Baseline azithromycin resistance in the gut microbiota of preterm born infants.

BACKGROUND: Macrolides, including azithromycin, are increasingly used in preterm-born infants to treat Ureaplasma infections. The baseline carriage of macrolide resistance genes in the preterm stool microbiota is unknown. OBJECTIVES: Identify carriage of azithromycin resistant bacteria and the incidence of macrolide resistant genes. METHODS: Azithromycin resistant bacteria were isolated from serial stool samples obtained from preterm infants (≤32 weeks' gestation) by culturing aerobically/anaerobically, in the presence/absence of azithromycin. Using quantitative PCR, we targeted 6 common macrolide resistance genes (erm(A), erm(B), erm(C), erm(F), mef(A/E), msr(A)) in DNA extracted from selected bacteria resistant to azithromycin. RESULTS: From 89 stool samples from 37 preterm-born infants, 93.3% showed bacterial growth in aerobic or anaerobic conditions. From the 280 azithromycin resistant isolates that were identified, Staphylococcus (75%) and Enterococcus (15%) species dominated. Macrolide resistance genes were identified in 91% of resistant isolates: commonest were erm(C) (46% of isolates) and msr(A) (40%). Multiple macrolide resistance genes were identified in 18% of isolates. CONCLUSION: Macrolide resistance is common in the gut microbiota of preterm-born infants early in life, most likely acquired from exposure to the maternal microbiota. It will be important to assess modulation of macrolide resistance, if macrolide treatment becomes routine in the management of preterm infants. IMPACT STATEMENT: Azithromycin resistance is present in the stool microbiota in the first month of life in preterm infants 91% of azithromycin resistant bacteria carried at least one of 6 common macrolide resistant genes Increasing use of macrolides in the preterm population makes this an important area of study.

Dissimilarity of the gut-lung axis and dysbiosis of the lower airways in ventilated preterm infants.

BACKGROUND: Chronic lung disease of prematurity (CLD), also called bronchopulmonary dysplasia, is a major consequence of preterm birth, but the role of the microbiome in its development remains unclear. Therefore, we assessed the progression of the bacterial community in ventilated preterm infants over time in the upper and lower airways, and assessed the gut-lung axis by comparing bacterial communities in the upper and lower airways with stool findings. Finally, we assessed whether the bacterial communities were associated with lung inflammation to suggest dysbiosis. METHODS: We serially sampled multiple anatomical sites including the upper airway (nasopharyngeal aspirates), lower airways (tracheal aspirate fluid and bronchoalveolar lavage fluid) and the gut (stool) of ventilated preterm-born infants. Bacterial DNA load was measured in all samples and sequenced using the V3-V4 region of the 16S rRNA gene. RESULTS: From 1102 (539 nasopharyngeal aspirates, 276 tracheal aspirate fluid, 89 bronchoalveolar lavage, 198 stool) samples from 55 preterm infants, 352 (32%) amplified suitably for 16S RNA gene sequencing. Bacterial load was low at birth and quickly increased with time, but was associated with predominant operational taxonomic units (OTUs) in all sample types. There was dissimilarity in bacterial communities between the upper and lower airways and the gut, with a separate dysbiotic inflammatory process occurring in the lower airways of infants. Individual OTUs were associated with increased inflammatory markers. CONCLUSIONS: Taken together, these findings suggest that targeted treatment of the predominant organisms, including those not routinely treated, such as Ureaplasma spp., may decrease the development of CLD in preterm-born infants.

Estimate of incidence of ROP requiring treatment in extreme preterms and impact on service-7 year review in tertiary unit.

BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a potentially blinding disorder affecting premature infants. Our Eye Unit supports two neonatal intensive care units (NICUs), one provides neonatal surgical and medical facilities and the other is exclusively medical. Our objectives were to (1) to identify the annual rate of ROP treatments during the period 2009-2015 and (2) to estimate the incidence of ROP treatment in babies born very prematurely (<27 weeks). SUBJECTS/METHODS: Records for all infants treated for ROP by our unit during the period 2009-2015 were reviewed. We calculated numbers treated in each year. Records of babies born under 27 weeks of gestation and cared for in the non-surgical NICU were also reviewed. Their requirement for laser treatments for ROP was calculated by the week of gestation at birth. RESULTS: In the two NICUs combined, 95 infants were treated for ROP between 2009 and 2015. The numbers treated increased from 9/158 (5.7%) of babies screened in 2009 to 22/159 (13.8%) in 2015 (ptrend = 0.004). The rate of laser treatment for ROP increased as gestation at birth decreased: from 12/100 (12%) of babies born at 26 weeks to 17/29 (59%) of babies born at 23 weeks (ptrend = 0.001). CONCLUSION: The number of laser treatments for ROP carried out by this unit has increased steadily between 2009 and 2015 and this may in part be due to the increased need for ROP treatment in extremely preterm babies, whose survival has increased in the same period. These data may aid planning for ROP services.

Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants.

OBJECTIVE: To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24 h of life, and development of intraventricular haemorrhage (IVH) in extremely preterm infants. STUDY DESIGN: Single centre retrospective cohort study of 108 preterm infants born less than 28 weeks' gestation. Main outcome measure was degree of IVH at day 7 postnatal age. RESULTS: The mean GA of the study group was 25.4 weeks. Mean SVCF was lower (75 ml/kg/min) in infants later diagnosed with IVH (n = 46) compared to infants, who did not develop IVH (87.7 ml/kg/min, p = 0.055). PDA diameter was inversely associated with SVCF (p = 0.024) and reversal of flow in the descending aorta (p = 0.001). Sensitivity analysis did not confirm an independent association of SVCF with development of IVH [OR 0.990 (0.978-1.002), p = 0.115]. CONCLUSION: Our study describes early SVCF in extremely preterm infants is associated with the extent of ductal shunting, but insensitive in predicting IVH.

Elevated umbilical cord ghrelin concentrations in small for gestational age neonates.

Ghrelin has orexigenic effects. It is present in umbilical cord plasma in full-term neonates, raising the prospect that ghrelin plays a role in fetal and neonatal energy balance. We measured ghrelin in small (SGA), appropriate (AGA), and large (LGA) for gestational age neonates and evaluated whether ghrelin levels are modulated by neonatal insulin and glucose concentrations. Plasma concentrations of ghrelin, insulin, and glucose were measured in cord blood sampled at birth in 123 SGA, AGA, and LGA neonates (gestational age, 24-41 wk) born to mothers with and without diabetes. Ghrelin was detected in samples from all infants. Its concentration was 40% higher in SGA neonates (mean +/- SD, 2436 +/- 657 pg/ml) compared with AGA (1738 +/- 380) and LGA (1723 +/- 269) neonates. There was a positive correlation between ghrelin and gestational age in AGA/LGA (r = 0.23; P < 0.05) and a negative correlation in SGA (r = -0.67; P < 0.005) neonates. Therefore, the difference in ghrelin between SGA and AGA/LGA neonates decreases with advancing gestational age. Birth weight z-score, maternal hypertension, and glucose concentrations were significant determinants of ghrelin concentrations. In conclusion, SGA neonates present with higher umbilical cord ghrelin plasma concentrations than AGA/LGA neonates. Ghrelin may play a physiological role in fetal adaptation to intrauterine malnutrition.