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Abstract Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p

Background: Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI).Methods: A prospective, case-control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.Results: A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively).Conclusion: We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management. [ABSTRACT FROM AUTHOR]

Objectives: Procalcitonin (PCT) is a critical diagnostic biomarker for bacterial infections in patients. Numerous studies have shown that PCT have high sensitivity and specificity for diagnosing bloodstream infection. However, the cut-off value of PCT for the diagnosis of bloodstream infections in patients with hematolgic diseases is still unclear and unreliable. Methods: We conducted a retrospective study involving 2299 cases with hematological diseases and who had been performed blood culture and PCT test within 24 h. Results: For patients with hematological diseases, the serum PCT was slightly elevated in the BSI group. We found that most hematological patients with bloodstream infection were in the stage of severe neutropenia. The main infected strains were Escherichia coli (n = 84, 21%), Klebsiella pneumoniae (n = 61, 15.25%) and Pseudomonas aeruginosa (n = 65, 16.25%), and the increasing trend of PCT level was more obvious in patients infected with Gram-negative bacteria. ROC analysis results showed that the area under the receiver operating characteristic curve for distinguishing bacterial infection from non-bacterial infection was 0.554 (95%CI: 0.522–0.585) with the diagnostic threshold of BSI (PCT > 0.5ng/mL). Conclusions: In our study, low PCT levels were found in patients with hematological diseases, and a better cut-off value may be necessary to determine infection in hematology patients. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis is a leading cause of death in low- and middle- income countries (LMIC). Increasing antibiotic resistance in early onset (< 72 h of life) bloodstream infection (EO-BSI) pathogens in LMIC has reduced the effectiveness of the recommended empiric antibiotic regimen (ampicillin plus gentamicin). Methods: We retrospectively analysed blood culture-confirmed EO-BSI episodes at nine neonatal units from three central and six peripheral hospitals in the Western Cape Province, South Africa between 1 January 2017 and 31 December 2018. Clinical and electronic laboratory records were reviewed to determine pathogen profile, empiric antibiotic coverage rates and factors associated with EO-BSI attributable mortality, stratified by hospital type. Results: Of the 8252 blood culture specimens submitted for the investigation of suspected EO-BSI, 136 EO-BSI episodes yielding 141 pathogens were identified with an EO-BSI rate of 1.3 and 0.5 episodes/1000 live births at central and peripheral hospitals respectively. Preterm (93/136; 68.3%) and low birth weight (84/136; 61.8%) neonates were most affected. The predominant pathogens were Streptococcus agalactiae (46/136; 34%), Klebsiella pneumoniae (17/136; 13%), Listeria monocytogenes (11/136; 8%), Acinetobacter baumannii (11/136; 8%) and Escherichia coli (11/136; 8%). The empiric antibiotic (ampicillin plus gentamicin) coverage rate was 64% (95% CI 51–74) at central hospitals and 84% (95% CI 74–94) at peripheral hospitals. Neonates with Gram-negative EO-BSI and discordant empiric antibiotic therapy had almost four-fold and three-fold higher odds of death respectively. Conclusion: Preterm and low birth weight neonates are most vulnerable to EO-BSI and have higher odds of death with Gram-negative pathogens and discordant empiric antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods: A prospective study was performed to assess the potential value of IL-6, IL-8 and Creactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results: The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%). Conclusion: These findings may have clinical implications for risk-based antimicrobial treatment strategie [ABSTRACT FROM AUTHOR]

Background: The emergence and rapid spread of gram-negative bacteria resistant to carbapenems among newborns is concerning on a global scale. Nonetheless, the pooled estimate of gram-negative bacteria resistant to carbapenem that cause neonatal sepsis in developing nations remains unknown. Thus, this study aimed to determine the combined prevalence of gram-negative bacteria resistant to carbapenem in African newborns who were suspected of having sepsis. Methods: All studies published from January 1, 2010, up to December 30, 2023, from PubMed, Science Direct, Scopus electronic databases, and the Google Scholar search engine were researched. Isolates tested for carbapenem from neonates with sepsis, English language papers conducted in Africa, and cross-sectional and cohort studies papers were included. Using PRISMA guidelines, we systematically reviewed and meta-analyzed studies that assessed the prevalence of carbapenem-resistant gram-negative bacteria. The "Joanna Briggs Institute" was used critically to evaluate the quality of the included studies. The data analysis was carried out using STATA™ version 17. Heterogeneity across the studies was evaluated using Q and I 2 tests. The subgroup analysis was done and, funnel plot and Egger's regression test were used to detect publication bias. A sensitivity analysis was conducted. Results: All 36 studies were included in the meta-analysis and systematic review. The pooled prevalence of carbapenem resistance in Africa was 30.34% (95% CI 22.03–38.64%). The pooled estimate of gram-negative bacteria resistant to imipenem, and meropenem was 35.57% (95% CI 0.67–70.54%) and 34.35% (95% CI 20.04% – 48.67%), respectively. A. baumannii and Pseudomonas spp. had pooled prevalence of 45.9% (95% CI 33.1–58.7%) and 43.0% (95% CI 23.0–62.4%), respectively. Similarly, Pseudomonas spp. and A. baumannii also exhibited strong meropenem resistance, with a pooled prevalence of 29.2% (95% CI 4.8–53.5%) and 36.7% (95% CI 20.1–53.3%), respectively. E. coli and K. pneumoniae were the two most common isolates. Conclusion: There should be urgent antimicrobial stewardship practices, strengthened surveillance systems and effective treatment for neonates with sepsis. There was remarkable variation in resistance across the continent. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a threat in developing countries (DCs) because of the high burden of bacterial disease and the presence of risk factors for its emergence and spread. This threat is of particular concern for neonates in DCs where over one-third of neonatal deaths may be attributable to severe infections and factors such as malnutrition and HIV infection may increase the risk of death. Additional, undocumented deaths due to severe infection may also occur due to the high frequency of at-home births in DCs. Methods: We conducted a systematic review of studies published after 2000 on community-acquired invasive bacterial infections and antibiotic resistance among neonates in DCs. Twenty-one articles met all inclusion criteria and were included in the final analysis. Results: Ninety percent of studies recruited participants at large or university hospitals. The majority of studies were conducted in Sub-Saharan Africa (n = 10) and the Indian subcontinent (n = 8). Neonatal infection incidence ranged from 2.9 (95% CI 1.9-4.2) to 24 (95% CI 21.8-25.7) for 1000 live births. The three most common bacterial isolates in neonatal sepsis were Staphylococcus aureus, Escherichia coli, and Klebsiella. Information on antibiotic resistance was sparse and often relied on few isolates. The majority of resistance studies were conducted prior to 2008. No conclusions could be drawn on Enterobacteriaceae resistance to third generation cephalosporins or methicillin resistance among Staphylococcus aureus. Conclusions: Available data were found insufficient to draw a true, recent, and accurate picture of antibiotic resistance in DCs among severe bacterial infection in neonates, particularly at the community level. Existing neonatal sepsis treatment guidelines may no longer be appropriate, and these data are needed as the basis for updated guidelines. Reliable microbiological and epidemiological data at the community level are needed in DCs to combat the global challenge of antibiotic resistance especially among neonates among whom the burden is greatest. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile. Methods: 52 adult patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at the onset of fever. The patients were divided into 2 groups, one with severe infection (n = 26) and the other in which the patients did not present such an infection (n = 26). Then PCT and CRP concentrations at the fever onset were compared between groups using non parametric statistical tests, ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient. Results: The mean of PCT was significantly higher in the group with severe infection (6.7 ng/mL versus 0.6 ng/mL - p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of 2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any concentration of CRP. Conclusion: PCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenic patients, probably better than CRP. [ABSTRACT FROM AUTHOR]

Background: Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. Methods: This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. Results: In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). Conclusion: After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over-prescribing of unnecessary antibiotics. The aims of this study were to describe the antibiotic prescribing practices for children less than 24 months of age with symptoms of ARI, that were admitted to Kenema Government Hospital (KGH) in the Eastern Province of Sierra Leone, and to identify the number of children empirically prescribed antibiotics who were admitted to hospital with ARI, as well as their clinical signs, symptoms, and outcomes. Methods: We conducted a prospective study of children < 24 months of age admitted to the KGH pediatric ward with respiratory symptoms between October 1, 2020 and May 31, 2022. Study nurses collected data on demographic information, medical and medication history, and information on clinical course while hospitalized. Results: A total of 777 children were enrolled. Prior to arrival at the hospital, 224 children (28.8%) reported taking an antibiotic for this illness without improvement. Only 15 (1.9%) children received a chest radiograph to aid in diagnosis and 100% of patients were placed on antibiotics during their hospital stay. Conclusions: Despite the lives saved, reliance on clinical decision-support tools such as IMCI and ETAT + for pediatric ARI, is resulting in the likely over-prescribing of antibiotics. Greater uptake of implementation research is needed to develop strategies and tools designed to optimize antibiotic use for ARI in LMIC settings. Additionally, much greater priority needs to be given to ensuring clinicians have the basic tools for clinical diagnosis, as well as greater investments in essential laboratory and radiographic diagnostics that help LMIC clinicians move beyond the sole reliance on algorithm based clinical decision making. [ABSTRACT FROM AUTHOR]

Background: Patients’ race and ethnicity may play a role in mortality from Covid-19. Studies in China, the US, and Europe have been conducted on the predictors of Covid-19 mortality, yet in the EMR countries, such studies are scarce. Therefore, we aimed to describe the hospitalization rate, ICU-admission, and in-hospital mortality of Covid-19 and predictors of in-hospital mortality in Saudi Arabia. Methods: E-medical records were examined for all Covid-19 patients diagnosed in five tertiary hospitals affiliated with the Saudi-National Guard-Health Affairs during March 21, 2020, and September 12, 2021, based on a positive SARS-CoV-2 RT-PCR test, (n = 35,284). Data were collected on patients’ characteristics, comorbidities, laboratory findings, hospitalization, ICU admission, and in-hospital and overall mortality. Logestic regressions were used to identify the independent predictors of in-hospital mortality. The best laboratory parameters cut-off values to predict in-hospital mortality were identified using the area under the receiver operating characteristic curve (AUC). Significance was considered at p < 0.05. Results: Of all 35,284 Covid-19 patients, 81.8% were adults and 21.7% were hospitalized. Compared to non-hospitalized patients, hospitalized patients were more of female gender (52.1% versus 47.3%, p < 0.001) and had higher mean age (p < 0.001), higher mean BMI (p < 0.001), and higher rates of: diabetes (p < 0.001), hypertension (p < 0.001), ischemic heart disease (p < 0.001), cancer (p < 0.001), COPD (p < 0.001) and asthma (p = 0.011). The study showed 3.1% overall case-fatality, 20.3% ICU admission rate, and 9.7% in-hospital mortality. Predictors of in-hospital mortality among adult patients were; patients’ age ≥ 70 years (OR = 6.93, 95% CI 1.94–24.79), ischemic heart disease (OR = 1.80, 95% CI 1.05–3.09), ICU admission (OR = 24.38, 95% CI 15.64–38.01), abnormal C-reactive protein “CRP” (OR = 1.85, 95% CI 1.08–3.16), abnormal D-dimer (OR = 1.96, 95% CI 1.15–3.36), lymphopenia (OR = 2.76, 95% CI 2.03–3.3.76), high neutrophil count (OR = 2.10, 95% CI 1.54–2.87), and abnormal procalcitonin (OR = 3.33, 95% CI 1.88–5.90). The best laboratory parameters cut-off values to predict in-hospital mortality were CRP > 72.25 mg/L (AUC = 0.64), d-dimer > 1125 µg/L (AUC = 0.75), neutrophils count > 5,745 × 10^9/L (AUC = 0.70), lymphocytic count < 1.10 × 10^9/L (AUC = 0.72), and procalcitonin > 0.18 ng/mL (AUC = 0.76). Conclusions: Rates of hospitalization, ICU-admission, in-hospital mortality and overall case fatality were nearly comparable to the rates in western countries. Early interventions are necessary for high-risk Covid-19 patients, especially elderly patients and those with cardiac diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Invasive meningococcal disease (IMD) is a rare but severe bacterial infection, of which a high proportion of survivors are affected by sequelae. In Denmark, IMD is a notifiable disease and data collection on sequelae information has been automated, enabling studies of sequelae due to IMD diagnosed after discharge. The aim of this study was to examine possible determinants for sequelae after IMD and to describe the distribution of sequelae by age, serogroup and clinical presentation, for all cases in Denmark from 2005–2020. Methods Data from The National Database for Notifiable Infectious Diseases was linked to data from The Danish National Patient Register and the Civil Registration System. Logistic regression models were used to study whether age, serogroup and/or clinical presentation were associated with sequelae. A descriptive analysis of the proportion of different types of sequelae across age groups, serogroups and clinical presentations was performed. Results In total, 25% of IMD survivors experienced one or more sequelae. We found no significant association between sequelae and age. The five most common sequelae in decreasing order of incidence were hearing loss, epilepsy, learning disabilities, headache and visual defects/loss of vision, with rates ranging from 8.2 to 2.8% of IMD survivors. The proportion of survivors with hearing loss and visual defects/loss of vision was not significantly different between clinical presentations. Conclusions We suggest revising IMD treatment guidelines, to include routine referral to hearing and vision tests, irrespective of clinical presentation. Furthermore, it is important to increase the awareness among parents of children who have had IMD of possible future learning disabilities to make sure that necessary measures are taken in a timely manner.

Background: Deep neck infection (DNI) is a serious disease that can lead to severe morbidity, including esophageal perforation, and mortality. However, no previous study has explored the risk factors associated with esophageal perforation in patients with DNI. This study investigated these factors.Methods: Between September 2015 and September 2021, 521 patients with DNI were studied. Relevant clinical variables and deep neck spaces were assessed.Results: In a multivariate analysis, involvement of the retropharyngeal space (OR 5.449, 95% CI 1.603-18.51, p = 0.006) and the presence of mediastinitis (OR 218.8, 95% CI 55.98-855.3, p < 0.001) were independent risk factors associated with esophageal perforation in patients with DNI. There were no differences in pathogens between 32 patients with and 489 patients without esophageal perforation (all p > 0.05).Conclusion: Involvement of the retropharyngeal space and the presence of mediastinitis were independent risk factors associated with esophageal perforation in patients with DNI. There were no differences in pathogens between the groups with and without esophageal perforation in DNI. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients.Methods: This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs.Results: Out of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs.Conclusion: We found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO. [ABSTRACT FROM AUTHOR]

Background: The use of complement inhibition is well established for complement mediated thrombotic microangiopathy, but its role in secondary forms of thrombotic microangiopathy is debated. We here present a case of thrombotic microangiopathy triggered by Capnocytophaga canimorsus, illustrating the diagnostic difficulties in discriminating between different thrombotic microangiopathies, and the dilemmas regarding how to treat this disease entity.Case Presentation: A previously healthy 56-year-old woman presented with fever and confusion. She was diagnosed with sepsis from Capnocytophaga canimorsus and thrombotic microangiopathy. Marked activation of both T-cells, endothelium and complement were documented. She was successfully treated with antimicrobial therapy, the complement inhibitor eculizumab and splenectomy. After several weeks, a heterozygote variant in complement factor B was localized, potentially implying the diagnosis of a complement mediated TMA over an isolated infection related TMA.Conclusions: We discuss the possible interactions between complement activation and other findings in severe infection and argue that complement inhibition proved beneficial to this patient's rapid recovery. [ABSTRACT FROM AUTHOR]

Background: A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis.Methods: A comprehensive literature search was carried out in Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for studies assessing PCT accuracy in the diagnosis of sepsis in children and neonates with suspected sepsis. Studies in which the presence of infection had been confirmed microbiologically or classified as "probable" by chart review were included. Studies comparing patients to healthy subjects were excluded. We analysed data on neonates and children separately. Our primary outcome was the diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary outcomes we analysed PCT cut-offs <2 ng/ml and >2.5 ng/ml. Pooled sensitivities and specificities were calculated by a bivariate meta-analysis and heterogeneity was graphically evaluated.Results: We included 17 studies, with a total of 1408 patients (1086 neonates and 322 children). Studies on neonates with early onset sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90) and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In the paediatric group it was not possible to undertake a pooled analysis at the PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies.Conclusions: PCT shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological quality are warranted, particularly in neonates, studies considering EOS and LOS separately are needed to improve specificity.Trial Registration: PROSPERO Identifier: CRD42016033809 . Registered 30 Jan 2016. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin (PCT) has become a commonly used serum inflammatory marker. Our aim was to describe the kinetics and usefulness of serial post-operative PCT measurements to detect bacterial infection in a cohort of children immediately after pediatric liver transplantation (pLT).Methods: We performed a retrospective chart review of a cohort of pLT recipients with serial serum PCT measurements in the first week following pLT. The presence of infection was determined on clinical and biological parameters. Normal PCT was defined as < 0.5 (ng/ml).Results: Thirty-nine patients underwent 41 pLT. PCT was measured daily during the first week post pLT. Values first increased following surgery and then decreased, nearing 0.5 ng/ml at day seven. Peak PCT reached a median of 5.61 ng/ml (IQR 3.83-10.8). Seventeen patients were considered to have an infection. There was no significant difference in daily PCT or peak PCT between infected and non infected patients during the first post-operative week. AUC of ROC curve for PCT during first week was never higher than 0.6.Conclusions: We conclude that serial PCT measurements during the first week after pLT is not useful to identify patients with bacterial infections. Rather, we propose that serum PCT may be useful after the first week post pLT. [ABSTRACT FROM AUTHOR]

Background: Antimicrobially pre-treated children with systemic inflammation often pose a diagnostic challenge to the physician. We aimed to evaluate the additional use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative pathogens in children with suspected systemic bacterial or fungal infection.Methods: Prospective observational study in 39 children with systemic inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary outcome was the rate of positive blood cultures (BC), compared to the rate of positive SeptiFast (SF) results.Results: In total, 14 SF-samples yielded positive results, compared to 4 positive BC (p < 0.05). All blood cultures and 13 of 14 positive SF-tests were considered infection. Median time for positive BC was 2 days, and time to definite result was 6 days, compared to 12 h for SF. Antimicrobial therapy was adapted in 7 of the 14 patients with positive SeptiFast, and in 3 of the 4 patients with positive BC. Best predictive power for positive SF shown by receiver-operating characteristic was demonstrated for procalcitonin PCT (Area under the curve AUC: 0.79), compared to C-reactive protein CRP (AUC: 0.51) and leukocyte count (AUC: 0.46). A procalcitonin threshold of 0.89 ng/ml yielded a sensitivity of 0.82 and a specifity of 0.7. Children with a positive SeptiFast result on day 0 had a significantly higher risk to require treatment on the Pediatric Intensive Care Unit or to be deceased on day 30 (Odds-Ratio 8.62 (CI 1.44-51.72).Conclusions: The additional testing with SeptiFast in antimicrobially pre-treated children with systemic inflammation enhances the rate of pathogen detection. The influence of multiplex PCR on clinically relevant outcome parameters has to be further evaluated. (Trial Registration: DRKS00004694). [ABSTRACT FROM AUTHOR]

Background: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. Methods: Within the International epidemiological Database to Evaluate AIDS (IeDEA)-West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever > 38°5C, Karnofsky index < 70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. Results: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. Conclusions: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion. [ABSTRACT FROM AUTHOR]

Background: Daily throughout 2011, about 900 new HIV infections occurred in children and 630 children died as a result of AIDS-related complications worldwide. Late diagnosis, mortality trends, causes of and risk factors for death were evaluated in vertically HIV-infected children. Methods: A retrospective 11-year study was conducted with Brazilian vertically HIV-infected children and adolescents using patients' charts. Medical records, death certificates and the Ministry of Health's mortality database were verified for mortality and cause of death. Diagnoses were made according to the CDC Revised Classification System for HIV infection. Results: Of 177 patients included, 97 were female (54.8%). Median age at admission was 30 months (IQR: 5-72 months). Median follow-up was 5 years (IQR: 2-8 years). After 11 years, 132 (74,6%) patients continued in follow-up, 11 (6.2%) had been transferred and 8 (4.5%) were lost to follow-up. Twenty-six deaths occurred (14,7%), the majority (16/26; 61.5%) in children <3 years of age. Death cases decreased over time and the distribution of deaths was homogenous over the years of evaluation. In 17/26 (65.4%) of the children who died, diagnosis had been made as the result of their becoming ill. Beginning antiretroviral therapy before 6 months of age was associated with being alive (OR = 2.86; 95% CI: 1.12-7.25; p = 0.027). The principal causes of death were severe bacterial infections (57%) and opportunistic infections (33.3%). Conclusions: In most of the HIV-infected children, diagnosis was late, increasing the risk of progression to AIDS and death due to delayed treatment. The mortality trend was constant, decreasing in the final two years of the study. Bacterial infections remain as the major cause of death. Improvements in prenatal care and pediatric monitoring are mandatory. [ABSTRACT FROM AUTHOR]

Background: Although neonatal infections cause a significant proportion of deaths in the first week of life, little is known about the burden of neonatal disease originating from maternal infection or colonization globally. This paper describes the prevalence of vertical transmission - the percentage of newborns with neonatal infection among newborns exposed to maternal infection. Methods: We searched Pubmed, Embase, Scopus, Web of Science, Cochrane Library, and WHO Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection. Studies that measured prevalence of bacterial vertical transmission were included. Random effects meta-analyses were used to pool data to calculate prevalence estimates of vertical transmission. Results: 122 studies met the inclusion criteria. Only seven studies (5.7%) were from very high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of infection (lab-confirmed, clinical signs), colonization, and risk factors of infection. The prevalence of early onset neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 17.2% (95%CI 6.5-27.9). The prevalence of neonatal lab-confirmed infection among newborns of colonized mothers was 0% (95% CI 0.0-0.0). The prevalence of neonatal surface colonization among newborns of colonized mothers ranged from 30.9-45.5% depending on the organism. The prevalence of neonatal lab-confirmed infection among newborns of mothers with risk factors (premature rupture of membranes, preterm premature rupture of membranes, prolonged rupture of membranes) ranged from 2.9-19.2% depending on the risk factor. Conclusions: The prevalence of early-onset neonatal infection is high among newborns of mothers with infection or risk factors for infection. More high quality studies are needed particularly in high neonatal mortality settings to accurately estimate the prevalence of early-onset infection among newborns at risk. [ABSTRACT FROM AUTHOR]

Background Dengue fever and leptospirosis have partially overlapping geographic distributions, similar clinical presentations and potentially life-threatening complications but require different treatments. Distinguishing between these cosmopolitan emerging pathogens represents a diagnostic dilemma of global importance. We hypothesized that perturbations in host biomarkers can differentiate between individuals with dengue fever and leptospirosis during the acute phase of illness. Methods We randomly selected subjects from a prospective cohort study of acute febrile illness in Bucaramanga, Colombia and tested 19 serum biomarkers by ELISA in dengue fever (DF, n = 113) compared subjects with leptospirosis (n = 47). Biomarkers were selected for further analysis if they had good discriminatory ability (area under the ROC curve (AUC) >0.80) and were beyond a reference range (assessed using local healthy controls). Results Nine biomarkers differed significantly between dengue fever and leptospirosis, with higher levels of Angptl3, IL-18BP, IP-10/CXCL10, Platelet Factor 4, sICAM-1, Factor D, sEng and sKDR in dengue and higher levels of sTie-2 in leptospirosis (p < 0.001 for all comparisons). Two biomarkers, sEng and IL18BP, showed excellent discriminatory ability (AUROC >0.90). When incorporated into multivariable models, sEng and IL18BP improved the diagnostic accuracy of clinical information alone. Conclusions These results suggest that host biomarkers may have utility in differentiating between dengue and leptospirosis, clinically similar conditions of different etiology. [ABSTRACT FROM AUTHOR]

Background: HIV-1-related inflammation is associated with increased levels of biomarkers of vascular adhesion and endothelial activation, and may increase production of the inflammatory protein angiopoietin-2 (ANG-2), an adverse prognostic biomarker in severe systemic infection. We hypothesized that antiretroviral therapy (ART) initiation would decrease endothelial activation, reducing plasma levels of ANG-2. Methods: Antiretroviral-naïve Kenyan women with advanced HIV infection were followed prospectively. Endothelial activation biomarkers including soluble intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, and plasma ANG-2 and angiopoietin-1 (ANG-1) were tested in stored plasma samples from 0, 6, and 12 months after ART initiation. We used Wilcoxon matched-pairs signed rank tests to compare endothelial activation biomarkers across time-points, generalized estimating equations to analyze associations with change in log10-transformed biomarkers after ART initiation, and Cox proportional-hazards regression to analyze associations with mortality. Results: The 102 HIV-1-seropositive women studied had advanced infection (median CD4 count, 124 cells/μL). Soluble ICAM-1 and plasma ANG-2 levels decreased at both time-points after ART initiation, with concomitant increases in the beneficial protein ANG-1. Higher ANG-2 levels after ART initiation were associated with higher plasma HIV-1 RNA, oral contraceptive pill use, pregnancy, severe malnutrition, and tuberculosis. Baseline ANG-2 levels were higher among five women who died after ART initiation than among women who did not (median 2.85 ng/mL [inter-quartile range (IQR) 2.47-5.74 ng/mL] versus median 1.32 ng/mL [IQR 0.35-2.18 ng/mL], p = 0.01). Both soluble ICAM-1 and plasma ANG-2 levels predicted mortality after ART initiation. Conclusions: Biomarkers of endothelial activation decreased after ART initiation in women with advanced HIV-1 infection. Changes in plasma ANG-2 were associated with HIV-1 RNA levels over 12 months of follow-up. Soluble ICAM-1 and plasma ANG-2 levels represent potential biomarkers for adverse outcomes in advanced HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: The incidence and mortality from necrotizing fasciitis (NF) are increasing in New Zealand (NZ). Triggered by a media report that traditional Samoan tattooing was causing NF, we conducted a chart review to investigate the role of this and other predisposing and precipitating factors and to document NF microbiology, complications and interventions in NZ. Methods: We conducted a retrospective review of 299 hospital charts of patients discharged with NF diagnosis codes in eight hospitals in NZ between 2000 and 2006. We documented and compared by ethnicity the prevalence of predisposing and precipitating conditions, bacteria isolated, complications and interventions used. Results: Out of 299 charts, 247 fulfilled the case definition. NF was most common in elderly males. Diabetes was the most frequent co-morbid condition, followed by obesity. Nearly a quarter of patients were taking non-steroidal anti-inflammatory drugs (NSAID). Traditional Samoan tattooing was an uncommon cause. Streptococcus pyogenes and Staphylococcus aureus were the two commonly isolated bacteria. Methicillin-resistant Staphylococcus aureus was implicated in a relatively small number of cases. Shock, renal failure, coagulation abnormality and multi-organ dysfunction were common complications. More than 90% of patients underwent surgical debridement, 56% were admitted to an intensive care unit (ICU) and slightly less than half of all patients had blood product transfusion. One in six NF cases had amputations and 23.5% died. Conclusion: This chart review found that the highest proportion of NF cases was elderly males with co-morbidities, particularly diabetes and obesity. Tattooing was an uncommon precipitating event. The role of NSAID needs further exploration. NF is a serious disease with severe complications, high case fatality and considerable use of health care resources. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of acquiring fungal infections. Antifungal prophylaxis shortly after transplantation is therefore indicated, but data for pediatric patients under 12 years of age are scarce. To address this issue, we retrospectively assessed the safety, feasibility, and initial efficacy of prophylactic posaconazole in children. Methods: 60 consecutive pediatric patients with a median age of 6.0 years who underwent allogeneic HSCT between August 2007 and July 2010 received antifungal prophylaxis with posaconazole in the outpatient setting. 28 pediatric patients received an oral suspension at 5 mg/kg body weight b.i.d., and 32 pediatric patients received the suspension at 4 mg/kg body weight t.i.d. The observation period lasted from start of treatment with posaconazole until its termination (maximum of 200 days post-transplant). Results: Pediatric patients who received posaconazole at 4 mg/kg body weight t.i.d. had a median trough level of 383 µg/L. Patients who received posaconazole at 5 mg/kg body weight b.i.d. had a median trough level of 134 µg/L. Both regimens were well tolerated without severe side effects. In addition, no proven or probable invasive mycosis was observed. Conclusion: Posaconazole was a well-tolerated, safe, and effective oral antifungal prophylaxis in pediatric patients who underwent high-dose chemotherapy and HSCT. Posaconazole at a dosage of 12 mg/kg body weight divided in three doses produced consistently higher morning trough levels than in patients who received posaconazole 5 mg/kg body weight b.i.d. Larger prospective trials are needed to obtain reliable guidelines for antifungal prophylaxis in children after HSCT. [ABSTRACT FROM AUTHOR]

Background: Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear. Methods: In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined. Results: The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation. Conclusions: Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous downregulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important coinfection. [ABSTRACT FROM AUTHOR]

Background: Until now, the prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) infection among adult patients has been low, and severe MP pneumonia due to a macrolide-resistant strain has seldom been reported. Here, we describe a rare case of severe life-threatening MP pneumonia due to a macrolide-resistant strain in an adult, which was finally treated with fluoroquinolone and tetracycline after failed treatment with macrolide and corticosteroid.Case Presentation: A 39-year-old apparently healthy woman complained of fever and productive cough. Three days after onset, she was admitted to a local general hospital. On admission, her vital signs were stable except for high-grade fever. The patient's chest X-ray and chest computed tomography images revealed subsegmental consolidation in her right lower lobe. Treatment with ampicillin/sulbactam, and azithromycin were initiated under a clinical diagnosis of community-acquired pneumonia. After treatment initiation, her fever had not subsided, and the pulmonary lesion had extended to the entire lower lobe. Thus, treatment with prednisolone as steroid pulse therapy was initiated from clinical day 7. However, neither her symptoms nor her pulmonary lesion improved; therefore, she was transferred to our hospital for further examination and treatment. On admission (clinical day 14), her indirect hemagglutination titer for MP was elevated at 1:2560, and bronchoalveolar fluid examination yielded positive results for the mycoplasma antigen. Based on these clinical findings, we confirmed a case of severe life-threatening MP pneumonia. Since her respiratory condition was extremely severe, we initiated levofloxacin and tetracycline. Two days later (clinical day 16), her fever, malaise, and hypoxia resolved, and her pulmonary lesions had significantly improved. Further molecular identification yielded the DNA of MP from her bronchoalveolar fluid, and mutation of A2063G in the 23S rRNA gene was revealed. Based on these results and the clinical course, we confirmed our case as severe MP pneumonia due to a macrolide-resistant strain.Conclusion: More awareness is needed on the emergence of macrolide-resistant MP infection in adults, because severe infection could develop despite initial treatment with macrolide and steroid therapy, which are generally considered as standard therapy for MP. [ABSTRACT FROM AUTHOR]

Background: It is difficult to diagnose ascites infection early in cirrhotic patients. The present study was to create and evaluate a new bioscore combined with PCT, sNFI and dCHC in the diagnosis of ascites infection in cirrhotic patients.Methods: Two hundred and fifty-nine consecutive patients were enrolled; of which 51 patients were culture-positive spontaneous bacterial peritonitis (culture-positive SBP) and 58 patients were culture-negative SBP. The efficacy of procalcitonin(PCT), c-reactive protein (CRP), white blood cell (WBC), mean fluorescence intensity of mature neutrophils(sNFI) and difference in hemoglobin concentration between newly formed and mature red blood cells(dCHC) for diagnosing ascites infection was examined. These parameters were used to create a scoring system. The scoring system was analyzed by logistic regression analysis to determine which parameters were statistically different between ascites infection and non-ascites infection patients. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic ability of bioscore for ascites infection.Results: In ROC analysis, the area under the curves (AUC) for PCT was 0.852 (95% CI 0.803-0.921, P < 0.001), dCHC 0.837 (95% CI 0.773-0.923, P < 0.001), CRP 0.669 (95% CI 0.610-0.732, P = 0.0624), sNFI 0.838 (95% CI 0.777-0.903, P < 0.001), and WBC 0.624 (95% CI 0.500-0.722, P = 0.0881). Multivariate analysis revealed PCT, dCHC and sNFI to be statistically significant. The combination of these three parameters in the bioscore had an AUC of 0.937 (95% CI 0.901-0.994, P < 0.001). A bioscore of ≥3.40 was considered to be statistically significant in making a positive diagnosis of ascites infection. In different groups of ascites infection, bioscore also shown a high diagnostic value of AUC was 0.947(95% CI 0.882-0.988, P < 0.001) and 0.929 (95% CI 0.869-0.974, P < 0.001) for culture-positive SBP and culture-negative SBP group respectively.Conclusion: The composite markers of combining PCT, dCHC and sNFI could be a valuable diagnostic score to early diagnose ascites infection in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Early antiretroviral therapy (ART) initiation is crucial to achieve HIV viral suppression and reduce transmission. HIV-infected Chinese men who have sex with men (MSM) were less likely to initiate ART than other HIV-infected individuals. We assessed predictors of ART initiation among Chinese MSM.Methods: In 2010-2011, a cross-sectional study was conducted among MSM in Beijing, China. We examined ART initiation within the subgroup who were diagnosed with HIV infection prior to participation in the survey. Logistic regression models were fitted to evaluate socio-demographic and behavioral factors associated with ART initiation. The eligibility criterion in the 2010/2011 national HIV treatment guidelines was CD4 cell count <350 cells/μL or World Health Organization (WHO) clinical stage III/IV.Results: Of 238 eligible HIV-infected participants, the median duration of HIV infection was 15 months (range: 31 days-12 years); 62 (26.1 %) had initiated ART. Among 103 men with CD4 counts <350 cells/μL, 38 (36.9 %) initiated ART. Being married to a woman (adjusted odd ratios [aOR]: 2.50; 95 % confidence interval [CI]: 1.07-5.87), longer duration of HIV infection (aOR: 10.71; 95 % CI: 3.66-31.32), and syphilis co-infection (aOR: 2.58; 95 % CI: 1.04-6.37) were associated with a higher likelihood of ART initiation. Of 135 men with CD4 count ≥350 cells/μL, 24 (18 %) initiated ART. Being married to a woman (aOR: 4.21; 95 % CI: 1.60-11.06), longer duration of HIV infection (aOR: 22.4; 95 % CI: 2.79-180), older age (aOR: 1.26; 95 % CI: 1.1-1.44), Beijing Hukou (aOR: 4.93; 95 % CI: 1.25-19.33), presence of AIDS-like clinical symptoms (aOR: 3.97; 95 % CI: 1.32-14.0), and history of sexually transmitted infections (aOR: 4.93; 95 % CI: 1.25-19.43) were associated with ART initiation. Compared with men who did not initiated ART, those with ART were more likely to receive counseling on benefits of ART (96.8 % vs. 66.4 %, P = 0 < 0.01), HIV stigma coping strategy (75.8 % vs. 65.9 %, P = 0.04), mental health (66.1 % vs. 52.9 %, P = 0.02), and substance use (46.7 % vs. 36.6 %, P = 0.04).Conclusions: We documented low rates of ART initiation among Chinese MSM. Policy changes for expanding ART eligibility and interventions to improve the continuum of HIV care are in progress in China. Impact evaluations can help assess continuing barriers to ART initiation among MSM. [ABSTRACT FROM AUTHOR]