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).

In order to review the epidemiology of Gram-negative infections in the pediatric and neonatal intensive care units (PICUs and NICUs) of Latin America a systematic search of PubMed and targeted search of SciELO was performed to identify relevant articles published since 2005. Independent cohort data indicated that overall infection rates were higher in Latin American PICUs and NICUs versus developed countries (range, 5%–37% vs 6%–15%, respectively). Approximately one third of Latin American patients with an acquired PICU or NICU infection died, and crude mortality was higher among extremely low-birth-weight infants and those with an infection caused by Gram-negative bacteria. In studies reporting > 100 isolates, the frequency of Gram-negative pathogens varied from 31% (Colombia) to 63% (Mexico), with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli the predominant pathogens in almost all countries, and Acinetobacter spp. and Serratia spp. isolated sporadically. The activity of quinolones and third-generation cephalosporins against P. aeruginosa, Acinetobacter spp., and Enterobacteria was seriously compromised, coincident with a high prevalence of circulating extended-spectrum β-lactamases. Furthermore, we identified two observational studies conducted in Chile and Brazil reporting infections by P. aeruginosa and Acinetobacter baumannii in PICUs, demonstrating resistance to carbapenems, and two outbreaks of carbapenem-resistant K. pneumoniae in Colombia and Brazil. The endemicity of multidrug-resistant Gram-negative infections in Latin American PICUs and NICUs is punctuated by intermittent clonal outbreaks. The problem may be alleviated by ensuring ICUs are less crowded, increasing staffing levels of better-trained health care personnel, and implementing antimicrobial stewardship and surveillance programs.

Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group.

To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010. A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis. Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%–44.6% of all IPD in children under 5 yrs. PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.

Household contacts are important sources of Bordetella pertussis in infants. A total of 353 household contacts of 97 index cases were evaluated for pertussis by culture and polymerase chain reaction. Twenty eight contacts were positive (8.0%). The presence of symptoms did not influence the rate of diagnosed bacteriologic pertussis in communicants. We conclude that contacts with an index case can be positive for B. pertussis independently of the presence of symptoms.

Summary Objectives It is well established that respiratory viruses are an important cause of hospitalizations in young children worldwide, but data are limited on the contribution of specific viruses to severe illness in South America. We describe clinical and laboratory findings from prospective surveillance for acute respiratory infections at a tertiary hospital in São Paulo, Brazil. Methods We screened children < 2 years old with acute respiratory tract infections admitted to an urban tertiary hospital for respiratory viruses from March 2008 through February 2010, using polymerase chain reaction assays. Results Respiratory viruses were identified in 378 (53%) of the 715 samples analyzed. Respiratory syncytial virus was the most commonly identified virus (52%), followed by adenovirus (27%) and Human metapneumovirus (12%). More than one virus was identified in 19% of specimens. Almost half of the samples (46%) were from children with underlying health conditions. We demonstrated that compared to the previously healthy group, those with comorbidities had a worse outcome in terms of severity, with prolonged hospital stay and more need of intensive care. Conclusion Identification of this high-risk population along with strategies for fast diagnosis might each help to reduce morbidity and mortality in this group.