Pathogen Distribution and Antimicrobial Resistance of Early Onset Sepsis in Very Premature Infants: A Real-World Study.

INTRODUCTION: Early onset sepsis (EOS) remains a potentially fatal newborn condition, especially in very preterm infants. Data on the pathogen distribution and antibiotic susceptibility patterns of EOS among very preterm infants are scarce but essential for the choice of empirical antibiotic administration. We sought to assess the epidemiologic characteristics and antibiotic susceptibility patterns of pathogens causing EOS among a cohort of very preterm infants in China. METHODS: This prospective, observational study included a cohort of infants born at a gestational age (GA) less than 32 weeks of 32 newborn intensive care units (NICUs) in China between January 1, 2018 and December 31, 2020. EOS was defined by isolation of pathogenic species from blood culture within 72 h of birth. RESULTS: A total of 108 EOS cases (18.4 per 1000 admissions) were identified among 5865 very preterm infants. Incidence of EOS increased with the decrease of GA and birthweight. Escherichia coli (n = 44, 40.7%) was the most common pathogen, followed by Klebsiella spp. (n = 10, 9.3%). The distribution and proportion of pathogenic bacteria varied significantly by GA. E. coli and Klebsiella spp. showed high resistance to ampicillin and third-generation cephalosporins, while they showed good susceptibility to carbapenem antibiotics and piperacillin-tazobactam. CONCLUSION: Our data demonstrated that pathogens causing neonatal EOS showed high rates of resistance to ampicillin and third-generation cephalosporins. This raised questions about the best empirical antibiotic choice for preterm infants suspected of having EOS in low- and middle-income countries (LMICs).

Association Between Antibiotic Overexposure and Adverse Outcomes in Very-Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis: A Multicenter Prospective Study.

OBJECTIVES: To explore the associations between higher antibiotic use rates (AURs) and adverse outcomes in very-low-birth-weight (VLBW) infants without culture-proven sepsis or necrotizing enterocolitis (NEC) in a multicenter of China. METHODS: A prospective cohort study was performed on VLBW infants admitted to 24 neonatal intensive care units from January 1, 2018, to December 31, 2018. AUR was calculated as calendar days of antibiotic therapy divided by total hospital days. The composite primary outcome was defined as mortality or severe morbidity, including any of the following: severe neurologic injury, bronchopulmonary dysplasia (BPD), and stage 3 or higher retinopathy of prematurity. RESULTS: A total of 1,034 VLBW infants who received antibiotics without culture-proven sepsis or NEC were included in this study. The overall AUR of eligible VLBW infants was 55%, and the AUR of each eligible VLBW infant ranged from 3 to 100%, with a median of 56% (IQR 33%, 86%). After generalized propensity score and logistic regression analysis of 4 groups of VLBW infants with different AUR range, infants in the higher quartile AUR, (Q3, 0.57~0.86) and (Q4, 0.87~1.00), had higher odds of composite primary outcome (adjusted OR: 1.81; 95% CI: 1.23-2.67; adjusted OR 2.37; 95% CI: 1.59-3.54, respectively) and BPD (adjusted OR: 3.09; 95% CI: 1.52-6.57; adjusted OR 3.17; 95% CI: 1.56-6.57, respectively) than those in the lowest AUR (Q1). CONCLUSIONS: Antibiotic overexposure in VLBW infants without culture-proven sepsis or NEC was associated with increased risk of composite primary outcome and BPD. Rational empirical antibiotic use in VLBW infants is urgently needed in China.

Association between admission hypothermia and outcomes in very low birth weight infants in China: a multicentre prospective study.

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.

Dynamic Change of Thyroid Hormones With Postmenstrual Age in Very Preterm Infants Born With Gestational Age <32 Weeks: A Multicenter Prospective Cohort Study.

Background: At present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries. Objectives: To investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA) <32 weeks and to derive thyroid function reference charts based on PMA. Methods: A prospective cohort study was performed on VPIs born with GA<32 weeks and born in or transferred to the 27 neonatal intensive care units from January 1, 2019 to December 31, 2019. Serial TSH and FT4 values were measured at the end of each week during the first month after birth and also at PMA36 weeks, PMA40 weeks and at discharge, respectively. The 2.5th, 5th, 50th, 95th, and 97.5th percentiles of TSH and FT4 of different PMA groups were calculated to draw the percentile charts based on PMA. Results: 1,093 preterm infants were included in this study. The percentile charts of TSH and FT4 levels based on PMA were drawn respectively, and the result indicated that the percentile charts of TSH values were gradually increased initially and then decreased with increasing PMA. The 97.5th percentile chart reached the peak at PMA30 weeks (17.38µIU/ml), and then decreased gradually, reaching the same level as full-term infants (9.07µIU/ml) at PMA38-40 weeks. The 2.5th percentile chart of FT4 was at its lowest point at PMA26-27 weeks (5.23pmol/L), then increased slowly with PMA and reached the same level as full-term infants at PMA38-40 weeks (10.87pmol/L). At PMA36 weeks, the reference intervals of the 2.5th to 97.5th percentiles of TSH and FT4 were 1.18-12.3µIU/ml and 8.59-25.98pmol/L, respectively. Conclusion: The percentile charts of TSH and FT4 in VPIs showed characteristic change with PMA. The results prompt that age-related cutoffs, instead of a single reference range, might be more useful to explain the thyroid function of VPIs. And repeated screening is necessary for preterm infants.