Neonatal bacterial infections: Diagnosis, bacterial epidemiology and antibiotic treatment.

Severe bacterial infections have a higher incidence in the neonatal period than at any other pediatric age. Incidence is even higher in premature babies than in term newborns, and severity is increased in the absence of early diagnosis and treatment. By contrast, clinical signs are nonspecific and sometimes trivial, and biomarkers perform poorly during the first 24 hours of infection. For decades, this has led to having too many children treated for extended periods with broad-spectrum antibiotics. Today, the challenge is to prescribe antibiotics in a targeted way, by identifying truly infected newborns. Over the last ten years, major paradigm shifts have occurred and should be taken into account, as a result of growing awareness of the ecological impact of early antibiotic therapy, notably antibiotic resistance, by choosing the narrowest spectrum antibiotic and stopping antibiotic therapy as soon as the diagnosis of infection has been reasonably ruled out. Among the biological tests, the most important are blood cultures. At least one blood culture, taken under aseptic conditions, of sufficient volume (1 to 2 mL), and using pediatric bottles must be taken as soon as the decision to treat has been made, before starting any antibiotic therapy. The bacteria responsible for early-onset bacterial neonatal infections (EBNI) have not changed significantly over recent years and remain dominated by Group B Streptococcus and Escherichia coli, which are the main targets of treatment. GBS is largely predominant in full-term infants, but the proportion of infections due to E. coli increases with prematurity.

Taste and smell alterations affect nutritional status in children under chemotherapy.

AIM: This study aimed to evaluate the incidence of self-reported taste and smell alterations (TSA) in cancer paediatric patients and evaluate the impact of TSA on nutritional status in this population. We also developed and validated a composite score to detect TSA in children undergoing chemotherapy. METHODS: Paediatric patients who were undergoing chemotherapy in a paediatric oncology unit were included. TSA were assessed from the Gustonco questionnaire from which a composite score was developed and internally validated, eating behaviour was assessed using Child Eating Behaviour Questionnaire, and major weight loss was defined from nutritional status. All data were calculated at 1, 3 and 6 months after chemotherapy start. Associations between nutritional status and scores were studied by using logistic models. RESULTS: Among 49 patients included, TSA occurred in 71.7% of patients at 1 month after chemotherapy start and persisted at 3 and 6 months. TSA led to altered appetite since 1 month after chemotherapy start. The occurrence of a major weight loss at 6 months seemed to be associated with a high Gustonco score. CONCLUSION: Taste and smell alterations often occurred in paediatric cancer patients after chemotherapy start and seemed to be associated with impaired nutrition at 6 months after chemotherapy.

Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe: A cross-sectional survey of paediatricians.

BACKGROUND: Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability. METHODS AND FINDINGS: A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04-2.58) for lactate to 7.28 (95%CI: 3.04-24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04-1.80) for lactate to 11.93 (95%CI:3.35-72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. CONCLUSION: There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. METHODS: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. FINDINGS: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. CONCLUSIONS: These results provide potential for a better understanding of disease pathophysiology. FUNDING: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.

Diagnosis of Neonatal Late-Onset Infection in Very Preterm Infant: Inter-Observer Agreement and International Classifications.

BACKGROUND: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of "bronchopulmonary dysplasia or death". METHODS: A retrospective (2017-2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as "certain or probable" or "doubtful" independently by five experts and according to four international classifications with concordance assessed by Fleiss's kappa test. RESULTS: LOS was suspected at seven days (IQR: 5-11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as "certain or probable" (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = -0.08). Using the expert classification, "bronchopulmonary dysplasia or death" occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. CONCLUSION: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

[Complementary and alternative medicine use in two French pediatric oncology centers: A common practice]. / Utilisation des médecines complémentaires et alternatives chez l'enfant et l'adolescent atteint de cancer : une pratique fréquente.

BACKGROUND: The use of complementary and alternative medicine (CAM) in children with cancer is commonly used. However, studies and data on this topic are still scarce in France. METHODS: Our aim was to investigate the prevalence of CAM usage in pediatric cancer patients and describe the modality of use. Our study population comprised children and young people treated from 2011 to 2012 in 2 French centers (Nantes, Paris). An anonymous self-administered questionnaire was addressed to families and data was collected from them and from the medical record. RESULTS: Out of the 202 patients selected for the study, 111 families answered the questionnaire (55%). Fifty-four (48.6%) of respondents reported CAM used. Forty-seven (87%) patients used CAM during initial therapy of cancer. Thirty-two (59.3%) of them talked about their CAM usage with health professionals, whose 25 (75.8%) with their oncologist. The three most common therapies used were homeopathy (75.8%), chiropractic (31.5%) and faith healing (42.6%). The main reason for the use of CAM was to control the side effects of conventional treatment (85.2%). Overall perceived satisfaction was rated 7.4/10. CONCLUSION: The prevalence of complementary and alternative medicines administration is high, even if scientific evidence is limited regarding the effects, mechanisms of action and security of CAM. Research is necessary to improve the communication and council quality to the family, optimize supportive cares and reinforce the pharmacovigilance.

Serum S100ß Neuroprotein Reduces Use of Cranial Computed Tomography in Children After Minor Head Trauma.

Minor head trauma is a common reason for consultation in pediatric emergency departments. In 2009, the Pediatric Emergency Care Applied Research Network (PECARN) published a clinical decision rule for its management. It aimed to help clinicians identify children with a very low risk of developing intracranial lesions, so that unnecessary cranial computed tomography (CCT) scan radiation could be avoided, as such exposure is associated with a rising risk of cancer in this young population. In the meantime, the serum S100ß neuroprotein showed encouraging results, with a 30% potential decrease in CCTs for the management of minor head traumas in adults and children. The aim of this study was to determine if the serum S100ß neuroprotein, associated with the PECARN clinical decision rule, could safely reduce the use of CCTs. We included children who were examined at the pediatric emergency department for minor head trauma, who underwent a CCT, whose blood samples were analyzed to determine the level of the serum S100ß protein. They were managed according to the PECARN clinical decision rule. We afterward assessed the potential decrease in the number of CCTs, according to a modified PECARN clinicobiological decision rule, had we taken into account the result of the blood tests. One hundred nine children were included, and nine of them had clinically important traumatic brain injury. Four of them had a negative S100ß value but were classified as high risk of developing intracranial lesion according to the PECARN clinical decision rule. Had we taken into account the modified PECARN clinicobiological decision rule, none of them would have been missed. However, there were 32 true negatives of the rule, allowing a potential decrease in CCTs rated at 29% (95% confidence interval, 21-38). Integrating the serum S100ß neuroprotein assessment in the PECARN clinical decision rule could avoid deleterious exposure to CCT radiation, with the condition of using a clinicobiological rule to avoid missing clinically important traumatic brain injuries. Those results have yet to be confirmed relying on a large multicentric study.

Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy.

Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.

Development of intestinal microbiota in infants and its impact on health.

Throughout the human lifetime, the intestinal microbiota performs vital functions, such as barrier function, metabolic reactions, trophic effects, and maturation of the host's innate and adaptive immune responses. Development of the intestinal microbiota in infants is characterized by rapid and large changes in microbial abundance, diversity, and composition. These changes are influenced by medical, cultural, and environmental factors such as mode of delivery, diet, familial environment, diseases, and therapies used. Thus, it is nearly impossible to define a universal standard for intestinal colonization and development of the intestinal microbiota. This review discusses recent data on the early colonization of the gut by microbial species, development of the intestinal microbiota, and its impact on health.

Eradication of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit: which measures for which success?

BACKGROUND: Various strategies for controlling methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in neonatal intensive care units (NICUs) have been tried, with varying levels of success. We report a MRSA outbreak occurring between April 2004 and August 2007 in a 24-bed NICU in a large university hospital. We describe the difficulties involved in implementing measures to control the MRSA outbreak and the possible contribution of each measure. METHODS: Cases were defined as neonates with MRSA obtained from either clinical cultures or surveillance cultures (from the anterior nares). Systematic screening of neonates for colonization was performed only between February and December 2005. Successive control strategies included barrier precaution and isolation in individual rooms, mupirocine ointment for neonates and health care workers, cohort isolation, hand hygiene observation, and staff training. RESULTS: During the routine surveillance culture period (February to December 2005; 48 weeks), 46 neonates were found to be positive for MRSA and were treated with mupirocin. After December 2005, the outbreak was controlled, but the ongoing spread was not eradicated; 9 sporadic MRSA cases were detected by clinical culture up to August 2007. CONCLUSION: The widespread use of mupirocine in staff and patients did not control the outbreak and is not recommended. The later control appeared to coincide with increased hand hygiene audits and training for staff, along with appropriate cohort isolation of neonates and cohort nursing.

Effects of hydroxyethyl starch on cardiac output in hypotensive neonates: a comparison with isotonic saline and 5% albumin.

AIM: To evaluate the effects of hydroxyethyl starch (6% HES 200/0.5) on cardiac output in hypotensive neonates with low cardiac output and absence of myocardial dysfunction. METHODS: In a prospective randomized blinded trial, 21 hypotensive neonates (mean gestational age of 29+/-3 wk) were randomly allocated to receive infusions of either 5% albumin (albumin group), isotonic saline (saline group) or hydroxyethyl starch (HES group). Infants had to show low cardiac output and an absence of myocardial dysfunction for inclusion in the study. Cardiac output was assessed by Doppler-derived mean aortic flow velocity. RESULTS: Ten minutes after infusion, 67% of all infants had more than a 10% increase in cardiac output. Increases in mean aortic flow velocity (m/s; median and range) were 0.05 (-0.02, +0.07), 0.03 (-0.03, +0.12) and 0.03 (-0.04, +0.11) for the albumin, saline and HES groups, respectively (p = 0.79). The percentage of blood pressure normalization (95% confidence interval) was 86% (60-100) in the albumin group, 57% (20-94) in the saline group and 71% (37-100) in the HES group (p = 0.50). CONCLUSION: This study did not provide evidence that hydroxyethyl starch is more efficient than isotonic saline or albumin.

The effects of milrinone on hemodynamics in an experimental septic shock model.

OBJECTIVE: To investigate the specific hemodynamic effects of the phosphodiesterase inhibitor milrinone in a rabbit model of septic shock in the absence of any other treatment. DESIGN: A prospective, controlled, interventional study. Animal Model: Fourteen sedated New Zealand rabbits. SETTING: Research laboratory of a health sciences university. INTERVENTIONS: Rabbits were anesthetized and vascular catheters inserted in femoral artery and jugular vein. After a stabilization period and the recording of baseline measurements (H0), all animals received a 10-mL infusion of Pseudomonas aeruginosa. Two hours later (H2rabbits were randomly assigned to receive 5% dextrose (control group) or milrinone (milrinone group). MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP) was monitored continuously, and a cardiac index (CI) was determined every 30 mins by a transpulmonary thermodilution technique using an integrated monitoring device (PICCO). No differences were detected between the two groups after stabilization (H0) or before the treatment (H2) for either CI (mL/min(-1)/kg(-1)) or MAP (mm Hg). CI decreased progressively in the control group during the following 4 hrs, but not in the treated group (at H6: 122 +/- 4 vs. 207 +/- 16 mL/min(-1)/kg(-1); p < .05). No drop of MAP occurred after milrinone infusion. A comparison of the treated and control group reveals that milrinone improved tissue perfusion as evidenced by measurements of central venous saturation (at H4: 0.59 +/- 0.05 vs. 0.71 +/- 0.03, p = .04), lactacidemia (at H6: 10.3 +/- 2.4 vs. 3.9 +/- 0.9 mmol/L, p = .03), creatinemia (at H6: 95 +/- 11 vs. 60 +/- 5 micromol/L, p = .02) and survival (at H6: 5 vs. 7, not significant). CONCLUSION: Milrinone improves cardiac output and tissue perfusion in a rabbit model involving severe septic shock.

Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with patent ductus arteriosus.

We investigated the effects of dopamine on pulmonary artery pressure in 18 ventilated hypotensive preterm neonates by using the flow characteristics of the ductal shunt. Dopamine has variable effects on pulmonary/systemic mean arterial pressure ratio with half the neonates showing an increase in pulmonary pressure relative to systemic pressure.