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PubMed2006

The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis.

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67), "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) % predicted levels at >or=2 yrs after presentation, longitudinal behaviour was characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or "stability". Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/-25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV(1) levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.

Adult↗

PubMed2005

Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa.

BACKGROUND: The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the alpha, beta and gamma subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na+-K+-ATPase. METHODS: Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c) and susceptible (DBA/2, C57BL/6 and A/J) mouse strains. The mRNA expression of ENaC and Na+-K+-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. RESULTS: The infection of the different mouse strains evoked regulation of alpha and beta ENaC mRNA. Following Pseudomonas instillation, the expression of alphaENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p < 0.05). The relative expression of betaENaC mRNA was transiently increased to a median of 241%, 24 h post-infection before decreasing to a median of 43% and 54% of control on days 3 and 7 post-infection (p < 0.05). No significant modulation of gammaENaC mRNA was detected although the general pattern of expression of the subunit was similar to alpha and beta subunits. No modulation of alpha1Na+-K+-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. CONCLUSIONS: These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs.

Adaptation, Physiological↗

PubMed1983

Pseudomonas-infected cystic fibrosis patient sputum inhibits the bactericidal activity of normal human serum.

Sputum samples were obtained from nineteen cystic fibrosis (CF) patients with respiratory tract infections due to Pseudomonas aeruginosa and were examined for the presence of a specific local protective or blocking factor, which might partially explain the inability of CF patients' pulmonary defense mechanisms to clear their lungs of Pseudomonas infection. Using an assay that measures the bactericidal activity of fresh normal human serum (FHS), eighteen of nineteen CF sputa examined were capable of protecting either autologous or heterologous strains of P. aeruginosa from serum bactericidal activity. Most of this protective activity was absorbable at 4 degrees C by Pseudomonas, and could be reduced by dilution in phosphate buffered saline or counteracted by an increase in serum concentration. This protective activity is believed to be due to a Pseudomonas-specific bactericidal blocking antibody. In contrast, only two of 17 non-CF sputa were found to significantly inhibit the bactericidaL activity of FHS for P. aeruginosa. Furthermore, three out of five CF sputa also protected Escherichia coli from the bactericidal activity of FHS. This protective activity was much less than that observed with P. aeruginosa, and was not absorbable at 4 degrees C, suggesting the presence of a second blocking or protective factor in CF sputum. From these observations, we conclude that sputum from CF patients infected with P. aeruginosa contains one or more factors that interfere with the bactericidal activity present in FHS.

Adolescent↗

PubMed1996

Pseudomonas aeruginosa bronchopulmonary infection in patients with advanced human immunodeficiency virus disease.

Pseudomonas aeruginosa is increasingly reported as a respiratory pathogen in patients with advanced human immunodeficiency virus (HIV) disease. We retrospectively reviewed the chest radiographic appearances of 29 HIV-infected adults with bronchopulmonary infection in whom Pseudomonas aeruginosa was the sole respiratory pathogen isolated. The commonest radiographic abnormality was a diffuse reticular (11 patients) or reticulonodular (9 patients) infiltrate in the pulmonary interstitium. Alveolar opacification was seen in seven patients. Cavitation was rare (2 patients), as was ground-glass opacification (2 patients). Five patients had pleural effusions. No patient had mediastinal or hilar lymphadenopathy. Normal chest radiographs were seen in eight patients. Although the radiographic appearances of Pseudomonas bronchopulmonary infection in HIV-infected patients are non-specific, an interstitial infiltrate is a common finding. Pseudomonas aeruginosa should be considered along with the commoner pathogen Pneumocystis carinii in the differential diagnosis of an interstitial infiltrate in this group of patients.

AIDS-Related Opportunistic Infections↗

PubMed1992

In vitro interactions of Pseudomonas RNA polymerases with tac and RNA I promoters.

The activities of RNA polymerases from Pseudomonas putida and Pseudomonas aeruginosa were compared with that of Escherichia coli RNA polymerase in an in vitro transcription system. All three enzymes initiated transcription at the tac promoter and the RNA I promoter of E. coli. We measured the rate of open complex formation between the RNA polymerases and the promoters, and the saturation level of open complex formation at equilibrium in single-round transcription. The relative rates of open complex formation were P. putida > E. coli > P. aeruginosa and the relative saturation levels of open complex formation at equilibrium were E. coli > P. putida > P. aeruginosa for the tac and RNA I promoters. The interaction of the RNA polymerases with the promoters was also studied by DNase I footprinting. The patterns of protection of the Pseudomonas RNA polymerases on the tac promoter were similar to that of E. coli RNA polymerase. However, the protection patterns of the Pseudomonas RNA polymerases on the RNA I promoter were slightly different from that of E. coli RNA polymerase.

DNA Fingerprinting↗

PubMed2005

TLRs 2 and 4 are not involved in hypersusceptibility to acute Pseudomonas aeruginosa lung infections.

TLRs are implicated in defense against microorganisms. Animal models have demonstrated that the susceptibility to a number of Gram-negative pathogens is linked to TLR4, and thus LPS of many Gram-negative bacteria have been implicated as virulence factors. To assess the role of this pathogen-associated molecular pattern as it is exposed on intact Pseudomonas aeruginosa, the susceptibility of mice lacking TLR4 or both TLR2 and TLR4 was examined in a model of acute Pseudomonas pneumonia. These mutant mice were not hypersusceptible to the Pseudomonas challenge and mounted an effective innate response that cleared the organism despite low levels of TNF-alpha and KC in the airways. Bacterial and neutrophil counts in the lung were similar in control and TLR-deficient mice at 6 and 24 h after infection. MyD88(-/-) mice were, however, hypersusceptible, with 100% of mice dying within 48 h with a lower dose of P. aeruginosa. Of note there were normal levels of IL-6 and G-CSF in the airways of TLR mutant mice that were absent from the MyD88(-/-) mice. Thus, the susceptibility of mice to P. aeruginosa acute lung infection does not go through TLR2 or TLR4, implying that Pseudomonas LPS is not the most important virulence factor in acute pneumonia caused by this organism. Furthermore, G-CSF treatment of infected MyD88(-/-) mice results in improved clearance and survival. Thus, the resistance to infection in TLR2/TLR4(-/-) mice may be linked to G-CSF and possibly IL-6 production.

Acute Disease↗

PubMed2001

[Effects of erythromycin and fosfomycin on Pseudomonas aeruginosa biofilm in vitro].

OBJECTIVE: To observe the effects on Pseudomonas aeruginosa biofilm of non-antipseudomonal drugs such as erythromycin and fosfomycin. METHODS: Clinical isolates of Pseudomonas aeruginosa in respiratory infection and ATCC27853 were cultivated in TSB-Teflon and NS-Teflon system respectively for biolfilm formation. Biofilm was observed under scanning electronic microscope (SEM). MICs were determined by broth micro-dilution. RESULTS: SEM showed that biofilm of clinical isolate in TSB-Teflon system and ATCC27853 in NS-Teflon system increased as being cultivated for longer in 1, 3 and 7 days. And biofilm formation in the process of cultivating was inhibited by SubMIC of erythromycin and fosfomycin. MICs evaluation suggested that there were synergetic effects against biofilm Pseudomonas aeruginosa when SubMIC of erythromycin and fosfomycin were combined with ceftazidime or levofloxacin in vitro. CONCLUSION: SubMIC of erythromycin and fosfomycin could inhibit Pseudomonas aeruginosa biofilm in vitro.

Anti-Bacterial Agents↗

PubMed1979

Pseudomonas aeruginosa: prevention better than cure?

Pseudomonas aeruginosa is a common pathogen in certain groups of patients. The use of antibiotics in these patients may be associated with toxic side effects, drug resistance and therapeutic failure. Pseudomonas vaccines have been prepared by many workers and one vaccine has been widely used in clinical trials. Administration of this vaccine was associated with a high incidence of toxic reactions. A new polyvalent pseudomonas vaccine has recently been prepared. We report the reactivity of this polyvalent vaccine in healthy volunteers and compare this with the reactivity of the earlier pseudomonas vaccine reported in the literature. The vaccine is at present being used in burned patients and has been associated with a significant reduction in mortality. We suggest that this new polyvalent vaccine has a low incidence of toxic effects and promises a considerable advance upon earlier vaccines.

Bacterial Vaccines↗

PubMed1979

Lytic manifestations in the bacterial strains of Pseudomonas aeruginosa (bacteriophages bacteriocines, autoplaques).

Ps. aeruginosa strains--a frequement resuet of an irresponsible antibiotic therapy--represent a common agent of nosocomial infektions. At the same time, gravity of Pseudomonas diseases is also increasing. Lysogeny, bacteriocinogeny and frequent occurrence of autoplaques are the lytic manifestations of Pseudomonas aeruginosa strains which play a great role in the complexity of solving diagnostic, epidemiological end therapeutical problems connected with infections induced by these microbes. A survey is presented of the importance and utilization of the lytic properties of bacterial strains of Pseudomonas aeruginosa during the differentiation, epidemiological typing and further expansion of therapeutical possibilities in infections caused by Pseudomonas aeruginosa bacteria.

Bacteriophage Typing↗

PubMed1992

Immunoglobulin allotypes and IgG subclass antibody response to Pseudomonas aeruginosa antigens in chronically infected cystic fibrosis patients.

Chronic Pseudomonas aeruginosa lung infection is the leading cause of death in patients with cystic fibrosis (CF). Poor prognosis correlates with a high number of anti-pseudomonas precipitins and with high levels of IgG2 and IgG3 anti-pseudomonas antibodies. Reports of several highly significant associations between certain Gm (genetic markers of IgG on human chromosome 14) and Km (k-type light chain determinants on chromosome 2) phenotypes and immune responsiveness to various antigens suggest that allotype-linked immune response genes do exist in man. Furthermore correlation between Gm types and IgG subclass levels has been reported. A group of 143 CF patients were investigated (31 non-infected and 112 chronic infected). The IgG subclass antibodies to three different P. aeruginosa antigens (P. aeruginosa standard antigen (St-Ag), alginate and LPS) were determined. Immunoglobulin allotypes were determined by haemagglutination inhibition. Samples were typed for G1m(1,2,3, and 17), G2m(23), G3m(5,21), and Km(1,3). Statistical analysis of our data demonstrate that IgG3 anti-pseudomonas antibody levels and Gm markers are related. IgG3 antibody levels to all investigated P. aeruginosa antigens are significantly higher in sera homozygous for Gm(3;5), somewhat lower in heterozygous sera, and significantly lower in sera homozygous for Gm(1,2,17;21). We suggest that genetic differences between the patients may explain the present differences in subclass patterns.

Antibodies, Bacterial↗

PubMed1992

Emergence and persistence of Pseudomonas aeruginosa in the cystic fibrosis airway.

Colonization in the respiratory tracts of cystic fibrosis (CF) patients by mucoid Pseudomonas aeruginosa correlates with the progression of bronchial airway pathology. There is a direct correlation between the incidence of Pseudomonas colonization and age, clinical score, extent of pulmonary disease, severity of radiographic changes, and level of serum immunoglobulins. The central propensity to Pseudomonas colonization in patients with CF is not freely understood, but we discuss the acquisition and persistence of P aeruginosa in the CF airway. Elucidation of pathogenetic mechanisms of CF inflammatory airways disease is the first essential step to initiating novel therapies. It has been difficult to prove that the ability of P aeruginosa to adhere to the respiratory epithelium and provide selective advantage for this gram-negative bacillus over other potential pathogens for infection in the CF airway. However, flexible filaments (pili) extending from the Pseudomonas cell wall are thought to medicate epithelial cell adherence for nonmucoid P aeruginosa, and similarly, the gelatinous exopolysaccharide alginate produced by mucoid variants of P aeruginosa seems to be the adhesive to tracheal cells. Following the signal event of adherence, this bacterial pathogen competes successfully for iron cofactor and multiplies, releasing proteases with broad substrate specificities that dramatically alter the airway antiprotease screen, and the pathogen creates defects in local antibacterial defenses. Lung inflammation in CF is characterized by massive neutrophil infiltration. Although critical to host defense, neutrophils also cause progressive airway damage by release of bioactive lipids, oxygen metabolites, and granule enzymes such as hydrolases, myeloperoxidase (MPO), lysozyme, and neutral serine proteases. The necessarily circumscribed discussion that follows will focus narrowly on the host cell-derived factors (macrophages and neutrophils) proposed as important components in this pathogenetic scheme.

Adult↗

PubMed2004

[Investigation of cross-infection of Pseudomonas aeruginosa in an intensive care unit].

OBJECTIVE: To investigate the factors responsible for Pseudomonas aeruginosa nosocomial cross-infection in the intensive care unit (ICU) and provide effective measure for the prevention and management. METHODS: The homology of 7 Pseudomonas aeruginosa strains isolated from the patients in the ICU and the environment was examined by biological, serological, drug-resistance and plasmid analysis. RESULTS: The results of serological and plasmid analyses had good consistency, which demonstrated that the 7 Pseudomonas aeruginosa strains originated from solution in the oxygen humidifier, with uniform serological and plasmid type, and belonged to the same clone with cross-infection by contact between the patients or nursing staff and the objects in the ICU. CONCLUSION: Serological and plasmid analyses are more practical for identifying the sources of Pseudomonas aeruginosa cross-infection, which can be prevented by strict disinfection of the instrument and supervision of the nursing staff in the ICU.

Cross Infection↗

PubMed1992

Fusions of anthrax toxin lethal factor to the ADP-ribosylation domain of Pseudomonas exotoxin A are potent cytotoxins which are translocated to the cytosol of mammalian cells.

The lethal factor (LF) and edema factor (EF) components of anthrax toxin are toxic to animal cells only if internalized by interaction with the protective antigen (PA) component. PA binds to a cell surface receptor and is proteolytically cleaved to expose a binding site for LF and EF. To study how LF and EF are internalized and trafficked within cells, LF was fused to the translocation and ADP-ribosylation domains (domains II and III, respectively) of Pseudomonas exotoxin A. LF fusion proteins containing Pseudomonas exotoxin A domains II and III were less toxic than those containing only domain III. Fusion proteins with a functional endoplasmic reticulum retention sequence, REDLK, at the carboxyl terminus of domain III were less toxic than those with a nonfunctional sequence, LDER. The most potent fusion protein, FP33, had an EC50 = 2 pM on Chinese hamster ovary cells, exceeding that of native Pseudomonas exotoxin A (EC50 = 420 pM). Toxicity of all the fusion proteins required the presence of PA and was blocked by monensin. These data suggest that LF and LF fusion proteins are efficiently translocated from acidified endosomes directly to the cytosol without trafficking through other organelles, as is required for Pseudomonas exotoxin A. This system provides a potential vehicle for importing diverse proteins into the cytosol of mammalian cells.

ADP Ribose Transferases↗

PubMed2006

[Treatment of Pseudomonas aeruginosa in cystic fibrosis in a child].

The report deals with the case of a 10-year-old girl with chronic cystic fibrosis. She has been repeatedly treated at the hospital. She has been hospitalized due to respiratory deterioration. Cystic fibrosis is a rare disease, inherited autosomaly recessively, but is very complex in terms of diagnostic and treatment. Fibrosis is the formation of scar tissue due to injury or long term inflammation. The diagnosis is confirmed based on a clinical picture of the child, measure of Chloride in the sweat, chest X-ray, CT thorax, laboratory findings--genetic confirmation CFTR genes. The diagnosis is originally set when she was 4 years old. She is now admitted due to a deterioration of the main disease. Five days before the admission, the girl had a higher bodily temperature, cough and difficult breathing. Due to the deteriorated general condition and the respiratory insufficiency and respiratory acidosis in blood gas analysis, the girl was intubated and put on the complete mechanical ventilation (IPPV). Since the girl is a chronic patient with bronchiectasie chronic walls of bronchi changes full of the mucus, who is not responding to conservative treatment (antibiotics), therapeutic and diagnostic flexible bronchoscopy had to be performed, resulting in a gram-negative bacteri Pseudomonas aeruginosa--a typical bacteri for chronically sick C. F. patient. Pseudomonas aeruginosa is typically acquired in early childhood. This bacteria is giving progressive lung disease and often aggravates morbidity and mortality. So the main thing as a respiratory management is prevention of lung infection with this bacteria. A Pseudomonas therapy was prescribed according to the sensitive antibiogram, (Garamycin). Antibiotics are crucial to treating cystic fibrosis lung infections. Therapy with an amynoglicoside in combination with a B-lactam or a quinolone antibiotic is standard. It is a difficult to deliver a high doses at these antibiotics via the iv. route without significant systemic adverse events (otoxicity and nephrotoxicity). A reformulation of the aminoglycoside antibiotic tobramicin or garamycin therapy is solution for inhalation. To be well established infections the suppression of Pseudomonas aeruginosa has been shown to lead to decreasing same bacteria and benefits lung function from antibiotic therapy in a way that can be maintained over extended period. During bronchoscopy was given locally on changes mucous pulmozyme (to destroy a very hard mucous) and garamycin. So, after taking out a lot of mucus, it was later continued spontaneously. Control chest x ray and blood gas analysis are now very improved.

Child↗

PubMed2006

Resolution of a Pseudomonas aeruginosa outbreak in a hematology unit with the use of disposable sterile water filters.

We observed a significant increase of Pseudomonas aeruginosa bacteremias during 2002. Eighty-five microbiological samples were taken from different potential sources of infection. Twenty-nine out of 46 specimens obtained from water taps, shower heads and siphons tested positive for Pseudomonas aeruginosa. Weekly pharyngeal and rectal swabs in high risk patients, use of tap water after running the tap for at least 5 minutes and use of weekly disposable sterile filters in all taps and showers resulted in a significant decrease in Pseudomonas aeruginosa bacteremias. Moreover, we observed a significant reduction in Pseudomonas aeruginosa-positive surveillance cultures after implementation of these measures.

Cross Infection↗

PubMed2006

[Quantification for biofilm formation of pseudomonas aeruginosa isolates and their genotypic analysis].

OBJECTIVE: To probe the correlation between the ability of biofilm formation of Pseudomonas aeruginosa isolates and their genotypes. METHODS: Forty-eight Pseudomonas aeruginosa isolates were tested for their biofilm formation with a modified microtiter test and were analyzed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). The percent similarity between their genetic fingerprints and cluster analysis was performed and worked out using computer software. RESULTS: Forty-eight Pseudomonas aeruginosa isolates demonstrated different abilities of biofilm formation in vitro. And the 48 isolates with different abilities of biofilm formation showed different genotypes in fingerprints by ERIC-PCR. Among the 48 isolates of Pseudomonas aeruginosa tested, five clusters (A, B, C, D, E), were identified at the 17% genetic similarity level. The isolates with strong ability of biofilm formation were in D cluster at the 42% genetic similarity level. CONCLUSION: Most of the 48 PA isolates tested formed strong biofilm, and their genotypes were of correlation.

Biofilms↗

PubMed1991

Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis.

The major causes of morbidity and mortality in cystic fibrosis are chronic pulmonary obstruction and infection. Mucoid Pseudomonas aeruginosa is the primary pathogen in up to 90% of these patients. Once Pseudomonas organisms colonize the airways, they are virtually never eradicated. No defect in systemic host defense has been elucidated, however, several mechanisms contribute to the breakdown in host defenses that allow persistence of this organism in the endobronchial space. These mechanisms involve both bacterial adaptation to an unfavorable host environment and impaired host response. P aeruginosa adapts to the host by expressing excessive mucoid exopolysaccharide and a less virulent form of lipopolysaccharide. These features make it less likely to cause systemic infection, yet still enable it to resist local host defenses. Mucociliary clearance becomes impaired due to abnormal viscoelastic properties of sputum, squamous metaplasia of the respiratory epithelium, and bronchiectasis. Despite a brisk antibody response to a variety of Pseudomonas antigens, several defects in antibody-mediated opsonophagocytosis have been identified. These include (1) development of antibody isotypes that are suboptimal at promoting phagocytosis, (2) formation of immune complexes that inhibit phagocytosis, and (3) proteolytic fragmentation of immunoglobulins in the endobronchial space. Complement-mediated opsonophagocytosis is also compromised by proteolytic cleavage of complement receptors from the cell surface of neutrophils and complement opsonins from the surface of Pseudomonas. The resultant chronic inflammation and infection lead to eventual obliteration of the airways.

Antibodies, Bacterial↗

PubMed1986

[Testing the protective effectiveness of vaccines against infection with Pseudomonas aeruginosa in mink (Lutreola vison)].

Infections by Pseudomonas aeruginosa have caused losses on mink farms in recent years, particularly with a clinical manifestation of haemorrhagic pneumonia. This paper includes the first results of the practical use of the Czechoslovak soluble monovaccine of polyvalent action in the treatment of mink infected by Pseudomonas aeruginosa. The action of the vaccine is based on the protective effect of Original Endotoxin Protein (OEP), antigen common to all species of the genus Pseudomonas. After due testing, the vaccine was given to mink. Doses of 50, 200 and 500 micrograms, and in another series 50 and 200 micrograms of the vaccine were tested in subcutaneous administration at 0.2 ml volume in a 7-day interval. No adverse side-effects and reactions were observed in the animals. A protective action was demonstrated, resulting in a higher number of reared mink in comparison with the control groups. After vaccination, titres ranging from 2 to 160 were determined by the indirect haemagglutination method and from 320 to 164,000 by the RIA method. In 1984 the vaccine was used for practical treatment on a mink farm with the stock exposed to Pseudomonas aeruginosa infection (5551 mink were treated). In the vaccinated group losses amounted to 3.1% whereas in the control group the mortality level was above 17%. Vaccination was demonstrated to have a favourable effect and the vaccine was then preventively used on the same farm in the subsequent year; the treatment of 29,350 mink had the required protective effect.

Animals↗