scholarly journals Combination testing of multidrug-resistant cystic fibrosis isolates of Pseudomonas aeruginosa: use of a new parameter, the susceptible breakpoint index

2009 ◽  
Vol 65 (1) ◽  
pp. 82-90 ◽  
Author(s):  
K. E. N. Milne ◽  
I. M. Gould
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant

scholarly journals In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (3) ◽  
pp. 478
Author(s):  
Ersilia Vita Fiscarelli ◽  
Martina Rossitto ◽  
Paola Rosati ◽  
Nour Essa ◽  
Valentina Crocetta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
In Vitro Test ◽  
Chronic Infections ◽  
Hospital Environments ◽  
Vitro Test ◽  
General Reliability ◽  
Phage Activity

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.

scholarly journals 1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S731-S731
Author(s):  
Laura J Rojas ◽  
Mohamad Yasmin ◽  
Jacquelynn Benjamino ◽  
Steven Marshall ◽  
Kailynn DeRonde ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Transplantation ◽  
Precision Medicine ◽  
Clinical Sample ◽  
Phylogenetic Reconstruction ◽  
Multidrug Resistant ◽  
Population Diversity ◽  
Before And After ◽  
Research Grant

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

scholarly journals Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

2016 ◽  
Vol 60 (11) ◽  
pp. 6735-6741 ◽  
Author(s):  
Muhammad-Hariri Mustafa ◽  
Hussein Chalhoub ◽  
Olivier Denis ◽  
Ariane Deplano ◽  
Anne Vergison ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Content Type ◽  
The United Kingdom ◽  
Genes Encoding ◽  
Control Criteria ◽  
Susceptibility Profiles ◽  
And Control

ABSTRACTPseudomonas aeruginosais a major cause of morbidity and mortality in cystic fibrosis patients. This study compared the antimicrobial susceptibilities of 153P. aeruginosaisolates from the United Kingdom (UK) (n =58), Belgium (n =44), and Germany (n =51) collected from 118 patients during routine visits over the period from 2006 to 2012. MICs were measured by broth microdilution. Genes encoding extended-spectrum β-lactamases (ESBL), metallo-β-lactamases, and carbapenemases were detected by PCR. Pulsed-field gel electrophoresis and multilocus sequence typing were performed on isolates resistant to ≥3 antibiotic classes among the penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility rates were ≤30%/≤40% (penicillins, ceftazidime, amikacin, and ciprofloxacin), 44 to 48%/48 to 63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independent of patient age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease Prevention and Control criteria). Genes encoding the most prevalent ESBL (BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo-β-lactamases (VIM, IMP, and NDM), or carbapenemases (OXA-48 and KPC) were not detected. The Liverpool epidemic strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR sequence type 958 (ST958) isolates were found to be spread over the three countries. The other MDR clones were evidenced in ≤3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and nonclonal isolates with different susceptibility profiles were found in 20 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with meropenem, tobramycin, and colistin remaining the most active drugs.

scholarly journals New Sequence Type ST3449 in Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 491
Author(s):  
Catalina Díaz-Ríos ◽  
Marta Hernández ◽  
David Abad ◽  
Laura Álvarez-Montes ◽  
Athanasia Varsaki ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Drug Targets ◽  
Galleria Mellonella ◽  
Fatal Outcome ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Chronic Infections ◽  
Virulence Potential ◽  
End Stage

Pseudomonas aeruginosa is one of the most critical bacterial pathogens associated with chronic infections in cystic fibrosis patients. Here we show the phenotypic and genotypic characterization of five consecutive multidrug-resistant isolates of P. aeruginosa collected during a month from a CF patient with end-stage lung disease and fatal outcome. The isolates exhibited distinct colony morphologies and pigmentation and differences in their capacity to produce biofilm and virulence potential evaluated in larvae of Galleria mellonella. Whole genome-sequencing showed that isolates belonged to a novel sequence type ST3449 and serotype O6. Analysis of their resistome demonstrated the presence of genes blaOXA-396, blaPAO, aph(3’)-IIb, catB, crpP and fosA and new mutations in chromosomal genes conferring resistance to different antipseudomonal antibiotics. Genes exoS, exoT, exoY, toxA, lasI, rhlI and tse1 were among the 220 virulence genes detected. The different phenotypic and genotypic features found reveal the adaptation of clone ST3449 to the CF lung environment by a number of mutations affecting genes related with biofilm formation, quorum sensing and antimicrobial resistance. Most of these mutations are commonly found in CF isolates, which may give us important clues for future development of new drug targets to combat P. aeruginosa chronic infections.

scholarly journals The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics

Lung India ◽  
2017 ◽  
Vol 34 (6) ◽  
pp. 527 ◽  
Author(s):  
Atqah AbdulWahab ◽  
Khalid Zahraldin ◽  
MazenA Sid Ahmed ◽  
SuliemanAbu Jarir ◽  
Mohammed Muneer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Inhaled Antibiotics

scholarly journals Multidrug-resistant Pseudomonas aeruginosa from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam

2018 ◽  
Vol Volume 11 ◽  
pp. 1499-1510 ◽  
Author(s):  
Stan Atkin ◽  
Shadaan Abid ◽  
Michael Foster ◽  
Moumita Bose ◽  
Ashley Keller ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
High Rate

Association of Intensity of Antipseudomonal Antibiotic Therapy With Risk of Treatment-Emergent Organisms in Children With Cystic Fibrosis and Newly Acquired Pseudomonas Aeruginosa

2021 ◽  
Author(s):  
Jonathan D Cogen ◽  
Frankline M Onchiri ◽  
Nicole Mayer Hamblett ◽  
Ronald L Gibson ◽  
Wayne J Morgan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Proportional Hazards ◽  
Controlled Trial ◽  
Multidrug Resistant ◽  
Cox Proportional Hazards ◽  
Achromobacter Xylosoxidans ◽  
Drug Resistant ◽  
Antibiotic Exposure ◽  
Cox Proportional Hazards Models

Abstract Background While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection. Methods We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics or ever versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 years of follow-up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism. Results Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR, 1.24; 95% CI: 1.02–1.50; P = .03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR, 2.47; 95% CI: 1.28–4.78; P = .01) and MRSA (HR, 1.57; 95% CI: 1.03–2.40; P = .04). Conclusions Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing risk of acquisition of drug-resistant organisms.

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