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

Abstract

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.

Restrictive Use of Empirical Antibiotics Is Associated with Improved Short Term Outcomes in Very Low Birth Weight Infants: A Single Center, Retrospective Cohort Study from China

“…This is consistent with the authors’ previous report that in VLBW infants the total antibiotic use accounted for more than half of their entire hospital stay (mean AUR > 50%) in 24 NICUs of Hunan Province [ 9 ]. Similarly, Hou SS et al [ 19 ] reported an AUR of 56% in VLBW infants from 24 NICUs of the Northern China Neonatal Network. In the United States, Flannery et al [ 20 ] collected data from 297 NICUs and found that 78.6% of VLBW infants had early antibiotic initiation.…”

Prevalence, Prevention and Management of Bronchopulmonary Dysplasia

“…218 The combination of dysbiosis and hyperoxia has also been linked to more severe disturbances in lung architecture in animal models. 219,220 Exposure to antibiotics both in the first week of life 221,222 and throughout the NICU stay 119 is associated with BPD, with evidence of a dose-response relationship. 119 Significantly higher odds of moderate-severe BPD were noted in a cohort of infants <32 weeks GA without risk factors for infection who were exposed to antibiotics within the 24 hr of life (OR: 2.30, 95% CI: 1.21-4.38).…”

“…219,220 Exposure to antibiotics both in the first week of life 221,222 and throughout the NICU stay 119 is associated with BPD, with evidence of a dose-response relationship. 119 Significantly higher odds of moderate-severe BPD were noted in a cohort of infants <32 weeks GA without risk factors for infection who were exposed to antibiotics within the 24 hr of life (OR: 2.30, 95% CI: 1.21-4.38). 108 These results suggest that movement towards a selective approach to early antibiotic treatment may be a more effective BPD preventive strategy.…”

“…Preterm infants remain at risk for sepsis, but antibiotics used in the absence of infection can increase risk for BPD119 I AStrongly consider discontinuing antibiotics at 48h if cultures are negative Nutrition Same as for early phase Methylxanthines Same as for early phase I A Established phase (>36 weeks PMA) Echocardiographic screening for BPD PH Ventilatory strategy 25% of infants with moderate or severe BPD have echocardiographic evidence of pulmonary hypertension 120 III A SIMV or NAVA modalities over HFOV III A Use large tidal volumes (8-15mL/kg), long I-time (0.5-1s), low respiratory rates (12-20 per minute), high PEEP (8-12 cmH 2 O) Wean slowly, with goals to reduce work of breathing, improve growth and participation in developmental therapies 33 Abbreviations: nCPAP, nasal continuous positive airway pressure; FiO 2 , fraction of inspired oxygen; PEEP, positive end-expiratory pressure; InSurE, intubation, surfactant administration, extubation; LISA, less invasive surfactant administration; TV, tidal volume; BPD, bronchopulmonary dysplasia; IVH, intraventricular hemorrhage; PIP, peak inspiratory pressure; NIPPV, nasal intermittent positive pressure ventilation; SIP, spontaneous intestinal perforation; NDI, neurodevelopmental impairment; CP, cerebral palsy; RSV, respiratory syncytial virus, FRC, functional residual capacity; NIV-NAVA, non-invasive ventilation-neurally adjusted ventilatory assist. https://doi.org/10.2147/RRN.S405985 DovePress Research and Reports in Neonatology 2024:14…”

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies

“…The only indication for neonatal antibiotic use remains infection and sepsis [ 251 ]. Based on a novel multicenter prospective study, antibiotic overexposure triples the risk of BPD [ 252 ]. After exposure of human bronchial epithelioid cells to mechanical stretch, IL-13, metalloprotein-9, and transient receptor potential canonical 1 (TRCP1) are significantly increased within half an hour of the initiation of stretch stress [ 253 ].…”