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Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis.

PLoS One. 2015;10(1):e0116029

Authors: Boutin S, Graeber SY, Weitnauer M, Panitz J, Stahl M, Clausznitzer D, Kaderali L, Einarsson G, Tunney MM, Elborn JS, Mall MA, Dalpke AH

Abstract
Changes in the airway microbiome may be important in the pathophysiology of chronic lung disease in patients with cystic fibrosis. However, little is known about the microbiome in early cystic fibrosis lung disease and the relationship between the microbiomes from different niches in the upper and lower airways. Therefore, in this cross-sectional study, we examined the relationship between the microbiome in the upper (nose and throat) and lower (sputum) airways from children with cystic fibrosis using next generation sequencing. Our results demonstrate a significant difference in both α and β-diversity between the nose and the two other sampling sites. The nasal microbiome was characterized by a polymicrobial community while the throat and sputum communities were less diverse and dominated by a few operational taxonomic units. Moreover, sputum and throat microbiomes were closely related especially in patients with clinically stable lung disease. There was a high inter-individual variability in sputum samples primarily due to a decrease in evenness linked to increased abundance of potential respiratory pathogens such as Pseudomonas aeruginosa. Patients with chronic Pseudomonas aeruginosa infection exhibited a less diverse sputum microbiome. A high concordance was found between pediatric and adult sputum microbiomes except that Burkholderia was only observed in the adult cohort. These results indicate that an adult-like lower airways microbiome is established early in life and that throat swabs may be a good surrogate in clinically stable children with cystic fibrosis without chronic Pseudomonas aeruginosa infection in whom sputum sampling is often not feasible.

PMID: 25629612 [PubMed - in process]

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Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC.

J Thorac Oncol. 2015 Jan 27;

Authors: van den Berg LL, Klinkenberg TJ, Groen HJ, Widder J

Abstract
INTRODUCTION:: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurrence in patients with clinical stage I NSCLC treated with surgery or SABR.
METHODS:: Clinical data from all subsequent FDG-PET/CT-based stage I NSCLC patients (cT1-T2aN0M0) treated with surgery or SABR at our center between 2007 and 2010 were collected. Primary endpoints were overall survival and tumor recurrences/new primary lung tumors. Treatment groups were compared using multivariable Cox regression and competing risk analyses.
RESULTS:: Three-hundred-forty patients treated with surgery (n=143) or SABR (n=197) were included. Surgical patients were younger, had a better WHO performance status and less comorbidities. After adjustment for prognostic covariables, treatment did not influence overall survival (adjusted hazard ratio [HR], SABR vs. surgery 1.07; 95% CI, 0.74 to 1.54; P= .73). Local control and distant recurrence were equal, while locoregional recurrences were significantly more frequent after SABR compared with surgery (adjusted subhazard ratio 2.51; 95% CI, 1.10 to 5.70; P=.028). Nodal failure (HR 2.16; 95% CI, 1.34 to 3.48) and distant metastases (HR 2.12; 95% CI, 1.52 to 2.97), but not local failure (HR 1.00; 95% CI, 0.53 to 1.89) predicted overall survival.
CONCLUSIONS:: In patients with FDG-PET-CT-based stage I NSCLC, SABR confers worse locoregional tumor control due to more nodal failures compared to surgery, stressing the need to improve mediastinal and hilar staging.

PMID: 25629639 [PubMed - as supplied by publisher]

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The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of pseudomonas-infecting myoviridae.

PLoS One. 2015;10(1):e0117163

Authors: Henry M, Bobay LM, Chevallereau A, Saussereau E, Ceyssens PJ, Debarbieux L

Abstract
In a previous study, six virulent bacteriophages PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5 and CHA_P1 were evaluated for their in vivo efficacy in treating Pseudomonas aeruginosa infections using a mouse model of lung infection. Here, we show that their genomes are closely related to five other Pseudomonas phages and allow a subdivision into two clades, PAK_P1-like and KPP10-like viruses, based on differences in genome size, %GC and genomic contents, as well as number of tRNAs. These two clades are well delineated, with a mean of 86% and 92% of proteins considered homologous within individual clades, and 25% proteins considered homologous between the two clades. By ESI-MS/MS analysis we determined that their virions are composed of at least 25 different proteins and electron microscopy revealed a morphology identical to the hallmark Salmonella phage Felix O1. A search for additional bacteriophage homologs, using profiles of protein families defined from the analysis of the 11 genomes, identified 10 additional candidates infecting hosts from different species. By carrying out a phylogenetic analysis using these 21 genomes we were able to define a new subfamily of viruses, the Felixounavirinae within the Myoviridae family. The new Felixounavirinae subfamily includes three genera: Felixounalikevirus, PAK_P1likevirus and KPP10likevirus. Sequencing genomes of bacteriophages with therapeutic potential increases the quantity of genomic data on closely related bacteriophages, leading to establishment of new taxonomic clades and the development of strategies for analyzing viral genomes as presented in this article.

PMID: 25629728 [PubMed - in process]

Antibiotics for respiratory tract infections: a comparison of prescribing in an outpatient setting.

Infect Control Hosp Epidemiol. 2015 Feb;36(2):153-9

Authors: Barlam TF, Morgan JR, Wetzler LM, Christiansen CL, Drainoni ML

Abstract
OBJECTIVE: To examine inappropriate antibiotic prescribing for acute respiratory tract infections (RTIs) in ambulatory care to help target antimicrobial stewardship interventions. Design and Setting Retrospective analysis of RTI visits within general internal medicine (GIM) and family medicine (FM) ambulatory practices at an inner-city academic medical center from 2008 to 2010.
METHODS: Patient, physician, and practice characteristics were analyzed using multivariable logistic regression to determine factors predictive of inappropriate prescribing; physicians in the highest and lowest antibiotic-prescribing quartiles were compared using χ2 analysis.
RESULTS: Visits with FM providers, female gender, and self-reported race/ethnicity as white or Hispanic were significantly associated with inappropriate antibiotic prescribing. Physicians in the lowest quartile prescribed antibiotics for 5%-28% (mean, 21%) of RTI visits; physicians in the highest quartile prescribed antibiotics for 54%-85% (mean, 65%) of RTI visits. High prescribers had fewer African-American patients and more patients who were younger and privately insured. High prescribers had more patients with chronic lung disease. A GIM practice pod with a low prescriber was 3.0 times more likely to have a second low prescriber than other practice pods, whereas pods with a high prescriber were 1.3 times more likely to have a second high prescriber.
CONCLUSIONS: Medical specialty was the only physician factor predictive of inappropriate prescribing when patient gender, race, and comorbidities were taken into account. Possible disparities in care need further study. Stewardship education in medical school, enlisting low prescribers as physician leaders, and targeting interventions to the highest prescribers might be more effective approaches to antimicrobial stewardship. Infect Control Hosp Epidemiol 2014;00(0): 1-7.

PMID: 25632997 [PubMed - in process]