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Pediatric oncology and hematopoietic stem cell transplantation patients are facing many gastrointestinal side effects of chemotherapy, including nausea, vomiting, mucositis, and diarrhea. International guidelines advise early enteral tube feeding as the first option of nutritional support in children undergoing myeloablative hematopoietic stem cell transplantation. When using enteral feeding tubes for nutritional purposes as well as drug administration, some pharmaceutical, nursing, and technical issues have to be taken into account. Ciprofloxacin is a fluoroquinolone, widely used because of its broad spectrum antimicrobial activity and favorable pharmacokinetic properties. However, its co-administration with polyvalent cations (as present in enteral feeding) makes the absorption of ciprofloxacin more difficult and may alter the pharmacokinetic parameters. Literature data are conflicting on how long the enteral feeding should be discontinued for patients receiving ciprofloxacin via an enteral feeding tube, ranging from 2 h before to 6 h after the administration of ciprofloxacin. Our research question was guided by challenges and concerns of nurses about the delay time between ciprofloxacin administration and restart of the enteral feeding without compromising the nutritional intake of the children. Our guideline was adapted, nurses were instructed accordingly, and patient leaflets with correct information were created.

Prospective audit with feedback during infectious diseases ward rounds (IDWR) is a common antibiotic stewardship (AS) practice on the Pediatric Intensive Care Unit (PICU). These interdisciplinary meetings rely on the quality of handover, with high risk of omission of information. We developed an electronic platform integrating infection-related patient data (COSARAPed). In the mixed PICU of a Belgian tertiary hospital we conducted an observational prospective cohort study comparing patient handovers during IDWRs using the COSARAPed-platform to those with access only to conventional resources. The quality of handover was investigated directly by assessment if the narrative was in accordance with SBAR (Situation-Background-Assessment-Recommendation) principles and if adequate demonstration of diagnostic information occurred, and also indirectly by registration if this was only achieved after intervention by the non-presenting AS team members. We also recorded all AS-recommendations. During a 6-month study period, 24 IDWRs and 82 patient presentations were assessed. We found a statistically significant advantage in favor of COSARAPed by indirect evaluation. We registered 92 AS-recommendations, mainly resulting in reduced antibiotic pressure. We concluded that the IDWR is an appropriate platform for AS-interventions on the PICU and that the utilisation of COSARAPed enhances the quality of patient handover.

Objectives: Congenital tracheomalacia can be the cause of respiratory failure in young children. Although the indication for surgical treatment has already been dis-cussed vigorously, no clear guidelines about the modality are available.Methods: Through a sternotomy approach, a combination of posterior pexy and anterior tracheopexy using a tailored ringed polytetrafluoroethylene prosthesis is performed. Patient demographic characteristics, as well as operative details and postoperative outcomes, are included in the analysis.Results: Between 2018 and 2022, 9 children underwent the operation under review. All patients showed severe clinical symptoms of tracheomalacia, which was confirmed on bronchoscopy. The median age was 9 months. There was no opera-tive mortality. Eight patients could be weaned from the ventilator. One patient died because of interstitial lung disease with bronchomalacia and concomitant severe cardiac disease. The longest follow-up now is 4 years, and shows overall excellent clinical results, without any reintervention. Conclusions: Surgical treatment of tracheomalacia through a combination of pos-terior and anterior pexy is feasible, with acceptable short-and midterm results. (JTCVS Techniques 2023;17:159-63)

Background Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment. Objective To assess target attainment after initial dosing and dose adjustments, and to determine compliance to dosing and TDM guidelines. Setting Tertiary care university hospital in Belgium. Method A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines. Main outcome measures Target attainment of vancomycin after initial dosing and dose adjustments. Results Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1-Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates). Conclusion Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved.

Background: Molecular detection of SARS-CoV-2 in respiratory samples is the gold standard for COVID-19 diagnosis but it has a long turnaround time and struggles to detect low viral loads. Serology could help to diagnose suspected cases which lack molecular confirmation. Two case reports are presented as illustration. Objectives: The aim of this study was to evaluate the performance of several commercial assays for COVID-19 serology. We illustrated the added value of COVID-19 serology testing in suspect COVID-19 cases with negative molecular test. Study design: Twenty-three sera from 7 patients with a confirmed molecular diagnosis of SARS-CoV-2 were tested using 14 commercial assays. Additionally, 10 pre-pandemic sera and 9 potentially cross-reactive sera were selected. We calculated sensitivity and specificity. Furthermore, we discuss the diagnostic relevance of COVID-19 serology in a retrospective cohort of 145 COVID-19 cases in which repetitive molecular and serological SARS-CoV-2 tests were applied. Results: The interpretation of the pooled sensitivity of IgM/A and IgG resulted in the highest values (range 14–71% on day 2–7; 88–94% on day 8–18). Overall, the specificity of the assays was high (range 79–100%). Among 145 retrospective cases, 3 cases (2%) remained negative after sequential molecular testing but positive on final SARS-CoV-2 serology. Conclusion: Sensitivity of COVID-19 serological diagnosis was variable but consistently increased at >7 days after symptom onset. Specificity was high. Our data suggest that serology can complement molecular testing for diagnosis of COVID-19, especially for patients presenting the 2nd week after symptom onset or later.

Antibiotics are one of the most prescribed drug classes in the pediatric intensive care unit, yet the incidence of inappropriate antibiotic prescribing remains high in critically ill children. Optimizing the use of antibiotics in this population is imperative to guarantee adequate treatment, avoid toxicity and the occurrence of antibiotic resistance, both on a patient level and on a population level. Antibiotic stewardship encompasses all initiatives to promote responsible antibiotic usage and the PICU represents a major target environment for antibiotic stewardship programs. This narrative review provides a summary of the available knowledge on the optimal selection, duration, dosage, and route of administration of antibiotic treatment in critically ill children. Overall, more scientific evidence on how to optimize antibiotic treatment is warranted in this population. We also give our personal expert opinion on research priorities.

Cystic fibrosis is a lethal inherited disease that affects multiple organs. To provide optimal pharmacological treatment of comorbidities associated with cystic fibrosis, relevant alterations in pharmacokinetics must be known. The objective of this study was to compare the pharmacokinetics of drugs between patients with cystic fibrosis and controls, based on clinical study reports published from 1999 to 2019. Clinical studies were considered if patients with cystic fibrosis and patients without cystic fibrosis/healthy volunteers were included, a drug was administered orally/intravenously and pharmacokinetic parameters were compared. In total, 32 clinical studies were included. Twenty-one studies reported absorption parameters. For multiple drugs, speed and/or extent of oral absorption were lower in cystic fibrosis. This phenomenon is possibly related to pathophysiological changes in the gastrointestinal tract associated with cystic fibrosis. However, a large proportion of drugs had comparable absorption kinetics. Twenty-one studies discussed volume of distribution, which was comparable between groups for most drugs. Initial differences became smaller when scaled to body composition. For some highly protein-bound drugs, inflammation-related changes in plasma proteins helped explain residual variability between cystic fibrosis and controls. Twenty-four studies elaborated on clearance, whereby higher clearances were observed in cystic fibrosis. In contrast with previously published reviews, no evidence was found for increased activities of drug-metabolising enzymes nor for up-regulation of active transport processes involved in drug disposition. In most cases, scaling clearance parameters to body composition and/or incorporating differences in plasma protein concentration accounted for these larger clearances. There is no evidence that genetic defects causing cystic fibrosis directly lead to altered pharmacokinetics. However, co-morbidities can have a potential impact on drug absorption and disposition. Because of gastrointestinal complications, it is not advisable to extrapolate drug absorption parameters from healthy volunteers to patients with cystic fibrosis. Differences observed in the volume of distribution and clearance in patients with cystic fibrosis can potentially be explained by correcting for lean body mass.

BackgroundThe comparative performance of saliva and nasopharyngeal samples for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcriptase polymerase chain reaction (RT-PCR) in children remains unclear. As schools reopen around the world, there is an interest in the use of saliva samples for the detection of SARS-CoV-2 in children to circumvent barriers with nasopharyngeal sampling. We systematically reviewed the literature to understand the performance of saliva sampling using RT-PCR on naso- and/or oropharyngeal swabs as the reference standard.MethodsArticles from PubMed/MEDLINE and Living Evidence were accessed until 28th April 2021. A search method without restriction to children population was applied and during the review phase, if a study included patients ResultsTen studies were included, comprising 1486 matched saliva and on naso- and/or oropharyngeal pairs from children aged 0 to 18 years old. The pooled absolute sensitivity and specificity of saliva sampling using RT-PCR on nasopharyngeal samples as the reference standard was 84.5% (95% CI; 78.0%-90.3%) and 99.5% (95% CI; 98.2%-100.0%). Comparable performance of saliva to nasopharyngeal samples was shown in both symptomatic and asymptomatic children. Stratified analyses of various covariates showed no significant differences.DiscussionOur pooled accuracy estimates of RT-PCR SARS-CoV-2 testing on saliva in children did not seem to be different from meta-analyses of studies that enrolled mainly adults. Saliva could potentially be considered an alternative sampling method for screening in children and to pick up those with high viral load.

Objective The COVID-19 pandemic and associated quarantine measures highly impacted parental psychological well-being. Parents of children with chronic diseases might be specifically vulnerable as they already face multiple challenges to provide adequate care for their child. The research questions of the current study were twofold: (a) to examine whether parents of children with a chronic disease experienced more anxiety and depression compared to parents of healthy children and (b) to examine a series of risk factors for worsened well-being (i.e., depression, anxiety, and sleep problems), such as sociodemographic variables, COVID-19-specific variables (i.e., financial worries, living space, and perceived quality of health care), and parental psychological experiences (i.e., parental burn-out and less positive parenting experiences). Methods Parents of children with a chronic disease (i.e., the clinical sample; N = 599 and 507 for Research Questions 1 and 2, respectively) and parents of healthy children (i.e., the reference sample: N = 417) filled out an online survey. Results Findings demonstrated that the parents in the clinical sample reported higher levels of anxiety than parents in the reference sample. Analyses within the clinical sample indicated that COVID-19-specific stressors and parental psychological experiences were associated with higher levels of anxiety, depression, and sleep problems. Mediation analyses furthermore indicated that the association of COVID-19-specific stressors with all outcome measures was mediated by parental burn-out. Conclusions Parents of children with a chronic disease constitute a vulnerable group for worse well-being during the current pandemic. Findings suggest interventions directly targeting parental burn-out are warranted.

Vallecular cyst: a rare cause of progressive inspiratory stridor in a neonate The medical history of an infant with progressive inspiratory stridor caused by a vallecular cyst is presented. The cyst was diagnosed via a laryngoscopy and treated by means of an excision. The postoperative course was complicated by severe stridor induced by post-intubation edema. This report elaborates on the clinical presentation and work-up. The differential diagnosis of neonatal stridor is exhaustive. A congenital vallecular mass rarely causes it. These masses can manifest in various ways. Symptoms usually develop during the first week(s) of life. Key symptoms are upper airway obstruction and feeding difficulties. Life threatening situations are also possible. Given that the exact etiology of vallecular cysts remains unclear, different hypotheses were proposed. The differential diagnosis should include a dermoid cyst, a thyroglossal duct cyst, a teratoma, an hemangioma or lingual thyroid. The diagnosis usually requires a flexible and/or direct laryngoscopy. Radiographic imaging may also contribute to the work-up, adding information about the anatomical dimensions (for example with regard to the surrounding structures), the exact location, the magnitude, the content, etc. The definitive diagnosis is made through pathological evaluation. Different treatment options are proposed, preferably endoscopic excision or marsupialization.

Background Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment. Objective To assess target attainment after initial dosing and dose adjustments, and to determine compliance to dosing and TDM guidelines. Setting Tertiary care university hospital in Belgium. Method A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines. Main outcome measures Target attainment of vancomycin after initial dosing and dose adjustments. Results Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1-Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates). Conclusion Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved.

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Background Allergic bronchopulmonary aspergillosis (ABPA) is a major complication in cystic fibrosis (CF) patients. Risk factors for ABPA and clinical deterioration in CF patients, negative for Pseudomonas aeruginosa (Pa), were explored. Methods We performed a retrospective case-control study in 73 Pa-negative patients. Each patient was matched with 2 controls for age, gender, pancreas sufficiency, DeltaF508 mutation (homozygous or heterozygous), and Pa colonization. Results Median FEV1 at the year of diagnosis (index year) was significantly lower in patients with ABPA. The median of cumulative values of FEV1 and FVC before the index year was not significantly different. After the index year, the median of cumulative data for FEV1 and FVC was significantly lower; there were significantly more hospitalization days and more IV antibiotic days compared to controls. Comparing pre- and post-index year data in patients with ABPA, significantly more hospitalization days and more IV antibiotic days were observed after the index year. During the period preceding the index year, significantly more ABPA patients were treated with rhDNase and inhaled corticosteroids. Conclusions Bronchial damage cannot be considered as a facilitating factor for ABPA. ABPA causes a significant increase in bronchial damage. In patients with ABPA, further bronchial damage can be controlled by an increase in hospitalization days and use of IV antibiotics. rhDNase and inhaled corticosteroids were associated with the development of ABPA.

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Studies in children evaluating the long term impact of lobectomy on pulmonary function are rare. The aim of the study was to evaluate lung function parameters in children, several years after lobectomy. A retrospective study was conducted in 3 Belgian university hospitals, on children under the age of 16 years who underwent lobectomy between 1996 and 2016. Demographic data, associated anomalies, lobectomy indication, surgical procedure, complications and pulmonary function tests were extracted from patient files and analyzed. Hundred-eight patients were included. The most common indication for lobectomy was a congenital lung lesion (41%). Seventy-seven patients performed postoperative pulmonary function tests at different time intervals (mean 5.2 yrs post-surgery; range 2 months -15 yrs). TLC, FVC, FEV1 and FEV1/FVC were within limits of normal for 84%, 74%, 72% and 68% of the population respectively. Almost two thirds of the study population had maximal expiratory flows (MEF) at 25%, 50%, 75% and 25%-75% below 80% predicted. Fifty percent of patients had a residual volume (RV) above 120% predicted. Pulmonary function parameters were not significantly different between children who had surgery below versus above the age of 1 and 2 years. There was no short or long term mortality from the lobectomy. Twenty-six patients had a minor complication, the most common being pneumothorax, and two patients had a major complication. In conclusion, the majority of the study population had normal TLC, FEV1 and FVC post lobectomy, however decreased MEF values and increased RV suggest an increased incidence of small airway obstruction. Larger prospective studies are needed to confirm and explain these findings.

Hyperinflammatory syndromes are life-threatening disorders caused by overzealous immune cell activation and cytokine release, often resulting from defects in negative feedback mechanisms. In the quintessential hyperinflammatory syndrome familial hemophagocytic lymphohistiocytosis (HLH), inborn errors of cytotoxicity result in effector cell accumulation, immune dysregulation and, if untreated, tissue damage and death. Here, we describe a human case with a homozygous nonsense R688* RC3H1 mutation suffering from hyperinflammation, presenting as relapsing HLH. RC3H1 encodes Roquin-1, a posttranscriptional repressor of immune-regulatory proteins such as ICOS, OX40 and TNF. Comparing the R688* variant with the murine M199R variant reveals a phenotypic resemblance, both in immune cell activation, hypercytokinemia and disease development. Mechanistically, R688* Roquin-1 fails to localize to P-bodies and interact with the CCR4-NOT deadenylation complex, impeding mRNA decay and dysregulating cytokine production. The results from this unique case suggest that impaired Roquin-1 function provokes hyperinflammation by a failure to quench immune activation., Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Pulmonary interstitial glycogenosis (PIG) is a rare interstitial lung disease in children. The clinical hallmark is a rapid onset with respiratory distress and hypoxemia shortly after birth in the absence of an infectious cause or a surfactant dysfunction syndrome. The diagnosis can only be made by lung biopsy. The histopathological pattern defining PIG can exist in diffuse or patchy distribution. Only few cases have been reported. Not much is known on clinical features, outcomes, CT imaging and histopathology. Methods: The clinical course, CT-scans and tissue samples of children diagnosed with PIG were collected and systematically re-analysed by clinicians, radiologists and pathologists all specialized in interstitial lung diseases in children. All data were uploaded into the Kidslungregister for follow up. Results: 11 children diagnosed with PIG were included in this study. All presented with respiratory distress shortly after birth. More than half of the children were diagnosed with additional abnormalities, especially congenital heart defects. The CT-scan of the lungs showed mainly groundglass opacities, consolidations and septal thickening. Of interest each tissue sample had signs of reduced alveolarization. The prognosis was favourable in almost all cases. When systemic glucocorticosteroids were given a fast improvement was noticed. Conclusion: PIG is a interstitial lung disease in infants with mostly favourable outcome. As alveolar growth retardation was present in all subjects this can support a theory of an underlying maturation delay. In all infants with congenital heart defects and unexplained respiratory distress an interstitial lung disease due to PIG should be considered.

BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients.METHODS: In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically.RESULTS: 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization.CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.

Background: This study aims to determine the prevalence and characteristics of Staphylococcus aureus in Belgian cystic fibrosis (CF) patients. Methods: Non-duplicate respiratory samples from 510 CF-patients (2012−2013) were examined. One isolate per patient was analysed unless different phenotypes were recovered. Isolates were investigated for mecA/mecC, toxins presence, spa-typing, MLST and SCCmec-typing. Potential livestock-associated (LA) isolates were examined for their immune-evasion-cluster (IEC) genes. Results: S. aureus (n = 380), including 41 small-colony variants (SCVs), were isolated from 66.7% patients. The prevalence of methicillin-resistant S. aureus (MRSA) colonization was 4.9%. Two MRSA isolates carried toxic shock syndrome toxin 1 (TSST-1). Most MRSA (65%) belonged to two nosocomial epidemic clones (CC5, CC8) widespread in Belgium. Methicillin susceptible S. aureus (MSSA) showed great genetic diversity. Five of 33 isolates belonging to potential LA-lineages were IEC negative, including three methicillin-resistant isolates, suggesting an animal origin. Conclusions: The MRSA-prevalence in Belgian CF-patients remained constant (2001−2013), but SCV-prevalence increased. Most MRSA belonged to health-care-associated clones. Three patients carrying LA-MRSA were found, requiring further investigation to determine the risk factors for LA-MRSA acquisition., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Vancomycin (VCM) is a renally cleared glycopeptide commonly used against (pre-emptive/documented) infections caused by gram-positive species. Therapeutic drug monitoring is strongly recommended to achieve target trough serum concentrations. Augmented renal clearance (ARC) has been reported in children with malignancies and has been associated with subtherapeutic antibiotic concentrations. Aim Investigation of ARC prevalence and risk factors in a pediatric hematology-oncology (PHO) and Stem Cell Transplantation (SCT) center. Methods A 2-year, single-center, retrospective study. The ARC was defined as glomerular filtration of > 130 ml/min/1.73m² (modified Schwartz formula). A VCM ‘episode' was defined as the period from start till stop of VCM therapy. Approval of the local ethical committee was obtained. Results Sixty-eight patients (29/68; 43%) males; mean age 7.6 year (+/- 5.2y) representing 102 VCM-episodes, with hematological malignancies (47/68; 69.1%), solid tumors (10/68; 14.7%) and ‘others' (SCT/non-SCT indications) (11/68; 16.2%). ARC was observed in 55/102 episodes (53.9%) before start and 51/102 (50.0%) at stop of VCM therapy. Neutropenia and especially febrile neutropenia were identified as risk factor for ARC (p = 0.044 and 0.013, respectively). Of 68 patients, 16 underwent SCT (1 autologous, 22 allogeneic), representing 23 episodes of VCM. ARC was observed in 11/23 (47.8%) before start and 3/23 (13.0%) episodes after stop of VCM therapy. A significant trend toward decreasing filtration at stop of VCM therapy (p Discussion ARC is commonly present in pediatric PHO/SCT patients. Febrile neutropenia is identified as a significant risk factor for ARC. SCT patients commonly have a state of ARC, which significantly decreases over time during VCM therapy. This inverse correlation highlights the need for close monitoring of VCM in order to maintain adequate therapeutic levels in SCT patients.

Case description The use of i.v. colistin reappeared recently for the treatment of multidrug-resistant Gram negative organisms in the intensive care and cystic fibrosis (CF) setting. According to the latest pharmacokinetic data, a loading dose and high antibiotic doses are given. Two cases of adverse events (paraesthesias, bad taste) were observed immediately after the start of infusion of a high dose of i.v. colistin in adult CF patients at the Ghent University Hospital. Conclusion Recommendations for optimal administration of i.v. colistin in adult CF patients are scarce. This article highlights the importance of mode of administration to avoid toxicity and relates it to recent pharmacokinetic/-dynamic literature.

Purpose Protective immunity to vaccine preventable infectious diseases might be lost over time following hematopoietic stem cell transplantation (HSCT). Limited data are available on the appropriate follow-up of vaccination schedules in pediatric HSCT patients. This study aims to ascertain whether the guidelines for vaccination recommended in our hospital are followed and to which extent of conformity they are used. Methods A 5-year survey, including all pediatric allogeneic HSCT patients, transplanted at the Ghent University hospital, Belgium. Data were collected from the patient's electronic (nursing and medical) charts. Results Data on vaccination schedules of 28 patients (54.9%) eligible for the recommended vaccinations were collected. Eleven patients (11/28; 39.3%) were vaccinated timely. In 14 out of 17 patients (82.4%) vaccination was postponed for medical reasons, while vaccination was postponed without medical reason in 17.6% (3/17). Vaccination data could not be retrieved in 43.1 (22/51) of patients. Vaccination was declined by the parents in one patient (2.0%). Conclusion There is high level of agreement between the hospital guideline and the vaccination of pediatric HSCT patients. Health-care providers play a crucial role in effectively appropriate follow-up of vaccination schedules.

After antibiotic eradication treatment for a first ever Pseudomonas aeruginosa isolation, the European consensus criteria (ECC) are widely used to assess colonization status with P. aeruginosa in CF-patients. We evaluated to what extent genotyping (GT) of subsequent P. aeruginosa isolates could predict/assess chronic colonization (CC), in comparison with the ECC. Methods Over a 14-year period, sputa were cultured from 80 CF-patients (age range: 2–51 years), from a first ever isolation of P. aeruginosa onwards. Patients with a positive culture for P. aeruginosa received antibiotic eradication treatment. For the 40 patients for whom three or more P. aeruginosa isolates were available, these isolates were genotyped. Results According to the ECC, 27 out of the 40 patients (67.5%) became CC during the study period (ECC-positive patients). Genotyping confirmed persistence of the same genotype for 25 of these ECC-positive patients. Genotyping indicated persistence of the same genotype for at least two subsequent isolates for 5 out of 13 ECC-negative patients. Culture-positivity characteristics of the 27 ECC-positive patients corresponded well to those of the 30 GT-positive patients, with an overall higher number of positive cultures as well as a shorter interval in between first and second isolate compared to ECC-negative and GT-negative patients. Genotyping indicated persistence of the same genotype on average 9.3 months earlier than CC according to the ECC (P Conclusions Genotyping of P. aeruginosa isolates confirmed CC for 25 out of 27 ECC-positive patients (92.6% specificity) and predicted CC 9.3 months earlier than the ECC.

This study evaluates the impact of antibiotic treatments and hospitalization on exercise performance and health-related quality of life (QOL) in children with mild cystic fibrosis (CF) lung disease. Forty-seven children between 7 and 17 years with mild CF underwent a maximal exercise test including spiro-ergometry and filled out a QOL-questionnaire (PedsQL™). Amount of antibiotic treatments (AB) and hospitalization days in the last 3 years were reviewed. FEV1% was mildly decreased (91.7 ± 17.9 L/min, p = 0.02). Maximal oxygen consumption (VO2max), test duration and anaerobic threshold were lower compared to a control population (VO2max% 94 ± 15 vs 103 ± 13, p = 0.009). FEV1% correlated with AB and hospitalization episodes in the last year and 3 years before testing, VO2max% only correlated with AB in the last 3 years. Domains of school functioning and emotional functioning were low. Children with higher VO2max% and less AB in the last 3 years had better physical health. Physical health and school functioning were negatively correlated with hospitalization days in the last year. Conclusion: Patients with mild CF lung disease have good exercise performance although still lower than the normal population. VO2max% is affected by number of antibiotic treatments over a longer period. There is an impact of hospitalization days on quality of life.

Objectives: Antibiotic therapy is of vital importance for the control of infectious exacerbations in cystic fibrosis (CF) patients. However, very little is known regarding the fraction of systemically administered antibiotics reaching the lower respiratory tract secretions. We developed and validated amethod to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonamin CF sputum, and present the validation data. Methods: Ultra-performance LC coupled to tandem MS was used. A single sample can be measured in 2.5 min with multiple reaction monitoring in positive electrospray ionization mode. Deuterated internal standards were used and a concentration range of 0.7-160 mg/L was covered. The method was validated according to the EMA guideline on analytical method validation. Results: The boundaries within which a reliable measurement in CF sputum can be performed were determined. A few constraints are linked to the instability of the antibiotics in sputum. Piperacillin showed limited stability at room temperature and during freeze-thaw cycles. Autosampler instability was observed after 15 h for aztreonam at low concentrations. Conclusions: The method allows a reliable measurement of the selected antibiotics, if precautions are taken regarding the limited stability of piperacillin at room temperature. Due to freeze-thaw instability, piperacillin should always be analysed on the day of sampling. Quick review of the analytical data and reanalysis are needed as low concentrations of aztreonam are not stable in the autosampler.

Pseudomonas aeruginosa (Pa) is one of the most common and clinically important pathogens in patients with cystic fibrosis (CF). Chronic Pa colonization in CF patients is associated with increased morbidity and mortality. Pa strains causing early infection are usually antibiotic sensitive and have low bacterial density in the airways. As a result, the treatment strategy has shifted from suppressive therapy in patients chronically colonized by Pa to attempts at early eradication therapy as soon as Pa is detected. In the literature, different treatment regimens have been studied. However, the optimal treatment regimen and duration of treatment are not yet determined.In this article, an overview on the natural history of early Pa colonization and the history of eradication treatment is given. Moreover, the results of the different eradication treatment trials and directions for future research are discussed.

Background Achromobacter xylosoxidans is increasingly being recognized as an emerging pathogen in cystic fibrosis. Recent severe infections with A. xylosoxidans in some of our cystic fibrosis (CF) patients led to a re-evaluation of the epidemiology of CF-associated A. xylosoxidans infections in two Belgian reference centres (Antwerp and Ghent). Several of these patients also stayed at the Rehabilitation Centre De Haan (RHC). In total, 59 A. xylosoxidans isolates from 31 patients (including 26 CF patients), collected between 2001 and 2014, were studied. We evaluated Matrix Assisted Laser Desorption Ionisation -Time of Flight mass spectrometry (MALDI-TOF) as an alternative for McRAPD typing. Results Both typing approaches established the presence of a major cluster, comprising isolates, all from 21 CF patients, including from two patients sampled when staying at the RHC a decade ago. This major cluster was the same as the cluster established already a decade ago at the RHC. A minor cluster consisted of 13 isolates from miscellaneous origin. A further seven isolates, including one from a non-CF patient who had stayed recently at the RHC, were singletons. Conclusions Typing results of both methods were similar, indicating transmission of a single clone of A. xylosoxidans among several CF patients from at least two reference centres. Isolates of the same clone were already observed at the RHC, a decade ago. It is difficult to establish to what extent the RHC is the source of transmission, because the epidemic strain was already present when the first epidemiological study in the RHC was carried out. This study also documents the applicability of MALDI-TOF for typing of strains within the species A. xylosoxidans and the need to use the dynamic cutoff algorithm of the BioNumerics® software for correct clustering of the fingerprints. Electronic supplementary material The online version of this article (doi:10.1186/s12866-016-0736-1) contains supplementary material, which is available to authorized users.

Genes of innate immunity may be involved in early onset of chronic Pa (Pseudomonas aeruginosa) colonization (cPaC) in cystic fibrosis (CF) patients. We studied 19 single nucleotide polymorphisms (SNPs) in 5 genes coding for proteins of the lectin complement pathway: MBL2 (Mannose binding lectin 2), MASP 1, 2, 3 (MBL-associated serine Protease) and FCN 1, 2 (Ficolin) gene in 96 CF patients. Association survival analysis using different genetic models was performed looking for an association between SNPs and age at onset of cPaC. CF patients who are MBL deficient are earlier chronic Pa colonized compared to MBL sufficient patients. Also patients with MBL2 genotype YO/YO, YO/XA, XA/XA, YA/YO and YA/XA are earlier chronic Pa colonized. CF patients heterozygous or homozygous for mutant alleles of two linked SNPs in the FCN1 gene (rs2989727 and rs1071583) are earlier colonized with Pa. Similarly, earlier onset of Pa colonization is seen in CF patients heterozygous for linked SNPs of FCN2 gene (rs7865453 and rs7851696) and MASP3 gene (rs7851696). Variants in MBL2, FCN1, FCN2 and MASP3 genes are significantly associated with earlier onset of chronic P. aeruginosa colonization. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

This study aimed to study differences in lung function after surgical and percutaneous atrial septal defect (ASD) closure. Several studies have demonstrated abnormalities of pulmonary function in adults and children with ASD. These abnormalities persist even a few years after correction. This study compared pulmonary function between patients who underwent ASD closure by surgery and those who had closure by device. This is the ideal pediatric population for studying changes in lung function caused by cardiopulmonary bypass or sternotomy. The 46 patients in this study were treated by percutaneous closure (group 1) or surgical closure (group 2) of ASD and then scheduled for pulmonary function testing an average of 5.8 years after ASD closure. The mean values of functional residual capacity, total lung capacity, and residual volume did not differ between the two groups. The surgical group showed a significant decrease in expiratory reserve volume (p < 0.04) and forced vital capacity (p < 0.03). Expiratory flow at 25, 50, and 75% of forced vital capacity did not differ between the two groups but was on the lower limit of normal in both groups. Percutaneous closure of ASD can minimize the side effects of surgical closure on lung function. Longitudinal lung function follow-up assessment after cardiac surgery is warranted to detect and measure restrictive abnormalities in this type of congenital heart disease and others.

Background Longitudinal data regarding the genotypes of Pseudomonas aeruginosa isolates after eradication treatment are limited. We followed cystic fibrosis patients after a first ever isolation of P. aeruginosa and evaluated the P. aeruginosa -free time period after eradication therapy. Methods Between January 2003 and December 2008 respiratory samples were cultured prospectively from 41 patients with a first ever P. aeruginosa isolate. Twenty five patients had at least one subsequent isolate. Treatment efficacy was assessed based on the time to a second isolation and on comparison of the RAPD genotypes of the P. aeruginosa isolates. Results Eleven patients became chronically colonized during the study period. For ten of these the second isolate had the same genotype as the first isolate. Moreover, these patients had a significantly shorter P. aeruginosa -free time interval between the first ever and the second isolate compared to the 14 not chronically colonized patients (median 0months versus 7.5months, p Conclusion Our results indicate that the presence of a genotypically identical subsequent P. aeruginosa isolate and/or a short P. aeruginosa -free time interval after treatment are ominous signs and might be useful additional tools to predict impending chronic colonization. Current routine bacteriological methods for the detection of P. aeruginosa may lack the sensitivity to discriminate between true eradication and low bacterial persistence.

The source of acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) patients remains unknown. Patient-to-patient transmission has been well documented but the role of the environment as a source of initial infection is as yet unclear. In the present study, the origin of the first P. aeruginosa isolate in CF patients was investigated by comparing the P. aeruginosa genotype(s) from newly infected patients with genotypes of P. aeruginosa isolates from the home environment and from other patients from the same CF centre. A total of 50 newly infected patients were studied. P. aeruginosa could be cultured from 5.9% of the environmental samples, corresponding to 18 patients. For nine of these, the genotype of the environmental P. aeruginosa isolate was identical to the patient's isolate. In total, 72% of the environmental P. aeruginosa isolates were encountered in the bathroom. Patient-to-patient transmission within the CF centre could not be ruled out for three patients. In summary, a low prevalence of Pseudomonas aeruginosa was found in the home environment of the newly infected cystic fibrosis patients. The bathroom should be targeted in any preventive cleaning procedures. An environmental source of the new infection could not be ruled out in nine patients.

BackgroundAchromobacter xylosoxidans is increasingly cultured in sputum from cystic fibrosis (CF) patients; nevertheless, there are few published data on the clinical impact of this infection or chronic colonisation.MethodsRelying on DNA fingerprinting techniques we studied the prevalence of A. xylosoxidans in our CF population. In a retrospective case control study the clinical status of patients with at least 3 sputum cultures positive for A. xylosoxidans over at least 9 months, at the moment of the first positive culture and during the period of colonisation were compared to age (±1 year), gender and to Pseudomonas aeruginosa colonisation controlled CF patients who had never A. xylosoxidans positive sputum cultures.ResultsThe prevalence of patients with at least one positive A. xylosoxidans culture was 17.9%. 5.3% of the patients fulfilled the criteria of our definition of colonisation.Colonised patients had a median age of 20 years (range 11–27 years) and a mean colonisation period of 1.5 (±0.9) years.At the moment of the first positive culture we found significantly lower Bhalla scores on HRCT scans of the lungs (11±3 versus 16±3, p

We confirmed that chlorhexidine decontamination yielded more nontuberculous mycobacteria than did the N -acetyl- l -cysteine-NaOH-oxalic acid procedure from respiratory samples of cystic fibrosis patients on solid cultures. However, this improved recovery is mostly balanced if the latter is combined with liquid culture. Furthermore, none of the 145 cough swabs, used to sample young children, cultured positive, suggesting that swabs are low-quality samples.

Summary We report a 12-year-old boy with progressive bronchiolitis obliterans caused by Achromobacter xylosoxidans (Ax) colonization after liver transplantation, resulting in a steep decline in lung function. Pediatr Pulmonol. 2014; 49:414–416. © 2013 Wiley Periodicals, Inc.

Controversy remains about the need for antibiotic therapy of group A streptococcal (GAS) pharyngitis in high-resource settings. Guidelines on the management of GAS pharyngitis differ considerably, especially in children. We performed a literature search on the diagnosis and treatment of GAS pharyngitis in children and compared different guidelines with current epidemiology and the available evidence on management. Some European guidelines only recommend antibiotic treatment in certain high-risk patients, while many other, including all American, still advise antimicrobial treatment for all children with GAS pharyngitis, given the severity and re-emerging incidence of complications. Empirical antimicrobial treatment in children with sore throat and a high clinical suspicion of GAS pharyngitis will still result in significant overtreatment of nonstreptococcal pharyngitis. This is costly and leads to emerging antibiotic resistance. Early differential diagnosis between viral and GAS pharyngitis, by means of a 'rapid antigen detection test' (RADT) and/or a throat culture, is therefore needed if 'pro treatment' guidelines are used. Conclusion: Large scale randomized controlled trials are necessary to assess the value of antibiotics for GAS pharyngitis in high-resource countries, in order to achieve uniform and evidence-based guidelines. The severity and the possibly increasing incidence of complications in school-aged children suggests that testing and treating proven GAS pharyngitis can still be beneficial.

Complement regulators control the activated complement system. Defects in this homeostasis can result in tissue damage and autoimmune diseases with a heterogeneity in clinical presentation. Complement factor I (FI), a serine protease, is an important regulator of alternative pathway activation. We report a diagnostic work-up of a patient with relapsing inflammatory mediated meningo-encephalitis. Our work-up revealed a rare genetic factor I (FI) deficiency. So far, all cases of reported complete factor I deficiency have absent serum levels of FI. We present here a unique case of a complete factor I deficiency based on a functional FI defect. Complement assays and measurement of FI activity were performed in the patient, her family, factor H-deficient patients, a patient with C3-nephritic factor and 11 healthy controls. Genetic sequencing of the FI coding regions in the patient and her parents was performed. The patient had absent alternative pathway activity with low levels of C3 and normal serum level of FI. The patient’s plasma FI did not degrade C3b, with normalisation of C3b degradation after adding purified FI. Mutation analysis of the complement factor I gene revealed two heterozygous mutations (I322T and D506V). To our knowledge, this paper describes a complete FI deficiency caused by a defect of FI activity for the first time. Normal FI concentration does not exclude a complete FI defect, additional functional analysis of FI is required in any patient with a defect of complement activation. Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.

Recombinant tissue type plasminogen activator (rt-PA) has been used successfully in neonates for resolution of thrombotic processes, both arterial and venous. We report on 2 neonates with vena cava inferior thrombosis and with biochemical evidence of liver dysfunction in whom rt-PA treatment had to be interrupted because of significant bleeding tendency, without complete resolution of the thrombus. Therapy failure may be due to the age of the thrombus and the systemic way of administration, bypassing the site of the thrombus by collateral circulation. Impaired liver function may result in decreased degradation of rt-PA with prolonged effect and higher risk for bleeding complications. We suggest that lower doses should be administered in these patients.

We report on a 7-month old infant with severe respiratory distress secondary to a paratracheal bronchogenic cyst. Respiratory relief was achieved by transtracheal puncture of the cyst. Surgical removal of the cyst was performed 1 week later because of radiological evidence of reaccumulation of fluid.