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PubMed1997

Vaccine strategies against Pseudomonas aeruginosa infection in the lung.

Pseudomonas aeruginosa is an environmentally ubiquitous, extracellular opportunistic gram-negative bacteria that causes significant morbidity and mortality to a disproportionately high degree for infections with this bacteria compared with other gram-negative bacteria. Patients at particular risk of infection are those with compromised respiratory function, in intensive-care support and taking immunocompromising pharmaceutical agents. Once acquired, infection is difficult to eradicate with chemotherapy and attempts to vaccinate against infection have been of little success. Over the past five years, we have pursued the concept of mucosal immunisation against respiratory infection with P. aeruginosa. Initial studies in an acute animal model clearly demonstrated that mucosal immunisation with a killed whole bacterial cell preparation could induce protective immune responses in the lung. Subsequent studies have shown that the protective immune mechanisms were dependent on antigen specific CD4+ T cells, the activation of alveolar macrophages, the recruitment and activation of polymorphs, predominantly neutrophils, the controlled secretion of TNF-alpha, IL-1 and IFN gamma and the presence of antibody. We have hypothesised that the protective response is under the control of T cells. A pre-clinical human trial of an oral whole killed cell preparation has been completed with no adverse side effects. A limited open trial in patients with bronchiectasis has also been completed. Preliminary analysis of the results has demonstrated that after oral vaccination, specific lymphocyte responses were observed to P. aeruginosa.

Animals↗
PubMed1953

Pseudomonas aeruginosa infections of the eye.

Pseudomonas aeruginosa seldom invades the body except in persons or in organs lacking natural defenses, and usually the infection is chronic rather than acute, evoking little systemic response. When introduced into the cornea, however, as in penetration by a foreign body or in contaminated medicines, it acts with extreme virulence, in many cases causing blindness and even necessitating enucleation. Although many attempts at control of Ps. aeruginosa, even with powerful antibiotics, have been unsuccessful, polymyxin B appeared to have good effect and was tested in experimental infection of the cornea in rabbits. It was demonstrated by preliminary studies in vitro that polymyxin B was effective against nine strains of Ps. aeruginosa which on inoculation caused rapidly progressive ulcers in the corneas of rabbits.A strain of proved virulence was introduced into both eyes of each of 18 rabbits. The left eyes only were treated with subconjunctival injections at 48-hour intervals of a solution of polymyxin B, to which epinephrine was added as a vasoconstrictor to prevent rapid dispersion. The right eyes remained untreated as controls. In five of the six rabbits treated immediately after inoculation, the treated eyes remained clear, while moderate infiltration developed in the sixth. In the six rabbits not treated for 24 hours after inoculation, ulcers developed but remained localized during therapy. In those not treated for 48 hours after inoculation, ulcers developed before treatment began but did not spread as rapidly as in the controls. Hyaluronidase was added to the preparation for half the rabbits in each group but had no perceptible beneficial effect.

Animals↗
PubMed1977

Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic significance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis.

A total of 133 patients with cystic fibrosis have been followed for up to 5 years with monthly examinations including bacteriological examinations of sputum. Sera from the patients were examined by means of crossed immunoelectrophoresis for the occurence and number of precipitating antibody specificites against Pseudomonas aeruginosa. Poor prognosis in cystic fibrosis was associated with chronic colonization (9 months - more than 5 years) of the respiratory tract with mucoid Pseudomonas aeruginosa, and with an onset of the chronic colonization before puberty. Among the patients with chronic Pseudomonas aeruginosa colonization, poor prognosis was associated with high numbers of precipitins against antigens from these bacteria (up to 61). The number of Pseudomonas aeruginosa precipitins increased on an average with five per year in chronically colonized patients. Rapidly increasing number of precipitins was associated with poor prognosis. Patients with any degree of impairment of the ventilatory function and any changes on the chest radiographs could contract chronic Pseudomonas aeruginosa colonization. Poor ventilatory function and severe changes on the chest radiographs was associated with high numbers of Pseudomonas aeruginosa precipitins and with poor prognosis. Although many O groups of Pseudomonas aeruginosa were found in the chronically colonized group of patients, 53% of the patients harboured strains belonging to O group 3 or 3/9, and the highest numbers of precipitins were found in serum from these patients.

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↗
PubMed1985

Evolving epidemiology of Pseudomonas aeruginosa infections.

The dramatic increase in infections caused by Pseudomonas aeruginosa over the last three decades is examined in this review. By virtue of its unique growth characteristics, this organism occupies a firm niche in the hospital environment where it continues to be a major nosocomial pathogen, with particularly high rates of infection in traditionally susceptible patient subpopulations: the compromised host, patients with malignancy, cystic fibrosis, burn wounds and trauma. In recent years infection with Pseudomonas aeruginosa has become more prominent in other patient subpopulations: for example, post-surgical, pediatric and dialysis patients, as well as the elderly. A more interesting evolution in the epidemiology of infections caused by Pseudomonas aeruginosa is the appearance, often anecdotal, of new manifestations in healthy, non-hospitalized hosts e.g. the water-associated syndromes, puncture wounds, drug addiction. The need for better data on the prevalence of these infections, the required host-organism interactions and their practical impact sets an agenda for future investigation.

Cross Infection↗
PubMed1982

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections.

In four patients with Pseudomonas aeruginosa infections, the infecting strain developed resistance to moxalactam during therapy with this drug. In addition, P. aeruginosa isolates from two of these four patients showed increased resistance to aminoglycosides. Isolates from a third patient acquired cross-resistance to other antipseudomonal beta-lactams. In three of the cases, disk susceptibility tests failed to detect the resistance that was demonstrated in broth dilution assays. Isolate identities were confirmed by serotyping. No new plasmids were found by agarose gel electrophoresis. The mechanisms for this resistance did not involve enzymatic antibiotic degradation. These findings suggest that currently available expanded-spectrum cephalosporin derivatives should probably not be used alone for most serious infections due to P. aeruginosa. They also suggest that strains with multiple antibiotic resistance may become more prevalent in hospitals if these drugs are used extensively.

Aminoglycosides↗
PubMed2002

Macrophage inflammatory protein-2 and vascular endothelial growth factor regulate corneal neovascularization induced by infection with Pseudomonas aeruginosa in mice.

Pseudomonas aeruginosa ocular infection causes extensive corneal neovascularization. The purpose of the present study was to investigate the role of the angiogenic factors macrophage inflammatory protein-2 (MIP-2) and vascular endothelial growth factor (VEGF) in the regulation of corneal neovascularization during P. aeruginosa ocular infection. After administering anti-MIP-2 antibody or control antibody, mouse corneas were challenged with P. aeruginosa. The expression of MIP-2 and VEGF was detected using an ELISA from ocular homogenates. Corneal neovascularization was examined by histology. The cellular sources of MIP-2 and VEGF were identified by immunohistochemistry. In addition, protein expression of MIP-2 and VEGF in isolated corneas was measured to determine the ability of the cornea to produce these two mediators. Results showed that the expression of MIP-2 and VEGF was significantly (P < 0.05) elevated after bacterial infection, and high levels of these two mediators paralleled the extensive corneal neovascularization seen at later stages of the infection. Anti-MIP-2 antibody treatment resulted in a significant (P < 0.05) reduction in VEGF expression and in corneal neovascularization. Both corneal resident cells and infiltrating neutrophils had the ability to produce MIP-2 and VEGF after stimulation. The present study demonstrates that both MIP-2 and VEGF are important mediators in the regulation of corneal neovascularization caused by P. aeruginosa infection, and that MIP-2 regulates the production of VEGF.

Animals↗
PubMed1970

Agar-Gel Precipitating Antibody in Pseudomonas aeruginosa Infections.

The human immune response to Pseudomonas aeruginosa infection was studied by using the double diffusion in agar-gel technique. Antigens from Fisher-Devlin-Gnabasik immunotypes were prepared by both trichloroacetic acid extraction and ultrasonic disruption. Serum from 72 of 168 patients (43%) from whom P. aeruginosa was isolated formed from one to eight precipitin bands. Precipitins were demonstrated in the sera of 60 of 66 (91%) patients recovering from bacteremia and deep infections; however, they were usually absent when Pseudomonas infection was fatal or when there was no clinical evidence of significant infection. Precipitating antibody was detectable at serum dilutions as high as 1:32, and appearance of single bands correlated with hemagglutinating antibody titers of >/=1:128. Antigen from sonically disrupted organisms usually resulted in stronger precipitin bands than trichloroacetic acid extracts, and antigen from the homologous infecting strain occasionally increased test sensitivity. None of 50 normal controls had Pseudomonas precipitins as was the case in patients convalescing from Escherichia coli (15 patients), Klebsiella-Enterobacter-Serratia (18), and Proteus (14) bacteremias. Measurement of agar-gel precipitins was useful and specific in evaluating the circulating antibody response to P. aeruginosa infections.

Journal Article↗
PubMed1975

Use of a Pseudomonas Aeruginosa vaccine in pateints with acute leukemia and cystic fibrosis.

A heptavalent lipopolysaccharide Pseudomonas vaccine was evaluated in 22 patients with acute leukemia and 12 patients with cystic fibrosis during an 18 month interval at the Clinical Center of the National Institutes of Health. Of the 34 patients, 32 had an excellent serum hemagglutinating (HA) antibody response to immunization. In comparison to the patients with cystic fibrosis, the patients with leukemia had a smaller HA antibody response, which lasted a shorter period of time, and also experienced greater toxicity from the vaccine. The mixing of adrenal corticosteroids with vaccine greatly decreased side reactions among the patients with leukemia without significantly inhibiting antibody production. Previous antineoplastic chemotherapy had little influence on antibody response in patients with leukemia, with the exception of methortrexate. Vaccinated patients with leukemia had 1 Pseudomonas infection of 14 bacterial or fungal infections, whereas 2 pseudomonas infections of 5 bacterial or fungal infections occurred in a control group of 20 patients with acute leukemia. Of the 12 patients with cystic fibrosis, 4 had a Pseudomonas infection after vaccination.

Adolescent↗
PubMedDate not supplied

[An experimental validation of the use of levomycetin preparations for the treatment of burns infected with Pseudomonas aeruginosa].

Application of 1% of chloramphenicol (gel and cream) for local treatment of Pseudomonas aeruginosa burn infection has been studied in experiment. In vivo, both medical forms show pronounced therapeutic effect, they promote elimination of P. aeruginosa from wounds and decrease inflammation. In noninfected thermal trauma in laboratory animals application of gel and cream of chloramphenicol reduces transition from the phase of inflammation to the phase of reparation by 3-8 days and prevents infection of the burn wound by conditionally pathogenic microflora.

Animals↗
PubMed2004

Pseudomonas fluorescens infection by bacteriophage PhiS1: the influence of temperature, host growth phase and media.

The influence of host growth temperature, phase and media, together with the effect of infection temperature on bacteriophage PhiS1 infection of Pseudomonas fluorescens were examined. The rates of cell lysis and phage release were determined and showed that the efficacy of phage infection was optimal with host cells grown and infected at 26 degrees C. The host physiological state also affected these rates. Infection was dependent on the presence of cell wall proteins with molecular weights of 17.5+/-1 and 99+/-5 kDa.

Culture Media↗
PubMed1993

[Combined effects of anti-Pseudomonas antibiotics with G-CSF on systemic infections by Pseudomonas aeruginosa in a leukocytopenic mouse model].

A model with cyclophosphamide-induced leukocytopenic mice was employed to investigate combined effects of each of several antibiotics (sulbactam/cefoperazone (SBT/CPZ), ceftazidime, piperacillin and imipenem/cilastatin (IPM/CS)) with G-CSF on systemic infections caused by Pseudomonas aeruginosa. The ED50's of all the antibiotics except that of SBT/CPZ in these leukocytopenic mice were approximately two-fold higher than those in normal mice. No differences were observed between 2 groups of mice, one administered with G-CSF and the other without G-CSF, hence no additive or synergistic effects were observed between G-CSF and there antibiotics. With SBT/CPZ, however, the G-CSF-administered group showed higher ED50 than the group without G-CSF, and the ED50 of the former group was similar to that of normal mice, thus a synergistic effect was observed between SBT/CPZ and G-CSF.

Animals↗
PubMed1989

Analysis of the kinetics of natural killer cell activity in mice during an active infection with Pseudomonas aeruginosa.

The present study was designed to determine the effect of Pseudomonas aeruginosa (PA) infection on the activity of natural killer (NK) cells in mice. Following a sublethal injection of the bacterium, increased NK cell activity is evident as early as 24 h and peaks within 72 h, returning to normal levels by 168 h. Interestingly, the route by which PA was administered was very important with respect to increased NK activity. For example, the greatest augmentation of activity was seen in the peritoneal cavity when mice were injected intraperitoneally and in the spleen when injected intravenously. Peripheral blood leukocytes expressed the greatest augmentation in animals which received an intravenous injection of viable PA. In addition, a nonviable preparation of PA was used and found to significantly augment NK cell activity in a dose-dependent manner. To determine whether the presence of the organism is required for augmentation of NK activity, the rate at which PA is cleared from the animals was evaluated. Regardless of the route of injection, PA is effectively cleared within 24 h, thus eliminating the possibility that viable PA is required for augmentation of NK activity. This augmentation is proximal to the route of injection with little systemic effect seen. The data presented in this report illustrate that both viable and nonviable preparations of PA produce a significant increase in NK cell activity. This augmentation may suggest a role for these cells as effectors in natural resistance to infectious disease.

Animals↗