Clinical, Bacteriological Profile and Outcome of Neonatal Sepsis.

BACKGROUND: Sepsis is a major cause of morbidity and mortality among neonates in Nepal. This study was conducted to determine the clinical-bacteriological profile, their antibiotic susceptibility patterns, and clinical outcome of culture-positive neonatal sepsis. METHODS: This was a prospective study conducted at B.P Koirala Institute of Health Sciences from July 2018 to June 2019. Neonates with clinically diagnosed sepsis having blood culture positive were included in the study. Blood samples culture and antimicrobial susceptibility testing were performed with the standard microbiological method. Demographic, clinical information, and clinical outcomes were documented. RESULTS: The incidence of culture-positive sepsis was 10.3% (183/1773) of neonatal admissions. Poor feeding 85(46%) and fever 68(37%) were the common clinical features at presentation. The incidence of early-onset sepsis and late-onset sepsis were found to be 116 (63%) and 67(37%) respectively. Staphylococcus aureus was the common pathogen in both early-onset 61(49%) and late-onset 34(41%) sepsis. The incidence of multidrug-resistant cases was 41% (75/183) with 20% (15/75) extensively drug-resistant gram-negative bacilli, 36% (20/75) multidrug-resistant gram-negative bacilli, and 44% (33/75) Methicillin-resistant Staphylococcus aureus cases. In-hospital mortality rate was 12 (7%) with a higher frequency in multidrug-resistant sepsis 92% (11/12) than non- multidrug-resistant 8% (1/12). The median hospital days were longer in multidrug-resistant cases than non- multidrug-resistant [11(9-13) verses 3(2-5)]. CONCLUSIONS: The incidence of multidrug-resistant pathogens causing neonatal sepsis is high at our hospital and are associated with more in-hospital mortality and longer hospital stay. Implementation of effective preventive strategies to combat the emergence of antimicrobial resistance is immediately needed.

Severe Disease Caused by Community-Associated MRSA ST398 Type V, Australia, 2017.

Using whole-genome sequencing, we identified a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type (ST) 398 type V (5C2&5) isolate (typically found in China) in Australia in 2017. This CA-MRSA ST398 variant was highly virulent, similar to other related CA-MRSAs of ST398. This strain should be monitored to prevent more widespread dissemination.

An early increase in endothelial protein C receptor is associated with excess mortality in pneumococcal pneumonia with septic shock in the ICU.

BACKGROUND: This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients. METHODS: Clinical data and samples were extracted from the prospective "STREPTOGENE" cohort. We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors (n = 194) and non-survivors (n = 84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables. RESULTS: In-hospital mortality was 30.2% (n = 84). Plasma sEPCR level was significantly higher at D1 and D2 in non-surviving patients compared to patients surviving to hospital discharge (p = 0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group (p = 0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75. CONCLUSIONS: Our findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.

Reduced circulating B cells and plasma IgM levels are associated with decreased survival in sepsis - A meta-analysis.

BACKGROUND: B cell function and antibody production are crucial factors in host protection during inflammation. We aimed to synthesize the available evidence on the association between the reduction of circulating B cells and plasma immunoglobulin (IgM) levels and decreased survival during sepsis. METHODS: We performed a systematic search in PubMed, Embase, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials, BioMed Central, and Science Direct. We selected studies with data on circulating B cells and plasma IgM levels within the initial 24 h after sepsis onset. RESULTS: In total nine studies (n = 992 patients) were identified. Circulating B cells were reduced in septic patients as compared to non-septic patients (mean difference [MD] -88.2 cells/µl; 95% confidence interval [CI] -148.6--27.9). Sepsis non-survivors showed a significant reduction of circulating B cells and IgM levels compared to sepsis survivors (MD -77.1 cells/µl; 95% CI -111.4--42.7 and MD -20.9 mg/dl; 95% CI -33.8--8.0, respectively). CONCLUSIONS: Our results suggest that a reduction of circulating B cells and IgM levels at sepsis onset are associated with decreased sepsis survival. However, due to methodological limitations and the risk of bias, we need further prospective studies to confirm this association. REGISTRATION: The protocol was registered (PROSPERO 2016:CRD42016053184).

The role of genetics and antibodies in sepsis.

During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity.

INTRODUCTION: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. MATERIALS AND METHODS: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. RESULTS: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1alpha, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1alpha, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1beta and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1alpha and IP-10. CONCLUSION: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.