Macrophage Migration Inhibitory Factor Polymorphisms and Invasive Streptoccus Pneumoniae Infections

Streptococcus pneumoniae[italicized everytime] (S. pneumoniae) causes a spectrum of disease severity, and human host factors likely play a role in this variation. One candidate factor is macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine and upstream regulator of innate immunity. The MIF[italicized when not in parenthesis] promoter contains two functional polymorphisms, a tetranucleotide (CATT) repeat such that MIF expression increases with repeat number from 5-8 and a single nucleotide polymorphism (SNP) leading to a G-to-C transition, which results in increased MIF expression in cell line reporter assays. Emerging data suggest an association between high-expression MIF alleles and inflammatory disease. This study comprised two parts. For the in vitro portion, we hypothesized that peripheral blood monocytic cells (pBMCs) cultured from healthy individuals with low-expressing MIF genotypes (5-CATT alleles or SNP-GG) would have lower MIF content and release than those from individuals with high-expressing MIF genotypes (7-CATT or SNP-C alleles). For the in vivo study, we hypothesized that individuals with low-expressing MIF genotypes would have less severe systemic inflammatory responses than individuals with high-expressing MIF genotypes in response to S. pneumoniae infection. Blood samples and chart findings were collected prospectively at three Connecticut hospitals from 30 inpatients with documented invasive S. pneumoniae infections. Genomic DNA was isolated from host blood, amplified, and genotyped using fragment analysis (CATT repeat) and allelic discrimination (SNP) methods. Fishers exact tests were used to compare genotypes and disease severity. For the in vitro experiments, there were no differences observed in serum MIF levels or MIF content or release from pBMCs based on MIF genotype. In the cohort of patients infected with S. pneumoniae, serum MIF levels among enrolled subjects were significantly higher than the reported normal values, but levels did not vary with genotype or disease severity. The SNP genotype was not correlated with disease severity or occurrence of meningitis. The CATT genotype did not correlate significantly with disease severity or occurrence of meningitis, although there was a trend suggesting an association between the 7-CATT allele and meningitis (p = 0.1188, 8% without meningitis had a 7-CATT allele vs. 40% with meningitis). More patient samples will need to be analyzed in order to definitively elucidate the role of MIF genetics in infection with S. pneumonia

Clinical Characteristics and Outcomes Among Individuals With Spinal Implant Infections: A Descriptive Study.

Little is known about the clinical presentation and outcomes associated with spinal implant infections. Here, we describe a single center's experience in a retrospective cohort of 109 individuals with spinal implant infections, including clinical, microbiological, therapeutic, and outcome data

Sentinel Case of Candida auris in the Western United States Following Prolonged Occult Colonization in a Returned Traveler from India.

Candida auris is an emerging multidrug-resistant yeast with high mortality. We report the sentinel C. auris case on the United States West Coast in a patient who relocated from India. We identified close phylogenetic relatedness to the South Asia clade and ERG11 Y132F and FKS1 S639Y mutations potentially explaining antifungal resistance

Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics

Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test\u27s accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, since the right answer is unknown. Solutions consist of multi-test comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no pre-defined test or composite of tests is sufficiently accurate; they emulate clinical practice in that multiple data pieces are clinically assessed together

Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia

Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to <2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission

Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia

Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to &lt;2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission