Background There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1—Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2—“Low” Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3—“Medium” Watch), 18.0% (n = 566) started a carbapenem (Group 4—“High” Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration ClinicalTrials.gov, (NCT03721302).

Annealing study of amorphous bulk and nanoparticle iron at temperatures from 500 K to 1000 K has been carried out using molecular dynamics (MD) simulations. The simulation is performed for models containing 104 particles Fe at both crystalline and amorphous states. We determine changes of the potential energy, pair radial distribution function (PRDF) and distribution of coordination number (DCN) as a function of annealing time. The calculation shows that the aging slightly reduces the potential energy of system. This result evidences that the amorphous sample undergoes different quasi-equilibrated states during annealing. Similar trend is observed for nanoparticles sample. When the samples are annealed at high temperatures we observe the crystallization in both bulk and nanoparticle. In particular, the system undergoes three stages. At first stage the relaxation proceeds slowly so that the energy of system slightly decreases and the samples structure remains amorphous. Within second stage a structural transformation occurs which significantly changes PRDF and DCN for the relatively short time. The energy of the system is dropped considerably and the amorphous structure transforms into the crystalline. Finally, the crystalline sample undergoes the slow relaxation which reduces the energy of system and eliminates structural defects in crystal lattices.

Objective: Data on the management and outcomes of acute myocarditis treated with extracorporeal membrane oxygenation (ECMO) among low- and middle-income countries are limited. This study aimed to determine the short-term outcomes and also identify factors associated with ECMO use among children with acute myocarditis at a tertiary children's hospital in Vietnam.Methods: A single-center, retrospective observational study was conducted between January 2016 and February 2021. Pediatric patients with acute myocarditis, aged 1 month to 16 years, were included.Results: In total, 54 patients (male, 46%; median age, 7 years) with acute myocarditis were included; 37 of them received ECMO support. Thirty percent (16/54) of the patients died, and 12 of them received ECMO. Laboratory variables that differed between survivors and non-survivors included median left ventricular ejection fraction (LVEF) at 48 h (42 vs. 25%; p = 0.001), platelet count (304 g/L [interquartile range (IQR): 243–271] vs. 219 g/L [IQR: 167–297]; p = 0.014), and protein (60 g/dl [IQR: 54–69] vs. 55 [IQR: 50–58]; p = 0.025). Among patients who received ECMO, compared with the survivors, non-survivors had a low LVEF at 48 h (odds ratio (OR), 0.8; 95% confidence interval (CI): 0.6–0.9; p = 0.006) and high vasoactive-inotropic score (OR, 1.0; 95% CI: 1.0–1.0; p = 0.038) and lactate (OR, 2.8; 95% CI, 1.2–6.1; p = 0.013) at 24 h post-ECMO.Conclusions: The case fatality rate among children with acute myocarditis was 30 and 32% among patients requiring ECMO support. Arrhythmia was an indicator for ECMO in patients with cardiogenic shock.

Background Sepsis severity scores are used in clinical practice and trials to define risk groups. There are limited data to derive hospital-based sepsis severity scores for neonates and young infants in high-burden low- and middle-income country (LMIC) settings where trials are urgently required. We aimed to create linked sepsis severity and recovery scores applicable to hospitalized neonates and young infants in LMIC which could be used to inform antibiotic trials. Methods & Findings A prospective observational cohort study was conducted across 19 hospitals in 11 countries in sub-Saharan Africa, Asia, Latin America and Europe. Infants aged <60 days with clinical sepsis fulfilling at least two clinical or laboratory criteria (≥1 clinical) were enrolled. Primary outcome was 28-day mortality. Two prediction models were developed for 1) 28-day mortality from factors at sepsis presentation (baseline NeoSep Severity Score), and 2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. 3204 infants were enrolled between 2018-2020. Median age was 5 days (IQR 2-15), 90.4% (n=2,895) were <28 days. Median birth weight was 2500g (1400-3000g), and a median of 4 clinical (IQR 2-5) and 1 laboratory (0-2) signs were present. Overall mortality was 11.3% (95%CI 10.2-12.5%; n=350). A baseline NeoSep Severity Score from infants characteristics, respiratory support, and clinical signs (no laboratory tests) at presentation had a C-index 0.77 (95%CI: 0.75-0.80) and 0.76 (0.69-0.82) in derivation and validation samples, respectively. Mortality in the validation sample was 1.6% (3/189; 95%CI: 0.5-4.6%), 11.0% (27/245; 7.7-15.6%), and 27.3% (12/44; 16.3-41.8%) in low (score 0-4), medium (5-8) and high (9-16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score based on evolving post-baseline clinical signs and supportive care discriminated well between infants who died or survived the following day or subsequent few days. The area under the ROC curve for score on day 2 and death in the following 5 days was 0.82 (95%CI 0.78-0.85) and 0.85 (95%CI 0.78-0.93) in the derivation and validation data, respectively. Conclusion The baseline NeoSep Severity Score predicted 28-day mortality and could identify infants with high risk of mortality for inclusion in hospital-based sepsis trials. The NeoSep Recovery Score predicts day-by-day inpatient mortality and could, with further validation, help to identify poor response to antibiotics.

Pertussis is an infectious disease that causes epidemics and outbreaks and is associated with a high mortality rate, especially in infants, in both developed and developing countries. We aimed to characterize infants with pertussis with respiratory failure and shock and investigated the factors related to mortality.