Optimal Antibiotic Duration for Bloodstream Infections Secondary to Intraabdominal Infection.

BACKGROUND: Bloodstream infections (BSIs) secondary to intraabdominal infections (IAIs) are common in the intensive care unit (ICU). The Surgical Infection Society guidelines recommend treatment duration after achieving source control in patients with secondary bacteremia; however, literature supporting this recommendation is limited. The purpose of this study was to compare outcomes in patients who received shorter versus extended duration of antibiotics for bacteremia secondary to IAI. MATERIALS AND METHODS: A retrospective cohort analysis was conducted in adult surgical ICU patients (n = 42) with BSIs and source control procedure(s) for IAI. The primary outcome was recurrent IAI. Secondary outcomes included surgical site infections (SSIs), Clostridium difficile infections (CDIs), secondary fungal infections, and in-hospital mortality. RESULTS: Forty-two patients met inclusion criteria and were divided into groups according to antimicrobial duration; 12 patients received <7 d, and 30 patients received >7 d of antibiotics. There were no differences in baseline characteristics between the two cohorts except for the presence of sepsis [4/12 (33.3%) versus 27/30 (90.0%); P = 0.001]. Thirty-one percent (13/42) of all organisms isolated from blood cultures were gram-negative bacteria, 12/42 (28.6%) were MDROs, and 2/42 (4.8%) patients experienced a culture mismatch in which cultured bacteria were not susceptible to empiric antibiotic therapy. Rates of recurrent IAI were similar between the two cohorts [1/12 (8.3%) versus 4/30 (13.3%), P = 0.554]. CONCLUSIONS: Among surgical ICU patients with BSI secondary to IAI, cessation of antibiotic therapy within 7 d of source control was not associated with an increased incidence of recurrent IAI.

Detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR: A better predictor of bacterial vaginosis.

The present study aimed to determine the utility of detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR for diagnosing bacterial vaginosis (BV). Vaginal samples (n = 385) categorized as positive (n = 108) or negative (n = 208) for bacterial vaginosis based on the Nugent scoring system, were analyzed for the presence of G. vaginalis and A. vaginae by conventional PCR. We compared the sensitivity, specificity, positive predictive value, negative predictive value and odds ratio for the detection of each bacterium alone with the combination of the two bacteria for diagnosing BV. The detection of co-infection of the two bacteria demonstrated a sensitivity of 96%, a specificity of 82.9%, a positive predictive value of 68.5%, a negative predictive value of 98.2% with an odds ratio of 116 (CI -32 - 409). In our study, we found a high sensitivity, specificity, negative predictive value and odds ratio for the detection of co-infection of A. vaginae and G. vaginalis for the diagnosis of BV.

[Master genes and co-expression network analysis in peripheral blood mononuclear cells of patients with gram-positive and gram-negative sepsis].

OBJECTIVE: To investigate the functional pathways enriched and differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of patients with gram-positive and gram-negative sepsis. METHODS: Dataset GSE9960 obtained from NCBI GEO database containing PBMC samples from 16 non-infectious systematic inflammatory response syndrome (SIRS) patients, 17 gram-positive septic patients and 18 gram-negative septic patients were included in the study. Functional pathway annotations were conducted by gene set enrichment analysis and weighted gene co-expression network analysis. DEGs were filtered and master DEGs were then validated in PBMCs of gram-positive septic, gram-negative septic and non-infectious SIRS patients. RESULTS: The enriched gene sets in gram-positive sepsis and gram-negative sepsis were significantly different. The results indicated the opposite co-expression networks in SIRS and gram-negative sepsis, and the entirely different co-expression networks in gram-positive and gram-negative sepsis. Furthermore, we validated that TYMS was up-regulated in gram-positive sepsis (P<0.05), CD3D was down-regulated in gram-negative sepsis (P<0.01), while IRAK3 was up-regulated in gram-negative sepsis (P<0.05). CONCLUSIONS: The results indicate that there are differences in the mechanism and pathogenesis of gram-positive and gram-negative sepsis, which may provide potential markers for sepsis diagnosis and empirical antimicrobial therapy.

Staphylococcus epidermidis: A Potential New Player in the Physiopathology of Acne?

BACKGROUND: Cutibacterium acnes has been identified as one of the main triggers of acne. However, increasing knowledge of the human skin microbiome raises questions about the role of other skin commensals, such as Staphylococcus epidermidis, in the physiopathology of this skin disease. SUMMARY: This review provides an overview of current knowledge of the potential role of S. epidermidis in the physiopathology of acne. Recent research indicates that acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis,according to dedicated interactions. Current treatments act on C. acnesonly. Other treatment options may be considered, such as probiotics derived from S. epidermidis to restore the naturally balanced microbiota or through targeting the regulation of the host's AMP mediators. Key Messages: Research seems to confirm the beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation.

Mitral Annular Plane Systolic Excursion as a Predictor of Mortality in Children With Septic Shock.

OBJECTIVES: Myocardial dysfunction is well recognized in severe sepsis and septic shock. Echocardiography provides rapid, noninvasive, and bedside evaluation of cardiac function in patients with hemodynamic instability. Mitral annular plane systolic excursion is an M-mode-derived echocardiographic variable used to assess longitudinal left ventricular systolic function. No data are available about the uses of mitral annular plane systolic excursion in children with septic shock. Therefore, we aimed to assess the prognostic significance of mitral annular plane systolic excursion in children with septic shock and to correlate it with the most commonly used measures of left ventricular systolic function and myocardial injury. DESIGN: A prospective cohort study. SETTING: The study carried out at the PICU of Menoufia University Hospital in the period from March 2015 to September 2016. PATIENTS: We serially enrolled 50 children with septic shock. INTERVENTIONS: Complete diagnostic workup was performed for each patient including calculation of Pediatric Risk of Mortality III score. Transthoracic echocardiography was done to obtain mitral annular plane systolic excursion and the left ventricular ejection fraction measurement within 24 hours of inclusion then repeated on third and fifth days. Patients were followed up until hospital discharge or death. The predictive power of mitral annular plane systolic excursion was determined using the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS: Mitral annular plane systolic excursion was significantly lower in nonsurvivors compared with survivors (p < 0.001). Receiver operating characteristic curve analysis showed an area under the curve of 0.892 for mitral annular plane systolic excursion on day 1. The cut-off point was 7.9 mm with 82.76% sensitivity and 80.95% specificity. Furthermore, follow-up of the patient's systolic function showed that mitral annular plane systolic excursion was significantly lower in nonsurvivors compared with survivors on days of follow-up, whereas left ventricular ejection fraction was not significantly different between survivors and nonsurvivors at any day. Mitral annular plane systolic excursion was positively correlated with left ventricular ejection fraction (p = 0.044) and duration of hospital stay (p < 0.001) and negatively correlated with Pediatric Risk of Mortality III score (p < 0.001) and cardiac troponin I level (p < 0.001). CONCLUSIONS: Measurement of mitral annular plane systolic excursion at admission added a prognostic value in septic shock children. Compared with the left ventricular ejection fraction, longitudinal systolic function might be more sensitive in the detection of myocardial dysfunction in critically ill children and should receive more attention.

Factors shaping the composition of the cutaneous microbiota.

From birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and lifestyle, have been suggested to shape the composition of this microbial community. Propionibacterium acnes is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions. Currently, the role of this bacterium in the pathogenesis of the most common inflammatory skin disease, acne vulgaris, is a topic of intense scientific debate. Recent results suggest that Westernization strongly increases the dominance of the Propionibacterium genus in human skin compared with natural populations living more traditional lifestyles. According to the disappearing microbiota hypothesis proposed by Martin Blaser, such alterations in the composition of our microbiota are the possible consequences of socioeconomic and lifestyle changes occurring after the industrial revolution. Evanescence of species that are important elements of the human ecosystem might lead to the overgrowth and subsequent dominance of others because of the lack of ecological competition. Such changes can disturb the fine-tuned balance of the human body and, accordingly, our microbes developed through a long co-evolutionary process. These processes might lead to the transformation of a seemingly harmless species into an opportunistic pathogen through bacterial dysbiosis. This might have happened in the case of P. acnes in acne pathogenesis.

Behavior of anastomozed vessels and transferred flaps after anastomosed site infection in head and neck microsurgical reconstruction.

OBJECTIVE: This report evaluates the behavior of anastomosed vessels and transferred flaps after anastomosed site infection in head and neck reconstruction. PATIENTS AND METHODS: Eleven free-flap cases after infection at the vascular pedicle site were included, the patency of which was observed macroscopically after re-exploration and pus drainage. Location was in the tongue (5 cases), oropharynx (3 cases), mouth floor (1 case), mandible (1 case), and hypopharynx (1 case). Transferred flaps originated from rectus abdominis (3 cases), anterolateral thigh (3 cases), radial forearm (3 cases), jejunum (1 case), and latissimus dorsi (1 case). Days for infection found were ranged 3-14 days postoperatively. Causes of infection were the salivary fistula formation in 5 cases, and precise etiology was not defined in the other 6 cases. RESULTS: Disruption of the vascular pedicles occurred with high frequency after infection. Disruption of vein occurred most frequently (5 cases), followed by both artery and vein (2 cases) and artery only (1 case). Of the eight flaps, two flaps failed, but the other six flaps survived despite pedicle disruption, indicating overall survival of nine flaps after pedicle site infection. Five of the nine survived cases were healed with simple washing and ointment application. However, the other four patients, whose cause of infection was a salivary fistula, needed second flap transfer to treat those fistulas. CONCLUSION: Disruption of anastomosed vessels can occur with high frequency after infection, causing subsequent flap loss. Therefore, surgeons need to deal with pedicle site infection to save the flap. © 2015 Wiley Periodicals, Inc. Microsurgery 36:658-663, 2016.

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy.

STUDY QUESTION: What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome? SUMMARY ANSWER: Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle. WHAT IS KNOWN ALREADY: We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). LIMITATIONS, REASONS FOR CAUTION: Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases. WIDER IMPLICATIONS OF THE FINDINGS: A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.

What's new in the physiopathology of acne?

There are four central factors that contribute to acne physiopathology: the inflammatory response, colonization with Propionibacterium acnes, increased sebum production and hypercornification of the pilosebaceous duct. In addition, research in the areas of diet and nutrition, genetics and oxidative stress is also yielding some interesting insights into the development of acne. In this paper we review some of the most recent research and novel concepts revealed in this work, which has been published by researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology. We discuss the implications of their findings (particularly in terms of opportunities to develop new therapies), highlight interrelationships between these novel factors that could contribute to the pathology of acne, and indicate where gaps in our understanding still exist.

Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.

RATIONALE: Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers. OBJECTIVES: To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing. METHODS: Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNA and fungal internal transcribed spacer sequencing was used to profile organisms present. Outlier analysis plots defining taxa enriched in lung relative to OW were used to identify bacteria enriched in lung against a background of oropharyngeal carryover. MEASUREMENTS AND MAIN RESULTS: Lung transplant recipients had higher bacterial burden in BAL than control subjects, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respiratory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites or by Aspergillus in BAL but not OW. 16S outlier analysis identified lung-enriched taxa indicating bacteria replicating in the lower respiratory tract. In some cases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora and provided quantitative data on relative abundances of bacteria found by culture. CONCLUSIONS: Respiratory tract microbial communities in lung transplant recipients differ in structure and composition from healthy subjects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome and aid in assessing lung infections.

Acne sans P. acnes.

Acne vulgaris is a common disease that carries an enormous financial and psychosocial impact. Androgens, excessive sebum production, ductal hypercornification, changes in the microbial flora, as well as inflammation and immunological host reactions are considered the major contributors to acne pathogenesis. Despite extensive research on acne pathogenesis, the exact sequence of events and their possible mechanisms leading to the development of a microcomedone and its transformation into an inflamed lesion has remained unclear. There is a significant amount of in vitro evidence suggesting a possible pathogenetic role for Propionibacterium acnes in comedogenesis as well as inflammation in inflammatory acne. However, the microbiological data from non-inflamed as well as inflamed acne lesions, cultured individually, do not entirely support the hypothesis that these micro-organisms are actually responsible for their initiation. There appears to be comedones and inflamed lesions in which there is no clear evidence of Propionibacterium acnes involvement. Considering this microbiological data, alongside the in vitro evidence, we have tried to delineate the possible sequence of events and their mechanisms, leading to the development of a microcomedone and its transformation into an inflamed lesion. Based on the available literature we have analysed the evidence of both non-inflamed as well as inflamed acne lesions occurring in the absence of Propionibacterium acnes from the pilosebaceous follicles. We propose that the development of an inflamed acne lesion depends on an imbalance between the pro-inflammatory and anti-inflammatory pathways rather than the incitement of inflammation by Propionibacterium acnes.

Pregnancy coexisting with uterus didelphys with a blind hemivagina complicated by pyocolpos due to Pediococcus infection: a case report and review of the published reports.

A woman in early pregnancy was referred due to severe pelvic pain. Vaginal examination showed a severely protruding left vaginal wall with severe tenderness. A transvaginal ultrasound showed a double uterus and a mixed echogenic mass next to the cervix of the left uterus. After creating an opening in the left vaginal wall and inserting a Foley catheter through the opening into the vaginal wall for drainage with antibiotic therapy, the patient's condition rapidly improved. A culture of the pus drained from the vaginal wall showed Pediococcus species. The patient delivered a healthy infant by cesarean section at term gestation without recurrence of pyocolpos. Ten months after delivery, resection of the vaginal septum was performed and the left cervix was exposed. Ultrasound revealed normal kidneys.

CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia.

BACKGROUND: CD27 is a lymphocyte costimulatory molecule that regulates T-cell, natural killer (NK) cell, B-cell, and plasma cell function, survival, and differentiation. On the basis of its function and expression pattern, we considered CD27 a candidate gene in patients with hypogammaglobulinemia. OBJECTIVE: We sought to describe the clinical and immunologic phenotypes of patients with genetic CD27 deficiency. METHODS: A molecular and extended immunologic analysis was performed on 2 patients lacking CD27 expression. RESULTS: We identified 2 brothers with a homozygous mutation in CD27 leading to absence of CD27 expression. Both patients had persistent symptomatic EBV viremia. The index patient was hypogammaglobulinemic, and immunoglobulin replacement therapy was initiated. His brother had aplastic anemia in the course of his EBV infection and died from fulminant gram-positive bacterial sepsis. Immunologically, lack of CD27 expression was associated with impaired T cell-dependent B-cell responses and T-cell dysfunction. CONCLUSION: Our findings identify a role for CD27 in human subjects and suggest that this deficiency can explain particular cases of persistent symptomatic EBV viremia with hypogammaglobulinemia and impaired T cell-dependent antibody generation.

Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation.

BACKGROUND & AIMS: Matrix metalloproteases (MMPs) mediate pathogenesis of chronic intestinal inflammation. We characterized the role of the gelatinase (GelE), a metalloprotease from Enterococcus faecalis, in the development of colitis in mice. METHODS: Germ-free, interleukin-10-deficient (IL-10(-/-)) mice were monoassociated with the colitogenic E faecalis strain OG1RF and isogenic, GelE-mutant strains. Barrier function was determined by measuring E-cadherin expression, transepithelial electrical resistance (TER), and translocation of permeability markers in colonic epithelial cells and colon segments from IL-10(-/-) and TNF(ΔARE/Wt) mice. GelE specificity was shown with the MMP inhibitor marimastat. RESULTS: Histologic analysis (score 0-4) of E faecalis monoassociated IL-10(-/-) mice revealed a significant reduction in colonic tissue inflammation in the absence of bacteria-derived GelE. We identified cleavage sites for GelE in the sequence of recombinant mouse E-cadherin, indicating that it might be degraded by GelE. Experiments with Ussing chambers and purified GelE revealed the loss of barrier function and extracellular E-cadherin in mice susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) before inflammation developed. Colonic epithelial cells had reduced TER and increased translocation of permeability markers after stimulation with GelE from OG1RF or strains of E faecalis isolated from patients with Crohn's disease and ulcerative colitis. CONCLUSIONS: The metalloprotease GelE, produced by commensal strains of E faecalis, contributes to development of chronic intestinal inflammation in mice that are susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) by impairing epithelial barrier integrity.

Cytokine screening identifies NICU patients with Gram-negative bacteremia.

INTRODUCTION: Biomarkers and physiomarkers may be useful adjunct tests for sepsis detection in neonatal intensive care unit (NICU) patients. We studied whether measuring plasma cytokines at the time of suspected sepsis could identify patients with bacteremia in centers in which patients were undergoing continuous physiomarker screening using a heart rate characteristics (HRC) index monitor. RESULTS: Six cytokines were higher in Gram-negative bacteremia (GNB) than in Gram-positive bacteremia or candidemia (GPBC). A cytokine score using thresholds for granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α had 100% sensitivity and 69% positive predictive value (PPV) for GNB. A single cytokine marker, IL-6 < 130 pg/ml, had 100% sensitivity and 52% PPV for sepsis ruled out (SRO). The average HRC index was abnormal in this cohort of patients with clinical suspicion of sepsis and did not discriminate between the final sepsis designations. DISCUSSION: In summary, in NICU patients with suspected late-onset sepsis, plasma cytokines can identify those with SRO and those with GNB, potentially aiding in decisions regarding therapy. METHODS: Seven cytokines were measured in 226 plasma samples from patients >3 d old with sepsis suspected based on clinical signs, abnormal HRC index, or both. Cases were classified as SRO, clinical sepsis (CS), GPBC, or GNB.

Therapeutic Options for Infections due to vanB Genotype Vancomycin-Resistant Enterococci.

Enterococci are ubiquitous, facultative, anaerobic Gram-positive bacteria that mainly reside, as part of the normal microbiota, in the gastrointestinal tracts of several animal species, including humans. These bacteria have the capability to turn from a normal gut commensal organism to an invasive pathogen in patients debilitated by prolonged hospitalization, concurrent illnesses, and/or exposed to broad-spectrum antibiotics. The majority of vancomycin-resistant enterococcus (VRE) infections are linked to the vanA genotype; however, outbreaks caused by vanB-type VREs have been increasingly reported, representing a new challenge for effective antimicrobial treatment. Teicoplanin, daptomycin, fosfomycin, and linezolid are useful antimicrobials for infections due to vanB enterococci. In addition, new drugs have been developed (e.g., dalbavancin, telavancin, and tedizolid), new molecules will soon be available (e.g., eravacycline, omadacycline, and oritavancin), and new treatment strategies are progressively being used in clinical practice (e.g., combination therapies and bacteriophages). The aim of this article is to discuss the pathogenesis of infections due to enterococci harboring the vanB operon (vanBVRE) and their therapeutic, state-of-the-art, and future treatment options and provide a comprehensive and easy to use review for clinical purposes.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

The Food Poisoning Toxins of Bacillus cereus.

Bacillus cereus is a ubiquitous soil bacterium responsible for two types of food-associated gastrointestinal diseases. While the emetic type, a food intoxication, manifests in nausea and vomiting, food infections with enteropathogenic strains cause diarrhea and abdominal pain. Causative toxins are the cyclic dodecadepsipeptide cereulide, and the proteinaceous enterotoxins hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe) and cytotoxin K (CytK), respectively. This review covers the current knowledge on distribution and genetic organization of the toxin genes, as well as mechanisms of enterotoxin gene regulation and toxin secretion. In this context, the exceptionally high variability of toxin production between single strains is highlighted. In addition, the mode of action of the pore-forming enterotoxins and their effect on target cells is described in detail. The main focus of this review are the two tripartite enterotoxin complexes Hbl and Nhe, but the latest findings on cereulide and CytK are also presented, as well as methods for toxin detection, and the contribution of further putative virulence factors to the diarrheal disease.

C-X-C Chemokines Influence Intraocular Inflammation During Bacillus Endophthalmitis.

Purpose: The purpose of this study was to explore the C-X-C chemokines CXCL2 and CXCL10 as potential anti-inflammatory targets for Bacillus endophthalmitis. Methods: Bacillus endophthalmitis was induced in C57BL/6J, CXCL2-/-, and CXCL10-/- mice. At specific times postinfection, eyes were analyzed for Bacillus, retinal function, and inflammation. The efficacies of intravitreal anti-CXCL2 and anti-CXCL10 with or without gatifloxacin in B. cereus endophthalmitis were also assessed using the same techniques. Results: Despite similar Bacillus growth in eyes of C57BL/6J, CXCL2-/-, and CXCL10-/- mice, retinal function retention was greater in eyes of CXCL2-/- and CXCL10-/- mice compared to that of C57BL/6J mice. Neutrophil migration into eyes of CXCL2-/- and CXCL10-/- mice was reduced to a greater degree compared to that of eyes of C57BL/6J mice. Infected CXCL2-/- and CXCL10-/- mouse eyes had significantly less inflammation compared to that of C57BL/6J eyes. Retinal structures in infected eyes of CXCL2-/- mice were preserved for a longer time than in CXCL10-/- eyes. Compared to untreated eyes, there was less inflammation and significant retention of retinal function in eyes treated with anti-CXCL2 and anti-CXCL10 with or without gatifloxacin. Conclusions: For Bacillus endophthalmitis, the absence of CXCL2 or CXCL10 in mice resulted in retained retinal function and less inflammation. The absence of CXCL2 led to a better clinical outcome than the absence of CXCL10. The use of anti-CXCL2 and anti-CXCL10 limited inflammation during B. cereus endophthalmitis. These results highlight the utility of CXCL2 and CXCL10 as potential targets for anti-inflammatory therapy that can be tested in conjunction with antibiotics for improving treating Bacillus endophthalmitis.