Does Prolonged Initial Empirical Antibiotics Treatment Increase Morbidity and Mortality in Preterm Infants <34 Weeks?

Background: Antibiotics are commonly used in the early postnatal period in preterm infants; its overuse can affect gut colonization and increased the risk of invasive infection. Aims: This study aims to determine whether the prolonged initial empirical antibiotic treatment (PIEAT) increased the risk of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and death in preterm infants <34 weeks. The secondary study objective was to reveal if severity of illness and sepsis laboratory tests were potential causes for PIEAT. Design: The study was a retrospective study. Setting: This study was conducted at three Neonatal Intensive Care Units (NICUs). Materials and Methods: NICUs medical records from January 2013 to March 2017. Inclusion criteria: (1) preterm infants < 34 weeks, (2) antibiotics started in the 1st postnatal day, (3) negative initial blood culture, (4) patients survived >= 5 days, (5) patients free of NEC in the first 4 postnatal days, and (6) patients without major congenital anomalies. Statistical Analysis: Logistic regression analysis. Results: Five hundred and eighty-seven neonates were eligible. Mean gestational age +/- standard deviation (SD): 31.1 +/- 2.8 weeks. Mean birth weight +/- SD: 1440 +/- 380 g. Mean of the duration of initial empirical antibiotic treatment +/- SD: 7 +/- 3.6 days. PIEAT increased the risk of NEC (odds ratio [OR]: 1.11, confidence interval [CI]: 1.011-1.219), and LOS (OR: 1.133 CI: 1.027-1.251). PIEAT did not significantly increase mortality (OR: 1.083 CI: 0.82-1.42). Sepsis laboratory tests that predicted PIEAT were abnormal leukocytes counts (OR: 1.078 CI: 1.012-1.167) and positive C-reactive protein (CRP) (OR: 1.15 CI: 1.036-1.277). The indicators of severity of illness, high-frequency oscillation ventilation (OR: 0.956 CI. 826-1.106), and inotrope use (OR: 1.108 CI: 0.95-1.22) did not predict PIEAT. Conclusion: PIEAT >= 4 days for suspected early-onset sepsis with negative initial blood culture increased the risk of NEC and LOS in preterm infants < 34 weeks. Abnormal white blood cell count, thrombocytopenia, and positive CRP in the first 4 days with negative initial blood culture were potential causes of PIEAT.