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PubMed1986

[Protective effect of a corpuscular polyvalent Pseudomonas aeruginosa vaccine in generalized chronic Pseudomonas aeruginosa infection in mice with cyclophosphamide-induced leukopenia].

The prophylactic effect of immunization with P. aeruginosa polyvalent corpuscular vaccine has been shown on the model of P. aeruginosa generalized chronic infection in mice with leukopenia induced by the intraperitoneal injection of cyclophosphamids. This effect is manifested by the increased resistance of the animals to sublethal doses of P. aeruginosa strain, as well as by more intense general and specific immunological responses in the infected animals (the increase of specific antibody titers, the number of leukocytes in the blood serum and the phagocytic activity of the cells of peritoneal exudate).

Animals↗
PubMed1995

Role of exotoxin A in inducing severe Pseudomonas aeruginosa infections in mice.

The effects of exotoxin A (EXA) from Pseudomonas aeruginosa on polymorphonuclear leucocytes (PMNLs) were studied in a mouse model and in vitro. P. aeruginosa PA103, which produced EXA, was 20 times more virulent for normal mice than was its EXA-deficient mutant, PA103-29. EXA was detected in the plasma of mice infected with P. aeruginosa PA103, and its presence correlated with increasing numbers of bacteria in the blood and internal organs. A monoclonal antibody (MAb) against EXA prevented the death of the mice if it was given simultaneously with, or 2 h before, infection with strain PA103. The number of PMNLs in murine blood decreased by 50% within 30 min of intravenous injection of EXA, but this decrease was prevented by simultaneous or prior injection of MAb to the toxin. EXA inhibited in-vitro phagocytosis and killing of P. aeruginosa by human and murine PMNLs and decreased the number of the PMNLs by between 60 and 68%. Collectively, these results not only confirm that EXA is toxic in vivo, but also suggest that this toxin accelerates the growth of virulent P. aeruginosa in mice.

ADP Ribose Transferases↗
PubMed1984

Addition of rifampin to ticarcillin-tobramycin combination for the treatment of Pseudomonas aeruginosa infections: assessment in a neutropenic mouse model.

The efficacy of ticarcillin (100 mg/kg), tobramycin (1 mg/kg), and rifampin (43 and 7.2 mg/kg) individually and in combination was assessed in neutropenic mice infected with an LD90 of one of four Pseudomonas aeruginosa isolates. The study end point was survival at 120 hours after infection. Treatment with the triple combination, ticarcillin plus tobramycin plus rifampin (43 mg/kg), was significantly superior to the double combination of ticarcillin plus tobramycin (p less than 0.01). Although treatment with rifampin (43 mg/kg) alone yielded results similar to treatment with the triple combination in mice infected with three of the four isolates, rifampin-resistant mutants (minimal inhibitory concentration greater than 1000 micrograms/ml) of P. aeruginosa were frequently isolated from surviving mice (26% of mice sampled). In contrast, in mice treated with the triple combination, rarely were rifampin-resistant mutants isolated (3% of mice sampled). Rifampin alone was active against P. aeruginosa isolates only when peak serum concentrations of rifampin exceeded the rifampin minimal bactericidal concentration of the infecting isolate. The addition of rifampin to a "standard" therapy of antipseudomonal penicillin plus aminoglycoside may be useful in the treatment of serious P. aeruginosa infection.

Animals↗
PubMed2003

Effects of nitric oxide on Pseudomonas aeruginosa infection of epithelial cells from a human respiratory cell line derived from a patient with cystic fibrosis.

Cystic fibrosis (CF) is characterized by airway inflammation and chronic bacterial lung infection, most commonly with Pseudomonas aeruginosa, an opportunistic human pathogen. Despite the persistent airway inflammation observed in patients with CF, although phagocyte inducible nitric oxide synthase (iNOS) production is upregulated, expression of iNOS in the respiratory epithelium is markedly reduced. Given the antimicrobial action of NO, this may contribute to the chronic airway infection of this disease. To define the role of epithelium-derived NO in airway defense against P. aeruginosa, we infected differentiated human bronchial epithelial cells derived from a patient with CF (CFBE41o- cells) with different strains of this pathogen at low multiplicities of infection. Using cells transfected with human iNOS cDNA, we studied the effect of NO on P. aeruginosa replication, adherence, and internalization. P. aeruginosa adherence to iNOS-expressing cells was reduced by 44 to 72% (P = 0.02) compared with control values. Absolute P. aeruginosa uptake into these cells was reduced by 44%, but uptake expressed as a percentage of adherent bacteria did not differ from the control uptake. Survival of P. aeruginosa within iNOS-expressing cells was reduced at late times postinfection (P = 0.034). NO production did not alter host cell viability. NO production reduced P. aeruginosa adherence to human bronchial epithelial cells and enhanced killing of internalized bacteria, suggesting that a lack of epithelial iNOS in patients with CF may contribute to P. aeruginosa infection and colonization.

Bacterial Adhesion↗
PubMed1971

Carbenicillin and gentamicin in the treatment of Pseudomonas aeruginosa infection.

The administration separately and sequentially of carbenicillin and gentamicin eradicated Ps. aeruginosa infections, during the period over which they were given, in all of 25 critically ill patients. Electron microscopy revealed differences in the action of these two antibiotics against Ps. aeruginosa in vitro. Culture studies showed synergism between them and destruction by gentamicin of the carbenicillin-induced long, filamentous form of the organism.

Carbenicillin↗
PubMed2007

Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy.

BACKGROUND: Piperacillin-tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients. In an effort to improve clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center (Albany, New York). This study evaluates the clinical implications of extended infusion of piperacillin-tazobactam therapy for critically ill patients with P. aeruginosa infection. METHODS: We performed a cohort study of patients who received piperacillin-tazobactam therapy for a P. aeruginosa infection that was susceptible to piperacillin-tazobactam during the period January 2000-June 2004. Prior to February 2002, all patients received intermittent infusions of piperacillin-tazobactam (3.375 g intravenously for 30 min every 4 or 6 h); after this time, all patients received extended infusions of piperacillin-tazobactam (3.375 g intravenously for 4 h every 8 h). Data on demographic characteristics, disease severity, and microbiology were collected, and outcomes were compared between groups. RESULTS: A total of 194 patients comprised the 2 study groups: 102 patients received extended infusions of piperacillin-tazobactam, and 92 patients received intermittent infusions of piperacillin-tazobactam. No differences in baseline clinical characteristics were noted between the 2 groups. Among patients with Acute Physiological and Chronic Health Evaluation-II scores > or =17, 14-day mortality rate was significantly lower among patients who received extended-infusion therapy than among patients who received intermittent-infusion therapy (12.2% vs. 31.6%, respectively; P=.04), and median duration of hospital stay after collection of samples for culture was significantly shorter for patients who received extended-infusion therapy than for patients who received intermittent-infusion therapy (21 days vs. 38 days; P=.02).Conclusions. These results indicate that extended-infusion piperacillin-tazobactam therapy is a suitable alternative to intermittent-infusion piperacillin-tazobactam therapy, and they strongly suggest that improved outcomes may be realized by administering extended-infusion piperacillin-tazobactam therapy to critically ill patients with P. aeruginosa infection.

APACHE↗
PubMed2006

[Pseudomonas aeruginosa infections in a neonatal care unit at Reunion Island].

OBJECTIVE: To investigate an outbreak of Pseudomonas aeruginosa (PA) hospital-acquired infections in neonates. METHODS: Incidences were assessed retrospectively in the neonatal care units of the Groupe Hospitalier Sud-Réunion, from January 2003 to September 2005. Environmental survey, audit of health care workers and case-control study were performed to reinforce staff training and to determine risk factors. RESULTS: Of 1432 neonates, 40 were infected (median gestational age: 29 weeks, median birth weight: 1195 g), accounting for an attack rate of 2.8%. Between January 2003 and January 2004, incidence rates were less than 2 infections per 1000 hospitalisation days. In the last trimester of year 2004, the incidence rose to 5.6 infections per 1000 hospitalisation days and PA was found in all ocular swabs, leading to diagnose an epidemic. However, it was only 3 months later, after 3 new deaths of very preterm neonates, that the implementation of control measures and an audit of health care practices focused on water utilisation ruled out the outbreak. The overall fatality rate was 25%, and of 71% in severe diseases (septicemia or pneumonia). The epidemic pattern argued for a common unique source. Two risk factors were identified by logistic regression: exposure to mechanical ventilation beyond 4 days (OR 3.3; CI 95%: 1.3-8.4) and very preterm birth (OR 2.7; CI 95%: 1.0-7.7). CONCLUSION: Our findings highlight the need for a close collaboration between neonatologists and hygienists to improve health care practices and surveillance.

Birth Weight↗
PubMed1992

IgG antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis.

The relationship between IgG antibodies to Pseudomonas aeruginosa and its isolation from sputum was determined in 100 patients with cystic fibrosis observed at intervals of two months for a median period of one year. Only one patient had a raised antibody titre (greater than 22.9 ELISA units) before isolation of P aeruginosa. Initially 65 patients were antibody negative, of whom 48 were also culture negative. Of 24 patients with positive sputum culture and negative antibodies, seven became antibody positive at a median (range) 15 (6-25) months later. The remaining 17 patients continued antibody negative until the end of the study at a median range 15 (1-123) months after becoming culture positive. This latter group were younger and had more intermittently positive sputum cultures. In general positive IgG antibody titres do not predate isolation of P aeruginosa, but in some patients are present soon after acquisition of infection. A positive titre indicates significant exposure to P aeruginosa and could be used to detect infection in patients unable to produce sputum and possibly indicate the effect of early antipseudomonal treatment.

Adolescent↗
PubMed1982

[Experimental immunological effectiveness and safety of pyoimmunogen vaccine against Pseudomonas aeruginosa infection].

Pyoimmunogen, a polycomponent vaccine against P. aeruginosa infection, has been obtained in laboratory and semi-industrial conditions. The microbial biomass obtained from the strains belonging to O-serotypes (immunotypes) most frequently occurring in clinical practice has been used for producing protective antigens. The preparations have been found to contain proteins (peptides) and carbohydrates in the ratio 6 : 1 to 8 : 1, as well as traces of 2-keto-3-desoxyoctanate, which is indicative of the low content of endotoxin. The immunogenicity of the preparations has been studied experimentally by the active immunization of mice. In these experiments the animals vaccinated in a single injection were found to be protected from challenge with both homologous and heterologous P. aeruginosa strains. The high level of protection from infection caused by toxigenic strain PA-103 was registered. The preparations have low toxicity: LD50 for mice exceeds 2 mg (in protein content): after the multiple administration (7-10 times) of the preparation to mice and rats the weight of the experimental animals was not significantly different from the weight of the control animals.

Animals↗
PubMedDate not supplied

Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: effect of treatment with protease inhibitors.

Data are presented showing that treatment of burned, Pseudomonas aeruginosa-infected mice with the protease inhibitor alpha 2-macroglobulin but not treatment with phosphoramidon enhanced survival. Treatment with alpha 2-macroglobulin caused reductions in bacterial counts in the skin and livers of infected mice and also protected liver elongation factor 2. Similar results were observed when human IgG was used for treatment. The protective effect of the IgG treatment was probably due to the presence of opsonizing antibodies in the preparation. The protective capacity of the IgG could be removed by its adsorption with heat-killed cells of the strain used for infecting the mice. The protection afforded by alpha 2-macroglobulin was not due to the presence of opsonizing antibodies in the preparation used. It appeared to be due to inhibition of the proteolytic, not the elastolytic, activities of alkaline protease and elastase elaborated by the organisms growing in the burned skin tissue. Proteolytic activities of these enzymes appeared to serve as virulence factors in P. aeruginosa by decreasing the generation time in vivo of the microorganisms growing in the burned skin tissue and by allowing the organisms to spread from this local site into the systemic circulation. Treatment of pseudomonas infections of burn wounds with protease inhibitors may serve as an alternative to antibiotic treatment and/or immunotherapy.

Animals↗
PubMed2001

PcrV immunization enhances survival of burned Pseudomonas aeruginosa-infected mice.

Burned Pseudomonas aeruginosa-infected mice immunized against PcrV, a type III virulence system translocating protein, showed significantly enhanced survival compared to controls. Survival was non-O serotype specific and correlated with a reduced systemic microbial load. Infection with a high-level toxin A-producing strain required supplemental antitoxin treatment to enhance survival.

Animals↗
PubMed2004

Effects of quorum-sensing on immunoglobulin G responses in a rat model of chronic lung infection with Pseudomonas aeruginosa.

Levels of serum antibodies against Pseudomonas aeruginosa were observed for 106 days in a rat model of chronic lung infection. Significantly weaker responses of serum IgG and IgG1 and a lower ratio of IgG1/IgG2a were found in the rats infected with the quorum-signal-deficient mutant, PAO1 (rhlI, lasI), compared with the wild-type PAO1. Four out of 15 rats infected with wild-type PAO1 contained bacteria in the lungs on day 106, whereas no bacteria were found in the mutant PAO1 group. The results indicate that quorum signals contribute to the persistence of the infection and influence the immune response.

Animals↗
PubMed1983

[Evaluation of the immunological activity of a vaccine from mutant Salmonella minnesota R 595 on a model of experimental Pseudomonas aeruginosa infection in mice].

The comparative study of heated corpuscular vaccines prepared from S. minnesota mutant R 595 with defective lipopolysaccharide (LPS), chemotype Re, derived from S. minnesota strain SF 1111 with unchanged LPS, and from P. aeruginosa strain PA 103, was carried out. In contrast to the vaccine from S. minnesota strain SF 1111, the vaccine prepared from the mutant with chemotype Re induced the development of cell-mediated and humoral immunity to P. aeruginosa, and its immunogenicity was close to that of the vaccine from P. aeruginosa strain PA 103.

Animals↗
PubMed1999

[Molecular study of a false outbreak of ticarcillin-resistant Pseudomonas aeruginosa infections in a clinical hematology department].

Molecular methods for bacterial strain typing are becoming available outside teaching hospitals and large structures. Although it seems reasonable to use conventional markers, most notably the serotype, whenever possible, the limitations of these methods are particularly conspicuous with P. aeruginosa. Combined use of several methods such as quantitative antibiotic susceptibility testing and serotype determination has proved adequate for characterizing P. aeruginosa strains in some cases. In the case of the outbreak reported herein, this approach failed to provide high quality epidemiological data. In contrast, pulsed field gel electrophoresis ruled out epidemic spread of a P. aeruginosa strain in the clinical hematology department.

Disease Outbreaks↗
PubMed1980

Pseudomonas aeruginosa infection and vaccination in the rat.

A large molecular-weight fraction of Pseudomonas aeruginosa culture filtrate protected rats and mice against a lethal infection with a heterologous serotype, and to some extent against Escherichia coli and Listeria monocytogenes. The active components were obtained from cultures grown for several days in a simple synthetic medium. Infection and vaccination with P. aeruginosa serotype 16 induced agglutinating and precipitating antibodies to the components of this serotype only; in rats infected or vaccinated with serotype 1, low titres of agglutinating antibody against type 16 were found. Vaccine prepared from type 1 or 16 increased, within 3 days of infection, the resistance of rats to type-16 organisms; within the same period agglutinins or precipitins were not produced. It is possible that the protection was based on opsonic and antitoxic activities.

Agglutinins↗
PubMed1997

Effect of 6-fluoro-8-methoxy quinolone (AM-1155) against chronic airway infection with Pseudomonas aeruginosa in a rat model.

We studied the effect of AM-1155, a newly developed quinolone, against chronic airway infection with Pseudomonas aeruginosa using a previously described rat model. AM-1155 (25 mg/kg) or ciprofloxacin (25 mg/kg) or saline (controls) were injected s.c. for 14 days (from day 4 to day 17) after the inoculation of agar beads containing P. aeruginosa. The number of viable cells of intrapulmonary P. aeruginosa, histological findings of the lungs and immunoglobulin levels of serum and bronchoalveolar lavage fluid were examined in rats 11 and 18 days after the treatment. The findings indicated that the number of viable cells of P. aeruginosa in lungs was significantly decreased in the AM-1155- or ciprofloxacin-treated group compared with the non-treated control group. Histological examination in the non-treated control group showed hyperplasia of bronchus-associated lymphoid tissue as well as cellular infiltration in airways, but not prominently in the AM-1155- or ciprofloxacin-treated group. The IgG and IgA levels in serum and bronchoalveolar lavage fluid were significantly lower in the AM-1155- and ciprofloxacin-treated groups than in the control group. These in-vivo effects of AM-1155 were comparable to those of ciprofloxacin. These findings suggest that treatment with AM-1155 and ciprofloxacin suppressed excessive immune responses, preventing progression of airway damage in the chronic infectious state.

Animals↗
PubMed1977

Pseudomonas aeruginosa infection in cystic fibrosis. Relative prevalence of antibodies in serum against cathodic and anodic migrating P. aeruginosa antigens determined by immunoelectrophoretic methods.

Sera from 119 patients with cystic fibrosis were examined for precipitating antibodies against anodic migrating P. aeruginosa antigens by means of crossed immunoelectrophoresis. The presence of precipitins against cathodic migrating P. aeruginosa antigens was investigated by means of classical immunoelectrophoresis. Thirty-six per cent of the sera contained precipitins against both anodic and cathodic antigens, 20% contained only precipitins against anodic antigens, none contained only precipitins against cathodic antigens, and 44% had no demonstrable P. aeurginosa precipitins. The amount of extra information obtained by combining the results of classical immunoelectrophoresis with the results of crossed immunoelectrophoresis was small.

Adolescent↗