Sepsis In Pediatric Patients Research Articles

Heat shock protein 60 as a biomarker for acute kidney injury secondary to septic shock in pediatric patients, Egyptian multicenter experience.

Acute kidney injury (AKI) is an independent predictor of morbidity and mortality for critically ill children at pediatric Intensive Care Units (PICU). It is proposed that heat shock protein 60 (HSP60) may be either a biomarker or a co-factor of survival in PICU. The aim of this work is to assess plasma levels of HSP60 in critically ill pediatric patients with AKI secondary to septic shock within the first 24 h of admission. This study was carried out on 120 pediatric patients admitted to PICUs of four university hospitals. They were divided into Group 1 included 60 patients meeting the criteria of AKI Network and septic shock, the second group included 60 critically ill patients without AKI or septic shock and the third group was 60 healthy children as controls. HSP60 levels were measured in the plasma using a commercially available ELISA and difference between groups were analyzed with a Kruskal-Wallis one-way ANOVA. P <0.05 was considered significant. There was highly significant increase in plasma levels of HSP60 in Group 1 (median 25.85 ng/mL) compared to both Group 2 (median 6.15 ng/mL) and healthy controls (median 4.35 ng/mL) (P <0.001). At a cut-off value ≥10 ng/mL, HSP60 sensitivity for prediction of cases with AKI secondary to septic shock was 96.67% with specificity 86.67%, positive predictive value 87.9%, negative predictive value 96.3%, AUC 0.993. HSP60 levels are significantly elevated in pediatric patients in Group 1 when compared to Groups 2 and 3. Hence, HSP60 may play a role in the pathogenesis of sepsis in pediatric patients.

Clinical Benefits of High-Volume Hemofiltration in Critically Ill Pediatric Patients with Severe Sepsis: A Retrospective Cohort Study

Aims: The study aimed to assess the clinical benefits of high-volume hemofiltration (HVHF) in pediatric patients with severe sepsis compared with standard-volume continuous veno-venous hemofiltration (CVVH). Methods: We retrospectively analyzed the medical records of 155 pediatric patients with severe sepsis admitted to the pediatric intensive care unit of Shanghai Children's Hospital from January 2010 to June 2016. A total of 93 patients were treated with HVHF and 62 patients were treated with CVVH. Results: HVHF treatment did not significantly reduce 28-day mortality. Moreover, there was no significant difference in reducing the plasma level of inflammatory mediators and improving hemodynamic variables between HVHF and CVVH group. However, the incidence of hyperglycemia was significantly higher in HVHF group than in CVVH group. Conclusions: There is no evidence to indicate that HVHF is superior to CVVH in reducing 28-day mortality as an adjunct to the treatment of severe sepsis in pediatric patients.

Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis.

To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. Secondary retrospective analysis of a single-center sepsis registry. Freestanding children's hospital and tertiary referral center. Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. None. Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a useful surrogate outcome in pediatric sepsis.

Development and validation of a mortality risk model for pediatric sepsis.

Pediatric sepsis is a burdensome public health problem. Assessing the mortality risk of pediatric sepsis patients, offering effective treatment guidance, and improving prognosis to reduce mortality rates, are crucial.We extracted data derived from electronic medical records of pediatric sepsis patients that were collected during the first 24 hours after admission to the pediatric intensive care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014. A total of 788 children were randomly divided into a training (592, 75%) and validation group (196, 25%). The risk factors for mortality among these patients were identified by conducting multivariate logistic regression in the training group. Based on the established logistic regression equation, the logit probabilities for all patients (in both groups) were calculated to verify the model's internal and external validities.According to the training group, 6 variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate levels, and mechanical ventilation in 24 hours) were included in the final logistic regression model. The areas under the curves of the model were 0.854 (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups, respectively.The Mortality Risk Model for Pediatric Sepsis we established in this study showed acceptable accuracy to predict the mortality risk in pediatric sepsis patients.

Red cell distribution width and mortality in pediatric sepsis

Background Red cell distribution width (RDW) is a hematological parameter routinely obtained as part of the complete blood count. Recently, RDW has emerged as a potential independent predictor of clinical outcomes in adults with sepsis. However, RDW as a mortality predictor in pediatric populations has not been well established.Objective To determine the relationship between RDW value and mortality outcomes in pediatric sepsis patients.Methods We performed a cross-sectional study of 40 consecutive pediatric patients with sepsis admitted to the PICU from December 2013 to March 2014. All patients’ RDW were collected within 24 hours of sepsis diagnosis. We determined the association between RDW and hemoglobin (Hb) using Spearman’s correlation. The RDW values of 11.5-14.5% were considered to be normal while those &gt; 14.5% were considered to be elevated. We compared mortality and PICU length of stay (LoS) between the normal and elevated RDW groups using Chi-square and Mann-Whitney tests.Results The median age of patients was 34 months (range 2 months to 17 years). There were 28 (70%) male subjects. Subjects’ median RDW was 14.8% (range 11.2-27.8%) and was not correlated with Hb (r=0.056; P=0.73). Mortality rates in the normal and elevated RDW groups were 40% and 45%, respectively. There were no significant associations between RDW group and mortality (P=0.749) or PICU LoS (P=0.350).Conclusion Unlike in adults, RDW values are not correlated with mortality in pediatric sepsis patients.

Effectiveness of provider strategies for the early recognition of clinical deterioration due to sepsis in pediatric patients: a systematic review protocol.

The objective of this review is to determine the effectiveness of provider strategies for the early recognition of clinical deterioration due to sepsis in pediatric patients. Specifically, the review question is: among pediatric, hospitalized patients, up to 18 years of age, what is the effectiveness of clinical assessment compared with use of early recognition screening tools for the recognition of clinical deterioration due to sepsis?

Baicalin Inhibits Renal Cell Apoptosis and Protects Against Acute Kidney Injury in Pediatric Sepsis.

BackgroundPediatric sepsis has high morbidity in children, may lead to acute kidney injury (AKI), and further aggravate the disease. Baicalin is a kind of flavonoid in Scutellaria baicalensis Georgi and has been reported to protect against several diseases, but its roles in septic AKI remain unclear. This study aimed to uncover the effects of baicalin in AKI during pediatric sepsis.Material/MethodsBlood urea nitrogen (BUN) and serum creatinine (Cr) levels were detected in 50 pediatric patients, who underwent basic therapy with or without baicalin adjunctive therapy. Mouse sepsis models were constructed by cecal ligation and puncture (CLP) and treated with baicalin intragastrically, after which BUN and Cr examination, TUNEL apoptosis assay, and expression analyses of BAX and BCL2 were performed.ResultsBaicalin adjunctive therapy significantly decreased BUN and Cr levels in pediatric sepsis patients (P<0.05). CLP led to elevated BUN and Cr levels in the mouse model (P<0.01), indicating kidney injury accompanied by sepsis. Baicalin decreased BUN and Cr levels (P<0.05), and reduced the apoptotic cell percent in the renal tissue (P<0.05) of the CLP model. It inhibited BAX and promoted BCL2 in the renal tissue, which was consistent with cell apoptosis changes.ConclusionsBaicalin is capable of suppressing renal cell apoptosis and protecting against AKI in pediatric sepsis. This study provides a potential adjunctive therapy for treating AKI in pediatric sepsis, and further research is necessary to reveal its deeper mechanisms.

Outcomes of Fever in Infants and Young Children with SCD Presenting to the Emergency Room

The introduction of antibiotic prophylaxis and vaccinations has reduced the incidence of bacteremia and sepsis in pediatric patients with sickle cell disease (SCD). Due to concern of mortality from sepsis, SCD patients with fever require admission for IV antibiotics until bacteremia is ruled out. The 2014 NIH Evidence-Based Management of Sickle Cell Disease guidelines recommends hospitalization for patients with temperature ≥ 39.5 C and who appear ill. Prior pediatric research has defined "high risk patients" as those with temperature ≥ 40 C, WBC >30,000 or <5,000/mcl, appear ill, or have pulmonary infiltrates on chest x-ray (CXR). (Wilimas NEJM 1993) We reviewed all Emergency Room (ER) visits for febrile patients <6 years of age with HbSS or HbSB0 thalassemia to evaluate these predictive models for bacteremia.Methods: In a 16 year IRB approved cohort, we identified 609 ER visits to Children’s of Alabama for fever among 169 children < 6 years old with HbSS or SB0 thalassemia. All patients receive standard of care penicillin prophylaxis and vaccination. We reviewed every blood culture obtained during their ER visit and admission to determine the incidence of bacteremia including pneumococcal bacteremia. We recorded vital signs, blood counts, and CXR findings during the ER visit. We compared differences in these variables among patients with and without bacteremia. We created categorical variables (yes/no) to evaluate NIH fever guidelines (Temp >39.5C and ill appearance) and "high risk patient" recommendations (Temp >40C, ill appearance, abnormal white blood cell count (>30,000 or <5,000//mcl), or pulmonary infiltrates on CXR). Descriptive statistics, t-test for normally distributed data and Wilcoxon for non-normally distributed data, and Fisher’s exact test were performed in JMP12. Sensitivity and specificity were calculated from 2x2 tables. To examine the predictive models for bacteremia, we utilized multiple logistic regression to develop the receiving operating characteristics curves and area under the curve (AUC).Results: Among the 169 patients (0-5.99yrs) with HbSS or SB0 thalassemia that were evaluated in the Children’s of Alabama ER for fever, 95 (56%) were female. Five hundred and twelve (84%) admissions were identified among the 609 ER visits including all patients with bacteremia. Fourteen patients (2.3%) evaluated in the ER for fever were subsequently diagnosed with bacteremia including 9 (1.5%) positive for pneumococcus. The incidence of bacteremia among young patients presenting to the ER for fever was 1.4 events per 100 patient years and the rate of pneumococcus was 0.9 events per 100 patient years. Patients with bacteremia had higher WBC (27.0 ±7.8 vs 17.2 ±8.5, p<0.0001) than patients without bacteremia. No statistical differences were noted for patients with and without bacteremia for temperature (p=0.06) or heart rate (p=0.3). The sensitivity and specificity of individual variables for bacteremia were: Temp ≥ 39.5 (Sen: 57%, Specificity: 65%), Temp ≥ 40 (sensitivity: 29%, specificity 90%), Ill appearing (sensitivity: 43%, specificity: 86%), abnormal WBC (sensitivity: 36%, specificity 91%) abnormal CXR (appearing (sensitivity: 57%, specificity: 72%). To evaluate models for bacteremia, the AUC for NIH admission guidelines and "high risk patients" were 0.68 and 0.80 respectively.Conclusion: While the incidence of bacteremia is low, young children with SCD are frequently admitted for IV antibiotics until bacteremia is ruled out. Our data suggests using the "high risk model" for admission criteria in febrile children with SCD. Developing models that can accurately predict bacteremia are limited due to the low incidence of bacteremia. DisclosuresLebensburger:NHLBI: Research Funding; American Society of Hematology, Scholar Award: Research Funding.

Recognition, management, and prevention of burn sepsis in pediatric patients

Sepsis is one of the leading causes of morbidity and mortality in pediatric burn patients. This article discusses the signs and symptoms of burn sepsis in pediatric patients, diagnostic and therapeutic interventions, ongoing evaluations of therapy, and interventions to help prevent this potentially fatal infection.

Effect of different fluid resuscitation on kidney function in pediatric patients with sepsis

Objective To prospectively study the effects of different fluid resuscitation on kidney function in pediatric patients with sepsis. Methods One hundred and eighteen pediatric patients with sepsis shock who needed fluid resuscitation in Intensive Care Unit, Zhengzhou Children's Hospital from June 2012 to June 2015 were selected, and they were randomly divided into group A, B and C by random number in the table.The patients received fluid resuscitation of hydroxyethyl starch, 50 g/L albumin and 9 g/L saline.After that, neutrophil gelatinase associated lipocalin (NGAL), α-1 microglobulin, urea nitrogen, creatinine, urine volume, the incidence of acute kidney injury (AKI), and the renal replacement therapy rate accepted by the patients were recorded.Then all the data were analyzed with SPSS 19.0 software. Results Serum levels of NGAL and α-1 microglobulin in group A [(103.50±1.23) μg/L, (3.32±0.20) mg/L]were higher than those in group B [(93.54±1.42) μg/L, (2.71±0.18)mg/L]and group C[(79.57±1.54) μg/L, (2.08±0.14) mg/L], which were statistically different(all P 0.05). The urine volume in group A [(0.50±0.12) mL/(kg·h)] was less than that in group B[(0.90±0.23) mL/(kg·h)] and group C[(1.30±0.14) mL/(kg·h)], which was statistically different(all P 0.05). In three groups, there were 13 cases(34.2%) with AKI in group A, 9 cases(23.1%) with AKI in group B, and 8 cases(19.5%) with AKI in group C, the incidence of AKI in group C was less than that in group B and group C, which was statistically different(χ2=12.74, 10.43; all P<0.05). All the groups all had children accepted renal replacement therapy, there were 8 cases(21.1%)in group A, 7 cases(17.9%)in group B, and 6 cases (14.6%)in group C, and the cases who accepted renal replacement therapy rate in group C were less than those in group A and group B, which was statistically different(χ2=11.36, 8.73; all P<0.05). Conclusions The adverse effect of 9 g/L saline on kidney function is less than hydrox-yethyl starch and 50 g/L albumin, and hydroxyethyl starch has more adverse effects on kidney.Thus, 9 g/L saline is a better option for fluid resuscitation in pediatric sepsis patients. Key words: Fluid resuscitation; Sepsis; Kidney function; Child

Diagnostic value of soluble triggering receptor expressed on myeloid cells in paediatric sepsis: a systematic review.

BackgroundDifferential diagnosis between sepsis and non-infectious inflammatory disorders demands improved biomarkers. Soluble Triggering Receptor Expression on Myeloid cells (sTREM-1) is an activating receptor whose role has been studied throughout the last decade. We performed a systematic review to evaluate the accuracy of plasma sTREM-1 levels in the diagnosis of sepsis in children with Systemic Inflammatory Response Syndrome (SIRS).MethodsA literature search of PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and ISI Web of Knowledge databases was performed using specific search terms. Studies were included if they assessed the diagnostic accuracy of plasma sTREM-1 for sepsis in paediatric patients with SIRS. Data on sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic curve were extracted. The methodological quality of each study was assessed using a checklist based on the Quality Assessment Tool for Diagnostic Accuracy Studies.ResultsNine studies comprising 961 patients were included, four of which were in newborns, three in children and two in children with febrile neutropenia. Some data from single studies support a role of sTREM-1 as a diagnostic tool in pediatric sepsis, but cannot be considered conclusive, because a quantitative synthesis was not possible, due to heterogeneity in studies design.ConclusionsThis systematic review suggests that available data are insufficient to support a role for sTREM in the diagnosis and follow-up of paediatric sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13052-016-0242-y) contains supplementary material, which is available to authorized users.

Use of biomarkers in pediatric sepsis: literature review.

Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis.

Receptor for advanced glycation endproducts in pediatric sepsis: a pilot study

Background Sepsis in pediatric patients is still a leading cause of morbidity and mortality. Aim The aim of the study was to determine whether the serum level of receptor for advanced glycation endproducts (RAGEs) can be used as a potential diagnostic and prognostic marker in septic children. Patients and methods A pilot study was conducted on pediatric intensive care unit patients who had clinical evidence of sepsis over a 1-year period. Forty patients were enrolled in the study within the first 24 h after onset of sepsis; they were classified according to 28-day mortality into survivors and nonsurvivors. Complete blood count, erythrocyte sedimentation rate, C-reactive protein, and soluble form of RAGE (sRAGE) were measured. Bacterial cultures from suitable body fluids were prepared. Results There was a significantly higher mean serum sRAGE level among septic patients compared with controls (P=0.001); the level was higher in nonsurvivors compared with survivors (P=0.001). A cutoff value of 1325 pg/ml for serum sRAGE showed a sensitivity of 89.2% and a specificity of 78.3%. There were positive correlations with C-reactive protein and Pediatric Risk of Mortality III, and no correlation with bacterial culture. Multivariate logistic regression analysis showed that sRAGE level and leukocytic count were significant markers in the diagnosis of sepsis (P=0.047 and 0.001, respectively). sRAGE level and Pediatric Risk of Mortality III score were significant parameters in sepsis prognosis (P=0.019 and 0.043, respectively). Conclusion Serum sRAGE can be used as a diagnostic and prognostic marker in pediatric sepsis, especially in those with a negative blood culture.

Sulfhydryl variable-5 extended spectrum β-lactamase in nosocomial enteric bacteria causing sepsis in mexican children

&lt;p&gt;&lt;strong&gt;Introduction:&lt;/strong&gt; Enteric bacteria causing nosocomial infections are often resistant to third-generation cephalosporins due to the production of extended-spectrum β-lactamases (ESBLs).&lt;/p&gt;&lt;p&gt;&lt;br /&gt;&lt;strong&gt;Objective:&lt;/strong&gt; To describe and characterize the ESBLs pattern present in Klebsiella pneumoniae and Serratia marcescens strains, isolated as causative of nosocomial sepsis in pediatric patients at Instituto Nacional de Pediatría (National Institute of Pediatrics).&lt;/p&gt;&lt;p&gt;&lt;br /&gt;&lt;strong&gt;Material and methods:&lt;/strong&gt; We analyzed 94 strains of K. pneumoniae and 7 of S. marcescens isolated from clinical specimens from 2002-2005, causative of sepsis in a children’s hospital. We evaluated antibiotic susceptibility and detection of ESBL phenotypes by disk diffusion methods; ceftazidime-resistant isolates were further characterized by pulsed field gel electrophoresis (PFGE); and ESBLs were phenotypically and genotypically characterized by isoelectric focusing, polymerase chain reaction (PCR) and sequencing. We also assed for presence of conjugative plasmids bearing the ESBL gene.&lt;/p&gt;&lt;p&gt;&lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; 51/94 (54%) of K. pneumoniae isolates, and 5/7 (71%) of S. marcescens isolates were resistant to ceftazidime; all carried a blaSHV-5 gene. All K. pneumoniae isolates had a distinct PFGE profile, yet all carried a ~48-Kb plasmid, that was conjugatively transferable to an Escherichia coli receptor, which expressed the resistance phenotype. On the other hand, all S. marcescens isolates had a similar PFGE profile, were unable to transfer the ceftazidime-resistance phenotype, and were isolated from the same ward in a short time-span suggesting an outbreak.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The overall prevalence of ESBL-producing enteric bacteria in this hospital is high but similar to other Latin American reports. The sulfhydryl variable-5 (SHV-5) ESBL gene appears to reside in a highly mobile plasmid, capable of spreading among different K. pneumoniae clones and perhaps even to S. marcescens.&lt;/p&gt;

Study of acute phase reactants in children with sepsis, with special reference to C-reactive protein and procalcitonin

Background: Several inflammatory markers have failed to meet the requirements for an early diagnosis of sepsis in children. Study results and trends show that measurement of the combination of biochemical markers offers the best prospects for research on early diagnosis of sepsis. Objectives: To evaluate the serum levels of C-reactive protein (CRP) and procalcitonin (PCT) as markers of early sepsis in pediatric patients. Methods: All the hospitalized children aged more than 28 days with clinically suspected sepsis, as per the definition given by International Pediatric Sepsis Consensus Conference, were selected. The patients were divided into two groups; one with culture proven sepsis and the other with culture negative sepsis. CRP and PCT levels were measured at the time of admission and 48 h after admission. Results: A 40 patients were studied, out of that 15 had culture positive and 25 had culture negative sepsis. The mean PCT level was significantly higher at admission than at 48 h after admission, and the mean CRP level was significantly lower at admission than at 48 h after admission indicating PCT as early marker of sepsis. Conclusion: CRP and PCT levels have favorable test performance in differentiating between culture positive and culture negative sepsis. PCT is earlier to rise compared to CRP and PCT is best in predicting the severity followed by CRP.

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

&lt;p&gt;A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r&lt;sup&gt;2&lt;/sup&gt;=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T&gt;MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.&lt;/p&gt;

Risk factors for sepsis-related death in children and adolescents with hematologic and malignant diseases.

The aim of this study was to elucidate risk factors for mortality after developing sepsis in pediatric patients with hematologic and malignant disorders. A total of 90 patients (43 boys, 47 girls) with various hematologic and malignant diseases who experienced sepsis between June 2006 and March 2014 were enrolled. Clinical and laboratory features of 134 episodes of sepsis observed in the 90 patients were compared between those with and without sepsis-related death which was defined as death within 14 days after sepsis. Age at hospitalization, sex, and type of underlying disease did not differ between patients with and without sepsis-related death. Sepsis episode-based univariate analysis identified patients with a history of relapse or in a refractory state of underlying disease (p<0.01), those with high C-reactive protein concentrations (≥50mg/L) at the beginning of fever (p<0.01), those who had undergone hematopoietic stem cell transplantation (p<0.01), and those who were forced to change initial antibiotics (p=0.02) because of being at high risk of sepsis-related death. The former two factors were further confirmed by multivariate analysis. More than half (52.9%) the isolates from sepsis-related death were Gram-positive cocci resistant to β-lactam antibiotics, but susceptible to vancomycin. It was found that a history of relapse, a refractory state of underlying disease, and high C-reactive protein concentrations at the beginning of fever were significant risk factors for mortality after developing sepsis. Survival rate of patients with risk factors raised in this study might be improved by early introduction of vancomycin.

A cross-sectional study of risk factors of fungal sepsis in paediatric patients at a tertiary care centre in India

A cross-sectional study of risk factors of fungal sepsis in paediatric patients at a tertiary care centre in India

Determination of Optimal Amikacin Dosing Regimens for Pediatric Patients With Burn Wound Sepsis.

This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.

Relationship between expression of microRNA and inflammatory cytokines plasma level in pediatric patients with sepsis

Sepsis is the major cause of death in pediatric intensive care unit (PICU). The clinical manifestations of early sepsis is very similar to systemic inflammatory response syndrome (SIRS) caused by non-infectious reason. This study aimed to investigate the expression of miRNA and inflammatory cytokines in plasma in pediatric sepsis patients and its clinical significance. Forty children with sepsis seen in Shenzhen children's hospital PICU from April 2012 to March 2013 were enrolled in this study, the median age was 0.75 (0.52, 1.90) years; 27 were males and 13 females, of whom 16 had severe sepsis. We selected 20 postsurgical patients with SIRS and 15 healthy children as a control group. The expression levels of plasma miR-21, miR-125b, miR-132, miR-146a, miR-155 and miR-223 were detected by real-time quantitative PCR (qRT-PCR). The predictive value of miRNA, PCT and CRP for sepsis were evaluated by Receiver operating characteristic curve (ROC). TNF-α and IL-10 levels in plasma detected by Cytometric Beads Array (CBA). Quantitative data of normal distribution was compared with ANOVA among the three groups and LSD-t test between two groups. To non-normal distribution of data, multiple comparisons among three groups were conducted by Kruskal-Wallis H test and differences between two groups were assessed by Mann-Whitney U test for post hoc analysis. There were no significant differences between the age and gender of each group. Expression of miR-21, miR-125b, miR-132 and miR-155 in plasma had no significant difference in each group (all P > 0.05). MiR-146a and miR-223 levels in sepsis were upregulated compared with SIRS group and control group [(5.7 ± 3.5)×10(-5) vs. (2.4 ± 1.6)×10(-5) and (2.6 ± 1.2)×10(-5), (12.5 ± 7.7)×10(-4) vs. (8.3 ± 3.4)×10(-4) and (5.3 ± 2.2)×10(-4), all P < 0.01], expression levels of miR-223 in SIRS increased as compared to control group (P < 0.01). MiR-146a levels in severe sepsis were higher than those of the general sepsis [ (7.1 ± 3.3)×10(-5) vs. (4.6 ± 2.6)×10(-5), P < 0.01]. CRP and PCT levels are all higher in sepsis and SIRS groups than control group (all P < 0.01). The area under ROC curve (AUC) of miR-146a, miR-223, PCT and CRP to predict sepsis were 0.815 (95%CI: 0.708-0.922), 0.678(95%CI: 0.537-0.818), 0.706 (95%CI: 0.571-0.842) and 0.588 (95%CI: 0.427-0.748). Expression levels of IL-10 and IL-10/TNF-α in sepsis were upregulated compared with and SIRS group and the control group (all P < 0.01). There was a positive correlation between miR-146a, miR-223 and IL-10 and IL-10/TNF-α (r = 0.545, 0.305, 0.562, 0.373, all P < 0.01). The expression levels of miR-146a and miR-223 in plasma in pediatric patients with sepsis was significantly upregulated, and had a positive correlation with IL-10 and IL-10/TNF-α, which may be used as early diagnostic markers and can reflect the severity of condition to a certain degree.