Klebsiella pneumoniae is a common cause of sepsis and is particularly associated with healthcare-associated infections. New strategies are needed to prevent or treat infections due to the emergence of multi-drug resistant K. pneumoniae. The goal of this study was to determine the diversity and distribution of O (lipopolysaccharide) and K (capsular polysaccharide) antigens on a large (>500) global collection of K. pneumoniae strains isolated from blood to inform vaccine development efforts. A total of 645
There is a growing recognition that there is a need for a more personalized approach towards sepsis care. In most clinical trials investigating novel therapeutic interventions against sepsis, patients have been considered a rather homogeneous population. However, there is probably more individual variability between septic patients than previously considered. The pathophysiology of sepsis is a complex and dynamic process that originates from the host immune response to infection and varies according to the genetic predisposition, immune status and co‐morbid conditions of the host, the type of pathogen and the site and extent of infection. Until now, efforts to stratify septic patients according to their immune profile were hampered by the lack of specific biomarkers. Recent advances in molecular medicine have made it possible to develop tools that will facilitate a faster and more precise diagnosis of infection. Individual variability between each patient's responses to infection can assist in tailoring therapeutic interventions to the individual's disease profile and monitoring treatment response. In this review, we describe those recent advances in genomics and theragnostics, which are slowly entering clinical practice and which will make possible a more personalized approach to each septic patient in the next decade.
Currently the treatment mainstay of sepsis is early and appropriate antibiotic therapy, accompanied by aggressive fluid administration, the use of vasopressors when needed and the prompt initiation of measures to support each failing organ. Activated protein C and hydrocortisone, when used accordingly can affect mortality. As the pathophysiologic events that take place during sepsis are being elucidated, new molecules that target each step of those pathways are being tested. However, a lot of those molecules affect various mediators of the sepsis cascade including inflammatory cytokines, cellular receptors, nuclear transcription factors, coagulation activators and apoptosis regulators. Over the last decade, a multitude of clinical trials and animal studies have investigated strategies that aimed to restore immune homeostasis either by reducing inflammation or by stimulating the innate and adaptive immune responses. Antibiotics, statins and other molecules with multipotent immunomodulatory actions have also been studied in the treatment of sepsis.
The RAGE (receptor for advanced glycation end products) is believed to play a role in sepsis by perpetuating inflammation. The interaction of RAGE with a variety of host-derived ligands that accumulate during stress and inflammation further induces the expression of RAGE. It was previously shown that a rat anti-RAGE monoclonal antibody protected mice from lethality in a cecal ligation and puncture model. We studied the effects of a humanized anti-RAGE monoclonal antibody in the murine pneumococcal pneumonia model of sepsis. Moreover, a gene expression analysis was performed in lung tissue of animals that underwent cecal ligation and puncture and treated with the rat anti-RAGE monoclonal antibody, compared with controls. Administration of humanized anti-RAGE mAb 6 h after intratracheal infection with Streptococcus pneumoniae improved mortality in BALB/c mice whether a 7.5 mg/kg (P < 0.01) or a 15 mg/kg dose (P < 0.01) was administered in combination with antibiotics. Gene expression analysis showed that many of the genes modulated by treatment with the anti-RAGE antibody were those that play an important role in regulating inflammation. Anti-RAGE monoclonal antibody offered a survival advantage to septic mice. This protective role in treated animals is supported by the observed gene expression profile changes of genes involved in sepsis and inflammation.
In Europe, the respiratory syncytial virus (RSV) surveillance system is very heterogeneous and there is growing evidence of the importance of RSV infections resulting in hospitalization of elderly patients. The aim of this study was to assess the severity of RSV infection in the elderly living in the aged Southern European countries. We conducted a retrospective study of elderly patients ( ≥65‐year old) admitted for laboratory‐confirmed RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons (2017–2018). Uni‐multivariable analyses were carried out to evaluate the effect of clinical variables on radiologically confirmed pneumonia, use of noninvasive ventilation (NIV), and in‐hospital death (IHD). A total of 166 elderly patients were included. Pneumonia was evident in 29.5%. NIV was implemented in 16.3%, length of stay was 11.8 ± 12.2 days, and IHD occurred in 12.1%. Multivariable analyses revealed that the risk of pneumonia was higher in patients with chronic kidney disease (CKD) (odds ratio [OR]: 2.57; 95% confidence interval [CI]: 1.12–5.91); the use of NIV was higher in patients with obstructive sleep apnea or obesity hypoventilation syndrome (OSA or OHS) (OR: 5.38; 95% CI: 1.67–17.35) and CKD (OR: 2.52; 95% CI: 1.01–6.23); the risk of IHD was higher in males (OR: 3.30; 95% CI: 1.07–10.10) and in patients with solid neoplasm (OR: 9.06; 95% CI: 2.44–33.54) and OSA or OHS (OR: 8.39; 95% CI: 2.14–32.89). Knowledge of factors associated with RSV infection severity may aid clinicians to set priorities and reduce disease burden. Development of effective antiviral treatment and vaccine against RSV is highly desirable.
Water ecosystems can be rather sensitive to evolving or sudden changes in weather parameters. These changes can result in alterations in the natural habitat of pathogens, vectors, and human hosts, as well as in the transmission dynamics and geographic distribution of infectious agents. However, the interaction between climate change and infectious disease is rather complicated and not deeply understood. In this narrative review, we discuss climate-driven changes in the epidemiology of Vibrio species-associated diseases with an emphasis on cholera. Changes in environmental parameters do shape the epidemiology of Vibrio cholerae. Outbreaks of cholera cause significant disease burden, especially in developing countries. Improved sanitation systems, access to clean water, educational strategies, and vaccination campaigns can help control vibriosis. In addition, real-time assessment of climatic parameters with remote-sensing technologies in combination with robust surveillance systems could help detect environmental changes in high-risk areas and result in early public health interventions that can mitigate potential outbreaks.
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