Poor clinical outcomes associated with a multi-drug resistant clonal strain of Pseudomonas aeruginosa in the Tasmanian cystic fibrosis population

Background and objective: Clonal strains of Pseudomonas aeruginosa have been identified in large cystic fibrosis (CF) centres. Whether such strains are more virulent or whether cross-infection between patients explains their widespread prevalence is unknown. This study described the epidemiology of P. aeruginosa infection in CF patients in Tasmania, Australia, an area with a high CF birth incidence. Patients in Tasmania are geographically dispersed and when this study was conducted (2003) there was no central CF clinic, with patients receiving treatment in regional hospitals. Methods: P. aeruginosa isolates from CF adults aged 15 years and over in Tasmania were genotyped using random amplified polymorphic DNA (RAPD)-PCR and clonal strains confirmed with pulsed field gel electrophoresis. Results: Airway samples were obtained from 41 patients (82% of the adult CF population). P. aeruginosa was isolated from 34 patients and nine (26%) of these individuals harboured P. aeruginosa strains with identical RAPD-PCR and pulsed field gel electrophoresis patterns (Australian Epidemic Strain III – AES III). AES III was isolated from patients in all regions of Tasmania and was distinct from the epidemic CF strains described on mainland Australia (AES I and II). The possible link between CF adults infected with AES III was attendance at family camps more than 12 years previously. Patients harbouring AES III had suffered significantly more exacerbations requiring hospitalisation during the 2 years prior to the study compared with patients infected with unique strains (P < 0.01). AES III displayed increased multi-antibiotic resistance compared with other strains (P < 0.001). Conclusions: Clonal strains of P. aeruginosa may arise even in isolated CF populations. The increased exacerbation rate in patients infected with AES III and its antibiotic resistance profile strongly suggest increased virulence

Epidemiology of Pseudomonas aeruginosa in a tertiary referral teaching hospital

A genotypically indistinguishable strain of Pseudomonas aeruginosa (Australian epidemic strain III: AES III) has previously been found in a proportion of adults with cystic fibrosis (CF) in Tasmania, Australia. The aim of this study was to identify a source of these infections within the major tertiary referral hospital for the State of Tasmania, and to determine if this strain could be isolated from settings other than the CF lung. A total of 120 isolates of P. aeruginosa were collected from clinical and environmental sources within the hospital and from environmental locations in the hospital vicinity. These isolates were genotyped by random amplification of polymorphic DNA (RAPD)-polymerase chain reaction (PCR) and antimicrobial susceptibility testing was performed using the Clinical and Laboratory Standards Institute method. Confirmation of similar genotypes identified by RAPDePCR was performed using pulsed-field gel electrophoresis with restriction enzyme SpeI. AES III was not recovered from any source other than the respiratory secretions of CF patients. P. aeruginosa in the non-CF settings was found to be panmictic, and no cross-infection or acquisition of hospital environment strains by patients was observed

Urease production as a marker of virulence in Pseudomonas aeruginosa

In summary, the findings of this paper show that a urease negative phenotype is a potential marker for attenuated virulence in Pseudomonas aeruginosa isolates. Further investigation, including amplification and sequencing of rpoN, followed by correlation to quantitative measures of urease enzyme production, would determine if absence of urease enzyme expression is consequent on rpoN mutation in isolates of P. aeruginosa

Decreased virulence of cystic fibrosis Pseudomonas aeruginosa in Dictyostelium discoideum

The characteristics of clinical and environmental isolates of Pseudomonas aeruginosa from both hospital and community settings were analyzed in a eukaryotic virulence model employing the AX2 and X22 mutants of Dictyostelium discoideum. Thirty-one strains, including two Australian epidemic strains, of P. aeruginosa were analyzed, five from environmental sources, six from clinical sources other than cystic fibrosis (CF) patients and nineteen from CF patients’ respiratory secretions. The majority of CF isolates almost uniquely supported the growth of D. discoideum. CF isolates of P. aeruginosa were found to be less virulent than isolates from other sources. Varying degrees of inhibition of the developmental cycle of D. discoideum when growing on CF isolates were also noted. This is the first description of P. aeruginosa isolates from clinical and environmental sources supporting the growth of D. discoideum

Virulence gene distribution in clinical, nosocomial and environmental isolates of Pseudomonas aeruginosa

The virulence factor genotypes of a large cohort of clinical, nosocomial environment and community environment isolates (184 in total) of Pseudomonas aeruginosa from Tasmania, Australia, were determined by PCR. The virulence factor genotype of the majority of isolates was highly conserved, with the exception of the virulence gene exoU, which demonstrated low prevalence (33 isolates; 18 %) in the population tested. Isolates collected from the environment of intensive therapy wards (intensive care unit and neurosurgical units) of the major tertiary referral hospital in Tasmania were found to be more likely (P<0.001 and P<0.05, respectively) to possess the virulence factor gene exoU than all other isolates. Adult cystic fibrosis isolates showed a decreased prevalence of the exoU gene (P<0.01) when compared to other clinical isolates (P<0.01), which may indicate decreased virulence. No specific virulence factor genotype was associated with the cystic fibrosis epidemic strains tested

Virulence gene distribution in clinical, nosocomial and environmental isolates of Pseudomonas aeruginosa

The virulence factor genotypes of a large cohort of clinical, nosocomial environment and community environment isolates (184 in total) of Pseudomonas aeruginosa from Tasmania, Australia, were determined by PCR. The virulence factor genotype of the majority of isolates was highly conserved, with the exception of the virulence gene exoU, which demonstrated low prevalence (33 isolates; 18 %) in the population tested. Isolates collected from the environment of intensive therapy wards (intensive care unit and neurosurgical units) of the major tertiary referral hospital in Tasmania were found to be more likely (P<0.001 and P<0.05, respectively) to possess the virulence factor gene exoU than all other isolates. Adult cystic fibrosis isolates showed a decreased prevalence of the exoU gene (P<0.01) when compared to other clinical isolates (P<0.01), which may indicate decreased virulence. No specific virulence factor genotype was associated with the cystic fibrosis epidemic strains tested

Antimicrobial susceptibility testing of cystic fibrosis and non-cystic fibrosis clinical isolates of Pseudomonas aeruginosa : a comparison of three methods

Pseudomonas aeruginosa is an important pathogen in humans, particularly in the context of nosocomial infection and infections of the cystic fibrosis (CF) lung. In order to provide clinicians with information about the likely effectiveness of specific antimicrobial treatment for P. aeruginosa infections, clinical laboratories employ in vitro antimicrobial susceptibility testing. Two commonly employed methods are the CLSI disc diffusion and Etest methods. The purpose of this study is to compare the accuracy of susceptibility results generated by these two methods against agar dilution as the reference method. Susceptible or nonsusceptible (resistant and intermediate) results of the Etestand CLSI disc diffusion methods are compared with CLSI agar dilution results for a large cohort of clinical cystic fibrosis (CF, n=71) and non-cystic fibrosis (n=83) isolates using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria. An unacceptable number of major and very major errors were observed for various antimicrobials tested against both CF and non-CF isolates when using the Etest and CLSI disc-diffusion methods. The potential for error in standard laboratory antimicrobial susceptibility testing should be considered by clinicians when being guided by the results of such tests in the prescription of antimicrobial agents for P. aeruginosa infection

Synoptic conditions conducive for compound wind-flood events in Great Britain in present and future climates

Extreme wind is the main driver of loss in North-West Europe, with flooding being the second-highest driver. These hazards are currently modelled independently, and it is unclear what the contribution of their co-occurrence is to loss. They are often associated with extra-tropical cyclones, with studies focusing on co-occurrence of extreme meteorological variables. However, there has not been a systematic assessment of the meteorological drivers of the co-occurring impacts of compound wind-flood events. This study quantifies this using an established storm severity index (SSI) and recently developed flood severity index (FSI), applied to the UKCP18 12km regional climate simulations, and a Great Britain (GB) focused hydrological model. The meteorological drivers are assessed using 30 weather types, which are designed to capture a broad spectrum of GB weather. Daily extreme compound events (exceeding 99th percentile of both SSI and FSI) are generally associated with cyclonic weather patterns, often from the positive phase of the North Atlantic Oscillation (NAO+) and Northwesterly classifications. Extreme compound events happen in a larger variety of weather patterns in a future climate. The location of extreme precipitation events shifts southward towards regions of increased exposure. The risk of extreme compound events increases almost four-fold in the UKCP18 simulations (from 14 events in the historical period, to 55 events in the future period). It is also more likely for there to be multi-day compound events. At seasonal timescales years tend to be either flood-prone or wind-damage-prone. In a future climate there is a larger proportion of years experiencing extreme seasonal SSI and FSI totals. This could lead to increases in reinsurance losses if not factored into current modelling.</p

Synoptic conditions conducive for compound wind-flood events in Great Britain in present and future climates

Extreme wind is the main driver of loss in North-West Europe, with flooding being the second-highest driver. These hazards are currently modelled independently, and it is unclear what the contribution of their co-occurrence is to loss. They are often associated with extra-tropical cyclones, with studies focusing on co-occurrence of extreme meteorological variables. However, there has not been a systematic assessment of the meteorological drivers of the co-occurring impacts of compound wind-flood events. This study quantifies this using an established storm severity index (SSI) and recently developed flood severity index (FSI), applied to the UKCP18 12km regional climate simulations, and a Great Britain (GB) focused hydrological model. The meteorological drivers are assessed using 30 weather types, which are designed to capture a broad spectrum of GB weather. Daily extreme compound events (exceeding 99th percentile of both SSI and FSI) are generally associated with cyclonic weather patterns, often from the positive phase of the North Atlantic Oscillation (NAO+) and Northwesterly classifications. Extreme compound events happen in a larger variety of weather patterns in a future climate. The location of extreme precipitation events shifts southward towards regions of increased exposure. The risk of extreme compound events increases almost four-fold in the UKCP18 simulations (from 14 events in the historical period, to 55 events in the future period). It is also more likely for there to be multi-day compound events. At seasonal timescales years tend to be either flood-prone or wind-damage-prone. In a future climate there is a larger proportion of years experiencing extreme seasonal SSI and FSI totals. This could lead to increases in reinsurance losses if not factored into current modelling.</p