Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection.

Members of the Klebsiella pneumoniae species complex frequently colonize the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases (N = 85), where colonizing and invasive isolates were identical strain types, were matched to asymptomatically colonizing controls (N = 160). Thirty-seven genes are associated with infection, 27 of which remain significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes are not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many genes are plasmid borne, and for some, the relationship with infection is mediated by gut dominance. Five genes were validated in a geographically-independent cohort of colonized patients. This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella.

Risk Factors for Klebsiella Infections among Hospitalized Patients with Preexisting Colonization.

Klebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of health care-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear. A cohort study was performed, in which intensive care and hematology/oncology patients with Klebsiella colonization based on rectal swab culture were enrolled and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in a bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing. Among 2,087 hospitalizations from 1,978 colonized patients, 90 cases of infection (4.3%) were identified. The mean time to infection was 20.6 ± 24.69 (range, 0 to 91; median, 11.5) days. Of 86 typed cases, 68 unique wzi types were identified, and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression, and low albumin levels at the time of rectal swab collection were independently associated with subsequent Klebsiella infection (i.e., cases). Despite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates, and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at an increased risk of subsequent Klebsiella infection. IMPORTANCE Klebsiella is a leading cause of health care-associated infections. Patients who are intestinally colonized with Klebsiella are at a significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1,978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin levels in a blood test were more likely to develop infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The clinical variables associated with infection are readily available in the medical record and could serve as the foundation for developing an integrated risk assessment of Klebsiella infection in hospitalized patients.

Assessment of Salivary Levels of RANKL and OPG in Aggressive versus Chronic Periodontitis.

RANKL (receptor activator of nuclear factor kappa-ß ligand) and OPG (osteoprotegerin) are two proteins involved in bone remodelling. During the active phase of periodontal disease, an imbalance between the ratios of the two elements can be noticed. While the expression of RANKL is elevated compared with that of OPG, the RANKL is available to bond with RANK (receptor activator of nuclear factor kappa-ß). This study was conducted on 41 patients: 19 with generalized aggressive periodontitis, 18 with severe chronic periodontitis, and 4 periodontal healthy subjects. For each patient included, we determined the salivary levels of RANKL and OPG with the help of two Human ELISA kits. The results show that the patients affected by periodontitis, either aggressive or chronic, have significant higher values of RANKL and RANKL/OPG ratio. This values correlate with the local inflammation status.

THE ROLE OF SYSTEMIC BLOOD PRESSURE IN GLAUCOMA PROGRESSION.

The present paper aims to highlight the role of arterial hypotension in the progression of glaucoma. The data analyzed in this study was collected in a prospective manner for a period of one year, from september 2013 to august 2014. It includes newly diagnosed glaucoma patients treated with prostaglandin analogues and who have presented within normal range values of intraocular pressure during the study. In spite of good control of intraocular pressure, there was recorded a progression of glaucoma lesions documented using the visual field . All patients were evaluated through 24 h outpatient holter monitoring of systemic blood pressure (BP) and were consequently divided into three groups: Group A--non-dipper (within normal range of both diurnal and nocturnal BP values and no significant drop during the night). Group B--dipper (patients with nocturnal hypotension recording BP drops of more the X mmHg). Group C--patients with arterial hypertension (defined as diurnal values of more than 150 mmHg for systolic BP and 110 mmHg for dyastolic BP). After through statistical analysis of the patients data, we noticed that the most important progression of glaucoma changes objectified by visual field and OCT examinations was recorded in group B, which illustrates the importance of careful monitoring and strict control of blood pressure in order to eliminate this risk factor in the progress of glaucoma.