Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis

Daniels, T.; Rogers, Geraint B.; Stressmann, Franziska A.; Gast, Christopher J. van der; Bruce, Kenneth D.; Jones, Graeme R.; Connett, Gary; Legg, Julian; Carroll, Mary

doi:10.1016/j.jcf.2012.05.008

Cited by 56 publications

(58 citation statements)

References 28 publications

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“…time of exacerbation but before the administration of antibiotic therapy, which may have a significant impact on bacterial community structure (5,13).…”

Section: Original Researchmentioning

confidence: 99%

“…More specifically, it is not known whether significant changes in airway bacterial communities occur around the time of pulmonary exacerbations, events that are well known to be associated with a progressive and irreversible decline in lung function, increased hospitalization and antibiotic use, decreased quality of life, and increased mortality rates (7)(8)(9)(10)(11)(12). Studies addressing this important question have provided valuable insight but have been limited by cross-sectional design, small numbers of paired baseline-exacerbation samples from the same individual, and a focus on relatively narrow measures of bacterial community change (e.g., total bacterial density or community diversity) (5,6,(13)(14)(15).…”

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confidence: 99%

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Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Carmody¹,

Zhao²,

et al. 2013

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Rationale: In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood.Objectives: To characterize changes in airway bacterial communities around the time of exacerbations and to identify predictors for these changes.Methods: DNA prepared from 68 paired baseline and exacerbation sputum samples collected from 28 patients with CF were subjected to barcoded 16S rRNA gene pyrosequencing. Bacterial density was calculated by quantitative PCR. Measurements and Main Results:Overall, significant differences in bacterial community diversity and bacterial density between baseline and exacerbation samples were not observed. However, considerable changes in community structures were observed in a subset of patients. In these patients, the dominant taxa and initial level of community diversity were significant predictors of the magnitude of community structure changes at exacerbation. Pseudomonas-dominant communities became more diverse at exacerbation compared with communities with other or no dominant species. The relative abundance of Gemella increased in 24 (83%) of 29 samples at exacerbation and was found to be the most discriminative genus between baseline and exacerbation samples. Conclusions:The magnitude of changes in the CF lung microbiota around the time of exacerbation was found to be largely dependent on community diversity and composition at baseline. Certain genera appear to play important roles in driving change in airway bacterial community composition at exacerbation. Gemella might play a direct role in and/or be a biomarker for pulmonary exacerbation.

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“…time of exacerbation but before the administration of antibiotic therapy, which may have a significant impact on bacterial community structure (5,13).…”

Section: Original Researchmentioning

confidence: 99%

mentioning

confidence: 99%

Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Carmody¹,

Zhao²,

et al. 2013

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“…Our goal was to deter- mine if a bacteria-derived biomarker can be identified and result in antibiotic treatment being initiated early in the course of a PE and reduce the symptoms that would otherwise cause damage to the lungs. Identifying a change in microbiota that precedes a PE requires frequent patient sampling, since the length of time between the changes in the bacterial community and PE onset is unknown (14). Previous cross-sectional studies examining the diversity of the microbiota in the lungs of CF patients collected samples at a frequency or for a length of time that did not reveal potential short-term changes associated with a PE (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…(12) used quantitative PCR (qPCR) on bacterial DNA isolated from sputum samples collected weekly over a 12-month period to identify the cause of PEs in 12 CF patients. Using this quantitative analysis, Stressman et al (12) showed that the bacterial load, including the dominant pathogen, P. aeruginosa, did not change 1 to 3 weeks prior to the onset of a PE.Because a single sputum sample can provide only a snapshot of the community profile at any given time, the identification of changes in the microbiota that precede PE onset would require frequent longitudinal sampling (13,14). Our long-term study was designed to determine if combining quantitative and deep-sequencing techniques with intensive sampling from a single patient over a time period of years would reveal population changes, undetected in previous studies, prior to the onset of antibiotic treatment or a PE.…”

mentioning

confidence: 99%

“…Because a single sputum sample can provide only a snapshot of the community profile at any given time, the identification of changes in the microbiota that precede PE onset would require frequent longitudinal sampling (13,14). Our long-term study was designed to determine if combining quantitative and deep-sequencing techniques with intensive sampling from a single patient over a time period of years would reveal population changes, undetected in previous studies, prior to the onset of antibiotic treatment or a PE.…”

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confidence: 99%

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Analysis of Changes in Diversity and Abundance of the Microbial Community in a Cystic Fibrosis Patient over a Multiyear Period

et al. 2015

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The evolution of pulmonary disease in cystic fibrosis (CF) usually begins when bacteria get trapped in mucus in the lungs and become established as a chronic infection. While most CF patients experience periods of stability, pulmonary exacerbations (PEs) can occur multiple times per year and result in permanent damage to the lungs. Little is known of the shift from a period of stability to a PE, but this shift is likely to be attributed to changes in the bacterial community. Here, we identified changes in the lung microbiota to determine if they reflect patient health, indicate the onset of exacerbations, or are related to antibiotic treatment. In contrast to most bacterial studies on CF, we collected weekly samples from an adult CF patient over a period of 3 years and performed quantitative PCR (qPCR) and Illumina sequencing on those samples. While many DNA-based studies have shown the CF microbiota to be relatively stable, we observed an increase in the total bacterial abundance over time (P < 0.001), while the number of different taxa (bacterial richness) and the number of different taxa and their abundances (diversity) significantly decreased over time (P < 0.03), which was likely due to repeated antibiotic exposure. Using genus-specific primers with qPCR, we observed an increase in the abundance of Burkholderia multivorans, a CF-associated pathogen, prior to the occurrence of a PE (P ‫؍‬ 0.006). Combining these DNA-based techniques with frequent sampling identified a potential initiator for exacerbations and described a response of the CF microbiota to time and antibiotic treatment not observed in previous CF microbiota studies. Bacterial infections with consequent progressive lung disease are the leading cause of death in persons with cystic fibrosis (CF), a disease that affects an estimated 30,000 people in the United States and 70,000 people worldwide (1). Prior to the past 2 decades, it was assumed that the CF lungs were colonized with only a few different bacteria, including Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus aureus, and members of the Burkholderia cepacia complex (BCC) (2). It has been shown in CF patients that chronic infection with these CF-related bacteria (CFRB) is linked to an increase in mortality (3, 4).Pulmonary exacerbations (PEs), which may develop multiple times per year in CF patients, are often caused by a disturbance to a stable chronic bacterial infection (5, 6). The exact cause of a PE, often identified by an increase in pulmonary disease symptoms, remains uncertain but is commonly attributed to factors associated with established bacteria, and possibly to viruses or newly acquired bacterial strains (7,8). In 2004, Rogers et al. used terminal restriction fragment length polymorphism (TRFLP) analysis to target the bacterial 16S rRNA gene in order to analyze DNA extracted from sputum samples from CF patients. This method of analysis revealed a complexity that included 15 species not previously identified in the lungs. The study by Rogers et al. laid the founda...

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Examining changes in bacterial abundance in complex communities using next-generation sequencing is enhanced with quantitative PCR

Stokell

Hamp

Steck

2016

Antonie van Leeuwenhoek

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Changes in the composition of microbial communities are often examined using high-throughput sequencing (HTS). Here we analyzed bar-coded Illumina sequencing data from a previous work describing the microbial community found in the sputum of a cystic fibrosis patient by itself or in combination with qPCR to measure the absolute abundance of Pseudomonas aeruginosa and Burkholderia multivorans. Through this comparison we were able to determine the computational analysis accuracy of sequencing data to measure the relative abundance of specific taxa. While no correlation was found between relative abundance and absolute abundance of P. aeruginosa or B. multivorans, we did find conclusions derived from HTS data alone differed from those derived from a combination of HTS and qPCR. Our results highlight the importance of using qPCR with HTS when characterizing organisms in microbial communities having a dominant taxon.

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Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis

Abstract: Antibiotic treatment directed at P. aeruginosa has an additional significant impact on non-pseudomonal, co-colonising species.

Cited by 56 publications

References 28 publications

Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Analysis of Changes in Diversity and Abundance of the Microbial Community in a Cystic Fibrosis Patient over a Multiyear Period

Examining changes in bacterial abundance in complex communities using next-generation sequencing is enhanced with quantitative PCR

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