Staphylococcus capitis: insights into epidemiology, virulence, and antimicrobial resistance of a clinically relevant bacterial species.

SUMMARYStaphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.

Predicting Outcome of Congenital Cytomegalovirus Infection by Differentiating and Revisiting Severe versus Mild Prenatal Imaging Features.

INTRODUCTION: Our objective was to evaluate the outcome of fetuses with first- and second-trimester fetal cytomegalovirus infection (CMVi) according to prenatal imaging patterns, especially fetuses presenting with mild imaging features (MF), being currently of uncertain prognosis. MATERIAL AND METHODS: In a retrospective study of 415 suspected CMVi cases, 59 cases were confirmed. Among prenatal imaging features, microcephaly, cortical disorder, and cerebellar hypoplasia as well as severe IUGR and fetal hydrops were considered as severe imaging features (SF). Other imaging features were considered as MF. Postnatal outcome was classified as "normal outcome," "mild sequelae" characterized mainly by sensorineural disorder (SND) and "severe sequelae" characterized by cognitive impairment. RESULTS: Only first-trimester (T1) and second-trimester (T2) CMVi cases were included in our study (n = 49) since all third-trimester cases (n = 10) had normal imaging and outcome. Sixteen fetuses had normal prenatal imaging and normal outcome, except one showing SND. Abnormal ultrasound findings were present in 33 fetuses, including SF noted in 16 fetuses, related exclusively to first-trimester CMVi. Termination of pregnancy was performed in 18 cases. Twelve first-trimester infected fetuses presented SF, whereas 6 fetuses (T1: n = 5, T2: n = 1) presented isolated MF. Four fetal deaths were encountered. Live-born babies with abnormal imaging included 10 fetuses with MF and one with SF. Among the 10 live babies with isolated MF, SND was encountered in 5 cases, whereas 5 children demonstrated normal outcome. Overall, 50% of our babies showing MF suffered from SND. No case of cognitive disorders was reported in babies showing only MF. CONCLUSION: SF were encountered only in first-trimester CMVi and should be distinguished from MF. Among our 10 live babies with prenatal MF following first- or second-trimester infection, 50% showed SND, whereas none presented severe sequelae. In 16 fetuses displaying normal fetal imaging, SND was encountered in one first-trimester case (6%).

Heterogeneous vancomycin resistance in Staphylococcus aureus does not predict development of vancomycin resistance upon vancomycin pressure.

BACKGROUND: It is unclear whether Staphylococcus aureus with heterogeneous intermediate vancomycin resistance (hVISA) can develop vancomycin resistance faster than vancomycin-susceptible S. aureus (VSSA) strains. METHODS: We compared the kinetics of vancomycin MIC increase for 15 days of sustained in vitro vancomycin exposure for clinical hVISA (n = 12) and VSSA (n = 24) isolates, as well as for reference strains Mu3 (hVISA) and ATCC 29213 (VSSA). Clinical isolates were categorized as hVISA using the population analysis profile method. MICs were monitored for 15 days and the rate of MIC increase under exposure, for each strain, was evaluated in a linear regression model relative to time. RESULTS: All isolates acquired vancomycin resistance upon exposure. Vancomycin MICs increased faster for VSSA compared with hVISA isolates (P < 0.01). CONCLUSIONS: The hVISA phenotype does not correspond to an enhanced adaptation potential to in vitro vancomycin pressure.

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS). STUDY DESIGN: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores. RESULTS: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38). CONCLUSIONS: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.

High-frequency oscillatory ventilation versus conventional ventilation in the respiratory management of term neonates with a congenital diaphragmatic hernia: a retrospective cohort study.

Conventional mechanical ventilation (CMV) has been recommended as the first-line mode of respiratory support for neonates born with a congenital diaphragmatic hernia (CDH). However, older studies suggested that protective high-frequency oscillatory ventilation (HFOV) with low-mean airway pressure (MAP) may limit lung injury. We aimed to compare low-MAP HFOV with CMV in neonates with CDH in terms of patient outcomes. This retrospective cohort study was conducted in two French neonatal intensive care units: center 1 mainly used CMV, and center 2 mainly used HFOV with a low MAP. All term neonates with CDH born between 2010 and 2018 in these two centers were included. The primary outcome was the duration of oxygen therapy. Secondary outcomes were survival and duration of mechanical ventilation. A total of 170 patients (105 in center 1, 65 in center 2) were included. In center 2, 96% of patients were ventilated with HFOV versus 19% in center 1. After adjustment for perinatal data, there was no significant difference regarding duration of oxygen therapy (SHR 0.83, 95% CI [0.55-1.23], p = 0.35) or survival (HR 1.73, 95% CI [0.64-4.64], p = 0.28). Center 2 patients required longer mechanical ventilation and sedation. CONCLUSION: First-line mode of mechanical ventilation was not associated with the duration of oxygen therapy or survival in neonates with CDH. WHAT IS KNOWN: • Recommendations were given in favour of using the conventional mechanical ventilation in first intention in neonates with a congenital diaphragmatic hernia, since High frequency oscillation (HFO) has been associated with a higher morbidity. WHAT IS NEW: • No differences between HFO and conventional mechanical ventilation were observed concerning the length of oxygen supply and the survival..

Local protocol helped to deliver vitamin D levels more accurately in preterm infants.

AIM: This study retrospectively evaluated the effectiveness and safety of a local hospital protocol of vitamin D supplementation for preterm infants, which was modified in 2016. METHODS: We focussed on 99 preterm infants born before 31 weeks of gestation and admitted to the neonatal intensive care unit at the Femme Mere Enfant Hospital, Bron, France, from 1 January to 31 December 2018. Calcium and urinary calcium were measured, and 25-hydroxy vitamin D (25(OH)D) levels were monitored monthly and supplementation was adjusted, with 50-120 nmol/L considered normal. The results are presented as medians and interquartile ranges. RESULTS: The infants were enrolled at a gestational age of 28.0 [26.9-29.1] weeks and birth weight of 960 [800-1160] g. When they were discharged at 37.3 [35.2-39.8] weeks, the overall 25(OH)D level was 98 [79-140] nmol/L: 4% had low levels, 63% had normal levels and 33% had high levels. Vitamin D supplementation was withdrawn for 60% more than one month before discharge. Rickets or fractures were not reported. CONCLUSION: The modified protocol limited underdosing and significant overdosing, but moderate hypervitaminosis D was still frequent. Urgent studies are needed to determine the optimal supplementation and clinical impact of 25(OH)D on comorbidities in preterm infants.

Minimum evidence-based care in intrauterine growth-restricted fetuses and neonatal prognosis.

BACKGROUND: Introduction: There is clear evidence that fetuses with intrauterine growth restriction (IUGR) do not receive the minimum evidence-based care during their antenatal management. OBJECTIVE: Considering that optimal management of IUGR may reduce neonatal morbi-mortality in IUGR, the objective of the present study was to evaluate the impact of antenatal management of IUGR according to the recommendations of the French college of gynecologists and obstetricians (CNGOF) on the neonatal prognosis of IUGR fetuses. STUDY DESIGN: From a historical cohort of 31,052 children, born at the Femme Mère Enfant hospital (Lyon, France) between January 1, 2011 and December 31, 2017, we selected the population of IUGR fetuses. The minimum evidence-based care (MEC) in the antenatal management of fetuses with IUGR was defined according to the CNGOF recommendations and neonatal prognosis of early and late IUGR fetuses were assessed based on the whether or not they received MEC. The neonatal prognosis was defined according to a composite criterion that included neonatal morbidity and mortality. RESULTS: A total of 1020 fetuses with IUGR were studied. The application of MEC showed an improvement in the neonatal prognosis of early-onset IUGR (p = 0.003), and an improvement in the neonatal prognosis of IUGR born before 32 weeks (p = 0.030). Multivariate analysis confirmed the results showing an increase in neonatal morbi-mortality in early-onset IUGR in the absence of MEC with OR 1.79 (95% CI 1.01-3.19). CONCLUSION: Diagnosed IUGR with MEC had a better neonatal prognosis when born before 32 weeks. Regardless of the birth term, MEC improved the neonatal prognosis of fetuses with early IUGR. Improvement in the rate of MEC during antenatal management has a significant impact on neonatal prognosis.

Impact of a nurse education programme on oral feeding in a neonatal unit.

BACKGROUND: Premature neonates often experience feeding difficulties during their hospital stay, and evidence-based interventions have been shown to improve feeding outcomes. AIM: This study investigated whether an infant-cue based nurse educational feeding bundle accelerates the achievement of independent oral feeding in neonates in a neonatal intensive care unit. STUDY DESIGN: A quality improvement study with a pre, during and post intervention test design. All premature neonates admitted to the unit were eligible. The feeding programme included a four-month nurse training module and nurse coaching. RESULTS: A hundred and twenty-five nurses or nurse assistants attended the programme and 706 neonates were included. The median time to independent oral feeding (IOF) was 40, 36 and 37 days, respectively, for pre, during and post intervention. The reduction in time to IOF observed during the post-intervention period compared with the baseline period was significant (HR = 1.32, CI 95%: 1.01-1.74). No difference was noted in the length of hospital stay between the three study periods. CONCLUSIONS: An infant-cue based nurse educational feeding bundle can promote earlier achievement of IOF in preterm neonates. RELEVANCE TO CLINICAL PRACTICE: This quality improvement study demonstrates the impact that a nurse-driven intervention in neonatal care can have on improving practice. Feeding interventions involve the early introduction of oral feeding, non-nutritive sucking (NNS), and oral motor stimulation, and should be individualized for each neonate. These individualized feeding interventions applied by all nurses and assistant nurses, can facilitate the achievement of earlier independent oral feeding in preterm infants and should be included in neonatal critical care nurse education programs.

Persistent microbial contamination of incubators despite disinfection.

BACKGROUND: In neonatal intensive care units (NICUs), hygiene and disinfection measures are pivotal to protect neonates from nosocomial infections. This study aimed to evaluate the efficacy of the classical incubators disinfection procedure and to follow-up neonates housed in the incubators for the development of late-onset sepsis (LOS). METHODS: In a tertiary NICU, 20 incubators were monitored for bacterial contamination at three times: before disinfection, after disinfection, and 24 h after turning on and housing a new neonate. Clinical data of neonates housed in these incubators were retrieved from the medical records. RESULTS: All 20 incubators were contaminated at the 3 times of the study, mainly on mattresses and balances. Coagulase-negative Staphylococci, Enterococcus, and Bacillus-resisted disinfection while enterobacteria and Staphylococcus aureus were eradicated. After 24 h, the bacterial colonisation was similar to the one observed before disinfection. The bacteria isolated on incubators were also found on the caregivers' hands. During the study, two preterm neonates developed a LOS involving a bacterial species that has been previously isolated in their incubator. CONCLUSION: Pathogenic contaminants persist on incubators despite disinfection and represent a risk for subsequent infection in preterm neonates. Improvements are needed concerning both the disinfection process and incubator design. IMPACT: Procedures of disinfection that are usually recommended in NICUs do not allow for totally eradicating bacteria from incubators. Preterm neonates are housed in incubators colonised with potentially pathogenic bacteria. The control of nosocomial infections in NICUs requires further researches concerning mechanisms of bacterial persistence and ways to fight against environmental colonisation.

Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France.

The Rhône-Loire metropolitan areas' 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Enterobacter cloacae colonisation and infection in a neonatal intensive care unit: retrospective investigation of preventive measures implemented after a multiclonal outbreak.

BACKGROUND: Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU. METHODS: This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012-2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains. RESULTS: Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone. CONCLUSIONS: Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.

Worldwide Endemicity of a Multidrug-Resistant Staphylococcus capitis Clone Involved in Neonatal Sepsis.

A multidrug-resistant Staphylococcus capitis clone, NRCS-A, has been isolated from neonatal intensive care units in 17 countries throughout the world. S. capitis NRCS-A prevalence is high in some neonatal intensive care units in France. These data highlight the worldwide endemicity and epidemiologic relevance of this multidrug-resistant, coagulase-negative staphylococci clone.

A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial.

OBJECTIVE: Adherence to the International Liaison Committee on Resuscitation (ILCOR) algorithm optimizes the initial management of critically ill neonates. In this randomized controlled trial, we assessed the impact of a customizable sequential digital cognitive aid (DCA), adapted from the 2020 ILCOR recommendations, compared with a poster cognitive aid (standard of care [SOC]), on technical and nontechnical performance of junior trainees during a simulated critical neonatal event at birth. METHODS: For this prospective, bicentric video-recorded study, students were recruited on a voluntary basis, and randomized into groups of 3 composed of a pediatric resident and two midwife students. They encountered a simulated cardiac arrest at birth either (1) with DCA use and ILCOR algorithm poster displayed on the wall (intervention group) or (2) with sole ILCOR algorithm poster (poster cognitive aid [SOC]). Technical and nontechnical skills (NTS) between the two groups were assessed using a standardized scoring of videotaped performances. A neonate specific NTS score was created from the adult Team score. RESULTS: 108 students (36 groups of three) attended the study, 20 groups of 3 in the intervention group and 16 groups of 3 in the poster cognitive aid (SOC) group. The intervention group showed a significant improvement in the technical score (P < 0.001) with an average of 24/27 points (24.0 [23.5-25.0]) versus 20.8/27 (20.8 [19.9-22.5]) in poster cognitive aid (SOC) group. No nontechnical score difference was observed. Feedback on the application was positive. CONCLUSIONS: During a simulated critical neonatal event, use of a DCA was associated with higher technical scores in junior trainees, compared with the sole use of ILCOR poster algorithm.

Respiratory physiology during NAVA ventilation in neonates born with a congenital diaphragmatic hernia: The "NAVA-diaph" pilot study.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that delivers synchronized ventilation, proportional to the electrical activity of the diaphragm (EAdi). Although it has been proposed in infants with a congenital diaphragmatic hernia (CDH), the diaphragmatic defect and the surgical repair could alter the physiology of the diaphragm. AIM: To evaluate, in a pilot study, the relationship between the respiratory drive (EAdi) and the respiratory effort in neonates with CDH during the postsurgical period under either NAVA ventilation or conventional ventilation (CV). METHODS: This prospective physiological study included eight neonates admitted to a neonatal intensive care unit with a diagnosis of CDH. EAdi, esophageal, gastric, and transdiaphragmatic pressure, as well as clinical parameters, were recorded during NAVA and CV (synchronized intermittent mandatory pressure ventilation) in the postsurgical period. RESULTS: EAdi was detectable and there was a correlation between the ΔEAdi (maximal - minimal values) and the transdiaphragmatic pressure (r = 0.26, 95% confidence interval [CI] [0.222; 0.299]). There was no significant difference in terms of clinical or physiological parameters during NAVA compared to CV, including work of breathing. CONCLUSION: Respiratory drive and effort were correlated in infants with CDH and therefore NAVA is a suitable proportional mode in this population. EAdi can also be used to monitor the diaphragm for individualized support.

Neurodevelopmental Outcome at Two Years for Preterm Infants With Intraventricular Hemorrhage: A Case-Control Study.

BACKGROUND: High-grade intraventricular hemorrhage (IVH), including grade III and grade IV IVH, is known to impact neurodevelopmental outcome of preterm infants, but prognosis remains difficult to establish due to confounding factors and significant variations in the reported outcomes. The aim of this study was to compare the neurodevelopmental outcome of preterm infants with or without severe IVH. METHODS: A retrospective case-control study was conducted including preterm infants with gestational age <32 weeks hospitalized between 2009 and 2017 in a level III neonatal intensive care unit. This study included 73 cases with high-grade IVH and 73 controls who were matched to cases, based on the same gestational age, birth weight, sex, and year of birth. The neurodevelopmental outcome was compared at two years of age corrected for prematurity between cases and controls. Neurodevelopmental impairment was defined as cerebral palsy, hearing deficiency, visual impairment, or developmental delay. Multivariate analysis was used to identify whether high-grade IVH was an independent risk factor for neurodevelopmental impairment. RESULTS: In univariate analysis, high-grade IVH was associated with death or poor neurodevelopmental outcome at two years of age corrected for prematurity (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.93 to 57.8; P < 0.001), and this association remained significant after adjusting for confounding factors including neonatal infection and bronchopulmonary dysplasia in multivariate analysis (OR, 8.71; 95% CI, 2.48 to 38.09; P = 0.002). CONCLUSIONS: This study highlights the impact of high-grade IVH as an independent risk factor of poor neurodevelopmental outcomes in very preterm infants and suggests that early interventions could improve the prognosis of these infants.

Disinfection of incubators in neonatal intensive care units: impact of steam pulverization on bacterial colonization.

BACKGROUND: In neonatal intensive care units (NICUs), neonates requiring medical care after birth, including very vulnerable preterm infants, are housed in incubators. Previous studies have reported that the standard chemical disinfection measures used to disinfect these incubators are insufficient to eradicate contaminating bacteria, leading to a worrying infectious risk for preterm neonates. This study aimed to evaluate the efficacy of a disinfection method based on steam pulverization to eradicate the persistent bacterial contamination in such incubators. METHODS: In a tertiary NICU, 20 incubators were monitored qualitatively for bacterial contamination at five different sites (the rubber grommet, the left door handles, the temperature adjustment button, the mattress and the scale) using a culture method at three times: before and after steam pulverization then 24 h after turning on and housing a new neonate. Clinical data of neonates housed in each incubator were retrieved from the medical records to identify potential occurrence of late onset sepsis (LOS). RESULTS: Just after steam pulverization, only two incubators were free from bacteria. Before disinfection 87% of all the samples were contaminated compared to 61% after disinfection. After 24 h, the proportion of contaminated samples reached 85%. Mattresses and scales were the most frequently contaminated incubator sites with respectively 90% and 80% positive samples after disinfection compared to 100% and 90% before disinfection. Coagulase-negative staphylococci, Enterococcus, Enterobacteria and Bacillus resisted disinfection and were identified on respectively 90%, 20%, 5% and 45% of incubators just after disinfection. Three preterm neonates developed LOS after being housed in a disinfected incubator but the bacterial species involved have not been identified in their incubator after disinfection. In two cases, the bacterium had been isolated from the mattress 24 h after housing the infected patient. CONCLUSION: Steam pulverization is not sufficient to eradicate bacterial contamination of incubators. These results highlight the urgent need for an effective disinfection method, especially for mattresses that are in constant contact with patients. In parallel, new incubator designs and mattress protections must be developed.

Is 25OH Vitamin D Excess before 36 Weeks Corrected Age an Independent Risk Factor for Bronchopulmonary Dysplasia or Death?

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at <31 weeks gestational age without major malformations with at least a determination of 25(OH)D at <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120 nmol/L (50.5% vs. 43.9%, p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995-0.998]) and term (OR 0.737, 95% CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.