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Objective: Antibiotics are prescribed too often in acutely ill children in primary care. We examined whether a Point-of-Care (POC) C-reactive Protein (CRP) test influences the family physicians’ (FP) prescribing rate and adherence to the Evidence Based Medicine (EBM) practice guidelines. Design: Cluster randomized controlled trial. Setting: Primary care, Flanders, Belgium. Intervention: Half of the children with non-severe acute infections (random allocation of practices to perform POC CRP or not) and all children at risk for serious infection were tested with POC CRP. Subjects: Acutely ill children consulting their FP. Main outcome measure: Immediate antibiotic prescribing. Results: 2844 infectious episodes recruited by 133 FPs between 15 February 2013 and 28 February 2014 were analyzed. A mixed logistic regression analysis was performed. Compared to episodes in which CRP was not tested, the mere performing of POC CRP reduced prescribing in case EBM practice guidelines advise to prescribe antibiotics (adjusted odds ratio (aOR) 0.54 (95% Confidence Interval (CI) 0.33-0.90). Normal CRP levels reduced antibiotic prescribing, regardless of whether the advice was to prescribe (aOR 0.24 (95%CI 0.11-0.50) or to withhold (aOR 0.31 (95%CI 0.17-0.57)). Elevated CRP levels did not increase antibiotic prescribing. Conclusion: Normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. Key points: What is previously known or believed on this topic •Antibiotics are prescribed too often for non-severe conditions. Point-of-care (POC) C-reactive Protein (CRP) testing without guidance does not reduce immediate antibiotic prescribing in acutely ill children in primary care. What this research adds •FPs clearly consider CRP once available: normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. •Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 a method to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonam in 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. [ABSTRACT FROM AUTHOR]

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. What is Known: • Children with CF have lower exercise performance; there is an association between hospitalization frequency and exercise performance • Quality of life is diminished in children with CF and influenced by respiratory infections What is New: • Even patients with mild CF lung disease have lower maximal exercise performance (VO 2 max) and a lower anaerobic threshold; VO 2 max is lower in children who had more antibiotic treatments in the last 3 years • School and emotional functioning are diminished in children with mild CF lung disease; hospitalization is negatively correlated with school functioning and physical functioning. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) patients are vulnerable to airway colonization with Pseudomonas aeruginosa. In case eradication fails after antibiotic treatment, patients become chronically colonized with P. aeruginosa, with recurrent pulmonary exacerbation, for which patients typically are hospitalized for 2 weeks and receive intravenous antibiotic treatment. Normally, improvement of the patients' health is established. Aim: Determination of the correspondence between patient improvement and changes of the P. aeruginosa and total bacterial load in the sputum. Methods: Eighteen CF patients with exacerbation were included for a total of 27 hospitalization episodes. At day 1, 8 and 15, inflammation and lung function parameters were determined, together with the P. aeruginosa load in the sputum using culture, quantitative PCR (qPCR) and propidium monoazide qPCR. Results: Patients improved during hospitalization (decrease in levels of C-reactive protein, white blood cell counts and erythrocyte sedimentation rate, increase of FEV1), reaching normal values already after one week. Also the P. aeruginosa load and the total bacterial load decreased during the first week of antibiotic treatment (p<0.05), except for patients with a low lung function (FEV1≤39.4%), for whom no significant decrease of P. aeruginosa was established. Comparison of culture-based and propidium monoazide qPCR-based quantification of P. aeruginosa showed that at the end of the treatment on average 62% of the P. aeruginosa cells are not cultivable, indicating that many cells are alive but dormant, or dead but still structurally intact. Conclusion: Improvement of the clinical status is accompanied with a decrease of the P. aeruginosa load, whereby both occur mainly during the first week of antibiotic treatment. However, for patients with a low lung function, no decrease of the P. aeruginosa load is observed. Comparison of detection techniques shows that a large amount of noncultivable or dead bacteria are present in the samples. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients. Results: In this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86%) remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10%) were positive by both culture and qPCR. Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR. Conclusion: Based on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Achromobacter 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. Methods: Relying 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. Results: The 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 <0.002), lower Brasfield chest X-ray scores (14±3 versus 18±3, p <0.019), lower FVC values (70%±22 versus 94%±12, p <0.017) and lower FEV1 values (55%±32 versus 78%±23, p =0.123), although the latter did not reach significance. There was no significant difference in body mass index (BMI) (18.7±3 kg/m2 versus 19.6±3 kg/m2, p =0.8). Over the study period A. xylosoxidans-colonised patients did have more need for intravenous antibiotic treatment courses (19 versus 5, p <0.001); nevertheless, there was no significant difference in lung function decline over the study period (FVC: −6.25±12.34% versus −5.62±8.30%, p 0.77, FEV1: −5.62±8.30% versus −1.87±11.58%, p <0.47). Conclusions: The prevalence of A. xylosoxidans infection or colonisation is probably underestimated. Colonised patients are mostly older, with more pronounced lung damage and lower lung function values. Although there was more need for intravenous antibiotic treatment courses, no faster decline in lung function was observed in A. xylosoxidans positive patients. [Copyright &y& Elsevier]

Abstract 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 < 0.01). 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. [ABSTRACT FROM AUTHOR]