Low incidence of pulmonary Pseudomonas cepacia infection in Danish cystic fibrosis patients.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The purpose of the present study was to further delineate the role of natural killer (NK) cells in the early stages of resistance to infection by Pseudomonas aeruginosa, strain PAO1. Intravenous injection of the monoclonal antibody alpha-NK1.1 resulted in an 82% reduction in NK cell activity of normal mice, as measured by a standard 4-hour 51Cr release assay. Splenic bacterial clearance was examined in mice treated with this antibody 12 h prior to infection with a sublethal dose (10(6)) of PAO1. At 2, 4, and 6 h postinfection there was significant enhancement (up to 10-fold) of clearance in mice treated with alpha-NK1.1 when compared to untreated infected control animals. Interestingly, the enhanced clearance of PAO1 in the spleens of NK-depleted mice was found to be coupled to a significant increase in neutrophils. Normal murine spleens were found to contain 1-2% neutrophils, which increased to 6-7% following sublethal infection. However, in mice treated with alpha-NK1.1 and infected, splenic neutrophils increased up to 15% during the early stages of infection. The data presented here suggests that NK cells do not have direct bactericidal activity against Pseudomonas, but may regulate other effector cells, such as neutrophils-an indirect role for natural killer cells, probably mediated in vivo by their production and secretion of cytokines.
BACKGROUND: Despite dramatic improvements in the management of burns, infection still remains a serious risk for the burn patient. The aim of this study was to shed light on the impact of acute burn injury with or without infection on cytokine profiles. METHODS: Sprague-Dawley rats (n = 21) were randomized into three groups: 1) burn only 2) burn and infection or 3) sham burn. Weight was monitored and blood was collected for cytokine ELISA, LPS quantification, and peripheral blood analysis. Animals were sacrificed either after 6 or 12 days. RESULTS: Infected animals showed substantial weight loss until day 6 post-burn as compared to burn alone. Endotoxin and TNF-alpha levels were elevated early in the infected burn group within 48 hours post-burn. In contrast, significant up-regulation of the anti-inflammatory cytokine IL-10 occurred later in the clinical course and was associated with the recovery from weight loss. CONCLUSION: Our results suggest that in the presence of infection, you get a SIRS response possibly due to transient endotoxemia that is only seen in the infection group. In contrast, both burn and infection get a late IL-10 (CARS) response, which is then associated with a return to normal weight in the infection group.
A new multicomponent Pseudomonas vaccine 'pyoimmunogen' has been developed. It was tested for safety and immunogenicity by immunization of volunteer donors and burned patients. Immune plasma obtained from volunteers was used for treatment of severe forms of P. aeruginosa infections. Pyoimmunogen was shown to be of low toxicity for apparently healthy humans and to induce specific antibody formation. In 16 out of 20 burned patients it had a beneficial effect on the course of the disease and the period of hospitalization was shortened. As a result of complex treatment involving the use of anti-P. aeruginosa plasma 51 out of 60 patients recovered.
Explore the source record for details and available documents.
In the present study, we have investigated the mechanisms underlying mouse resistance to endobronchial infection with Pseudomonas aeruginosa enmeshed in agar beads. This was done by monitoring macrophage activation-associated gene expression in lung and alveolar cells harvested from resistant (BALB/c) and susceptible (DBA/2, C57BL/6, and A/J) strains of mice over the course of infection with P. aeruginosa. Interleukin-1 alpha, interleukin-1 beta, macrophage inflammatory protein-1 alpha, JE, and tumor necrosis factor alpha (TNF-alpha) mRNA expression levels were up-regulated in all strains of mice during the early phase of the infection. The level of TNF-alpha mRNA expression was increased to a greater extent in resistant BALB/c mice than in susceptible DBA/2, C57BL/6, and A/J strains of mice. This observation paralleled a higher secretion of TNF-alpha into the alveolar space of BALB/c mice at 3 and 6 h postinfection. The concentration of TNF-alpha released in alveoli returned to basal levels within 24 h of infection in mice of all strains, even though the TNF-alpha mRNA expression remained high until 3 days after infection. In vivo treatments with either anti-murine TNF-alpha monoclonal antibodies or with aminoguanidine significantly increased the number of P. aeruginosa bacteria detected in the lungs of resistant mice at 3 days postinfection. Overall, these findings indicate that both TNF-alpha and nitric oxide exert a protective role in response to pulmonary infection with P. aeruginosa.
Explore the source record for details and available documents.
Pseudomonal infections of the skin, soft tissue, bone, and toe web may often be very difficult to treat. This article reviews the microbiology, pathogenesis, and treatment of pseudomonal infections that are related to podiatric medicine and surgery.
Pseudomonas aeruginosa, an opportunistic respiratory pathogen that infects the majority of patients with cystic fibrosis, initiates host inflammatory responses through interaction with airway epithelial cells. The Toll-like receptors (TLRs) are a family of pathogen pattern recognition receptors that play key roles in host innate immunity. In this study we aimed to determine whether TLRs mediate the interaction between P. aeruginosa and airway epithelial cells. Individual murine TLRs (TLR1 to TLR9) and dual combinations of these TLRs that activate an NF-kappaB-driven luciferase reporter in response to PAO1 were screened in HEK 293 cells. TLR5, TLR2, a combination of TLR1 and TLR2, or a combination of TLR2 and TLR6 responded to PAO1. Another P. aeruginosa strain, strain PAK, activated TLR5 similarly, while the isogenic flagellin-deficient strain PAK/fliC and the flagellum-free bacterium Haemophilus influenzae failed to activate TLR5. Reverse transcription-PCR was used to probe the presence of multiple TLRs (including TLR5) in primary human airway epithelial cells (HAECs). Immunostaining with TLR5 antibodies showed that TLR5 was expressed in HAECs and on the apical surface of the human trachea epithelium. In HAECs, PAO1, PAK, and Burkholderia cepacia, but not flagellin-deficient strain PAK/fliC or a B. cepacia fliC mutant, activated the NF-kappaB reporter. Dominant negative TLR5 specifically blocked the response to P. aeruginosa but not to the response to lipoteichoic acid, a specific ligand of TLR2. We also determined that MyD88, IRAK, TRAF6, and Toll-interacting protein (Tollip), but not TIRAP, were involved in the TLR-mediated response to P. aeruginosa in HAECs. These findings demonstrate that the airway epithelial receptor TLR5 senses P. aeruginosa through its flagellin protein, which may have an important role in the initiation of the host inflammatory reaction to clear the invading pathogen.
PURPOSE: To characterize the presence of plasminogen activators and their inhibitors in the corneas during the inflammatory response in naïve and immunized mice intracorneally infected with Pseudomonas aeruginosa. METHODS: RT-PCR was used to detect gene expression for plasminogen activators and their inhibitors in naïve and immunized mice. Immunoblot analysis, zymography, and ELISA were used to demonstrate the syntheses of these proteins. RESULTS: Naïve mice intracorneally infected with P. aeruginosa showed a temporally enhanced expression of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), over a several-day holding period. Immunized mice demonstrated a lower and shorter expression of these factors over the same period. Expression of these factors at the mRNA and protein levels may have been due to enzymes and inhibitors present in inflammatory cells and in resident corneal cells. CONCLUSIONS: These results show a correlation between the overexpression of the PA system in infected naïve mice as part of the inflammatory response, with eventual ocular destruction. Immunized mice exhibit a more balanced and shorter expression of the PA system, which may contribute to the restoration of corneal clarity.
Explore the source record for details and available documents.
This multicenter trial compared treatment with either cefsulodin or reference antibiotics (gentamicin, tobramycin, amikacin, or ticarcillin) in 67 patients with Pseudomonas aeruginosa infection and burn injury. Safety of treatment was evaluated for all 67 patients; clinical efficacy, for 29; and bacteriologic efficacy, for 26. The average daily dose and duration of treatment for the 37 cefsulodin-treated patients were 5.6 g and 10.3 days, respectively. The percentage of total body surface burned was greater than or equal to 50% for 40% and greater than or equal to 25% for 85% of the patients. Rates of bacteriologic cure for 30 sites of infection were 64% (7/11) for skin and skin-structure infections treated with cefsulodin or reference antibiotics; 100% (1/1) for respiratory tract infections treated with cefsulodin and 33% (2/6) for those treated with reference antibiotics; and 100% (1/1) for septicemia treated with a reference antibiotic. Overall bacteriologic and clinical efficacy for cefsulodin treatment was 67% (8/12) and 73% (11/15), respectively, and for treatment with a reference antibiotic was 56% (10/18) and 64% (9/14), respectively. Cefsulodin was found to be safe and comparable in efficacy to reference antibiotics in this patient population.
We describe a study of the epidemiology of Pseudomonas aeruginosa (PA) infection in a group of adults with cystic fibrosis who attended a week-long summer camp in the U.K. Sputum samples were collected from 17 patients at the beginning and at the end of the holiday period. Examination of previous sputum samples had identified 11 patients who were chronically colonised with PA. They shared accommodation during the holiday. The sputum samples from these 11 patients were analysed so as to identify the strains of PA by their genotypic characters. All patients were colonised by unique strains before the beginning of the holiday, with the exception of two pairs of patients whose isolates were indistinguishable. After the holiday, eight of the 11 patients harboured strains of the same genotype as was found in their pre-holiday specimens. In three patients, a strain present post-holiday was different from that found in the pre-holiday specimen. In addition, in the case of one patient, two different genotypes were found in the pre-holiday specimen, only one of which was present after the holiday. Evidence of cross-infection of PA during the holiday was not found. Even so, evidence of person-to-person transmission of PA both within the hospital environment and through social contact is presented and discussed.
Six- to eight-week-old BALB/cJ (and BALB/cPi) mice were found able to restore corneal clarity within 3 to 4 weeks after intracorneal infection with Pseudomonas aeruginosa strain 19660. However, enzyme-linked immunosorbent assay (ELISA) for serum immunoglobulins directed specifically against P. aeruginosa indicated that the mice were initially non- or hypo-responsive for IgG and IgA over the 4-week holding period. Low IgM titers could be detected 1 week after infection, but tended to decrease with time. When the mice were re-infected by using the contralateral control eye, then the serum IgG levels began to gradually increase as the time interval following the secondary infection increased from 1 to 3 weeks. Re-infected mice did not show a significantly increased rate of corneal clarity restoration with time, when compared to the corneas of mice receiving only a primary infection despite the presence of serum antibodies specific to P. aeruginosa. When congenic mice of the BALB/c background carrying the DBA/2N Idh/Pep-3 locus found on chromosome 1 were intracorneally infected, they tended to restore corneal clarity at approximately the same rate as the BALB/cJ mice. However, the congenic mice mounted a faster and substantially greater magnitude of serum IgM and IgG response during the primary infection than BALB/cJ mice receiving either a primary and/or secondary infection. IgG subclass studies with the congenic mice indicated that serum IgG1, and IgG2a to a lesser extent, were the primary immunoglobulins produced and no major shift in subclass was noted with time during the primary infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.