Carsten Schwarz

Multilocus sequence typing of Scedosporium apiospermum and Pseudallescheria boydii isolates from cystic fibrosis patients

BACKGROUND Scedosporium and Pseudallescheria species are the second most common lung-colonising fungi in cystic fibrosis (CF) patients. For epidemiological reasons it is important to trace sources of infection, routes of transmission and to determine whether these fungi are transient or permanent colonisers of the respiratory tract. Molecular typing methods like multilocus sequence typing (MLST) help provide this data. METHODS Clinical isolates of the P. boydii complex (including S. apiospermum and P. boydii) from CF patients in different regions of Germany were studied using MLST. Five gene loci, ACT, CAL, RPB2, BT2 and SOD2, were analysed. RESULTS The S. apiospermum isolates from 34 patients were assigned to 32 sequence types (STs), and the P. boydii isolates from 14 patients to 8 STs. The results revealed that patients can be colonised by individual strains for years. CONCLUSIONS The MLST scheme developed for S. apiospermum and P. boydii is a highly effective tool for epidemiologic studies worldwide. The MLST data are accessible at http://mlst.mycologylab.org/.

Narrow band imaging (NBI) during medical thoracoscopy: first impressions

BackgroundThis is the first ever evaluation of narrow band imaging (NBI), an innovative endoscopic imaging procedure, for the visualisation of pleural processes.MethodsThe pleural cavity was examined in 26 patients with pleural effusions using both white light and narrow band imaging during thoracoscopy under local anaesthesia.ResultsIn the great majority of the patients narrow band imaging depicted the blood vessels more clearly than white light, but failed to reveal any differences in number, shape or size. Only in a single case with pleura thickened by chronic inflammation and metastatic spread of lung cancer did narrow band imaging show vessels that were not detectable under white light.ConclusionIt is not yet possible to assess to what extent the evidence provided by NBI is superior to that achieved with white light. Further studies are required, particularly in the early stages of pleural processes.

Value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules

The diagnostic value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules (SPN) is still under debate among pneumologists, radiologists and thoracic surgeons. In a prospective observational manner, flexible bronchoscopy was routinely performed in 225 patients with SPN of unknown origin. Of the 225 patients, 80.5% had lung cancer, 7.6% had metastasis of an extrapulmonary primary tumour and 12% had benign aetiology. Unsuspected endobronchial involvement was found in 4.4% of all 225 patients (or in 5.5% of patients with lung cancer). In addition, flexible bronchoscopy clarified the underlying aetiology in 41% of the cases. The bronchoscopic biopsy results from the SPN were positive in 84 (46.5%) patients with lung cancer. Surgery was cancelled due to the results of flexible bronchoscopy in four cases (involvement of the right main bronchus (impaired pulmonary function did not allow pneumonectomy) n=1, small cell lung cancer n=1, bacterial pneumonia n=2), and the surgical strategy had to be modified to bilobectomy in one patient. Flexible bronchoscopy changed the planned surgical approach in five cases substantially. These results suggest that routine flexible bronchoscopy should be included in the regular pre-operative work-up of patients with SPN.

Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters.

ObjectiveTo evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. Materials and MethodsInstitutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19–52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg−1 gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. ResultsThe overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3–21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3–20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4–31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4–33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. ConclusionsOne major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Patient experience in cystic fibrosis care: Development of a disease-specific questionnaire.

Objectives The aim of this study was to develop valid and reliable disease-specific questionnaires for adult patients with cystic fibrosis and for parents of minors with cystic fibrosis for assessing patient experience with cystic fibrosis care. Methods The pilot versions of the questionnaires were developed based on a literature review, interviews with health professionals and focus groups. A postal survey with two reminders was conducted in 56 German cystic fibrosis centres recruiting 2874 participants. Psychometric evaluation was done via exploratory factor analysis and reliability and regression analysis. The questionnaires’ ability to differentiate between subgroups and between cystic fibrosis centres was evaluated. Results Response rates were 74% for both adult patients and parents. Ten factors were extracted for both the adult and the parents’ models (Cronbach’s alpha between 0.6 and 0.9), explaining 50% and 48% of the variance, respectively. The factors organisation & access and the doctor–patient/parent-interaction had the highest relevance for a good overall care experience. The questionnaires were able to distinguish between different cystic fibrosis centres. Discussion The questionnaires are well suited for use in internal and external quality management of cystic fibrosis care due to their good psychometric properties, the ability to differentiate between centres and its practicability.

Scedosporium and Lomentospora: an updated overview of underrated opportunists

Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

Allergic bronchopulmonary aspergillosis is associated with pet ownership in Cystic Fibrosis

Late diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is associated with significant lung function decline and morbidity in cystic fibrosis (CF). The association of ABPA and domestic pet ownership in patients with CF has not been elucidated yet. Our objective was to determine the association of ABPA with pet ownership in patients with CF.

Piperacillin-induced mild haemolytic anaemia in a 44-year-old patient with cystic fibrosis

Piperacillin–tazobactam is an antipseudomonal antibiotic frequently used in patients with cystic fibrosis (CF) to treat pulmonary exacerbations. Drug-induced immune haemolytic anaemia is a rare complication during treatment with piperacillin. So far, piperacillin-induced immune haemolytic anaemia (PIHA) is regarded as an acute and severe haemolytic anaemia resulting into life-threatening events. Here we report on a patient with mild PIHA, which did not result in any clinical symptoms or necessity for treatment. To the best of our knowledge, this is the first case report of PIHA without an acute severe haemolytic anaemia. Further research is needed to clarify if this case is a solitary clinical manifestation of PIHA or if mild clinical courses of PIHA might be under-reported. Cases of PIHA have been largely reported in patients with CF. This unequal distribution maybe due to the frequent administration of piperacillin for pulmonary exacerbation in patients with CF or due to CF-related cofactors of yet unknown aetiology.

Arxula adeninivorans causing invasive pulmonary mycosis and fungaemia in cystic fibrosis

1476 www.thelancet.com Vol 385 April 11, 2015 In April, 2012, a 34-year-old man with cystic fi brosis, bronchiectasis, airway colonisation with Pseudomonas aeruginosa and Achromobacter xylosoxidans, pancreatic insuffi ciency, diabetes mellitus related to cystic fi brosis, liver cirrhosis, and chronic hepatitis B presented to a rehabilitation hospital with pulmonary exacerbation. Sputum grew Staphylococcus aureus and A xylosoxidans but no fungi. Empirical treatment with antibiotics was unsuccessful and after 4 weeks he was transferred to our hospital with uncontrolled infection. Despite treatment with broad-spectrum antibiotics he deteriorated with progressive respiratory insuffi ciency, recurrent fever, worsening liver function, and raised infl ammatory markers. A thoracic CT scan (appendix) showed bilateral pulmonary infi ltrates and mediastinal and hilar lymphadenopathy. Bronchoalveolar lavage showed Pseudomonas coreensis and an uncommon yeast that was also grown from two separate blood cultures taken at diff erent times. We excluded allergic bronchopulmonary aspergillosis and line infection as possible causes of fungaemia. We continued empirical treatment including caspofungin and voriconazole but the patient’s condition worsened until he needed non-invasive ventilation. In-vitro susceptibility testing showed the yeast was sensitive only to amphotericin B and fl ucytosine, so we changed treatment to conventional amphotericin B 18 mg daily (0·3 mg/kg per day) and fl ucytosine 9 g four times daily (150 mg/kg per day) for 17 days, with rapid improvement after 3 days. The patient was discharged home with a stable but lower FEV1. Bacterial infections are the most common cause of pneumonia in patients with cystic fi brosis. In this case, failure of several combinations of antibiotics of diff erent classes and the repeated detection of an uncommon yeast in sputum and blood cultures pointed to a mycosis. The isolates were initially identifi ed as Stephanoascus ciferii by VITEK. We sent the isolates to a reference laboratory for further investigation. Phenotypical and molecular methods identifi ed the yeast as Arxula adeninivorans (fi gure), which is used in biotechnology as a transgenic organism and not previously identifi ed as a pathogen. Because A adeninivorans is used in the production of coff ee and tea, we screened the patient’s household but did not fi nd this yeast. At follow-up in April, 2014, the patient remained in stable health with ongoing detection of A adeninivorans in his sputum, but his cystic fi brosis disease progressed and he died in December, 2014, due to multiorgan failure. Fungi must be considered in the management of immunocompromised patients with severe pulmonary exacerbations refractory to treatment. Rare fungi such as scedosporium, exophiala, and A adeninivorans can be diffi cult to detect; in this case, the fungus was fi rst misidentifi ed as Stephanoascus ciferii. Therefore, although human infections from A adeninivorans have not previously been reported they might have occurred, especially if identifi cation of the yeast isolate was done by a commercial identifi cation system based on physiological traits. Yeasts in the respiratory tract of patients with cystic fi brosis are often regarded as harmless colonisers and are not identifi ed on a species or even genus level. Fungal organisms, especially if detected repeatedly, should be regarded as potential pathogenic agents. In our case, changing the treatment regimen on the basis of the in-vitro resistance pattern led to rapid improvement of the patient’s condition. When faced with unidentifi ed rare or unusual fungi, liposomal amphotericin B with or without fl ucytosine should be the fi rst choice of empirical treatment.