18 research outputs found
Chlorhexidine gluconate usage is associated with antiseptic tolerance in staphylococci from the neonatal intensive care unit
Background: Intravascular catheters are essential for care in Neonatal Intensive Care Units (NICUs) but predispose infants to catheter-associated infections including late-onset sepsis, commonly caused by CoNS. Antiseptics are applied to prevent infection with chlorhexidine (CHG) and octenidine (OCT) the most common agents used. Objectives: To investigate the association between antiseptic use and bacterial susceptibility. Methods: CoNS isolates were collected from two NICUs with differing antiseptic regimens: Norwich, UK (using CHG) and Lubeck, Germany (using OCT). CoNS were isolated from different body sites of babies upon admission, and weekly thereafter. Antiseptic susceptibility testing was performed, and a selection underwent genome sequencing. Results: A total of 1274 isolates were collected. UK isolates (n = 863) were significantly less susceptible than German isolates (n = 411) to both CHG (mean MIC: 20.1 mg/L versus 8.9 mg/L) and OCT (mean MIC: 2.3 mg/L versus 1.6 mg/L). UK isolates taken on admission were more susceptible to CHG than subsequent isolates. No cross-resistance between the agents was seen. Genome sequencing of 122 CoNS showed the most common species to be Staphylococcus epidermidis and Staphylococcus haemolyticus and phylogenetic analysis suggested antiseptic tolerance evolved multiple times in independent lineages. There was no evidence of dominant antiseptic tolerant clones and carriage of genes previously implicated in antimicrobial susceptibility (qac, smr, norA/B), did not correlate with CHG or OCT susceptibility. Conclusions: Long-term CHG use may select for CHG and OCT tolerance in CoNS. This highlights the different potential for separate antiseptic regimens to select for resistance development. This could be an important factor in developing future infection control policies
Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms
Background: In 2013 German infection surveillance guidelines recommended weekly colonization screening for
multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended
hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort.
We therefore aimed to evaluate sepsis related outcomes before and after the guideline update.
Methods: The German Neonatal Network (GNN) is a prospective cohort study including data from extremely
preterm infants between 22 + 0 and 28 + 6 gestational weeks born in 62 German level III NICUs.
Results: Infants treated after guideline update (n = 8.903) had a lower mortality (12.5% vs. 13.8%, p = 0.036), reduced
rates for clinical sepsis (31.4 vs. 42.8%, p < 0.001) and culture-proven sepsis (14.4% vs. 16.5%, p = 0.003) as compared
to infants treated before update (n = 3.920). In a multivariate logistic regression analysis, nine pathogens of cultureproven sepsis were associated with sepsis-related death, e.g. Pseudomonas aeruginosa [OR 59 (19–180), p < 0.001)].
However, the guideline update had no significant effect on pathogen-specific case fatality, total sepsis-related
mortality and culture-proven sepsis rates with MDRO. While the exposure of GNN infants to cefotaxime declined
over time (31.1 vs. 40.1%, p < 0.001), the treatment rate with meropenem was increased (31.6 vs. 26.3%, p < 0.001).
Conclusions: The introduction of weekly screening and extended hygiene measures is associated with reduced
sepsis rates, but has no effects on sepsis-related mortality and sepsis with screening-relevant pathogens. The high
exposure rate to meropenem should be a target of antibiotic stewardship programs
Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk
To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/
Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that
receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit
from probiotics in terms of sepsis prevention and growth. Methods: We performed an observational
study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013
and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm
infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively
human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or
donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727).
The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted
in linear/logistic regression models. Results: 5954 (76.5%) infants received L. acidophilus/B. infantisprophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated
with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size
B = 0.224; 95% CI: 2.82–4.35; p < 0.001) but not in the F group (effect size B = −0.06; 95% CI: −3.05–0.28;
p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the
Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation
proved to be protective against clinical sepsis (OR 0.69; 95% CI: 0.59–0.79; p < 0.001). Conclusion:
Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote
growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive
effect, probiotics seem to require human milk
Five Year Follow Up of Extremely Low Gestational Age Infants after Timely or Delayed Administration of Routine Vaccinations
This study is aimed at detecting the rate of untimely immunization in a large cohort
of extremely low gestational age neonates (ELGANs) of the German Neonatal Network (GNN)
and at addressing risk factors for delayed vaccination and associated long-term consequences. We
performed an observational study of the GNN between 1st January 2010 and 31st December 2019.
The immunization status for the hexavalent and pneumococcal immunization was evaluated in
n = 8401 preterm infants <29 weeks of gestation. Univariate analysis and logistic/linear regression
models were used to identify risk factors for vaccination delay and outcomes at a 5-year follow-up.
In our cohort n = 824 (9.8%) ELGANs did not receive a timely first immunization with the hexavalent
and pneumococcal vaccine. Risk factors for delayed vaccination were SGA status (18.1% vs. 13.5%;
OR 1.3; 95% CI: 1.1–1.7), impaired growth and surrogates for complicated clinical courses (i.e.,
need for inotropes, necrotizing enterocolitis). At 5 years of age, timely immunized children had
a lower risk of bronchitis (episodes within last year: 27.3% vs. 37.7%; OR 0.60, 95% CI: 0.42–0.86)
but spirometry measures were unaffected. In conclusion, a significant proportion of ELGANs
are untimely immunized, specifically those with increased vulnerability, even though they might
particularly benefit from the immune-promoting effects of a timely vaccination
Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network
INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care
Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period
Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials
Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period
Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials.Fil: Faust, Kirstin. Universidad de Lübeck; Alemania. German Center for Infection Research; AlemaniaFil: Freitag, Nancy. Max Delbruk Center For Molecular Medicine In The Helmholtz Association (mdc); AlemaniaFil: Barrientos, Gabriela Laura. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones CientÃficas y Técnicas; ArgentinaFil: Hartel, Christoph. Universität Würzburg; AlemaniaFil: Blois, Sandra M.. Max Delbruk Center For Molecular Medicine In The Helmholtz Association (mdc); Alemani
Antimicrobial Peptides (AMPs) and the Microbiome in Preterm Infants: Consequences and Opportunities for Future Therapeutics
Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment
Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants
Regulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein 3 (FoxP3)+ Tregs in peripheral blood of well-phenotyped preterm infants (n = 382; 23 + 0 – 36 + 6 weeks of gestational age) with a focus on the first 28 days of life and the clinical endpoint BPD (supplemental oxygen for longer than 28 days of age). In a subgroup of preterm infants, we characterized the immunological phenotype of Tregs (n = 23). The suppressive function of Tregs on CD4+CD25- T cells was compared in preterm, term and adult blood. We observed that extreme prematurity was associated with increased Treg frequencies which peaked in the second week of life. Independent of gestational age, increased Treg frequencies were noted to precede the development of BPD. The phenotype of preterm infant Tregs largely differed from adult Tregs and displayed an overall naïve Treg population (CD45RA+/HLA-DR-/Helios+), especially in the first days of life. On day 7 of life, a more activated Treg phenotype pattern (CCR6+, HLA-DR+, and Ki-67+) was observed. Tregs of preterm neonates had a higher immunosuppressive capacity against CD4+CD25- T cells compared to the Treg compartment of term neonates and adults. In conclusion, our data suggest increased frequencies and functions of Tregs in preterm neonates which display a distinct phenotype with dynamic changes in the first weeks of life. Hence, the continued abundance of Tregs may contribute to sustained inflammation preceding the development of BPD. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics