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At least 469 records · Page 26Linked to original sources
PubMed2005

Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study.

BACKGROUND: In cystic fibrosis (CF), chronic endobronchial infection with Pseudomonas aeruginosa is a serious complication. Macrolides can increase lung function and weight in patients, and reduce exacerbations. METHODS: In 2001, we introduced long-term, low-dose azithromycin (AZ) treatment as an integral part of our routine treatment of these patients. Our study is an observational cohort study of all CF patients with chronic P. aeruginosa infection in our CF center comparing clinical parameters of the patients 12 months prior to treatment with the same values during 12 months of treatment. RESULTS: 45 patients (27 men, median age 29 years) completed 1-year treatment. Median weight increased from 63.1 kg in the pre-treatment period to 63.9 kg during treatment (p=0.01). Median slope of decline in lung function increased from pre-treatment FEV1 -4.1% and FVC -3.0% to +0.8% (p<0.001) and +1.6% (p=0.01), respectively. 90% of sputum samples contained mucoid P. aeruginosa before treatment, decreasing to 81% during treatment (p=0.003). Median CRP decreased from 6.2 mmol/l to 5.8 mmol/l (ns). CONCLUSION: Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.

Adolescent↗
PubMed2004

Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection.

The object of this study was to investigate the impact of cigarette smoke on bacterial clearance and immune inflammatory parameters after infection with Pseudomonas aeruginosa in mice. We observed a delayed rate of bacterial clearance in smoke-exposed compared with sham-exposed mice. This was associated with increased inflammation characterized by greater numbers of neutrophils and mononuclear cells in the bronchoalveolar lavage. After infection, we observed increased levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) and chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-2 [MIP-2]) as well as myeloperoxidase and proteolytic activity in the lungs of smoke-exposed compared with sham-exposed animals. Delayed clearance was associated with increased morbidity and greater weight loss of smoke-exposed mice. After delivery of inactivated bacteria, we observed a similar inflammatory response, clinical score, and tumor necrosis factor-alpha expression in smoke- and sham-exposed animals, suggesting that increased inflammation and altered clinical presentation are due to the delayed rate of bacterial clearance. Our findings suggest that cigarette smoke affects respiratory immune-inflammatory responses elicited by bacteria. We postulate that altered respiratory host defense may be implicated in smoking-related diseases such as chronic obstructive pulmonary disease.

Animals↗
PubMed2001

Pseudomonas aeruginosa infection of respiratory epithelium in a cystic fibrosis xenograft model.

Pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) causes a chronic destructive bronchitis. A xenograft model was used to study the susceptibility of the CF respiratory epithelium to P. aeruginosa strain PAK and the virulence of certain mutants. Despite an early trend toward increased susceptibility, colonization of CF xenografts (ID(95), 62 colony-forming units [cfu]) was not statistically different (P=.5) than in xenografts with normal respiratory cells (ID(95), 1.2x10(3) cfu). Infection severity in 12 CF xenografts (mean polymorphonuclear leukocyte [PMNL] density, 1.88x10(6)+/-1.75x10(6)/xenograft) was similar to that in 16 non-CF xenografts (3.19x10(6)+/-2.45x10(6) PMNL/xenograft; P=.38), despite slightly greater bacterial density in the CF xenografts (mean, 1.57+/-2.73x10(6) cfu/xenograft) versus xenografts with normal epithelium (mean, 1.03+/-1.3x10(6) cfu/xenograft). P. aeruginosa mutants pilA and fliF, but not rpoN, colonized normal respiratory xenografts, indicating that colonization and infection in this model depend on an uncharacterized RpoN-controlled gene. This model appears to be suitable for genetic study of P. aeruginosa virulence but not of the CF respiratory tract's unique susceptibility.

Animals↗
PubMed1994

Pseudomonas aeruginosa invades corneal epithelial cells during experimental infection.

Pseudomonas aeruginosa is considered an extracellular pathogen. Using assays to determine intracellular survival in the presence of gentamicin, we have demonstrated that some strains of P. aeruginosa are able to invade corneal cells during experimental bacterial keratitis in mice. Although intracellular bacteria were detectable 15 min after inoculation, the number of intracellular bacteria increased in a time-dependent manner over a 24-h period. Levels of invasion were similar when bacteria were grown as a biofilm on solid medium and when they were grown in suspension. Intracellular bacteria survived in vitro for at least 24 h, although only minimal bacterial multiplication within cells was observed. P. aeruginosa PAK and Escherichia coli HB101 did not cause disease in this model and were not isolated from corneas after 24 h even when an inoculum of 10(8) CFU was applied. Transmission electron microscopy of corneal epithelium from eyes infected for 8 h revealed that intracellular bacteria were present within membrane-bound vacuoles, which suggests that bacterial entry was an endocytic process. At 24 h, the observation of many bacteria free in the cytoplasm indicated that P. aeruginosa was able to escape the endocytic vacuole. The ability of some P. aeruginosa strains to invade corneal epithelial cells may contribute to the pathogenesis or to the progression of disease, since intracellular bacteria can evade host immune effectors and antibiotics commonly used to treat infection.

Animals↗
PubMed1983

Clinical significance of serum antibody responses to exotoxin A and type-specific lipopolysaccharides in patients with Pseudomonas aeruginosa infections.

Serum antibodies to Pseudomonas aeruginosa exotoxin A and immunotype-specific lipopolysaccharides were evaluated as diagnostic and prognostic markers in patients with Pseudomonas disease. Hemagglutination titers to exotoxin A were 1:1,024 or higher and/or showed a fourfold acute-to-convalescent increase in 17 of 25 (68 percent) patients infected with Pseudomonas compared with only one of seven (15 percent) colonized (p = 0.01) and two of 24 (8 percent) culture-negative patients (p less than 0.001). By comparison, hemagglutination titers to the lipopolysaccharide of patients' Pseudomonas isolates were 1:1,024 or higher or showed a fourfold increase in only four of 17 (24 percent) infected patients and in none of six (0 percent) colonized patients (p = 0.96). Serial antibody titers to exotoxin A provided serologic confirmation of invasive disease, distinguished infection from colonization, and, in the case of decreasing titers, indicated successful therapy. It is concluded that serum antibodies to exotoxin A are useful serologic markers for the clinical assessment of Pseudomonas infections in man.

ADP Ribose Transferases↗
PubMedDate not supplied

The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections.

In nature Pseudomonas aeruginosa grows in two modes, the mobile "swarmer" cell and the glycocalyx-enclosed microcolony. The microcolony mode is numerically dominant perhaps because it provides adhesion in a favorable niche and protection from bacteriophages and phagocytic predators. When this organism colonizes the compromised human host, a broad spectrum of different types of infection is produced, ranging from asymptomatic persistent cystitis to the overwhelming bacteremia seen in neutropenic patients. These infections differ radically both in their degree of toxicity and invasiveness and in their susceptibility to control with specific antibodies and/or antibiotics. These differences may reflect the degree to which intact host defense mechanisms force the bacteria to adopt the defensive, microcolony mode of growth. As examples, the nearly intact host defense mechanisms and vigorous immune response of patients with cystic fibrosis force P. aeruginosa in pulmonary infections into a demonstrably cryptic, microcolony mode of growth that allows its persistence in the face of specific antibodies and antibiotics but limits its toxic activity and its dissemination. In contrast, the ruined defense mechanisms of burned skin allow the spread of bacteria in the mobile mode; toxic effects are seen in neighboring tissues, and a mixed mobile-microcolony reservoir population, whose mobile members can subsequently invade the circulatory system, is built up in the burned tissue. Thus, it is important to define the mode of bacterial growth in each type of P. aeruginosa infection and, where the microcolony mode is predominant, to understand the chemistry of the enveloping exopolysaccharide in order to limit its synthesis and/or facilitate its penetration by antibodies and antibiotics.

Animals↗
PubMed1995

[Immunomodulation in Pseudomonas urinary infection].

The urological department is as a rule of department with the highest incidence of nosocomial infections. They are often caused by Pseudomonas aeruginosa. In 1992 the authors started to use prophylactic immunization with antipseudomonas vaccine PSAEVA in 58 patients indicated for surgery on account of an prostate adenoma. During and after operation the incidence of Pseudomonas infection in immunized and control patients was compared. In the immunized group the incidence after operation was 1.72%, in the control group 12%. The drop of Pseudomonas infections in operated patients immunized with the anti-pseudomonas vaccine as compared with non-immunized ones was by 10.28% lower which is statistically significant--p.0.05.

Bacterial Vaccines↗
PubMed1984

Immunoserology of Pseudomonas aeruginosa infections in man. III. Site of infection, duration of the presence of Pseudomonas aeruginosa and antibody response.

In 39 patients of a respiratory intensive care unit the intensity of the serological response to the purified LPS of the causative Pseudomonas aeruginosa was found to change according to the site of infection. The highest titres were found in septic cases, when the antigenic assault reached all the immune-competent cells in the body. Short presence (only one positive bacteriological culture) of P. aeruginosa at the site of inflammation resulted in a low or moderate rise in antibody titre. Ten days were enough for the development of a maximum total antibody (approximately IgM) response, while IgG type antibodies moderately grew further when the presence of P. aeruginosa lasted more than 10 days. Only a 16-fold increase in total antibodies per se or a 4-fold rise in both total (approximately IgM) and IgG antibodies confirmed the pseudomonas infection.

Adolescent↗
PubMed1979

Pseudomonas aeruginosa infection depresses contact sensitivity to oxazolone by enhancing suppressor cell activity.

The depression of contact sensitivity to oxazolone in mice infected with Pseudomonas aeruginosa was studied. In oxazolone-sensitized mice, P. aeruginosa infection affects cell proliferation in the lymph nodes draining the site of sensitization. This impaired cell proliferation does not seem to be due to an altered lymphocyte reactivity, since lymph node and spleen cells from infected animals show a normal mitotic responsiveness to both T and B cell mitogens. In addition, the draining lymph nodes and spleens of mice exhibiting a depressed response to oxazolone contain a cell population able actively to suppress the response to the same antigen of syngeneic recipients sensitized immediately before the cell transfer. These suppressor cells require antigenic stimulation and appear to act on the induction phase of contact sensitivity.

Animals↗
PubMed2005

Eradication of early Pseudomonas aeruginosa infection.

Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

Anti-Bacterial Agents↗
PubMed1987

Protective effect of a traditional Chinese medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to), on Pseudomonas aeruginosa infection in mice.

Survival of mice after intraperitoneal (ip) or intravenous (iv) infection with Pseudomonas aeruginosa was augmented in the mice that had been pretreated ip with a Chinese traditional herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to) 6 hours or 4 days previously. 1) The pretreatment with shosaiko-to 6 hours previously induced an accumulation of polymorphonuclear leukocytes (PMN) in the peritoneal cavity, and its protective effect against ip infection was not impaired by treatment with carrageenan, a macrophage blocking agent. These results suggested that the protective effects of shosaiko-to against P. aeruginosa infection depended mainly on PMN in mice pretreated at this timing. 2) The pretreatment with shosaiko-to 4 days previously induced an accumulation of macrophages showing an augmented phagocytosis of P. aeruginosa in vitro in the presence of immune serum, and its protective effect against P. aeruginosa was impaired by treatment with carrageenan. In addition, the pretreatment with shosaiko-to accelerated the bacterial clearance from the blood. The sera obtained from mice treated with shosaiko-to 4 days previously showed a high titer of antibody specific to P. aeruginosa. When this sera was transferred to naive mice, these recipients showed an accelerated bacterial clearance and an increased survival to challenge infection with P. aeruginosa. These results suggested that protective effects of shosaiko-to against P. aeruginosa infection at this timing depended on cooperation of macrophages and antibody which produced by stimulation of shosaiko-to, a polyclonal B cell activator. Such polyclonal antibodies were also effective on protection against encapsulated Klebsiella pneumoneae to which antibody was essential in the expression of resistance. These results suggested that shosaiko-to could augment nonspecific resistance to a variety of bacteria to which antibody plays an effective role.

Animals↗
PubMed1994

Transmissibility of Pseudomonas cepacia infection in clinic patients and lung-transplant recipients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis, infection with Pseudomonas cepacia is associated with poor outcomes. However, the extent of person-to-person transmission and the source of P. cepacia infection after lung transplantation are not well defined. Using DNA-based typing systems, we sought to determine the genetic relatedness of P. cepacia infection at one cystic fibrosis center. METHODS: We analyzed 65 P. cepacia isolates gathered over a period of eight years at a single cystic fibrosis center from 17 clinic patients and from 5 patients who underwent double-lung transplantation. The isolates were analyzed by ribotyping and chromosomal fingerprinting based on pulsed-field gel electrophoresis. RESULTS: Analyses of serial isolates revealed that each clinic patient and transplant recipient harbored a different P. cepacia clone that was persistent. In the transplant recipients, the preoperative and postoperative isolates were identical. In the two patients with disseminated infection after lung transplantation, isolates from multiple sites were identical and indicated clonal expansion of the previous respiratory P. cepacia strain. Pulsed-field gel electrophoresis proved both more discriminative and more practical than ribotyping as a means of defining the genetic relatedness of the P. cepacia isolates. CONCLUSIONS: Our serial analyses in patients with cystic fibrosis at one center found distinct strains of P. cepacia persistently infecting each patient and no evidence of person-to-person transmission of this organism. P. cepacia infection after lung transplantation was due to the persistence of the strain present before transplantation.

Bacterial Typing Techniques↗
PubMed1987

Hypergammaglobulinemia in cystic fibrosis. Role of Pseudomonas endobronchial infection.

Hypergammaglobulinemia, chronic endobronchial infection with Pseudomonas aeruginosa (PA), and the resulting systemic humoral immune response to PA are each associated with worsened clinical status and prognosis in patients with cystic fibrosis (CF). Major serum immunoglobulin isotype levels (IgG, IgA, IgM, and IgG1-4 subclasses) were measured in 31 CF patients and ten control subjects. Immunoglobulin levels were related to airway infection with PA and the resulting IgG antibody response against PA lipopolysaccharide (LPS). Hyperimmunoglobulinemia G was present with elevated IgG1 and IgG2 in 48 percent, IgG3 in 52 percent, and IgG4 in 42 percent of CF patients. The PA infection was associated with striking increases in IgG2. IgG2 levels correlated well with IgG2 antibodies to PA LPS (r = +0.70, p less than 0.001). However, even CF patients who were not infected with PA had an increased prevalence of high IgG3 (p less than 0.05) and IgG4 (p less than 0.01). The PA infection thus appears to be a major, but not the only factor causing hypergammaglobulinemia in CF.

Adolescent↗
PubMed1984

Addition of rifampin to carboxypenicillin-aminoglycoside combination for the treatment of Pseudomonas aeruginosa infection: clinical experience with four patients.

Four patients infected with Pseudomonas aeruginosa were treated with the triple therapy of carboxypenicillin (carbenicillin or ticarcillin), aminoglycoside (gentamicin or tobramycin), and rifampin. Two patients had P. aeruginosa endocarditis, one had bacteremia associated with granulocytopenia, and one had neurosurgical meningitis. In all four cases, the clinical condition of the patient deteriorated on combined antipseudomonal penicillin and aminoglycoside therapy. All patients had persistent blood cultures (throughout a 3- to 30-day period) or cerebrospinal fluid cultures (throughout a 24-day period) while receiving penicillin-aminoglycoside therapy. Rifampin, 600 mg every 8 h orally, was added to the penicillin-aminoglycoside regimen. All four patients defervesced within 24 h after the initiation of rifampin. In addition, all four patients experienced sterilization of blood and cerebrospinal fluid cultures within 24 h of therapy. The emergence of rifampin-resistant P. aeruginosa was not observed. Ultimately, two patients survived their infection; the other two patients succumbed to complications of their underlying disease. This clinical experience should provide a stimulus for a controlled evaluation of rifampin as a component of multiple drug therapy directed against P. aeruginosa.

Adult↗
PubMed1995

Pseudomonas aeruginosa infections of intact skin.

Pseudomonas aeruginosa infections of healthy skin are uncommon. We report four cases of P. aeruginosa infections of intact skin. These cases illustrate the clinical spectrum of these cutaneous infections: localized, mild epidermal infections (the green nail syndrome and webbed space infections), moderately serious infections (cutaneous folliculitis and otitis externa), and, in immunocompromised patients, extremely serious infections (malignant otitis externa, perirectal infection, and ecthyma gangrenosum).

Adult↗