28 research outputs found
Pseudomonas aeruginosa infections in children with cystic fibrosis : Determinants, detection and directed intervention
No full textPulmonary infections in children with CF are a major cause of morbidity and mortality. In particular, infections with P. aeruginosa lead to rapid pulmonary function decline and are hard to eradicate once established and adapted to the host environment. In this thesis, determinants of host- and bacterial factors for P. aeruginosa infections were investigated. Because of the possible benefit of early detection of P. aeruginosa with respect to eradication strategies, the diagnostic value of direct and indirect detection methods was examined. Also, interventions directed at prevention of initial P. aeruginosa infection by cycled antibiotic prophylaxis and directed at prevention of further pulmonary decline after establishment of P. aeruginosa infection by macrolide antibiotics were analysed. The major findings of this thesis are: -In CF pulmonary infection, the genetic diversity of P. aeruginosa isolates is lower than in P. aeruginosa isolates from infections in non-CF hosts. Clonal genotypes were observed in Dutch patients with CF, but not in patients without CF . -In CF, both eradicated and persistent initial colonising P. aeruginosa isolates show highly variable bacterial characteristics. It is not possible to predict persistence in the airways after initial P. aeruginosa colonisation by estimating these bacterial characteristics alone . -Increasing the culture frequency of oropharyngeal swabs enhances the diagnostic values for P. aeruginosa presence in the lower airways. -Serological measurements of specific anti-P. aeruginosa antibodies are sensitive in detecting chronic P. aeruginosa infections but do not yet contribute substantially in early detection of P. aeruginosa colonisation in the majority of children . -Cycled 3-monthly anti-Pseudomonas antibiotic prophylaxis does not prevent initial and persistent P. aeruginosa infection and subsequent lung function decline in children with CF. -Azithromycin therapy leads to a temporary pulmonary function improvement, but induces rapid macrolide resistance in S. aureus without significant decline in S. aureus isolation. -Transmission of macrolide-resistant S. aureus to household contacts of patients with CF was not proven
Detection of Pseudomonas aeruginosa in patients with cystic fibrosis
No full textAbstractChronic pulmonary colonisation with Pseudomonas aeruginosa (PA) in patients with CF is associated with a high morbidity and mortality. Adequate treatment of first acquisition of PA might prevent or postpone chronic colonisation. Early detection of PA is therefore of major importance. Currently, cultures of oropharynx or sputum are most commonly practised. However, oropharyngeal culture has limitations both in the positive and negative predictive value for the presence of PA in the lower respiratory tract. Induction of sputum has little benefit in detection of PA. Serology might have additional value in early detection, when bacterial density is too low to be detected by culture. Molecular techniques are not yet widespread used for detection of PA, but have in general a high sensitivity. In this review, we describe the value of different diagnostic techniques for detecting PA
Improved pathogen detection in neonatal sepsis to boost antibiotic stewardship
No full textstatus: Publishe
Trends in paediatric inpatient antibiotic therapy in a secondary care setting
No full textThere is growing attention for antimicrobial stewardship in paediatrics. Currently, little is known about secondary care antibiotic practice. We analysed trends in time with respect to inpatient antibiotic use in a secondary paediatric care setting. Total inpatient antibiotic consumption per year (2010–2015) and antibiotic prescriptions for urinary tract infection (UTI) and lower respiratory tract infection (LRTI) were analysed. Variables were total, antibiotic-specific, and intravenous days of therapy (DOT/100PD) and for UTI/LRTI treatment type, route and duration. Third-generation cephalosporin use decreased (DOT/100PD 11.6 in 2011 vs. 5.1 in 2015; p < 0.001); intravenous antibiotics were prescribed less often (p = 0.06). These findings were confirmed for the specific diseases: third-generation cephalosporin use decreased for both UTI (93% vs. 45%; p = 0.002) and LRTI (14% vs. 6%; p = 0.18); the duration of intravenous therapy decreased (UTI p = 0.02; LRTI p < 0.001). Median LRTI treatment duration was 9.2 days in 2008 and 6.6 in 2015 (p < 0.001); penicillin prescriptions were more narrow in spectrum (p = 0.02). Conclusion: A decrease in third-generation cephalosporin use and intravenous route was identified. LRTI treatment was significantly shorter and more narrow in spectrum. This could be explained by awareness and interventions in the context of antimicrobial stewardship. A decrease in antibiotic use is also feasible and important in non-tertiary paediatric wards.(Table presented.
WS1.3 Respiratory microbiota dynamics in newborns with cystic fibrosis and healthy controls: A longitudinal study
No full textEffect of lockdowns on the epidemiology of pediatric respiratory disease-A retrospective analysis of the 2021 summer epidemic
No full textBackgroundThe imposition of lockdowns during the severe acute respiratory syndrome coronavirus-2 pandemic led to a significant decrease in pediatric care utilization in 2020. After restrictions were loosened, a surge in pediatric respiratory disease was observed in pediatric wards. The aim of this study was to quantify the effect of the lockdown(s) on the incidence of pediatric respiratory disease. MethodsFor this multicenter retrospective study, emergency department (ED) visit and admission data between January 2017 and September 2021 was collected from eight general hospitals in the Netherlands. Clinical diagnoses were extracted and categorized in groups ("communicable infectious disease," "all respiratory infections," "upper respiratory tract infection," "lower respiratory tract infection," and "asthma/preschool wheezing"). The incidence of admissions and ED visits during 2020 and 2021 was compared to the incidence in 2017-2019. ResultsSuccessive lockdowns resulted in a maximum decrease of 61% and 57% in ED visits and admissions, respectively. After loosening restrictions during the summer of 2021, a 48% overall increase in ED visits and 31% overall increase in admission numbers was observed in July compared to the average July in 2017-2019. This was explained by a 381% increase in ED visits and a 528% increase in ward admissions due to overall respiratory infections, mainly due to lower respiratory tract infections. ConclusionsSuccessive lockdowns in the spring and winter of 2020 and 2021 led to a decreased incidence of communicable infections, especially respiratory tract infections. The resulting lack of pediatric immunity resulted in an off-season surge in care utilization at an unexpected moment
RAIN study: A protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection
No full text__Introduction__ High morbidity and mortality rates of proven bacterial infection are the main reason for substantial use of intravenous antibiotics in neonates during the first week of life. In older children, intravenous-to-oral switch after 48 hours of intravenous therapy has been shown to have many advantages and is nowadays commonly practised. We, therefore, aim to evaluate the effectiveness, safety and cost-effectiveness of an early intravenous-to-oral switch in neonates with a probable bacterial infection.
__Methods and analysis__ We present a protocol for a multicentre randomised controlled trial assessing the non-inferiority of an early intravenous-to-oral antibiotic switch compared with a full course of intravenous antibiotics in neonates (0-28 days of age) with a probable bacterial infection. Five hundred and fifty patients will be recruited in 17 hospitals in the Netherlands. After 48 hours of intravenous treatment, they will be assigned to either continue with intravenous therapy for another 5 days (control) or switch to amoxicillin/clavulanic acid suspension (intervention). Both groups will be treated for a total of 7 days. The primary outcome will be bacterial (re)infection within 28 days after treatment completion. Secondary outcomes are the pharmacokinetic profile of oral amoxicillin/clavulanic acid, the impact on quality of life, cost-effectiveness, impact on microbiome development and additional yield of molecular techniques in diagnosis of probable bacterial infection.
__Ethics and dissemination__ This study has been approved by the Medical Ethics Committee of the Erasmus Medical Centre. Results will be presented in peer-reviewed journals and at international conferences
Pseudomonas aeruginosa diversity in distinct paediatric patient groups
No full textABSTRACTPseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157 patients (CF first infection (CF-1 group) (29); CF chronic infection (CF-chronic group) (27); urinary tract infection (34); chronic suppurative otitis media (43); and intensive-care hospitalization/immunodeficiency (24)). All 202 phenotypically different isolates were tested for antimicrobial resistance and further typed by pulsed-field gel electrophoresis. Simpson's diversity index was calculated for the five groups. CF-chronic patients carried the highest number of distinct P. aeruginosa phenotypes and genotypes per culture. Isolates from the CF-chronic group were significantly less diverse than those from the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups and among the clonal isolates. In conclusion, isolates of the CF-chronic group were less diverse than those in the other patient groups with P. aeruginosa infection; clonal isolates were not encountered in non-CF patients. Transmission of clonal CF isolates to other patient groups was not observed
Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates
No full textClin Microbiol Infect 2012; 18: 567574 Abstract Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments. Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared. Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (
Impact of immunomodulating medication on maternal Tdap vaccination-induced antibodies in infants.
No full textItem does not contain fulltextBACKGROUND AND AIMS: Current international guidelines on inflammatory bowel disease (IBD) advise to continue immunomodulating medication during pregnancy. Data on the effect of this medication on maternal Tdap (Tetanus-Diphtheria-acellular pertussis) vaccination and transfer of antibodies to the infant are scarce. METHODS: Pregnant women with IBD receiving various immunomodulating medications and their infants were prospectively recruited in the Pregnancy Exposure to TNF alpha inhibitors and Immunological effect (PETIT) study cohort from 16 hospitals in the Netherlands between December 2018 and March 2023. All women were offered maternal Tdap vaccination according to the Dutch National Immunization Program. IgG concentrations against all Tdap components were measured at birth (maternal and cord blood) and at 2 months of age in the infant, preceding active immunization. We compared geometrical mean concentrations (GMCs) in IBD mother-infant pairs with healthy control mother-infant pairs. RESULTS: Geometrical mean concentrations of antibodies against all Tdap components were significantly higher in 135 maternally vaccinated mothers and their infants compared with 25 unvaccinated IBD women-infant pairs treated with immunomodulating medication during pregnancy, at all timepoints. However, GMC against pertactin (PRN) was significantly lower in vaccinated IBD mother-infant pairs compared to healthy vaccinated control mother-infant pairs, particularly in mothers treated with anti-tumor necrosis factor alpha and their infants. CONCLUSIONS: Maternal Tdap vaccination in women with IBD receiving immunomodulating medication during pregnancy results in significantly higher Tdap-antibody concentrations in their infants compared to infants of unvaccinated IBD mothers, although GMC was lower for PRN compared to healthy controls. These results support current recommendations to advise maternal Tdap vaccination in pregnant women receiving immunomodulating medication
