Gut Microbiota and Other Factors Associated With Increased Regulatory T Cells in Hiv-exposed Uninfected Infants.

HIV-exposed uninfected infants (HEU) have higher infectious morbidity than HIV-unexposed infants (HUU). HEU have multiple immune defects of unknown origin. We hypothesized that HEU have higher regulatory T cells (Treg) than HUU, which may dampen their immune defenses against pathogens.

Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model.

Bacterial pneumonia is a common clinical syndrome leading to significant morbidity and mortality worldwide. In the current study, we investigate a novel, multidirectional relationship between the pulmonary epithelial glycocalyx and antimicrobial peptides in the setting of methicillin-resistant (MRSA) pneumonia. Using an in vivo pneumonia model, we demonstrate that highly sulfated heparan sulfate (HS) oligosaccharides are shed into the airspaces in response to MRSA pneumonia.

Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts.

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Unlabelled: Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts.

Miliary Histoplasmosis in a Patient with Rheumatoid Arthritis.

Miliary histoplasmosis is a rare presentation that may mimic miliary tuberculosis. We report a case of miliary histoplasmosis in a 52-year-old male who was being treated with hydroxychloroquine, methotrexate, and sulfasalazine for his rheumatoid arthritis and presented to the emergency department with shortness of breath and fevers. Computed tomography (CT) chest revealed miliary pulmonary nodules.

Cryptococcosis and cryptococcal meningitis: New predictors and clinical outcomes at a United States academic medical centre.

As the diagnosis of cryptococcosis is challenging in low-prevalence settings, uncovering predictive factors can improve early diagnosis and timely treatment. The aim of the study was to relate clinical outcomes to predictive variables for the presence of cryptococcosis. A retrospective case-control study matched by collection date, age and gender at a 1:2 ratio (55 cases and 112 controls) was performed in case patients diagnosed with Cryptococcus infection at the University of Colorado Hospital between 2000 and 2017 (n = 167).

Whole-Genome Sequencing Identifies In Vivo Acquisition of a blaCTX-M-27-Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection.

We report a case of ceftriaxone treatment failure for bacteremia caused by Salmonella enterica subsp. enterica serovar Typhimurium, due to the in vivo acquisition of a bla-encoding IncFII group transmissible plasmid. The original β-lactamase-susceptible isolate ST882S was replaced by the resistant isolate ST931R during ceftriaxone treatment.

Risk Factors for Cryptococcal Meningitis: A Single United States Center Experience.

Cryptococcal meningitis carries a high mortality. Further understanding of immune suppression factors associated with neuroinvasive infection will improve risk stratification and enhance early diagnosis and treatment with antifungal therapy. The aim of the study was to corroborate established or find novel clinical predictors for cryptococcal meningitis.

Risk factors and influence of carbapenem exposure on the development of carbapenem resistant Pseudomonas aeruginosa bloodstream infections and infections at sterile sites.

Background: Patients with Pseudomonas aeruginosa infections from blood or sterile sites were evaluated to determine risk factors associated with carbapenem resistance (CRPA) compared to carbapenem sensitivity (CSPA) as well as prior carbapenem use and the development of resistance.

Findings: Retrospective chart review of 80 patients hospitalized with a documented P. aeruginosa infection during 2010-2011.

Influence of Gelatin-Thrombin Matrix Tissue Sealant on Bacterial Colony Formation and Risk of Pelvic Infection.

Objective. Gelatin-thrombin matrix (GTM) tissue sealant use was previously identified as an independent predictor of pelvic infection following hysterectomies. We aim to elucidate contributing factors by assessing influence of GTM on bacterial colony formation and characterizing bacteria present at the vaginal cuff.

Failure of outpatient antibiotics among patients hospitalized for acute bacterial skin infections: What is the clinical relevance?

Background: Infectious Diseases Society of America guidelines recommend that patients hospitalized for acute bacterial skin infections after failure of outpatient antibiotic therapy be managed as "severe" infections; however, the clinical relevance of apparent failure of outpatient therapy is not clear.

Methods: This was a secondary analysis of a multicenter, retrospective cohort of adults and children hospitalized for cellulitis, abscess, or wound infection. We compared clinical features, laboratory and microbiology findings, antibiotic treatment, and outcomes among patients who received outpatient antibiotics prior to admission and those who did not.

Highly Bactericidal Polyurethane Effective Against Both Normal and Drug-Resistant Bacteria: Potential Use as an Air Filter Coating.

The battle against the prevalence of hospital-acquired infections has underscored the importance of identifying and maintaining the cleanliness of possible infection transmission sources in the patient's environment. One of the most crucial lines of defense for mitigating the spread of pathogens in a healthcare facility is the removal of microorganisms from the environment by air filtration systems. After removing the pathogenic microorganisms, the filters used in these systems can serve as reservoirs for the pathogens and pose a risk for secondary infection.

Microbiology and initial antibiotic therapy for injection drug users and non-injection drug users with cutaneous abscesses in the era of community-associated methicillin-resistant Staphylococcus aureus.

Objectives: The incidence of cutaneous abscesses has increased markedly since the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Injection drug use is a risk factor for abscesses and may affect the microbiology and treatment of these infections. In a cohort of patients hospitalized with cutaneous abscesses in the era of CA-MRSA, the objectives were to compare the microbiology of abscesses between injection drug users and non-injection drug users and evaluate antibiotic therapy started in the emergency department (ED) in relation to microbiologic findings and national guideline treatment recommendations.

Comparison of the microbiology and antibiotic treatment among diabetic and nondiabetic patients hospitalized for cellulitis or cutaneous abscess.

Background: Among diabetics, complicated skin infections may involve gram-negative pathogens; however, the microbiology of cellulitis and cutaneous abscess is not well established.

Objective: To compare the microbiology and prescribing patterns between diabetics and nondiabetics hospitalized for cellulitis or abscess.

Design: Secondary analysis of 2 published retrospective cohorts.

Antibiotic prescribing practices in a multicenter cohort of patients hospitalized for acute bacterial skin and skin structure infection.

Objective: Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitals.

Redox sensor SsrB Cys203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection.

We show herein that the Salmonella pathogenicity island 2 (SPI2) response regulator SsrB undergoes S-nitrosylation upon exposure of Salmonella to acidified nitrite, a signal encountered by this enteropathogen in phagosomes of macrophages. Mutational analysis has identified Cys(203) in the C-terminal dimerization domain of SsrB as the redox-active residue responding to nitric oxide (NO) congeners generated in the acidification of nitrite. Peroxynitrite and products of the autooxidation of NO in the presence of oxygen, but not hydrogen peroxide, inhibit the DNA-binding capacity of SsrB, demonstrating the selectivity of the reaction of Cys(203) with reactive nitrogen species (RNS).

Epidemiology of healthcare-associated bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals.

Objective: To describe the epidemiology of bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA), which are traditionally associated with cases of community-acquired infection, in the healthcare setting.

Design: Retrospective cohort study.

Setting: Three academically affiliated hospitals in Denver, Colorado.

Nitric oxide evokes an adaptive response to oxidative stress by arresting respiration.

Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery of low-molecular-weight thiol scavengers, a legion of detoxifying catalases, peroxidases, and superoxide dismutases, as well as a variety of repair systems.

N(2)O(3) enhances the nitrosative potential of IFNgamma-primed macrophages in response to Salmonella.

We show here that the nitric oxide (NO)-detoxifying Hmp flavohemoprotein increases by 3-fold the transcription of the Salmonella pathogenicity island 2 (SPI2) in macrophages expressing a functional inducible NO synthase (iNOS). However, Hmp does not prevent NO-related repression of SPI2 transcription in IFNgamma-primed phagocytes, despite preserving intracellular transcription of sdhA sdhB subunits of Salmonella succinate dehydrogenase within both control and IFNgamma-primed phagocytes. To shed light into the seemingly paradoxical role that Hmp plays in protecting intracellular SPI2 expression in various populations of macrophages, N(2)O(3) was quantified as an indicator of the nitrosative potential of Salmonella-infected phagocytes in different states of activation.

Constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar Typhimurium.

We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NADPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM.

Systemic CD8 T-cell memory response to a Salmonella pathogenicity island 2 effector is restricted to Salmonella enterica encountered in the gastrointestinal mucosa.

To better understand the evolution of a systemic memory response to a mucosal pathogen, we monitored antigen-specific OT1 CD8 T-cell responses to a fusion of the SspH2 protein and the peptide SIINFEKL stably expressed from the chromosome of Salmonella enterica and loaded into the class I pathway of antigen presentation of professional phagocytes through the Salmonella pathogenicity island 2 type III secretion system (TTSS). This strategy has revealed that effector memory CD8 T cells with low levels of CD62L expression (CD62L(low)) are maintained in systemic sites months after vaccination in response to low-grade infections with Salmonella. However, the CD8 T-cell pool eventually declines.

Repression of SPI2 transcription by nitric oxide-producing, IFNgamma-activated macrophages promotes maturation of Salmonella phagosomes.

By remodeling the phagosomal membrane, the type III secretion system encoded within the Salmonella pathogenicity island-2 (SPI2) helps Salmonella thrive within professional phagocytes. We report here that nitric oxide (NO) generated by IFNgamma-activated macrophages abrogates the intracellular survival advantage associated with a functional SPI2 type III secretion system. NO congeners inhibit overall expression of SPI2 effectors encoded both inside and outside the SPI2 gene cluster, reflecting a reduced transcript level of the sensor kinase SsrA that governs overall SPI2 transcription.