Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

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).

Pertussis Infants Needing Mechanical Ventilation and Extracorporeal Membrane Oxygenation: Single-Center Retrospective Series in Vietnam.

OBJECTIVES: 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. DESIGN: A retrospective, observational study conducted between January 2015 and October 2020. SETTING: This study was conducted at the Vietnam National Children's Hospital, which is a government hospital that serves as a tertiary care center in Hanoi, Vietnam. PATIENTS: Children who fulfilled the following inclusion criteria were included: 1) admitted to the PICU, 2) less than 16 years old, 3) pertussis confirmed by real-time polymerase chain reaction, and 4) treated with mechanical ventilation due to respiratory failure and shock. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Seventy-three mechanically ventilated children (40 boys; median age, 56 d), whereas 19 patients received extracorporeal membrane oxygenation support. Twenty-six patients (36%) died including 12 who received extracorporeal membrane oxygenation. Those who received extracorporeal membrane oxygenation support had higher leukocyte counts upon admission and were more frequently diagnosed with pulmonary hypertension and stage 3 acute kidney injury. Compared with survivors, nonsurvivors showed increased heart rates, leukocyte and neutrophil counts, and lower systolic and diastolic blood pressure at admission. Increased Vasoactive-Inotropic Score, stage 3 acute kidney injury, fluid overload, the use of renal replacement therapy, and extracorporeal membrane oxygenation use were prevalent among nonsurvivors. CONCLUSIONS: In this study, around one third of mechanically ventilated patients with pertussis died. Those who received extracorporeal membrane oxygenation had higher leukocyte counts, a higher prevalence of pulmonary hypertension, and advanced stages of acute kidney injury. Higher Vasoactive-Inotropic Score and advanced stages of acute kidney injury were associated with a greater risk of mortality.

Pediatric Acute Myocarditis With Short-Term Outcomes and Factors for Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study in Vietnam.

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.