Compliance with antibiotic therapy guidelines in french paediatric intensive care units: a multicentre observational study.

BACKGROUND: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance. METHODS: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded. RESULTS: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486). CONCLUSIONS: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations. TRIAL REGISTRATION: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020.

Rhythm in the Premature Neonate Brain: Very Early Processing of Auditory Beat and Meter.

The ability to extract rhythmic structure is important for the development of language, music, and social communication. Although previous studies show infants' brains entrain to the periodicities of auditory rhythms and even different metrical interpretations (e.g., groups of two vs three beats) of ambiguous rhythms, whether the premature brain tracks beat and meter frequencies has not been explored previously. We used high-resolution electroencephalography while premature infants (n = 19, 5 male; mean age, 32 ± 2.59 weeks gestational age) heard two auditory rhythms in the incubators. We observed selective enhancement of the neural response at both beat- and meter-related frequencies. Further, neural oscillations at the beat and duple (groups of 2) meter were phase aligned with the envelope of the auditory rhythmic stimuli. Comparing the relative power at beat and meter frequencies across stimuli and frequency revealed evidence for selective enhancement of duple meter. This suggests that even at this early stage of development, neural mechanisms for processing auditory rhythms beyond simple sensory coding are present. Our results add to a few previous neuroimaging studies demonstrating discriminative auditory abilities of premature neural networks. Specifically, our results demonstrate the early capacities of the immature neural circuits and networks to code both simple beat and beat grouping (i.e., hierarchical meter) regularities of auditory sequences. Considering the importance of rhythm processing for acquiring language and music, our findings indicate that even before birth, the premature brain is already learning this important aspect of the auditory world in a sophisticated and abstract way.SIGNIFICANCE STATEMENT Processing auditory rhythm is of great neurodevelopmental importance. In an electroencephalography experiment in premature newborns, we found converging evidence that when presented with auditory rhythms, the premature brain encodes multiple periodicities corresponding to beat and beat grouping (meter) frequencies, and even selectively enhances the neural response to meter compared with beat, as in human adults. We also found that the phase of low-frequency neural oscillations aligns to the envelope of the auditory rhythms and that this phenomenon becomes less precise at lower frequencies. These findings demonstrate the initial capacities of the developing brain to code auditory rhythm and the importance of special care to the auditory environment of this vulnerable population during a highly dynamic period of neural development.

Preterm neonates distinguish rhythm violation through a hierarchy of cortical processing.

Rhythm is a fundamental component of the auditory world, present even during the prenatal life. While there is evidence that some auditory capacities are already present before birth, whether and how the premature neural networks process auditory rhythm is yet not known. We investigated the neural response of premature neonates at 30-34 weeks gestational age to violations from rhythmic regularities in an auditory sequence using high-resolution electroencephalography and event-related potentials. Unpredicted rhythm violations elicited a fronto-central mismatch response, indicating that the premature neonates detected the rhythmic regularities. Next, we examined the cortical effective connectivity underlying the elicited mismatch response using dynamic causal modeling. We examined the connectivity between cortical sources using a set of 16 generative models that embedded alternate hypotheses about the role of the frontal cortex as well as backward fronto-temporal connection. Our results demonstrated that the processing of rhythm violations was not limited to the primary auditory areas, and as in the case of adults, encompassed a hierarchy of temporo-frontal cortical structures. The result also emphasized the importance of top-down (backward) projections from the frontal cortex in explaining the mismatch response. Our findings demonstrate a sophisticated cortical structure underlying predictive rhythm processing at the onset of the thalamocortical and cortico-cortical circuits, two months before term.

Evolution of cross-frequency coupling between endogenous oscillations over the temporal cortex in very premature neonates.

Temporal theta activity in coalescence with slow-wave (TTA-SW) is one of the first neurobiomarkers of the neurodevelopment of perisylvian networks in the electroencephalography (EEG). Dynamic changes in the microstructure and activity within neural networks are reflected in the EEG. Slow oscillation slope can reflect synaptic strength, and cross-frequency coupling (CFC), associated with several putative functions in adults, can reflect neural communication. Here, we investigated the evolution of CFC, in terms of SW theta phase-amplitude coupling (PAC), during the course of very early development between 25 and 32 weeks of gestational age in 23 premature neonates. We used high-resolution EEG and dipole models as spatial filters to extract the source waveforms corresponding to TTA-SW. We also carried out nonlinear phase-dependent correlation measurements to examine whether the characteristics of the SW slopes are associated with TTA-SW coupling. We show that neurodevelopment leads to temporal accumulation of the SW theta PAC toward the trough of SW. Steepness of the negative going slope of SW determined the degree of this coupling. Systematic modulation of SW-TTA CFC during development is a signature of the complex development of local cortico-cortical perisylvian networks and distant thalamo-cortical neural circuits driving this nested activity over the perisylvian networks.

Patent ductus arteriosus in preterm infants is associated with cardiac autonomic alteration and predominant parasympathetic stimulation.

BACKGROUND: Hemodynamic disorders in patent ductus arteriosus (PDA) may alter the stimulation of the autonomic nervous system. AIM: The objective of this study was to analyze the orthosympathetic-parasympathetic balance in preterm infants with PDA. STUDY DESIGN AND SUBJECTS: Patients were included from consecutive admissions to Amiens University Hospital from 2009 to 2011. We defined a PDA group and a Control group (echographic criteria). For each patient, three 4-minutes segments of ECG were recorded during quiet sleep and the RR chronologic series were extracted, and spectral (Fourier Transform) and time-domain analyses were performed. For each parameter of heart rate variability (HRV), average of three measures was determined and analysed. RESULTS: Forty-four patients were included for analysis. The total HRV power, LF/HF ratio and SDNN were lower in the PDA group (n = 22, gestational age 28.2 w ± 1.9) than in the Control group (n = 22, gestational age 28.8 w ± 2). The decrease in LF power destabilized the autonomic balance in favour of parasympathetic stimulation. After adjustment for postconceptional age, PDA was still associated with parameters of autonomic neural stimulation. CONCLUSION: These results suggest association of PDA with predominance of parasympathetic stimulation in preterm infants. The mechanisms of homeostasis in patients with PDA are very complex and involve both circulatory adaptations and control by autonomic pathway. If confirmed, our results could be interesting for future researches aiming to verify the interest of new targeted therapies for the management of PDA.