Association of interleukin-10 gene haplotypes with Pseudomonas aeruginosa airway colonization in cystic fibrosis

We genotyped three polymorphisms of the promoter region of the interleukin-10 (IL-10) gene in 220 CF patients from the CF Center of Bari, and tested for an association between genetic variants of the cytokine and chronic airway colonization with Pseudomonas aeruginosa. We found that carriers of the high-IL-10-producing-GCC haplotype had significantly higher risk of chronic pulmonary infection with the pathogen.     

Pseudomonas aeruginosa in public swimming pools and bathroom water of patients with cystic fibrosis

INTRODUCTION: Acquisition of Pseudomonas aeruginosa (PA) in the lungs of patients with cystic fibrosis (CF) is a marker of poor survival. PA is a ubiquitous pathogen prevalent in humid conditions. This study aimed to identify the prevalence of PA in public swimming pools, as well as from water taps. METHODS: Water was collected from public indoor and outdoor pools in the area of St. Gallen, Switzerland. In addition, standing and running water was sampled from bathroom water taps of 50 patients with CF. RESULTS: Outdoor pools: In 2002, none of the 72 specimens from 28 pools revealed PA. In 2003, three specimens from 46 pools (7%) revealed PA, each were from a different paddling pool. Indoor pools: two of 128 specimens from 56 pools (4%) identified PA, both were from non-public hydrotherapy pools. Water taps: in winter, none of the 102 specimens was colonized with PA. in summer, only two out of 50 specimens of the standing water were positive for PA but none of the running water revealed PA. CONCLUSION: The prevalence of PA in public swimming pools and bathroom water taps in the eastern part of Switzerland is very low. On hot summer days, outdoor paddling pools and standing tap water can contain PA. This study does not support recommendations to avoid public swimming pools or running tap water if the water is maintained according to hygiene guidelines.     

Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience

BackgroundSince 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment.MethodsAll isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype.Results146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1–14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p < 0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3–4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates.ConclusionTreatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.     

Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

Background

The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear.

Method

All patients treated in the Copenhagen CF centre (N = 278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S. maltophilia for at least 2 years without any other chronic Gram-negative infection were matched to two non-infected CF controls.

Results

Twenty-one patients were chronically infected with S. maltophilia during the 2-year study period. Fifteen were infected for at least 2 years.The patients in the S. maltophilia group had a steeper decline (− 3.2%/year vs. −0.3%/year) in FEV₁ compared to the non-infected CF controls (P = 0.03). The rate of decline was the same as observed 3 years before the patients became chronically infected.

Discussions

Chronic infection with S. maltophilia does not lead to a steeper decline in lung function when compared to the period before chronic infection.     

Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28 days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada. A total of 10 subjects (4 pediatric, 6 adult patients) were treated. There was a mean drop of 1.4 log (CFU/ml) in sputum bacterial density (p = 0.01) and sputum IL-8 levels decreased significantly after 28 days of TIP (p = 0.04). The mean relative change in FEV₁ (L) from Day 0 to Day 28 of TIP administration was a 4.6% increase but this was not statistically significant. The majority of patients (70%) had no or mild adverse events.     

PCR and the detection of Pseudomonas aeruginosa in respiratory samples of CF patients. A literature review

Previous studies proved the importance of rapid antibacterial intervention in case of Pseudomonas aeruginosa detection in respiratory samples of cystic fibrosis patients. To improve the early detection of P. aeruginosa, several culture, PCR and serology based approaches have been compared. Because an increasing number of routine microbiology laboratories have access to real-time PCR (qPCR), we reviewed the specificity and sensitivity of published PCR formats. The importance of choice of DNA-extraction methods and PCR formats and of the validation of their specificity and sensitivity with clinical samples is stressed.     

Staphylococcus aureus with decreased susceptibility to glycopeptides in cystic fibrosis patients

We report the isolation of Staphylococcus aureus with decreased susceptibility to glycopeptides in five CF patients and review the clinical and microbiological features of these cases. Three patients presented with pulmonary exacerbation that may be attributed to these strains and two of them were successfully treated using linezolid therapy. Glycopeptide-intermediate S. aureus (GISA) strains isolated in two patients were susceptible to methicillin, while the three other patients harbored methicillin-resistant GISA. Rarely reported in CF, GISA may remain underestimated due to the difficulty of detection, and both clinicians and microbiologists should be aware of the GISA emergence in CF patients’ population.     

Transient isolation of Burkholderia multivorans and Burkholderia cenocepacia from a Brazilian cystic fibrosis patient chronically colonized with Burkholderia vietnamiensis

Fifteen serial Burkholderia cepacia complex isolates recovered over a period of 4 years from a single cystic fibrosis patient were analysed for genomovar status by means of recA sequence determination, and genetic relatedness by RAPD-PCR. Twelve isolates were assigned as Burkholderia vietnamiensis, two as Burkholderia cenocepacia and one as Burkholderia multivorans. B. vietnamiensis persisted in the airways during 4 years, except in three occasions when B. cenocepacia or B. multivorans were isolated. The patient was chronically colonized by B. vietnamiensis with the RAPD-profile 12 and transiently by the RAPD-profile 15.     

Pseudomonas aeruginosa bacteraemia in an adult with cystic fibrosis and acute appendicitis

Despite their high bacterial load, bacteraemia is rare in patients with cystic fibrosis (CF). We report an adult with CF who developed Pseudomonas aeruginosa bacteraemia during an episode of acute appendicitis. The Pseudomonas aeruginosa isolated from the blood culture was confirmed by molecular typing to be the same transmissible strain responsible for the patient's chronic pulmonary infection. We hypothesise that this patient's bacteraemia was caused by Pseudomonas aerunginosa in swallowed sputum, crossing the inflamed appendiceal wall and entering the blood stream.     

Review: Staphylococcus aureus and MRSA in cystic fibrosis

Background

Staphylococcus aureus (S. aureus) is one of the earliest bacteria detected in infants and children with cystic fibrosis (CF). The rise of methicillin resistant S. aureus (MRSA) in the last 10 years has caused a lot of attention to this organism.

Results

The aim of this review is to provide a general overview of methicillin sensitive S. aureus (MSSA) and MRSA, discuss special aspects of S. aureus in cystic fibrosis, and to review treatment concepts. Microbiology of the organism will be reviewed along with data regarding the epidemiology of both MSSA and MRSA. Antibiotic treatments both in regards to acute management and eradication of MSSA and MRSA will be reviewed. Prophylaxis of MSSA in CF remains controversial. Treatment with anti-staphylococcal agents reduces the infection rate with MSSA but may lead to a higher rate of infection with P. aeruginosa. In regards to MRSA, there is a paucity of clinical data regarding approaches to eradication.

Conclusions

To advance the care of CF patients, controlled clinical trials are urgently needed to find the optimal approach to treating CF patients who are infected with either MSSA or MRSA.     

Antimicrobial susceptibility and ESBL prevalence in Pseudomonas aeruginosa isolated from burn patients in the North West of Pakistan

Pseudomonas aeruginosa is one of the most prevalent pathogen in burn infections. Infections with P. aeruginosa are associated with higher mortality rate and antibiotic costs in hospitalized patients. These bacteria also produce enzymes called Expanded Spectrum Beta-Lactamases (ESBL) which render penicillins and cephalosporins inactive. The aim of this study was to assess the antimicrobial susceptibility pattern and prevalence of ESBL in P. aeruginosa in Peshawar, North West of Pakistan. During 2005–2006, one hundred and six P. aeruginosa isolates were collected from burn patients at a tertiary care hospital. Antibiotic susceptibility testing and ESBL detection were carried out according to Clinical Laboratory and Standards Institute (CLSI) criteria. Eighteen antibiotics were tested in this study. A total of 38 (35.85%) isolates were found to be ESBL producers. Thirty one (29.24%) isolates were resistant to 3 or more antibiotics (multidrug resistance). Meropenem and imipenem showed high potency with 99% and 96% isolates being susceptible respectively. Susceptibility to amikacin was 70%; gentamicin 25%; ciprofloxacin 49%; enoxacin 47%; gatifloxacin 42%; doxycycline 21% and to co-trimoxazole only 16%. This study reveals that P. aeruginosa isolated from burns in this region are multidrug resistant and produce ESBL in large proportions.     

Different opinions of physicians on the importance of measures to prevent acquisition of Pseudomonas aeruginosa from the environment

BACKGROUND: Since chronic infection with mucoid Pseudomonas aeruginosa (PA) is associated with deteriorating lung function, many parents of young children with cystic fibrosis (CF) fear the first PA positive throat swab as a milestone in the progression of the disease. To reduce the risk of PA acquisition from the environment, they perform preventive measures at home or outdoors. METHODS: In an attempt to evaluate the attitude of CF physicians towards these measures and the respective consulting practice, we mailed a questionnaire to all 65 certified paediatric CF centres in Germany. RESULTS: Physicians from 54 (83%) CF clinics replied. They expressed widely different ideas about the impact of the environment for the acquisition of P. aeruginosa, and recommended a large spectrum of preventive measures. Some physicians proposed only few precautions, which focussed on the prevention of cross-infection between patients, whereas others suggested prevention of any contact with moist or wet places, e.g. use different toothbrushes for mornings and evenings, or do without air-conditioning in the car. CONCLUSIONS: CF physicians have different opinions on the risk of PA acquisition from the environment. Doctors who recommend strict precautions could engender a parental fear of a ubiquous threat from invisible bacteria. The resulting extended safety measures might impair the family's quality of life.     

Species distribution of Burkholderia cepacia complex isolates in cystic fibrosis and non-cystic fibrosis patients in New Zealand

Burkholderia cepacia complex (Bcc) isolates from 39 CF patients and 25 non-CF patients in New Zealand were speciated and characterised using the multilocus sequence typing (MLST) scheme for Bcc. B. multivorans predominated in CF patients (31/39, 79.5%) and in non-CF patients (7/25, 28%). Sequence types (ST) with an international distribution were identified (27/64, 42.2%) among the New Zealand Bcc isolates. MLST revealed a high level of diversity among Bcc isolates in CF patients indicating a lack of person-to-person transmission. Non-CF patients showed less diversity in MLST types, however, individuals with shared STs were geographically and chronologically separated. The use of MLST analysis allows continued surveillance of isolates with the potential to identify outbreaks. The identification of internationally distributed strains may provide an indicator of the relative transmissibility and infectivity of these strains and warrants further investigation.     

Outcomes of fundoplication in children with cystic fibrosis

Purpose

Children with cystic fibrosis (CF) have a high prevalence of gastroesophageal reflux disease (GERD). As GERD is associated with chronic respiratory symptoms and feeding problems, fundoplication is often performed in children with CF. Although the outcomes of fundoplication have been described across diverse pediatric groups, there is no published experience with CF.

Methods

The records of 25 children with CF who underwent fundoplication in our center were reviewed. Data on symptoms and diagnostic testing results as well as on complications related to fundoplication were collected. Nutritional parameters and pulmonary function were compared before and after fundoplication.

Results

There was no mortality associated with fundoplication, but 12% had complications that required a subsequent surgical procedure. Whereas 28% were able to discontinue their antireflux medications, 48% developed symptoms of recurrent GERD. Overall, there was no change in body mass index, body mass index percentile, or the slope of forced expiratory volume in 1 second (FEV₁) after fundoplication. Children who had an FEV₁ of less than 60% predicted at the time of fundoplication exhibited an improvement in FEV₁ slope compared to those with FEV₁ of 60% or more (+5.3% vs −8.6% per year, P = .004).

Conclusion

The complication rate of fundoplication is similar to what has been reported in large series in children without CF. There is a high rate of recurrent GERD and little apparent benefit for either nutritional or pulmonary outcomes. The observed difference on FEV₁ slope, in those with moderate-severe vs mild lung disease, highlights the need to thoroughly evaluate the role of fundoplication in children with CF.     

Voriconazole therapy in children with cystic fibrosis

BACKGROUND: There is increasing evidence for the efficacy of the antifungal voriconazole, particularly in immunosuppression. We describe our experience of using voriconazole in children with CF. METHODS: We performed a retrospective case note review of children with CF treated with voriconazole in a single centre over an 18 month period. RESULTS: A total of 21 children aged 5 to 16 years (median 11.3) received voriconazole for between 1 and 50 (22) weeks. Voriconazole was used as monotherapy in 2 children with recurrent allergic bronchopulmonary aspergillosis (ABPA); significant and sustained improvements in clinical and serological parameters for up to 13 months were observed, without recourse to oral steroids. Voriconazole was used in combination with an immunomodulatory agent in a further 11 children with ABPA, with significant improvement in pulmonary function and serology. 8 children without ABPA but who had recurrent Aspergillus fumigatus isolates and increased symptoms also received voriconazole; this group did not improve with treatment. Adverse effects occurred in 7 children (33%: photosensitivity reaction 3, nausea 2, rise in hepatic enzymes 1, hair loss 1). CONCLUSIONS: Voriconazole may be a useful adjunctive therapy for ABPA in CF. Voriconazole monotherapy appears to be an alternative treatment strategy when oral corticosteroids may not be suitable.     

Impact of azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis

Background

Concomitant use of oral azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic.

Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment

Background

Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients.

Acute Burkholderia cenocepacia pyomyositis in a patient with cystic fibrosis

IntroductionExtra-pulmonary complications of Burkholderia cepacia complex (Bcc) infection in patients with cystic fibrosis are unusual. To the best of the authors' knowledge no case of pyomyositis secondary to Bcc infection has been reported previously.Case presentationWe report a case of pyomyositis of the forearm caused by Bcc infection in a patient with CF. We also briefly discuss the management of pyomyositis.ConclusionPyomyositis is a potential extra-pulmonary complication of Bcc infection in patients with CF. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need MRI. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention are all essential for proper management of this condition.     

Open follow-up study of tobramycin nebuliser solution and colistin in patients with cystic fibrosis

A previous study of tobramycin nebuliser solution (TNS) compared with colistin [C] in cystic fibrosis (CF) patients, chronically infected with pseudomonas, showed benefit for the TNS treated patients over one treatment cycle only. The current report is of an extension of that study. An open randomised cross-over study of TNS compared with C was conducted on 21 patients who had previously been on the 1 cycle study. They continued for a further 5 months and then crossed over to the alternate treatment. There was an advantage for TNS over C in FEV(1) % predicted change over time. The C slope was -0.88% per month and the TNS slope 0.35% per month (p=0.0002). This suggests advantages of TNS over C in a study with a small number of patients. Larger studies are required.