Stacey A. Maskarinec

Increased Costs Associated with Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Bacteria Are Due Primarily to Patients with Hospital-Acquired Infections

ABSTRACT The clinical and economic impacts of bloodstream infections (BSI) due to multidrug-resistant (MDR) Gram-negative bacteria are incompletely understood. From 2009 to 2015, all adult inpatients with Gram-negative BSI at our institution were prospectively enrolled. MDR status was defined as resistance to ≥3 antibiotic classes. Clinical outcomes and inpatient costs associated with the MDR phenotype were identified. Among 891 unique patients with Gram-negative BSI, 292 (33%) were infected with MDR bacteria. In an adjusted analysis, only history of Gram-negative infection was associated with MDR BSI versus non-MDR BSI (odds ratio, 1.60; 95% confidence interval [CI], 1.19 to 2.16; P = 0.002). Patients with MDR BSI had increased BSI recurrence (1.7% [5/292] versus 0.2% [1/599]; P = 0.02) and longer hospital stay (median, 10.0 versus 8.0 days; P = 0.0005). Unadjusted rates of in-hospital mortality did not significantly differ between MDR (26.4% [77/292]) and non-MDR (21.7% [130/599]) groups (P = 0.12). Unadjusted mean costs were 1.62 times higher in MDR than in non-MDR BSI (

Results from a 13-Year Prospective Cohort Study Show Increased Mortality Associated with Bloodstream Infections Caused by Pseudomonas aeruginosa Compared to Other Bacteria

59,266 versus

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus

36,452; P = 0.003). This finding persisted after adjustment for patient factors and appropriate empirical antibiotic therapy (means ratio, 1.18; 95% CI, 1.03 to 1.36; P = 0.01). Adjusted analysis of patient subpopulations revealed that the increased cost of MDR BSI occurred primarily among patients with hospital-acquired infections (MDR means ratio, 1.41; 95% CI, 1.10 to 1.82; P = 0.008). MDR Gram-negative BSI are associated with recurrent BSI, longer hospital stays, and increased mean inpatient costs. MDR BSI in patients with hospital-acquired infections primarily account for the increased cost.

Genetic Susceptibility to Fungal Infections: What is in the Genes?

ABSTRACT The impact of bacterial species on outcome in bloodstream infections (BSI) is incompletely understood. We evaluated the impact of bacterial species on BSI mortality, with adjustment for patient, bacterial, and treatment factors. From 2002 to 2015, all adult inpatients with monomicrobial BSI caused by Staphylococcus aureus or Gram-negative bacteria at Duke University Medical Center were prospectively enrolled. Kaplan-Meier curves and multivariable Cox regression with propensity score models were used to examine species-specific bacterial BSI mortality. Of the 2,659 enrolled patients, 999 (38%) were infected with S. aureus, and 1,660 (62%) were infected with Gram-negative bacteria. Among patients with Gram-negative BSI, Enterobacteriaceae (81% [1,343/1,660]) were most commonly isolated, followed by non-lactose-fermenting Gram-negative bacteria (16% [262/1,660]). Of the 999 S. aureus BSI isolates, 507 (51%) were methicillin resistant. Of the 1,660 Gram-negative BSI isolates, 500 (30%) were multidrug resistant. The unadjusted time-to-mortality among patients with Gram-negative BSI was shorter than that of patients with S. aureus BSI (P = 0.003), due to increased mortality in patients with non-lactose-fermenting Gram-negative BSI generally (P < 0.0001) and Pseudomonas aeruginosa BSI (n = 158) in particular (P < 0.0001). After adjustment for patient demographics, medical comorbidities, bacterial antibiotic resistance, timing of appropriate antibiotic therapy, and source control in patients with line-associated BSI, P. aeruginosa BSI remained significantly associated with increased mortality (hazard ratio = 1.435; 95% confidence interval = 1.043 to 1.933; P = 0.02). P. aeruginosa BSI was associated with increased mortality relative to S. aureus or other Gram-negative BSI. This effect persisted after adjustment for patient, bacterial, and treatment factors.

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

BACKGROUND Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced significantly higher levels of PSM than MRSA isolates from hospital-acquired pneumonia (HAP) or infective endocarditis (IE). In this investigation, we sought to validate this finding in methicillin-susceptible S. aureus (MSSA) isolates. METHODS MSSA isolates (n = 162) from patients with SSTI, HAP, and IE were matched 1:1:1 based on geographic origin of the infection to form 54 triplets (North America n = 27, Europe n = 25, Australia n = 2). All isolates underwent spa typing and were classified using eGenomics. In vitro PSM production was quantified by high-performance liquid chromatography/mass spectrometry. Fischers Exact Test and the Kruskal-Wallis test were used for statistical analysis. RESULTS Spa1 was more common in SSTI (14.81% SSTI, 3.70% HAP, 1.85% IE) (p < 0.03). Spa2 was more common in HAP (0% SSTI, 12.96% HAP, 3.70% IE) (p < 0.01). Levels of PSMα1-4 all differed significantly among the three clinical groups, with SSTI isolates producing the highest levels and IE producing the lowest levels of PSMα1-4. Spa1 isolates produced significantly more delta-toxin (p < 0.03) than non-Spa1 isolates. No associations between PSM levels and clinical outcome of SSTI, HAP, or IE were identified. CONCLUSION Production of PSMα1-4 is highest in SSTI MSSA isolates, supporting the hypothesis that these peptides are important for SSTI pathogenesis. These findings are similar to those described in MRSA, and demonstrate that associations between PSM levels and type of infection are independent of the methicillin-resistance status of the isolate.

The Risk of Cardiac Device-Related Infection in Bacteremic Patients Is Species Specific: Results of a 12-Year Prospective Cohort

The development of severe fungal infections has long been associated with traditional risk factors such as profound immunosuppression, yet it remains challenging to understand why under similar conditions, only some patients will develop these infections while others will not. Recent studies have demonstrated the importance of host genetic variation in influencing the severity and susceptibility to invasive fungal infections. In this review, we examine selected primary immunodeficiencies characterized by their vulnerability to a narrow range of fungal pathogens and then focus on recently identified genetic polymorphisms associated with an increased susceptibility to invasive fungal infections.

A Prognostic Model of Persistent Bacteremia and Mortality in Complicated Staphylococcus aureus Bloodstream Infection

The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ2(1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P<5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P<9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.

On-demand release of Candida albicans biofilms from urinary catheters by mechanical surface deformation

Abstract Background The species-specific risk of cardiac device-related infection (CDRI) among bacteremic patients is incompletely understood. Methods We conducted a prospective cohort study of hospitalized patients from October 2002 to December 2014 with a cardiac device (CD) and either Staphylococcus aureus bacteremia (SAB) or Gram-negative bacteremia (GNB). Cardiac devices were defined as either prosthetic heart valves (PHVs), including valvular support rings, permanent pacemakers (PPMs)/automatic implantable cardioverter defibrillators (AICDs), or left ventricular assist devices (LVADs). Results During the study period, a total of 284 patients with ≥1 CD developed either SAB (n = 152 patients) or GNB (n = 132 patients). Among the 284 patients, 150 (52.8%) had PPMs/AICDs, 72 (25.4%) had PHVs, 4 (1.4%) had LVADs, and 58 (20.4%) had >1 device present. Overall, 54.6% of patients with SAB and 16.7% of patients with GNB met criteria for definite CDRI (P < .0001). Multivariable logistic regression analysis revealed that 3 bacterial species were associated with an increased risk for CDRI: Staphylococcus aureus (odds ratio [OR] = 5.57; 95% confidence interval [CI], 2.16–14.36), Pseudomonas aeruginosa (OR = 50.28; 95% CI, 4.16–606.93), and Serratia marcescens (OR = 7.75; 95% CI, 1.48–40.48). Conclusions Risk of CDRI among patients with bacteremia varies by species. Cardiac device-related infection risk is highest in patients with bacteremia due to S aureus, P aeruginosa, or S marcescens. By contrast, it is lower in patients with bacteremia due to other species of Gram-negative bacilli. Patients with a CD who develop bacteremia due to either P aeruginosa or S marcescens should be considered for diagnostic imaging to evaluate for the presence of CDRI.

Persistent Rash in a Patient Receiving Total Parenteral Nutrition.

BACKGROUND Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. METHODS To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes using 2 cohorts of patients with S. aureus bacteremia (n = 32 and n = 124). RESULTS We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia. Prognostic modeling identified interleukin (IL)-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers classifying fatal outcome with 89% sensitivity and 77% specificity (P < .0001). Baseline IL-17A levels were elevated in patients with persistent bacteremia (P < .0001), endovascular (P = .026) and metastatic tissue infections (P = .012). CONCLUSIONS These results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials.

Familial Adenomatous Polyposis Manifesting as Lactococcus Endocarditis: A Case Report and Review of the Association of Lactococcus with Underlying Gastrointestinal Disease

Abstract Candida albicans is a leading cause of catheter-associated urinary tract infections and elimination of these biofilm-based infections without antifungal agents would constitute a significant medical advance. A novel urinary catheter prototype that utilizes on-demand surface deformation is effective at eliminating bacterial biofilms and here the broader applicability of this prototype to remove fungal biofilms has been demonstrated. C. albicans biofilms were debonded from prototypes by selectively inflating four additional intralumens surrounding the main lumen of the catheters to provide the necessary surface strain to remove the adhered biofilm. Deformable catheters eliminated significantly more biofilm than the controls (>90% eliminated vs 10% control; p < 0.001). Mechanical testing revealed that fungal biofilms have an elastic modulus of 45 ± 6.7 kPa with a fracture energy of 0.4–2 J m−2. This study underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.