F. Teding van Berkhout

Diagnostic value of serological tests against Pseudomonas aeruginosa in a large cystic fibrosis population

Background: Serological methods to monitor Pseudomonas aeruginosa colonisation in patients with cystic fibrosis (CF) are advocated but the diagnostic value of a commercially available P aeruginosa antibody test to detect early and chronic P aeruginosa colonisation in a non-research setting has not been assessed. Methods: Colonisation with P aeruginosa was estimated by regular culture of sputum or oropharyngeal swabs during three consecutive years in 220 patients with CF aged 0–65 years. Commercially available ELISA tests with three P aeruginosa antigens (elastase, exotoxin A, alkaline protease) were performed at the end of the study period. In a subgroup of 57 patients (aged 4–14 years) serological tests were performed annually. Results: Using culture as the reference standard, the ELISA tests using the advised cut off values had a sensitivity of 79% and a specificity of 89% for chronic colonisation. Receiver-operator characteristic curves were created to optimise cut off values. Applying these new cut off values resulted in a sensitivity of 96% and a specificity of 79%. All three individual serological tests discriminated well between the absence and presence of chronic P aeruginosa colonisation. The sensitivity of the individual antibody test was 87% for elastase, 79% for exotoxin A, and 76% for alkaline protease. First colonisation was preceded by positive serological results in only five of 13 patients (38%). Conclusion: In patients with CF, serological tests using specific antigens are sensitive for diagnosing chronic P aeruginosa colonisation. However, the failure of serological tests to detect early colonisation in young patients emphasises the need for continued reliance on cultures.

Barriers to an early switch from intravenous to oral antibiotic therapy in hospitalised patients with CAP

Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not? In a multicentre prospective cohort study, adult patients admitted for i.v. CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice. 149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea >7 mmol·L−1, respiratory rate of ≥30 breaths·min−1, blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg, and age ≥65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice. The switch from i.v. to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.

Assessment of CFTR function in homozygous R117H-7T subjects

BACKGROUNDnR117H is a frequent missense mutation included in most CFTR mutation panels. However knowledge about the residual function of R117H-CFTR channels in cystic fibrosis-affected organs, e.g. airways, intestines and sweat glands is presently lacking.nnnMETHODSnWe evaluated clinical CF symptoms and assessed CFTR function by sweat tests, nasal potential difference and intestinal current measurements in 2 homozygous R117H individuals (7T variant).nnnRESULTSnThe CFTR activity in airways and intestine was within the normal range. However both individuals presented with a borderline sweat test and the male patient was infertile.nnnCONCLUSIONSnThe lack of impact of the R117H mutation on chloride secretion in intestine and nose contrasts with the ~80% loss of CFTR activity reported in patch clamp studies. Apparently CFTR activity is not rate-limiting for chloride secretion in both tissues at levels >20% of normal, or compensatory factors may operate that are absent in heterologous host cells in vitro.

Long-term effects of birth order and age at diagnosis in cystic fibrosis: a sibling cohort study.

Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross‐infection within families.

Cystic Fibrosis-Related Diabetes with strict glycaemic control is not associated with frequent intravenous antibiotics use for pulmonary infections.

AIMSnPulmonary infections are more frequent in and associated with higher mortality in Cystic Fibrosis-Related Diabetes (CFRD) patients compared to CF patients without CFRD. Hyperglycaemia can lead to a higher vulnerability for infections. Aim of the study was to test whether the infection rate in well-controlled CFRD patients was similar to that in CF patients without CFRD.nnnMETHODSnThis is a retrospective six-year cohort analysis on a consecutive series of 138 CF patients. They were categorized in two groups with CFRD or without CFRD. Pulmonary infection frequency was defined as the number of intravenous (IV) antibiotic treatments. Clinical factors associated with infection frequency were collected.nnnRESULTSnCFRD was diagnosed in 54 (39%) CF patients of whom 44 (81%) achieved target value for glycaemic control (HbA1c 7.0% (⩽53mmol/mol)). Median frequency of IV antibiotics was 0 without CFRD and 3 episodes in patients with CFRD (rate ratio (RR) 2.9 (95% CI 1.6-5.2)). Multivariate analysis showed that frequency of IV antibiotics was significantly related to Pseudomonas aeruginosa colonization (RR 3.7) and lower lung function at baseline (RR 0.97) but not to CFRD by itself.nnnCONCLUSIONSnIn this cohort with overall strict glycaemic control, the frequency of IV antibiotics use was related to chronic infection and impaired lung function at baseline, but not to CFRD by itself. Although this study in itself does not prove beneficial effect of strict glycaemic control, it does emphasize the potential role of glycaemic control on infection frequency in CF patients.

140 Population structure of Pseudomonas aeruginosa and the prevalence of epidemic clones in patients with cystic fibrosis over four years

Objectives: The extent and mechanism of cross-infection with Pseudomonas aeruginosa (PA) in specialist cystic fibrosis (CF) units remain controversial. Prevention of droplet spread by segregation and use of single patient rooms is advised by most authorities. Despite these measures, many centres continue to report outbreaks of clonal “epidemic” strains. We conducted an aerobiological study to examine airborne dispersal of PA in a large CF centre in the UK. Methods: Microbiological air sampling was conducted in outpatient and inpatient areas inhabited by patients known to harbour the Liverpool Epidemic Strain (LES) of PA. A volumetric air sampler was placed at least 1m from patients, working at a rate of 100 L/min with a sampling time of 10min. Any colonies growing on Pseudomonas selective agar were identified by phenotypic and molecular methods and the number of colony-forming units (CFUs) counted. Conclusion: Out of 177 samples obtained from 8 separate patient environments, 33 (19%) grew PA. Contamination was greater in patient rooms than corridor areas; 23% (29/125) vs 10% (4/51) respectively. Rooms inhabited by 3 of 8 patients yielded positive growth. Corridor air was positive in the vicinity of 1 patient’s closed room. Samples from this patient’s room demonstrated much higher counts than those from other rooms (mean 61CFU/m3 vs 0−3CFU/m3). These data confirm that PA can contaminate air >1m from patients and suggest that certain patients may act as “super-shedders”. Ventilation strategies and infection control precautions in CF centres should take into account the possibility of true airborne transmission of PA.

How we managed to improve a professional attitude in the nursing team to deal with topics of sexuality, fertility and reproduction in relation to CF patients

Background: During the annual European Cystic Fibrosis Congress in 2007 we presented the results of a questionnaire about dealing with topics of sexuality and fertility in relation to CF patients. The questionnaire was offered to the nursing staff of the Cystic-Fibrosis department of the University Medical Centre Utrecht in the Netherlands. The outcome showed the nursing staff was insufficient equipped to deal with these issues. It was evident the nursing staff needed knowledge and a model to help them bring up sexuality and fertility issues with the CF patient. Method: The poster mentioning the outcome was rewarded with the third prize during the annual European Cystic Fibrosis Congress in 2007. The money we won was used to hire a sexual therapist to lead a workshop. In the fall of 2007 the entire nursing team attended the programme. Aim: To develop a professional approach to handle these issues. Together we developed a manual. This manual was intended to be helpful to the nursing staff in order to develop a professional approach concerning sexuality, fertility and reproduction in relation to CF patients. In the fall of 2008 we offered the same questionnaire to the entire nursing staff. There was a response of 70% which was comparable to 2006. In the 2006 inquiry only 10% of respondents stated that they initiated such a discussion. In 2008 50% of the respondents did initiate a conversation about these topics. Conclusion: There was an improvement of 40% in the respondents to deal with issues concerning sexuality, fertility and reproduction compared to 2006. The outcome showed we are improving but we need to remain active in coaching the nursing staff concerning these topics.

Dietary treatment with probiotics in patients with cystic fibrosis

Methods We searched the Medline and Cochrane databases for controlled studies with probiotics published since 1988. If no studies were available in CF patients, we extended the search to other patient groups. We limited our search to probiotics found in Dutch diary products. Results Only 2 studies had been performed with CF patients; both with Lactobacillus GG in children. One study shows a reduction of inflammation in the intestine due to the use of Lactobacillus GG after 4 weeks (Bruzzese et al 2004). Another study suggests that the frequency of respiratory infections is reduced after 6 months using Lactobacillus GG with less clinical exacerbations (Bruzzese et al 2007). These results need confirmation. Well-established effects of probiotics studied in non-CF patients include prevention and enhanced recovery from diarrhoea due to infections or antibiotic use (especially Lactobacillus GG and Lactobacillus casei defensis) and amelioration of constipation (Bifidus ActiRegularis) (Hawrelak et al 2005). These effects should occur within 2 weeks, see Table 1.