Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Patients from Two Brazilian Cities (original) (raw)
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Antimicrobial Agents and Chemotherapy
Hypermutable Pseudomonas aeruginosa isolates (hypermutators) have been identified in patients with cystic fibrosis (CF). Hypermutators display a greatly increased mutation rate, an enhanced ability to become resistant to antibiotics during treatment and are associated with reduced lung function in patients. Their prevalence has been established amongst patients with CF, but has not been determined for patients with CF in Australia. This study aimed to determine the prevalence of hypermutable P. aeruginosa isolates from adult patients with CF from a healthcare institution in Australia, and to characterize the genetic diversity and antibiotic susceptibility of these isolates. A total of 59 P. aeruginosa clinical isolates from patients with CF were characterized. For all isolates, rifampicin mutation frequencies and susceptibility to a range of antibiotics were determined. Of the 59 isolates, 13 (22%) were hypermutable. Whole genome sequences were determined for all hypermutable isolat...
High Frequency of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Lung Infection
Science, 2000
The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa . This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.
International journal of antimicrobial agents, 2017
The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population...
Infection and Drug Resistance, 2014
Background: Pseudomonas aeruginosa is one of the primary pathogens isolated more frequently in cystic fibrosis (CF) and it exhibits innate resistance to a wide range of antibiotics. Purpose: We sought to determine whether the highly prevalent genotypes of P. aeruginosa are specifically linked to CF patients and have any related multidrug antibiotic resistance. Isolates from hospitalized non-CF patients and from environmental sources were also genotypically analyzed. Methods: Collections of P. aeruginosa from lower respiratory secretions (n=45) were genotyped using pulsed-field gel electrophoresis (PFGE). Phenotypic screening for antibiotic susceptibility was performed for the common antimicrobial agents by E-test and automated Phoenix method. Results: P. aeruginosa isolates from CF (n=32), hospitalized non-CF patients (n=13), and environment sources (n=5) were analyzed. The population structure of P. aeruginosa is highly diverse and population-specific. All PFGE results of P. aeruginosa isolates fall among four major clusters. Cluster 1 contained 16 P. aeruginosa isolates from CF patients and two from environmental sources; cluster 2 contained 11 P. aeruginosa isolates from CF and one each from non-CF and environmental sources; cluster 3 contained 12 P. aeruginosa isolates from hospitalized non-CF patients and two P. aeruginosa isolates from one CF patient and one environmental source; and cluster 4 consisted of three isolates from CF patients and one from the environment. The majority of multidrug-resistant P. aeruginosa isolates were in clusters 3 and 4. P. aeruginosa isolates from CF patients were resistant to ciprofloxacin (34.4%) followed by resistance to amikacin and gentamicin (each 28%), whereas the majority of isolates from non-CF patients were resistant to meropenem (69%) and were grouped in cluster 3. Conclusion: PFGE of P. aeruginosa isolates from CF patients shows a high degree of similarity, suggesting specific adaptation of these clones to CF-affected lungs. The hospitalized non-CF cluster has a different clonal origin, indicating specific clustering in a specific location, suggesting hospital-acquired P. aeruginosa infections.
BMC Microbiology, 2016
Background: Pseudomonas aeruginosa is the predominant pathogen associated with the decline of pulmonary function in cystic fibrosis (CF) patients. Both environment-to-host acquisition and patient-to-patient transmission have been described for P. aeruginosa infection. Epidemic clones and bacterial phenotypic adaptation to the CF lung have been recognised as independent risk factors for disease progression. So far, there is no established link between genotypic prevalence and phenotypic traits. Here, we look at the major CF patient cohort in Italy to identify shared P. aeruginosa clones and associated common phenotypic traits. Results: A comprehensive analysis of P. aeruginosa genotypes to determine the presence of high-risk shared clones and their association to specific phenotypic traits has been performed in a major Italian CF centre. Pulsed-field gel electrophoresis (PFGE) of P. aeruginosa isolates from 338 CF subjects identified 43 profiles shared by two or more patients and 214 profiles exclusive to individual patients. There was no evidence of a P. aeruginosa outbreak, but four most prevalent pulsotypes were detected. Common phenotypic traits were recorded intra-pulsotypes, but we detected heterogeneity inter-pulsotypes. Two of the four major pulsotypes included P. aeruginosa isolates with hallmarks of adaptation to the CF airways, including loss of motility, low production of siderophore, pyocyanin and proteases, and antibiotic resistance. One of these pulsotypes grouped a high percentage of hypermutable isolates. No clear correlation between epidemiological and clinical data was found. Conclusions: We conclude that CF patients of this cohort shared common pulsotypes, but their phenotypic heterogeneity indicates an absence of specific traits associated to P. aeruginosa genotypic prevalence.
DOAJ (DOAJ: Directory of Open Access Journals), 2010
Background: The aim of our study was to determine the genotypes and antimicrobial susceptibility profiles of Pseudomonas aeruginosa isolates of cystic fibrosis (CF) patients. Methods: We included 18 P. aeruginosa isolates from 10 patients treated as in-patients or outpatients at University Clinic of Respiratory and Allergic Diseases Golnik between 1 January 2006 and 31 December 2008. Results: We determined 8 pulsotypes of P. aeruginosa. Pulsotypes A and C had 4 subtypes each. Different antimicrobial susceptibility patterns were observed in isolates with closely related macrorestriction profiles. Conclusions: We conclude that at a given time, patients with CF attending our clinic were colonized or infected with phenotypically and genotypically distinct strains of P. aeruginosa. Izvleček Izhodišče: Namen naše raziskave je bil ugotoviti genotipe in občutljivost za izbrane antibiotike izolatov bakterije Pseudomonas aeruginosa, ki smo jih osamili pri bolnikih s cistično fibrozo (CF).
Zdravniski Vestnik, 2010
Background: The aim of our study was to determine the genotypes and antimicrobial susceptibility profiles of Pseudomonas aeruginosa isolates of cystic fibrosis (CF) patients. Methods: We included 18 P. aeruginosa isolates from 10 patients treated as in-patients or outpatients at University Clinic of Respiratory and Allergic Diseases Golnik between 1 January 2006 and 31 December 2008. Results: We determined 8 pulsotypes of P. aeruginosa. Pulsotypes A and C had 4 subtypes each. Different antimicrobial susceptibility patterns were observed in isolates with closely related macrorestriction profiles. Conclusions: We conclude that at a given time, patients with CF attending our clinic were colonized or infected with phenotypically and genotypically distinct strains of P. aeruginosa. Izvleček Izhodišče: Namen naše raziskave je bil ugotoviti genotipe in občutljivost za izbrane antibiotike izolatov bakterije Pseudomonas aeruginosa, ki smo jih osamili pri bolnikih s cistično fibrozo (CF).
PloS one, 2015
In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02) from two Queensland CF centres over two distinct time-periods (2001-2002 and 2007-2009) underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7) in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 ...
European Journal of Clinical Microbiology & Infectious Diseases, 1992
A combination of esterase electrophoretic typing and analysis of the restriction fragment length polymorphism of ribosomal DNA regions (ribotyping) was used to compare 27Pseudomonas aeruginosa strains isolated before and after two-week courses of anti-pseudomonal treatment in seven cystic fibrosis patients. A total of 12 courses of therapy were studied in which ciprofloxacin, ceftazidime, azlocillin or imipenem were used alone or in combination with tobramycin. Isolates at a count of ≥ 106 cfu/ml of sputum were collected when there was evidence of therapeutic failure on the basis of persistence of isolates whether or not they were resistant to the antibiotic used for therapy. Emergence of resistance was observed in ten cases and failure to eradicate sensitive strains in five cases. Among the 27 isolates, eight zymotypes and five ribotypes were identified. With this typing approach, resistant post-therapy isolates were found to be identical to pre-therapy isolates in all cases but one. However, in one case an additional resistant strain was isolated after therapy besides that initially present. In all five cases in which susceptibility was still observed after treatment, pretherapy and post-therapy isolates were indistinguishable. Using this molecular typing approach, all the strains were typable. Thus combination of esterase typing and ribotyping should improve the analysis of therapeutic failure in cystic fibrosis patients.