antibacterial therapy but no consistent directional trend. Analysis of Candida ITS1 sequences amplified from sputum or pure culture-derived genomic DNA from individual Candida species found little (<0.5%) or no variation in ITS1 sequences within or between strains, thereby validating this locus for the purpose of Candida species identification. We also report the enhancement of the publically available Visualization and Analysis of Microbial Population Structures (VAMPS) tool for the analysis of fungal communities in clinical samples. Conclusions Fungi are present in CF respiratory sputum. In CF, the use of intravenous antibiotic therapy often does not profoundly impact bacterial community structure, and we observed a similar stability in fungal species composition. Further studies are required to predict the effects of antibacterials on fungal burden in CF and fungal community stability in non-CF populations.http://deepblue.lib.umich.edu/bitstream/2027.42/134558/1/40168_2014_Article_67.pd

Characterization and Quantification of the Fungal Microbiome in Serial Samples from Individuals with Cystic Fibrosis

Background: Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required. Results: We characterized the fungi and bacteria in expectorated sputa from six CF subjects. Samples were collected upon admission for systemic antibacterial therapy and upon the completion of treatment and analyzed using a pyrosequencing-based analysis of fungal internal transcribed spacer 1 (ITS1) and bacterial 16S rDNA sequences. A mixture of Candida species and Malassezia dominated the mycobiome in all samples (74% – 99% of fungal reads). There was not a striking trend correlating fungal and bacterial richness, and richness showed a decline after antibiotic therapy particularly for the bacteria. The fungal communities within a sputum sample resembled other samples from that subject despite the aggressive antibacterial therapy. Quantitative PCR analysis of fungal 18S rDNA sequences to assess fungal burden showed variation in fungal density in sputum before and after antibacterial therapy but no consistent directional trend. Analysis of Candida ITS1 sequences amplified from sputum or pure culture-derived genomic DNA from individual Candida species found little (\u3c0.5%) or no variation in ITS1 sequences within or between strains, thereby validating this locus for the purpose of Candida species identification. We also report the enhancement of the publically available Visualization and Analysis of Microbial Population Structures (VAMPS) tool for the analysis of fungal communities in clinical samples. Conclusions: Fungi are present in CF respiratory sputum. In CF, the use of intravenous antibiotic therapy often does not profoundly impact bacterial community structure, and we observed a similar stability in fungal species composition. Further studies are required to predict the effects of antibacterials on fungal burden in CF and fungalcommunity stability in non-CF populations

Proteomic Changes of Alveolar Lining Fluid in Illnesses Associated with Exposure to Inhaled Non-Infectious Microbial Particles

Peer reviewe

Cystic fibrosis lung infections are polymicrobial, complex, and challenging to treat.

<p>The airways of patients with CF are colonized from various host (as indicated) and environmental (not depicted) sources. Patients subsequently develop chronic, polymicrobial infections composed of diverse bacterial, fungal, and viral organisms. These polymicrobial communities both influence and are impacted by their human host through complex, multifactorial interactions. As highlighted in the figure above and throughout this review, CF lung microbial communities encounter frequent antibiotic therapy, host immune factors, and an altered lung environment (including the presence of hypoxic [low oxygen] and anoxic [no oxygen] regions) throughout disease progression, all of which contribute to the development of chronic communities that often have decreased microbial diversity and are populated by organisms that have become highly adapted and resilient to treatment. The combination of diverse colonization sources, dynamic inter-domain interactions, microbial adaptation, environmental factors, and patient therapy mediates patient outcome. Eventually, chronic pulmonary infection culminates in a decline in lung function, which becomes most severe during pulmonary exacerbations and late stage disease progression. This steep decline in lung function ultimately leads to respiratory failure, the primary cause of morbidity and mortality in CF patients today [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005258#ppat.1005258.ref006" target="_blank">6</a>]. Figure illustration and design copyright 2015 William Scavone and used with permission.</p

Harnessing the Electronic Health Record and Computerized Provider Order Entry Data for Resource Management During the COVID-19 Pandemic: Development of a Decision Tree

BackgroundThe COVID-19 pandemic has resulted in shortages of diagnostic tests, personal protective equipment, hospital beds, and other critical resources. ObjectiveWe sought to improve the management of scarce resources by leveraging electronic health record (EHR) functionality, computerized provider order entry, clinical decision support (CDS), and data analytics. MethodsDue to the complex eligibility criteria for COVID-19 tests and the EHR implementation–related challenges of ordering these tests, care providers have faced obstacles in selecting the appropriate test modality. As test choice is dependent upon specific patient criteria, we built a decision tree within the EHR to automate the test selection process by using a branching series of questions that linked clinical criteria to the appropriate SARS-CoV-2 test and triggered an EHR flag for patients who met our institutional persons under investigation criteria. ResultsThe percentage of tests that had to be canceled and reordered due to errors in selecting the correct testing modality was 3.8% (23/608) before CDS implementation and 1% (262/26,643) after CDS implementation (P<.001). Patients for whom multiple tests were ordered during a 24-hour period accounted for 0.8% (5/608) and 0.3% (76/26,643) of pre- and post-CDS implementation orders, respectively (P=.03). Nasopharyngeal molecular assay results were positive in 3.4% (826/24,170) of patients who were classified as asymptomatic and 10.9% (1421/13,074) of symptomatic patients (P<.001). Positive tests were more frequent among asymptomatic patients with a history of exposure to COVID-19 (36/283, 12.7%) than among asymptomatic patients without such a history (790/23,887, 3.3%; P<.001). ConclusionsThe leveraging of EHRs and our CDS algorithm resulted in a decreased incidence of order entry errors and the appropriate flagging of persons under investigation. These interventions optimized reagent and personal protective equipment usage. Data regarding symptoms and COVID-19 exposure status that were collected by using the decision tree correlated with the likelihood of positive test results, suggesting that clinicians appropriately used the questions in the decision tree algorithm