Anthony C. Ryan

Identification of aminoglycoside and β-lactam resistance genes from within an infant gut functional metagenomic library.

The infant gut microbiota develops rapidly during the first 2 years of life, acquiring microorganisms from diverse sources. During this time, significant opportunities exist for the infant to acquire antibiotic resistant bacteria, which can become established and constitute the infant gut resistome. With increased antibiotic resistance limiting our ability to treat bacterial infections, investigations into resistance reservoirs are highly pertinent. This study aimed to explore the nascent resistome in antibiotically-naïve infant gut microbiomes, using a combination of metagenomic approaches. Faecal samples from 22 six-month-old infants without previous antibiotic exposure were used to construct a pooled metagenomic library, which was functionally screened for ampicillin and gentamicin resistance. Our library of ∼220Mb contained 0.45 ampicillin resistant hits/Mb and 0.059 gentamicin resistant hits/Mb. PCR-based analysis of fosmid clones and uncloned metagenomic DNA, revealed a diverse and abundant aminoglycoside and β-lactam resistance reservoir within the infant gut, with resistance determinants exhibiting homology to those found in common gut inhabitants, including Escherichia coli, Enterococcus sp., and Clostridium difficile, as well as to genes from cryptic environmental bacteria. Notably, the genes identified differed from those revealed when a sequence-driven PCR-based screen of metagenomic DNA was employed. Carriage of these antibiotic resistance determinants conferred substantial, but varied (2–512x), increases in antibiotic resistance to their bacterial host. These data provide insights into the infant gut resistome, revealing the presence of a varied aminoglycoside and β-lactam resistance reservoir even in the absence of selective pressure, confirming the infant resistome establishes early in life, perhaps even at birth.

Prolonged faecal excretion following a single dose of probiotic in low birth weight infants

Preterm infants at high risk of necrotizing enterocolitis are likely to be exposed to longer and more frequent courses of antibiotics, more frequent interruptions of feeds and slower acquisition of probiotics (1). Meta-analyses have shown significant reduction in the incidence of necrotising enterocolitis with the use of probiotics (2,3). However, these reviews suffer from significant heterogeneity and as of yet there is no consensus on the ideal probiotic or dosing regimen. While there have been some case reports of sepsis because of probiotics, these have tended to involve medically compromised children (4,5). One way to address these safety concerns would be to use a less frequent dosing regimen that had similar clinical benefits. As the neonatal gut is sterile at birth, with the microbiota being established early in life (6), we postulated that a single dose of probiotic given soon after birth may have a prolonged influence on the gut intestinal microbiota composition. This study was approved by the local ethics committee. Seven healthy low birth weight infants (<2500 g birth weight) admitted to the neonatal unit before the fourth day of life were enrolled following informed parental consent. The probiotic used in this study Lactobacillus paracasei NFBC 338 has been isolated from the neonatal intestinal tract (7). For this study, the probiotic was prepared at the concentration of 1 · 10 colony forming units (CFU) and stored at )22 C. On the fourth day of life, the probiotic was administered to the infant in their milk as a once off dose. Stool samples were collected at Days of life: 3 (control), 4, 5, 6, 7, 8, 9, 18 or until discharge from the neonatal unit and stored at 4 C until analysis. All samples were analysed within 12 h of collection. The outcome of this trial was stool probiotic counts. Faecal analysis consisted of culturedependent and culture-independent techniques as we have previously described (7). Table 1 summarizes patient characteristics. No adverse effects were observed with probiotic administration. No infant required antibiotic after probiotic administration. The average duration of stay in the neonatal unit was

Effects of Fractional Inspired Oxygen on Cerebral Oxygenation in Preterm Infants following Delivery

OBJECTIVES To explore regional cerebral oxygen saturations (rcSO2) in preterm neonates initially stabilized with 0.3 fractionated inspired oxygen (FiO2) concentrations. We hypothesized that those infants who received >0.3 FiO2 during stabilization following delivery would have relatively higher rcSO2 postdelivery compared with those stabilized with a lower FiO2. STUDY DESIGN A single center prospective observational study of 47 infants born before 32 weeks. Using near infrared spectroscopy, rcSO2 values were recorded immediately after birth. All preterm infants were initially given 0.3 FiO2 and were divided into 2 groups according to subsequent FiO2 requirements of either ≤0.3 or >0.3 FiO2. Using a mixed-effects model, we compared the difference between the groups over time. Also, the area measures below 55% (hypoxia) and above 85% (hyperoxia) were compared between the groups. RESULTS The mean (SD) gestation was 29.4 (1.6) weeks and the mean (SD) weight was 1.3 (0.4) kg. Less than one-half of the infants (20/45; 43%) required ≤0.3 FiO2. In the delivery suite, the median (IQR) rcSO2 in the low and high FiO2 groups were 81% (66%-86%) and 72% (62%-86%), respectively. Patients in the high FiO2 group had a larger rcSO2 area below 55% (P = .01). There was a significant difference in rcSO2 between the groups (P < .05), with the low group having higher rcSO2 values initially, but this difference changed over time. In the neonatal intensive care unit (NICU), rcSO2 values were lower by 7.1% (CI 12.13 to 2.06%) P = .008 in the high FiO2 group. CONCLUSIONS Infants given >0.3 FiO2 had more cerebral hypoxia than infants requiring ≤0.3 FiO2 but no difference in the degree of cerebral hyperoxia, both in the delivery suite and the NICU. This suggests that a more rapid increase in oxygen titration maybe be required initially for preterm infants.

Delivery room end tidal CO2 monitoring in preterm infants <32 weeks

Objectives To determine the feasibility of end tidal (EtCO2) monitoring of preterm infants in the delivery room, to determine EtCO2 levels during delivery room stabilisation, and to examine the incidence of normocapnia (5–8 kPa) on admission to the neonatal intensive care unit in the EtCO2 monitored group compared with a historical cohort without EtCO2 monitoring. Patients and methods Preterm infants (<32 weeks) were eligible for inclusion in this observational study. The evolution of EtCO2 values immediately after delivery was assessed and linear least-squares methods were used to fit a line to EtCO2 recordings. The partial pressure of CO2 in blood (PCO2) from the infants who received EtCO2 monitoring was compared with a historical cohort without EtCO2 monitoring. Results EtCO2 monitoring was feasible in the delivery room. EtCO2 values were successfully obtained in 39 (88.7%) of the 44 infants included in the study. EtCO2 gradually increased over the first 4 min. Intubated infants had higher EtCO2 values compared with infants who were not intubated, with median (IQR) values of 4.7 (3.3–8.4) kPa versus 3.2 (2.6–4.2) kPa (p=0.05). No difference was found between the proportions of PCO2 values within the range of normocapnia among infants who received EtCO2 monitoring compared with those who did not (56.8% vs 47.9%, p=0.396). Conclusions Delivery room EtCO2 monitoring is feasible and safe. EtCO2 values obtained after birth reflect the establishment of functional residual capacity and effective ventilation. The potential short-term and long-term consequences of EtCO2 monitoring should be established in randomised controlled trials.

Short-Term Effects of Phenobarbitone on Electrographic Seizures in Neonates

Background: Phenobarbitone is the most common first-line anti-seizure drug and is effective in approximately 50% of all neonatal seizures. Objective: To describe the response of electrographic seizures to the administration of intravenous phenobarbitone in neonates using seizure burden analysis techniques. Methods: Multi-channel conventional EEG, reviewed by experts, was used to determine the electrographic seizure burden in hourly epochs. The maximum seizure burden evaluated 1 h before each phenobarbitone dose (T-1) was compared to seizure burden in periods of increasing duration after each phenobarbitone dose had been administered (T+1, T+2 to seizure offset). Differences were analysed using linear mixed models and summarized as means and 95% CI. Results: Nineteen neonates had electrographic seizures and met the inclusion criteria for the study. Thirty-one doses were studied. The maximum seizure burden was significantly reduced 1 h after the administration of phenobarbitone (T+1) [-14.0 min/h (95% CI: -19.6, -8.5); p < 0.001]. The percentage reduction was 74% (IQR: 36-100). This reduction was temporary and not significant within 4 h of administrating phenobarbitone. Subgroup analysis showed that only phenobarbitone doses at 20 mg/kg resulted in a significant reduction in the maximum seizure burden from T-1 to T+1 (p = 0.002). Conclusions: Phenobarbitone significantly reduced seizures within 1 h of administration as assessed with continuous multi-channel EEG monitoring in neonates. The reduction was not permanent and seizures were likely to return within 4 h of treatment.

Randomised controlled trial of a mobile phone infant resuscitation guide

The aim of this study was to develop a mobile phone resuscitation guide (MPRG) and to evaluate its use during simulated resuscitation of a mannequin.

Use of Systemic Corticosteroids in Management of a Large Congenital Haemangioma of the Scalp

Abstract:  Congenital haemangiomas are rare and are estimated to have a combined incidence of less than 3% of all infantile haemangiomas. They are fully grown at birth, having undergone their proliferative phase in utero ( 1 ). Congenital hemangiomas can present at birth or in some cases can be detected antenatally on imaging (2,3). In the majority of patients no therapeutic intervention is required. Congenital hemangiomas also differ from infantile hemangiomas by staining negatively with GLUT1 antibody. They fall into two major subtypes: rapidly involuting congenital hemangiomas (RICHs) and noninvoluting congenital hemangiomas (NICHs) ( 4,5 ). Here we describe a case of RICH detected antenatally on ultrasound imaging. This lesion caused significant complications in the postnatal period due to the bulk of the lesion and the presence of incipient ulceration with the risk of possible catastrophic hemorrhage. A therapeutic trial of oral corticosteroid was commenced in an effort to accelerate involution due to the significant risk associated with other possible treatment modalities such as embolization or surgical intervention.

In vitro comparison of neonatal suction catheters using simulated 'pea soup' meconium

Background A variety of suction catheters (type, size and design) are recommended for oropharyngeal suctioning of meconium during newborn resuscitation, but it is not known which performs best. In this study we compared different sizes of soft catheters, the Yankauer (YK) and the portable bulb syringe (BS), in suctioning a solution of varying viscosity. Methods Simulated meconium (SM) was made using commercial canned pea soup in two strengths, full-strength thick-particulate (TP) and 50% strained soup diluted with water, that is, thin-non-particulate (TnP), with saline as a control. A 20 ml aliquot of solution was suctioned over 5 s with each device using an electrical suction pump set at two different pressures, 100 and 150 mm Hg (21 kpa). In addition, the negative pressure of five BSs was measured in order to compare generated pressures with the alternative devices. Results The YK and BS suctioned almost 100% of saline, while the 6F and 8F catheters suctioned 50% and 75% saline, respectively. The YK suctioned 100% of TnP, saline and 30% of TP. At reduced suction pressures (100 and 50 mm Hg) the YK also suctioned all TnP. The 12F and 14F catheters suctioned a minimal amount of TP, whereas YK was the most efficient, suctioning 30% of TP. The mean negative pressure generated with five BSs was 78 and 71 mm Hg by a male and female operator, respectively. Conclusions The YK and BS outperform the catheters in suctioning SM. The YK is the best for TP, but all devices perform poorly in suctioning fluid of this consistency.

Corrective ventilation strategies in delivery room resuscitation of preterm infants

Corrective ventilation strategies (CVS) during neonatal resuscitation and stabilisation (R&S) are taught through the MRSOPA mnemonic: Mask adjustment, Repositioning airway, Suctioning, Opening the mouth, Increasing inspiratory Pressure, and Alternative airway. The aim was to examine the use of CVS and to investigate the relationship between MRSOPA strategies and intubation of very preterm infants <32 weeks’ gestation in the delivery room.

Delivery room end tidal CO2monitoring in preterm infants <32 weeks

Objectives To determine the feasibility of end tidal (EtCO2) monitoring of preterm infants in the delivery room, to determine EtCO2 levels during delivery room stabilisation, and to examine the incidence of normocapnia (5–8 kPa) on admission to the neonatal intensive care unit in the EtCO2 monitored group compared with a historical cohort without EtCO2 monitoring. Patients and methods Preterm infants (<32 weeks) were eligible for inclusion in this observational study. The evolution of EtCO2 values immediately after delivery was assessed and linear least-squares methods were used to fit a line to EtCO2 recordings. The partial pressure of CO2 in blood (PCO2) from the infants who received EtCO2 monitoring was compared with a historical cohort without EtCO2 monitoring. Results EtCO2 monitoring was feasible in the delivery room. EtCO2 values were successfully obtained in 39 (88.7%) of the 44 infants included in the study. EtCO2 gradually increased over the first 4 min. Intubated infants had higher EtCO2 values compared with infants who were not intubated, with median (IQR) values of 4.7 (3.3–8.4) kPa versus 3.2 (2.6–4.2) kPa (p=0.05). No difference was found between the proportions of PCO2 values within the range of normocapnia among infants who received EtCO2 monitoring compared with those who did not (56.8% vs 47.9%, p=0.396). Conclusions Delivery room EtCO2 monitoring is feasible and safe. EtCO2 values obtained after birth reflect the establishment of functional residual capacity and effective ventilation. The potential short-term and long-term consequences of EtCO2 monitoring should be established in randomised controlled trials.