Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Umbilical Cord Procalcitonin to Detect Early-Onset Sepsis in Newborns: A Promising Biomarker.

Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship. Methods: Umbilical cord blood PCT was tested in newborns ≥ 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for <72 h (n = 49); C) Risk factor(s) for EOS without need for antibiotic treatment (n = 181); D) Healthy controls (n = 74). Additionally, venous or capillary blood PCT and C-reactive protein (CRP) were tested if blood drawing was necessary for standard care. Results: Between June 2019 and March 2021, 329 newborns were included. Umbilical cord blood PCT was significantly higher in group A than in group C and D. No difference between venous or arterial samples was found. Sensitivity and specificity for cord blood procalcitonin were 83 and 62%, respectively (cut-off 0.1 ng/mL). Antepartum maternal antibiotic administration was associated with decreased PCT levels in both cord blood and infant blood directly postpartum in all groups combined. Conclusion: Umbilical cord blood PCT levels are increased in newborns ≥32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.

Meningococcal carriage in Dutch adolescents and young adults; a cross-sectional and longitudinal cohort study.

OBJECTIVES: Current information on rates and dynamics of meningococcal carriage is essential for public health policy. This study aimed to determine meningococcal carriage prevalence, its risk factors and duration in the Netherlands, where meningococcal C vaccine coverage is >90%. Several methods to identify serogroups of meningococcal carriage isolates among adolescent and young adults were compared. METHODS: Oropharyngeal swabs were collected from 1715 participants 13-23 years of age in 2013-2014; 300 were prospectively followed over 8 months. Cultured isolates were characterized by Ouchterlony, real-time (rt-) PCR or whole-genome sequencing (WGS). Direct swabs were assessed by rt-PCR. Questionnaires on environmental factors and behaviour were also obtained. RESULTS: A meningococcal isolate was identified in 270/1715 (16%) participants by culture. Of MenB isolates identified by whole genome sequencing, 37/72 (51%) were correctly serogrouped by Ouchterlony, 46/51 (90%) by rt-PCR of cultured isolates, and 39/51 (76%) by rt-PCR directly on swabs. A sharp increase in carriage was observed before the age of 15 years. The age-related association disappeared after correction for smoking, level of education, frequent attendance to crowded social venues, kissing in the previous week and alcohol consumption. Three participants carried the same strain identified at three consecutive visits in an 8-month period. In these isolates, progressively acquired mutations were observed. CONCLUSIONS: Whole genome sequencing of culture isolates was the most sensitive method for serogroup identification. Based upon results of this study and risk of meningococcal disease, an adolescent meningococcal vaccination might include children before the age of 15 years to confer individual protection and potentially to establish herd protection.

A pseudoleukemic blood differentiation in a 13-year-old child: an extraordinary presentation of Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis of the small- and medium-size vessels. It is mostly seen in elderly patients presenting as de novo asthma, eosinophilia, and vasculitic organ involvement. In childhood, CSS is extremely rare. The course of pediatric CSS is usually severe and often lethal. We present a case of a 13-year-old girl with a short history of asthma, marked eosinophilia, and multiorgan involvement. The extremely high level of blood eosinophilic granulocytes (51.6 × 10(9)/L) prompted a workup for eosinophilic leukemia before the diagnosis CSS could be made. Subsequently, the disease was successfully treated. This case report shows a classical case of childhood CSS, remarkable because of the presence of extreme hypereosinophilia. It underlines the importance of CSS as a life-threatening cause of hypereosinophilia in children.

[Outbreak of coxsackievirus infection in children]. / Uitbraak van coxsackievirusinfectie bij kinderen.

During the summer of 2006 in the paediatric ward of the Spaarne Hospital in Hoofddorp, the Netherlands, a large number of children were admitted with a coxsackievirus type-B infection, one of the enteroviruses. A total of 27 children were diagnosed with this virus. Patient A, a one-month-old boy, was admitted with fever. The spinal fluid showed a high leukocyte count. He was treated with amoxicillin, ceftriaxon and acyclovir, and recovered rapidly. The spinal fluid culture was positive for coxsackievirus type B5. Patient B, a 3-year-old girl, presented with attacks of abdominal pain and groaning respiration. Infection parameters were mildly elevated. The chest X-ray was normal. She was admitted for observation and recovered spontaneously. Viral faeces culture revealed coxsackievirus type B4. Rapid recognition of an enterovirus infection is important to prevent unnecessary diagnostic and therapeutic interventions. PCR is a diagnostic technique of great importance.

[Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine cream]. / Coma bij een peuter na behandeling met de 'toverzalf' lidocaine-prilocaïnecrème.

A 2-year-old girl lost consciousness after the topical application of lidocaine-prilocaine cream (EMLA) in preparation for the removal of multiple mollusca contagiosa. Both the area on which cream was applied (80% of body surface) and the total amount of cream (90 g) exceeded the maximum dosage. Lidocaine-prilocaine cream is a widely used local anaesthetic with few side effects when used properly. Intoxication with a lidocaine-prilocaine preparation may have serious consequences, such as changes in intracardiac conduction, excitation or depression of the central nervous system and methaemoglobinaemia. In our patient both methaemoglobinaemia and depression of the central nervous system occurred, resulting in loss of consciousness. She was treated with 100% oxygen and fully recovered.

Does the empiric use of vancomycin in pediatrics increase the risk for Gram-negative bacteremia?

BACKGROUND: Gram-negative bacteremia in children, a major cause of morbidity and mortality, may in part be induced by intensive treatment procedures and nonspecific use of antibiotics. Our primary objective was to study the causal relationship between the use of vancomycin and Gram-negative bacteremia, for which this antibiotic is not specifically indicated. METHODS: The study was conducted in a 105-bed tertiary care children's hospital in the period of 1994 to 1997. The study pertains to a cohort of children with suspected bacteremia, in whom a blood culture was performed during hospital stay. Using the bacteriologic laboratory registration system, we selected all pediatric cases with bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample of 225 pediatric controls with negative blood cultures. Using logistic regression analysis we examined associations between Gram-negative bacteremia and the following factors: preceding use of antibiotics, antacids, corticosteroids, surgery, mechanical ventilation, parenteral nutrition, and invasive instrumentation; and the intensity of care assessed with the Therapeutic Intensity Scoring System (TISS 28). RESULTS: Gram-negative bacteremia was positively associated with the use of aminoglycosides, cephalosporins, surgical interventions, central venous catheters, parenteral nutrition, antacids and dexamethasone. The strongest association was with the use of vancomycin (odds ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic regression model containing all above-mentioned variables, the use of vancomycin remained positively and strongly associated with Gram-negative bacteremia (odds ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and restrictions in the analysis did not materially change these findings concerning vancomycin. CONCLUSIONS: Among children suspected of bacteremia there are several drugs and clinical procedures influencing the risk for Gram-negative bacteremia. Empiric use of vancomycin is strongly and independently associated with Gram-negative bacteremia. The safety of using vancomycin solely on the basis of suspicion of bacteremia in children may not be warranted.

Antibiotic utilisation for hospitalised paediatric patients.

Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such policies can be implemented, detailed knowledge of antibiotic prescribing patterns is important. In this combined retrospective and prospective study the utilisation of antibiotics in a paediatric university hospital over three consecutive years has been analysed. Over an 8-week period (1 November-22 December) in 1994, 1995 and 1996 patient charts were reviewed with regard to antibiotic prescription (generic class, dose, duration and indication). A total of 1120 patients were admitted during the study periods. Antibiotics were prescribed at least once for 36% of hospitalised children, although only 12.3% of the patients receiving antibiotics had a proven bacterial infection. During a single hospitalisation 13, 4.7, 2.6, and 2.7% of all children received 2, 3, 4 or more than four antibiotics, respectively. Infants less than 2 years received antibiotics more frequently than older children (25 and 11% respectively, P=0.0256). More children admitted to the intensive care unit received antibiotics compared with patients admitted on medium care units (49.7 and 29.3% respectively, P < 0.0001). They received more often several different antibiotic courses (2.6 courses per patient versus 1.9 courses per patient, P < 0.0001). These children were also given more often intravenous rather than oral antibiotics (P < 0.0001) Significant differences could be found between the generic classes of antibiotics prescribed to children admitted to the intensive care unit and the medium care. However high variability in dose and duration of antibiotic therapy for the same clinical indication was shown. A high percentage of all hospitalised children receive antibiotics. In most cases antibiotics are started on an empirical basis, without proof of a bacterial infection, either before the start of therapy or afterwards. The fact that children admitted to intensive care units and patients of younger age groups are at special risk of receiving multiple courses of antibiotics, together with the knowledge that antibiotic resistance develops in this setting, suggest that strategies to control antibiotic use should focus on these patient populations.

[Primary peritonitis due to Streptococcus pneumoniae in childhood]. / Primaire peritonitis door Streptococcus pneumoniae op de kinderleeftijd.

Three patients, two boys of 5 months and 6 years and one girl aged 4 years, presented with acute abdominal pain, vomiting and fever, suggesting peritonitis. Imaging examinations (abdominal survey roentgenogram and (or) echography), exploratory laparotomy (in two patients) and blood cultures with growth of Streptococcus pneumoniae led to the diagnosis of primary peritonitis. Intravenous antibiotics led to recovery, in one patient complicated by paralytic ileus, which was treated surgically. Primary peritonitis is a rare condition which should be considered in the differential diagnosis of children with an acute abdominal syndrome. Conditions requiring surgery should be excluded by imaging examinations or laparotomy. When the diagnosis is confirmed by paracentesis or laparotomy, antibiotic treatment has to be started.

Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics.

UNLABELLED: In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such a policy can be implemented, detailed knowledge of antibiotic prescribing patterns and related costs is important. In this study a shift of antibiotic prescription patterns over time is described in relation to hospital antibiotic expenditure. CONCLUSIONS: A considerable shift in prescription patterns towards more expensive and broader spectrum antibiotics occurs in paediatrics, carrying a risk for the development of antibiotic resistance among the most prevalent micro-organisms in this age group.