Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants:A Longitudinal, Multicenter, Case-Control Study

BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants:a multicenter cohort study

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics’ effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19–0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35–0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85–0.97]; p = 0.003). Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored.What is Known:• Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis.• The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated.What is New:• Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged.• A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life

Detection of volatile organic compounds as potential novel biomarkers for chorioamnionitis - proof of experimental models

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins. Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns. Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up. Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy

Pregnant patient with acute abdominal pain and previous bariatric surgery

Pregnant women who previously had bariatric surgery may develop acute abdominal pain during pregnancy. Two patients, 38-year-old twin primigravida (gestational age of 24+6 weeks) and a 26-year-old woman (gestational age of 24+0 weeks), both of whom had laparoscopic gastric bypass surgery previously, developed abdominal pain. The patients both had diffuse abdominal pain in combination with normal blood tests and imaging. Patient B had undergone laparoscopy at another centre after 5 weeks of gestation for internal herniation. After referral to our multidisciplinary bariatric-obstetric-neonatal (MD-BON) team, diagnostic laparoscopy was advised as internal herniation was deemed possible. In both patients, internal herniation was indeed found in Petersen's space and jejunal mesenteric defect, which was closed using laparoscopic surgery. Both women delivered healthy offspring afterwards. The presence of an MD-BON team allows for an increased awareness of potential long-term complications associated with earlier bariatric surgery in pregnancy

Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study

Contains fulltext : 206256.pdf (publisher's version ) (Open Access

Abdominal pain in a pregnant woman who had gastric reduction surgery:Risks associated with a history of bariatric surgery

Een nadeel van bariatrische chirurgie is dat de ingreep een risico geeft op complicaties op de lange termijn. Tijdens de zwangerschap kunnen deze complicaties leiden tot ernstige foetale en maternale morbiditeit en mortaliteit.1 In deze klinische les beschrijven we aan de hand van twee casussen het belang van multidisciplinaire expertise bij een zwangere patiënte met buikpijn door complicaties van eerdere bariatrische chirurgie.Patiënt A, een 38-jarige primigravida die 3 jaar eerder een laparoscopische ‘Roux-en-Y gastric bypass’ (RYGB) had ondergaan, was elders opgenomen met postprandiale buikpijn bij een tweelingzwangerschap met een amenorroeduur van 24/6 weken. Patiënte was normotensief, had een licht pijnlijke, niet-geprikkelde buik en een niet-afwijkend bloedbeeld. Het ongeboren kind was in goede conditie en er waren geen tekenen van dreigende vroeggeboorte. Differentiaaldiagnostisch werd gedacht aan obstipatie, galsteenlijden en inwendige herniatie van de dunne darm. Er werd een echo abdomen gemaakt waarop geen aanwijzingen waren voor galstenen of stuwing van de galwegen. Tevens ...In Nederland ondergaan jaarlijks ongeveer 6500 vrouwen in de vruchtbare levensfase een bariatrische operatie, waarbij de ‘Roux-en-Y gastric bypass’ (RYGB) de meest uitgevoerde operatie is. Gewichtsverlies na bariatrische chirurgie leidt tot een reductie van cardiovasculaire risico’s, verbeterde fertiliteit en vermindering van obesitas-gerelateerde complicaties tijdens de zwangerschap. Toch zijn er ook nadelen, zoals blijkt uit deze klinische les