scholarly journals 526: Understanding antimicrobial resistance within Pseudomonas aeruginosa populations sourced from cystic fibrosis lungs

2021 ◽  
Vol 20 ◽  
pp. S249
Author(s):  
J. Vanderwoude ◽  
S. Azimi ◽  
T. Read ◽  
S. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance

scholarly journals Multidimensional Clinical Surveillance of Pseudomonas aeruginosa Reveals Complex Relationships between Isolate Source, Morphology, and Antimicrobial Resistance

mSphere ◽  
2021 ◽  
Author(s):  
Laura J. Dunphy ◽  
Glynis L. Kolling ◽  
Matthew L. Jenior ◽  
Joanne Carroll ◽  
April E. Attai ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Nosocomial Infection ◽  
Clinical Setting ◽  
Content Type ◽  
Pathogen Virulence ◽  
Clinical Surveillance ◽  
Complex Relationships

P. aeruginosa is a leading cause of nosocomial infection and infection in patients with cystic fibrosis. While P. aeruginosa infection and treatment can be complicated by a variety of antimicrobial resistance and virulence mechanisms, pathogen virulence is rarely recorded in a clinical setting.

scholarly journals Respiratory pathogens in patients with acute exacerbation of non-cystic fibrosis bronchiectasis from a developing country

2021 ◽  
Author(s):  
Shayan Shahid ◽  
Kausar Jabeen ◽  
Nousheen Iqbal ◽  
Joveria Farooqi ◽  
Muhammad Irfan
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Acute Exacerbation ◽  
Bacterial Overgrowth ◽  
Adult Patients ◽  
Hemophilus Influenzae ◽  
Bronchial Inflammation ◽  
Respiratory Specimens

Bronchiectasis unrelated to cystic fibrosis (non-CF bronchiectasis) has become a major respiratory disease in developing nations. The dilated mucus filled airways promote bacterial overgrowth followed by chronic infection, bronchial inflammation, lung injury and re-infection Accurate pathogen identification and antimicrobial susceptibility allowing appropriate treatment, in turn, may break this vicious cycle. To study the spectrum and antimicrobial spectrum of pathogen yielded from respiratory specimens in adult patients with acute exacerbation of non-cystic fibrosis (CF) bronchiectasis. This cross-sectional study was performed at the pulmonology clinics of the Aga Khan University, Karachi, Pakistan from 2016-2019. Respiratory specimens were collected from adult patients with acute exacerbation of non-CF bronchiectasis presenting in pulmonology clinics. Microbial cultures were performed using standard methodology. Susceptibility testing was performed and interpreted using Clinical Laboratory Standard Institute criteria.  A total of 345 positive cultures from 160 patients presenting with acute exacerbation were evaluated. The most frequent organisms were Pseudomonas aeruginosa (n=209) followed by Hemophilus influenzae (n=40) and Staphylococcus aureus (n=24). High rates of antimicrobial resistance were found in all these pathogens. Proportion of Pseudomonas aeruginosa strains resistant to ciprofloxacin, imipenem, ceftazidime and piperacillin-tazobactam were 27.1%, 16.8%, 14.8% and 13.1% respectively. 65% of Hemophilus influenzae strains were resistant to cotrimoxazole and ciprofloxacin and 66.7% of Staphylococcus aureus strains were resistant to methicillin. High antimicrobial resistance in non-CF bronchiectasis patients against commonly used antimicrobials is a concern and highlight need for urgent community level interventions to improve clinical outcome in these patients.

scholarly journals An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms

2016 ◽  
Author(s):  
Freya Harrison ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Predictive Power ◽  
Ex Vivo ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Bacterial Virulence ◽  
Lung Model ◽  
Physical And Chemical

AbstractA key aim in microbiology is to determine the genetic and phenotypic bases of bacterial virulence, persistence and antimicrobial resistance in chronic biofilm infections. This requires tractable, high-throughput models that reflect the physical and chemical environment encountered in specific infection contexts. Such models will increase the predictive power of microbiological experiments and provide platforms for enhanced testing of novel antibacterial or antivirulence therapies. We present an optimised ex vivo model of cystic fibrosis lung infection: ex vivo culture of pig bronchiolar tissue in artificial cystic fibrosis mucus. We focus on the formation of biofilms by Pseudomonas aeruginosa. We show highly repeatable and specific formation of biofilms that resemble clinical biofilms by a commonly-studied lab strain and ten cystic fibrosis isolates of this key opportunistic pathogen.

scholarly journals Pseudomonas aeruginosa populations in the cystic fibrosis lung lose susceptibility to newly applied β-lactams within 3 days

2019 ◽  
Vol 74 (10) ◽  
pp. 2916-2925 ◽  
Author(s):  
Leif Tueffers ◽  
Camilo Barbosa ◽  
Ingrid Bobis ◽  
Sabine Schubert ◽  
Marc Höppner ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Antibiotic Therapy ◽  
De Novo ◽  
Bacterial Load ◽  
Interindividual Variation ◽  
Patient Specific ◽  
Airway Microbiome ◽  
The Impact

Abstract Background Chronic pulmonary infections by Pseudomonas aeruginosa require frequent intravenous antibiotic treatment in cystic fibrosis (CF) patients. Emergence of antimicrobial resistance is common in these patients, which to date has been investigated at long-term intervals only. Objectives To investigate under close to real-time conditions the dynamics of the response by P. aeruginosa to a single course of antibiotic therapy and the potentially associated rapid spread of antimicrobial resistance, as well as the impact on the airway microbiome. Methods We investigated a cohort of adult CF patients that were treated with a single course of antimicrobial combination therapy. Using daily sampling during treatment, we quantified the expression of resistance by P. aeruginosa (median of six isolates per daily sample, 347 isolates in total), measured bacterial load by P. aeruginosa-specific quantitative PCR and characterized the airway microbiome with a 16S rRNA-based approach. WGS was performed to reconstruct intrapatient strain phylogenies. Results In two patients, we found rapid and large increases in resistance to meropenem and ceftazidime. Phylogenetic reconstruction of strain relationships revealed that resistance shifts are probably due to de novo evolution and/or the selection of resistant subpopulations. We observed high interindividual variation in the reduction of bacterial load, microbiome composition and antibiotic resistance. Conclusions We show that CF-associated P. aeruginosa populations can quickly respond to antibiotic therapy and that responses are patient specific. Thus, resistance evolution can be a direct consequence of treatment, and drug efficacy can be lost much faster than usually assumed. The consideration of these patient-specific rapid resistance shifts can help to improve treatment of CF-associated infections, for example by deeper sampling of bacteria for diagnostics, repeated monitoring of pathogen susceptibility and switching between drugs.

scholarly journals Transcriptome analysis of Pseudomonas aeruginosa biofilm infection in an ex vivo pig model of the cystic fibrosis lung.

2021 ◽  
Author(s):  
Niamh E. Harrington ◽  
Jenny L. Littler ◽  
Freya Harrison
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Transcriptome Analysis ◽  
Ex Vivo ◽  
Clinical Diagnostics ◽  
Growth Environment ◽  
Key Aspects ◽  
Biofilm Infection

Pseudomonas aeruginosa is the predominant cause of chronic biofilm infections that form in the lungs of people with cystic fibrosis (CF). These infections are highly resistant to antibiotics and persist for years in the respiratory tract. One of the main research challenges is that current laboratory models do not accurately replicate key aspects of a P. aeruginosa biofilm infection, highlighted by previous RNA-sequencing studies. We compared the P. aeruginosa PA14 transcriptome in an ex vivo pig lung (EVPL) model of CF and a well-studied synthetic cystic fibrosis sputum medium (SCFM). P. aeruginosa was grown in the EVPL model for 1, 2 and 7 days, and in vitro in SCFM for 1 and 2 days. The RNA was extracted and sequenced at each time point. Our findings demonstrate that expression of antimicrobial resistance genes was cued by growth in the EVPL model, highlighting the importance of growth environment in determining accurate resistance profiles. The EVPL model created two distinct growth environments: tissue-associated biofilm and the SCFM surrounding tissue, each cued a transcriptome distinct from that seen in SCFM in vitro . The expression of quorum sensing associated genes in the EVPL tissue-associated biofilm at 48 h relative to in vitro SCFM was similar to CF sputum versus in vitro conditions. Hence, the EVPL model can replicate key aspects of in vivo biofilm infection that are missing from other current models. It provides a more accurate P. aeruginosa growth environment for determining antimicrobial resistance that quickly drives P. aeruginosa into a chronic-like infection phenotype. Importance Pseudomonas aeruginosa lung infections that affect people with cystic fibrosis are resistant to most available antimicrobial treatments. The lack of a laboratory model that captures all key aspects of these infections hinders not only research progression but also clinical diagnostics. We used transcriptome analysis to demonstrate how a model using pig lungs can more accurately replicate key characteristics of P. aeruginosa lung infection, including mechanisms of antibiotic resistance and infection establishment. Therefore, this model may be used in the future to further understand infection dynamics to develop novel treatments and more accurate treatment plans. This could improve clinical outcomes as well as quality of life for individuals affected by these infections.

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