Epidemiology and natural history ofPseudomonas aeruginosaairway infections in non-cystic fibrosis bronchiectasis (original) (raw)
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PCR fingerprinting was used for the epidemiological investigation of 64 Pseudomonas aeruginosa isolates collected from 16 chronic bronchiectasis patients without cystic fibrosis: 56% of the patients harbored one clone, 12.5% carried a single major type with minor variants, and 31.5% carried two clones. Only a minority of the acquisitions of antibiotic resistance was related to the acquisition of exogenous strains. Mucoid and nonmucoid sets of isolates did not display any consistent differences in their patterns. The genetic similarity among the clones ranged from 10 to 69%. Cross-infection or common-source exposure did not appear to have occurred.
ERJ open research, 2018
The natural history and epidemiology of infections in non-cystic fibrosis (non-CF) bronchiectasis is not well understood. As such it was our intention to determine the evolution of airway infection and the transmission potential of in patients with non-CF bronchiectasis. A longitudinal cohort study was conducted from 1986-2011 using a biobank of prospectively collected isolates from patients with non-CF bronchiectasis. Patients included were ≥18 years old and had ≥2 positive cultures over a minimum 6-month period. All isolates obtained at first and most recent clinical encounters, as well as during exacerbations, that were morphologically distinct on MacConkey agar were genotyped by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 203 isolates from 39 patients were analysed. These were compared to a large collection of globally epidemic and local CF strains, as well as non-CF isolates. We identified four patterns of infection in non-CF bronch...
Diagnostic Microbiology and Infectious Disease, 2010
Pseudomonas aeruginosa is isolated in sputum cultures from cystic fibrosis (CF) patients and adults with bronchiectasis (BS) and chronic obstructive pulmonary disease, but it is not well known if the characteristics of colonization in these latter patients are similar to those with CF. We examined 125 P. aeruginosa isolates obtained from 31 patients suffering from these diseases by pulsed field gel electrophoresis and genotyping of mucA and fpvA genes. The pattern of colonization, with dominance of a clonal strain and incidence of mucoid phenotypes, was similar in every group of patients; however, in some CF and BS patients, we detected the replacement or coexistence of 2 main clones. The main differences were found in the nucleotide position of less common mucA mutations, other than mucA22, and in the predominance of the different types of the pyoverdine receptor. Our results support a similar colonization pattern by P. aeruginosa in the different obstructive pulmonary diseases.
Scientific Reports, 2015
Chronic airway infections caused by Pseudomonas aeruginosa contribute to the progression of pulmonary disease in individuals with cystic fibrosis (CF). In the setting of CF, within-patient adaptation of a P. aeruginosa strain generates phenotypic diversity that can complicate microbiological analysis of patient samples. We investigated within-and between-sample diversity of 34 phenotypes among 235 P. aeruginosa isolates cultured from sputum samples collected from a single CF patient over the span of one year, and assessed colony morphology as a screening tool for predicting phenotypes, including antimicrobial susceptibilities. We identified 15 distinct colony morphotypes that varied significantly in abundance both within and between sputum samples. Substantial within sample phenotypic heterogeneity was also noted in other phenotypes, with morphotypes being unreliable predictors of antimicrobial susceptibility and other phenotypes. Emergence of isolates with reduced susceptibility to β-lactams was observed during periods of clinical therapy with aztreonam. Our findings confirm that the P. aeruginosa population in chronic CF lung infections is highly dynamic, and that intra-sample phenotypic diversity is underestimated if only one or few colonies are analyzed per sample. Cystic fibrosis (CF) is a fatal genetic disease that predisposes patients to polymicrobial infection of the lungs 1,2. Chronic infections caused by Pseudomonas aeruginosa are associated with increased severity of lung disease and premature death 3,4. In the diseased CF lung, P. aeruginosa is exposed to a range of selective pressures including host immune responses, competing organisms and antimicrobials, which are thought to drive genetic and phenotypic diversity within an infecting strain over time 1,5-7. Various airway-specific adaptations are postulated to favour persistence and lead to host-tolerant clonal lineages that are less cytotoxic, better at evading the immune system, more resistant to antimicrobials and less metabolically active than their
BMC Genomics, 2015
Background: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify mechanisms responsible for adaptation during bronchiectasis infections, a bronchiectasis isolate, PAHM4, was phenotypically and genotypically characterized. Results: This strain displays phenotypes that have been associated with chronic respiratory infections in CF including alginate overproduction , rough lipopolysaccharide, quorum-sensing deficiency, loss of motility, decreased protease secretion, and hypermutation. Hypermutation is a key adaptation of this bacterium during the course of chronic respiratory infections and analysis indicates that PAHM4 encodes a mutated mutS gene responsible for a~1,000-fold increase in mutation rate compared to wild-type laboratory strain P. aeruginosa PAO1. Antibiotic resistance profiles and sequence data indicate that this strain acquired numerous mutations associated with increased resistance levels to β-lactams, aminoglycosides, and fluoroquinolones when compared to PAO1. Sequencing of PAHM4 revealed a 6.38 Mbp genome, 5.9 % of which were unrecognized in previously reported P. aeruginosa genome sequences. Transcriptome analysis suggests a general down-regulation of virulence factors, while metabolism of amino acids and lipids is up-regulated when compared to PAO1 and metabolic modeling identified further potential differences between PAO1 and PAHM4. Conclusions: This work provides insights into the potential differential adaptation of this bacterium to the lung of patients with bronchiectasis compared to other clinical settings such as cystic fibrosis, findings that should aid the development of disease-appropriate treatment strategies for P. aeruginosa infections.
Journal of Medical Microbiology, 1993
The epidemiology of pulmonary colonisation by Pseudomonas aeruginosa was studied in 21 patients with cystic fibrosis (CF) by field inversion gel electrophoresis. DraI-DNA restriction patterns were analysed for 187 P. aeruginosa isolates from these patients. The results revealed that the strains present in individual patients varied during the course of chronic. colonisation ; the emergence of new strains often was associated with periods of antibiotic therapy. Patients often were colonised by more than one strain (two or three strains were present in 54% of the patients) and the strains obtained from unrelated patients were highly heterogeneous, in contrast to those isolated from a pair of twins. These results demonstrate the heterogeneity and variability of P. aeruginosa isolates in the pulmonary flora of chronically infected CF patients.
Epidemiology of chronic Pseudomonas aeruginosa infectionsin cystic fibrosis
International journal of …, 2001
Chronic lung infection with Pseudomonas aeruginosa is primarily responsible for the pulmonary deterioration and reduced life expectancy in patients with cystic fibrosis (CF) (Gilligan, 1991; Gowan and Deretic, 1996). Once P. aeruginosa has taken residence in the CF lungs, it is rarely possible to eradicate it by antimicrobial chemotherapy (Gowan and Deretic, 1996). Analysis of such therapeutic failure requires distinction between persistence of the same strain with the same susceptibility pattern, emergence of resistance in the same strain, or reinfection with a new strain. Due to the difficulties in typing isolates of P. aeruginosa from CF patients by conventional phenotypic typing techniques, the epidemiology of P. aeruginosa infections in CF patients is still not well defined. Genetic typing methods have shown to be more discriminatory than phenotypic methods for typing P. aeruginosa CF isolates (
Epidemiology of Pseudomonas aeruginosa in Cystic Fibrosis in British Columbia, Canada
American Journal of Respiratory and Critical Care Medicine, 2002
Pseudomonas aeruginosa is the most common respiratory pathogen views have been based on surveys of bacterial isolates from in patients with cystic fibrosis (CF), but the predominant mechanism patients with CF in different geographic locations. The most by which it is acquired is controversial. To determine the frequency compelling evidence for patient-to-patient spread has been of patient-to-patient spread, we evaluated P. aeruginosa isolates in the form of reports of unique bacterial clones shared by from 174 patients treated at the CF clinics in Vancouver, BC, Canada, multiple patients (9, 11). since 1981. Multiple isolates were obtained from each patient and Since 1981, we have saved isolates of P. aeruginosa from genetically typed by random amplified polymorphic DNA and all patients with CF who received care at clinics in Vancouver. pulsed field gel electrophoresis analyses. A total of 157 genetic These isolates have been evaluated by genetic "fingerprinttypes of P. aeruginosa was identified, 123 of which were unique to ing" in an attempt to determine whether patient-to-patient individual patients. A total of 34 types was shared by more than spread has occurred. The data from the 20-year analysis of one patient; epidemiologic evidence linked these individuals only these strains forms the basis of this report. in the cases of 10 sibships and 1 pair of unrelated patients. We conclude that there is an extremely low risk in Vancouver for pa-METHODS tients with CF to acquire P. aeruginosa from other patients. It appears that prolonged close contact, such as occurs between siblings, Bacterial Isolates is necessary for patient-to-patient spread. The major source of ac-Purified isolates of gram-negative, nonfermentative bacteria cultured quisition of P. aeruginosa in CF appears to be from the environment. from the respiratory secretions of patients with CF were obtained Considering these observations, we do not recommend segregation weekly from the Vancouver clinical microbiology laboratories. All iniof patients with CF on the basis of their colonization status with tial isolates and those from patients who were culture-positive intermit-P. aeruginosa. tently were evaluated to confirm species identification (16) and then frozen. Once a patient became persistently culture-positive for P. aeru-Keywords: cystic fibrosis; epidemiology; Pseudomonas aeruginosa ginosa, isolates of each colonial morphotype were frozen twice yearly. Bacterial cultures from each patient representing the first and most Pseudomonas aeruginosa is the predominant respiratory recent isolates and the midpoint of the course of the infection, were pathogen in patients with cystic fibrosis (CF), but the means selected and typed by pulsed field gel electrophoresis (PFGE) and/or by which the organism is acquired is controversial (1). Most random amplified polymorphic DNA analysis (RAPD) (see below). patients with CF are ultimately infected with P. aeruginosa, and once acquired, the infection is not readily eradicated (2, Genetic Strain Typing 3). The unique tropism of P. aeruginosa for the CF respiratory Two genetic typing analyses were performed to determine P. aeruginosa tract has not been adequately explained; competing and comstrain types, RAPD typing and PFGE fingerprinting. RAPD analysis plementary hypotheses abound (4-6). None of these theories was performed as previously described (17) using Primer 272. RAPD has been widely accepted as the single unifying explanation fingerprints obtained were analyzed both visually and by using Molecufor the peculiar propensity of P. aeruginosa to infect the CF lar Analyst Fingerprinting software (Bio-Rad Laboratories, Hercules, CA) as described previously (18). Isolates that appeared similar in airway. RAPD were then evaluated by PFGE, as previously described for Currently, there is great concern about the possible emer-Burkholderia cepacia isolates (19). The guidelines of Tenover and cogence and spread of transmissible strains of P. aeruginosa in workers (20) were used to assess the PFGE patterns. As observed in CF centers (1). It has been suggested that P. aeruginosa our previous studies (17-19), the results of both typing methods were is spread from patient to patient (7-11) and that stringent concordant, and genetically distinct strains were assigned a strain code. infection control policies should be able to limit the acquisition by uninfected patients. Others have failed to find evi-Epidemiology dence of patient-to-patient spread (12-15) and have sug-Patients who harbored P. aeruginosa of the same genetic type were gested that specific hygienic measures to prevent nosocomial assessed using information obtained from CF clinics and from previous acquisition are not indicated. Data supporting these divergent studies (13, 21) to determine if they had had any contact with one another in the clinic. All patients are followed by a full-time team of physicians, social workers, nurses, and dieticians. The social interactions of each patient are known to the CF clinical care team, and the patients