Oral antibiotics for neonatal infections: a systematic review and meta-analysis

BACKGROUND: Worldwide many neonates suffer from bacterial infections. Adequate treatment is important but is associated with prolonged hospitalization for intravenous administration. In older children, oral switch therapy has been proven effective and safe for several indications and is now standard care. OBJECTIVES: To evaluate the currently available evidence on pharmacokinetics, safety and efficacy of oral antibiotics and oral switch therapy in neonates (0-28 days old). METHODS: We performed systematic searches in Medline, Embase.com, Cochrane, Google Scholar and Web of Science. Studies were eligible if they described the use of oral antibiotics in neonates (0-28 days old), including antibiotic switch studies and pharmacological studies. RESULTS: Thirty-one studies met the inclusion criteria. Compared with parenteral administration, oral antibiotics generally reach their maximum concentration later and have a lower bioavailability, but in the majority of cases adequate serum levels for bacterial killing are reached. Furthermore, studies on efficacy of oral antibiotics showed equal relapse rates (OR 0.95; 95% CI 0.79-1.16; I2 0%) or mortality (OR 1.11; 95% CI 0.72-1.72; I2 0%). Moreover, a reduction in hospital stay was observed. CONCLUSIONS: Oral antibiotics administered to neonates are absorbed and result in adequate serum levels, judged by MICs of relevant pathogens, over time. Efficacy studies are promising but robust evidence is lacking, most importantly because in many cases clinical efficacy and safety are not properly addressed. Early oral antibiotic switch therapy in neonates could be beneficial for both families and healthcare systems. There is a need for additional well-designed trials in different settings.status: publishe

Chorioamnionitis Alters the Response to Surfactant in Preterm Infants

Objective To study the association between antenatal exposure to chorioamnionitis and the neonatal response to surfactant. Study design Prospective observational cohort of 301 preterm infants of gestational age Results Compared with HC- infants, HC + F+ infants had significantly greater FiO(2) requirement and prolonged time to extubation postsurfactant, not accounted for by differences in gestational age and birth weight. Infants with BPD/death had a strikingly similar pattern of increased FiO(2) requirement postsurfactant. Moreover, in infants who received surfactant, HC + F+ status was associated with increased risk for BPD (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.02-11.3; P = .047) and for BPD/death (OR = 2.72; 95% CI = 1.00-7.42; P = .049). Conclusions An impaired surfactant response was observed in preterm infants with severe chorioamnionitis and may be involved in the association between chorioamnionitis, mechanical ventilation, and the development of BPD. (J Pediatr 2010; 156: 10-5)

Early Postnatal Blood Pressure in Preterm Infants: Effects of Chorioamnionitis and Timing of Antenatal Steroids

Previous studies suggest postnatal blood pressure in preterm infants to be decreased by chorioamnionitis and increased by antenatal steroids (AS). We examined the adjusted effects of both antenatal modulators on postnatal blood pressure (BP), with separate effects reported for histologic chorioamnionitis with or without fetal involvement and timing of AS. General characteristics, BP, and heart rate values during the first 72 h after birth were obtained from 271 infants with gestational ag

Early Postnatal Blood Pressure in Preterm Infants:Effects of Chorioamnionitis and Timing of Antenatal Steroids

Previous studies suggest postnatal blood pressure in preterm infants to be decreased by chorioamnionitis and increased by antenatal steroids (AS). We examined the adjusted effects of both antenatal modulators on postnatal blood pressure (BP), with separate effects reported for histologic chorioamnionitis with or without fetal involvement and timing of AS. General characteristics, BP, and heart rate values during the first 72 h after birth were obtained from 271 infants with gestational ag

Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: a quasi-experimental study

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran (R)) on the primary outcome 'NEC or death'. Preterm infants (gestational ag

RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection

INTRODUCTION: High morbidity and mortality rates of proven bacterial infection are the main reason for substantial use of intravenous antibiotics in neonates during the first week of life. In older children, intravenous-to-oral switch after 48 hours of intravenous therapy has been shown to have many advantages and is nowadays commonly practised. We, therefore, aim to evaluate the effectiveness, safety and cost-effectiveness of an early intravenous-to-oral switch in neonates with a probable bacterial infection. METHODS AND ANALYSIS: We present a protocol for a multicentre randomised controlled trial assessing the non-inferiority of an early intravenous-to-oral antibiotic switch compared with a full course of intravenous antibiotics in neonates (0-28 days of age) with a probable bacterial infection. Five hundred and fifty patients will be recruited in 17 hospitals in the Netherlands. After 48 hours of intravenous treatment, they will be assigned to either continue with intravenous therapy for another 5 days (control) or switch to amoxicillin/clavulanic acid suspension (intervention). Both groups will be treated for a total of 7 days. The primary outcome will be bacterial (re)infection within 28 days after treatment completion. Secondary outcomes are the pharmacokinetic profile of oral amoxicillin/clavulanic acid, the impact on quality of life, cost-effectiveness, impact on microbiome development and additional yield of molecular techniques in diagnosis of probable bacterial infection. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of the Erasmus Medical Centre. Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03247920.status: publishe

Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Background: Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis. Methods: The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia). Results: A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support. Conclusions: Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy