Browsing by Author "Surette, Michael G"

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Azithromycin and the microbiota of cystic fibrosis sputum
    (2021-03-30) Acosta, Nicole; Thornton, Christina S; Surette, Michael G; Somayaji, Ranjani; Rossi, Laura; Rabin, Harvey R; Parkins, Michael D
    Abstract Background Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis – we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. Results Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders – demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. Conclusions Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.
  • Thumbnail Image
    ItemOpen Access
    Bacterial DNA patterns identified using paired-end Illumina sequencing of 16S rRNA genes from whole blood samples of septic patients in the emergency room and intensive care unit
    (2018-07-25) Faria, Monica M P; Winston, Brent W; Surette, Michael G; Conly, John M
    Abstract Background Sepsis refers to clinical presentations ranging from mild body dysfunction to multiple organ failure. These clinical symptoms result from a systemic inflammatory response to pathogenic or potentially pathogenic microorganisms present systemically in the bloodstream. Current clinical diagnostics rely on culture enrichment techniques to identify bloodstream infections. However, a positive result is obtained in a minority of cases thereby limiting our knowledge of sepsis microbiology. Previously, a method of saponin treatment of human whole blood combined with a comprehensive bacterial DNA extraction protocol was developed. The results indicated that viable bacteria could be recovered down to 10 CFU/ml using this method. Paired-end Illumina sequencing of the 16S rRNA gene also indicated that the bacterial DNA extraction method enabled recovery of bacterial DNA from spiked blood. This manuscript outlines the application of this method to whole blood samples collected from patients with the clinical presentation of sepsis. Results Blood samples from clinically septic patients were obtained with informed consent. Application of the paired-end Illumina 16S rRNA sequencing to saponin treated blood from intensive care unit (ICU) and emergency department (ED) patients indicated that bacterial DNA was present in whole blood. There were three clusters of bacterial DNA profiles which were distinguished based on the distribution of Streptococcus, Staphylococcus, and Gram-negative DNA. The profiles were examined alongside the patient’s clinical data and indicated molecular profiling patterns from blood samples had good concordance with the primary source of infection. Conclusions Overall this study identified common bacterial DNA profiles in the blood of septic patients which were often associated with the patients’ primary source of infection. These results indicated molecular bacterial DNA profiling could be further developed as a tool for clinical diagnostics for bloodstream infections.
  • Thumbnail Image
    ItemOpen Access
    The effects of inhaled aztreonam on the cystic fibrosis lung microbiome
    (2017-05-05) Heirali, Alya A; Workentine, Matthew L; Acosta, Nicole; Poonja, Ali; Storey, Douglas G; Somayaji, Ranjani; Rabin, Harvey R; Whelan, Fiona J; Surette, Michael G; Parkins, Michael D
    Abstract Background Aztreonam lysine for inhalation (AZLI) is an inhaled antibiotic used to treat chronic Pseudomonas aeruginosa infection in CF. AZLI improves lung function and quality of life, and reduces exacerbations-improvements attributed to its antipseudomonal activity. Given the extremely high aztreonam concentrations achieved in the lower airways by nebulization, we speculate this may extend its spectrum of activity to other organisms. As such, we sought to determine if AZLI affects the CF lung microbiome and whether community constituents can be used to predict treatment responsiveness. Methods Patients were included if they had chronic P. aeruginosa infection and repeated sputum samples collected before and after AZLI. Sputum DNA was extracted, and the V3-hypervariable region of the 16S ribosomal RNA (rRNA) gene amplified and sequenced. Results Twenty-four patients naïve to AZLI contributed 162 samples. The cohort had a median age of 37.1 years, and a  median FEV1 of 44% predicted. Fourteen patients were a priori defined as responders for achieving ≥3% FEV1 improvement following initiation. No significant changes in alpha diversity were noted following AZLI. Furthermore, beta diversity demonstrated clustering with respect to patients, but had no association with AZLI use. However, we did observe a decline in the relative abundance of several individual operational taxonomic units (OTUs) following AZLI initiation suggesting that specific sub-populations of organisms may be impacted. Patients with higher abundance of Staphylococcus and anaerobic organisms including Prevotella and Fusobacterium were less likely to respond to therapy. Conclusions Results from our study suggest potential alternate/additional mechanisms by which AZLI functions. Moreover, our study suggests that the CF microbiota may be used as a biomarker to predict patient responsiveness to therapy suggesting the microbiome may be harnessed for the personalization of therapies.