In contrast to infection of superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and suppress inflammation. To examine this, we analyzed the behavior of an S. pyogenes mutant deficient in expression of the cytolytic toxin streptolysin S (SLS ؊ ) and evaluated events that occur during the first few hours of infection by using several models including injection of zebrafish (adults, larvae, and embryos), a transepithelial polymorphonuclear leukocyte (PMN) migration assay, and two-photon microscopy of mice in vivo. In contrast to wild-type S. pyogenes, the SLS ؊ mutant was associated with the robust recruitment of neutrophils and significantly reduced lethal myositis in adult zebrafish. Similarly, the mutant was attenuated in embryos in its ability to cause lethality. Infection of larva muscle allowed an analysis of inflammation in real time, which revealed that the mutant had recruited PMNs to the infection site. Analysis of transepithelial migration in vitro suggested that SLS inhibited the host cells' production of signals chemotactic for neutrophils, which contrasted with the proinflammatory effect of an unrelated cytolytic toxin, streptolysin O. Using two-photon microscopy of mice in vivo, we showed that the extravasation of neutrophils during infection with SLS ؊ mutant bacteria was significantly accelerated compared to infection with wild-type S. pyogenes. Taken together, these data support a role for SLS in the inhibition of neutrophil recruitment during the early stages of S. pyogenes infection.
The signal recognition particle (SRP) pathway is a universally conserved pathway for targeting polypeptides for secretion via the cotranslational pathway. In particular, the SRP pathway is thought to be the main mechanism for targeting polypeptides in gram-positive bacteria, including a number of important human pathogens. Though widely considered to be an essential cellular component, recent advances have indicated this pathway may be dispensable in gram-positive bacteria of the genus Streptococcus under in vitro conditions. However, its importance for the pathogenesis of streptococcal disease is unknown. In this study, we investigated the importance of the SRP pathway for virulence factor secretion in the human pathogen Streptococcus pyogenes. While the SRP pathway was not found to be essential for viability in vitro, SRP mutants demonstrated a medium-specific growth defect that could be rescued by the addition of glucose. We also observed that a distinct subset of virulence factors were dependent upon the SRP pathway for secretion, whereas others were completely independent of this pathway. Significantly, deletion of the SRP pathway resulted in mutants that were highly attenuated in both a zebrafish model of necrotic myositis and a murine subcutaneous ulcer model, highlighting the importance of this pathway in vivo. These studies emphasize the importance of the SRP pathway for the in vivo survival and pathogenesis of S. pyogenes.
Objective To test the hypothesis that successful implementation of a care bundle designed to prevent nosocomial airway infection will be associated with decreased incidence of ventilator-associated tracheobronchitis. Design Prospective pre- and postinterventional. Setting PICU at an academic medical center Patients All patients admitted to the PICU who received invasive mechanical ventilation for greater than or equal to 48 hours between March 1, 2009, and December 31, 2011. Intervention Multidisciplinary, unitwide implementation of an evidence-based care bundle to prevent ventilator-associated airway infection. Measurements and Main Results There were 725 patients included in the analysis (338 patients preintervention and 387 patients postintervention). Baseline ventilator-associated tracheobronchitis rate in the preintervention period was 3.9 cases per 1,000 ventilator days compared with 1.8 cases per 1,000 ventilator days postintervention (p = 0.04, Fisher exact test). Compared with patients without ventilator-associated tracheobronchitis or ventilator-associated pneumonia, patients with ventilator-associated tracheobronchitis had fewer ventilator-free days in 28 days (4.9 vs 22; p < 0.0001, Mann-Whitney U test) and fewer ICU-free days in 28 days (0.5 vs 19; p < 0.0001, Mann-Whitney U test). These relationships remained significant after adjusting for covariates by multivariable linear regression. Conclusions Successful implementation of a care bundle to prevent ventilator-associated infection was associated with decreased incidence of ventilator-associated tracheobronchitis. Development of ventilator-associated tracheobronchitis was independently associated with adverse outcomes in our cohort of pediatric ICU patients.
Background: Critically ill children in a pediatric intensive care unit (PICU) have unique nutrition needs that are challenging to achieve and thus are at high risk of malnutrition. There is increasing evidence that children who reach caloric goals early have improved outcomes. The purpose of this initiative was to implement an enteral nutrition (EN) algorithm in a tertiary care PICU utilizing clinical decision support tools (CDSTs) and a standardized order set within an electronic health record. Methods: A quality improvement initiative was undertaken to implement an EN feeding protocol using electronic CDSTs, including a new standardized order set. Results: In a historical cohort of 376 patients, only 18% met goal EN in the first 48 hours of admission. The EN protocol was implemented in 272 patients who met 88% goal feed volume within 48 hours of intensive care unit admission. Median time to start EN (1.7 vs 1.3 days, P < 0.0001) and time to goal nutrition (2.8 vs 2.2 days, P < 0.001) improved after project implementation. Length of stay in the PICU was significantly reduced following protocol implementation (202 hours pre-implementation vs 156 hours post implementation, P < 0.0001). Conclusions: We used CDSTs and standardized order sets to implement a nutrition algorithm to facilitate and likely improve the nutrition care of critically ill children. (Nutr Clin Pract. 2019;34:916-921)
Dexmedetomidine is an α2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed.
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