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PubMed1971

Experimental Pseudomonas aeruginosa Infection of the Mouse Cornea.

Pseudomonas aeruginosa infection of human cornea is rare but serious. The work of previous investigators using experimental infection primarily of rabbit cornea resulted in successful therapy for 10 to 50% of clinical cases. The advantage of using the mouse is demonstrated. The methods we adapted for characterizing the untreated experimental infection included: incising the cornea to enable establishing the infection; corneal examination with a steroscopic microscope; grading corneal pathology; qualitative and quantitative monitoring of the infecting bacteria by culturing and staining sectioned and dissected tissues. The characteristics of the tissue pathology, host response, and infection were similar to those reported for other animals and man. Corneal pathology was frequently nearly maximal 1 day after infection; host response involved a progression of events of long duration; pathology persisted well beyond the period of bacterial infection. The infection was essentially noncommunicable, and invasiveness was limited to the tissues of the incised eye. The results show the possibility of tests for invasiveness of clinical isolates and for screening for therapeutic and prophylactic measures.

Journal Article↗
PubMedDate not supplied

[Infection by Pseudomonas aeruginosa in patients with human immunodeficiency virus infection. Descriptive study of 35 cases].

OBJECTIVE: Analysis of the spectrum of diseases attributed to Pseudomonas aeruginosa in patients with coinfection with the immunodeficiency virus (HIV). METHODS: Retrospective study of 35 cases of coinfection with P. aeruginosa-HIV, attended from 1985 until 1995. Analysis of putative factors implicated in mortality secondary to P. aeruginosa infection. RESULTS: The spectrum of infection due to P. aeruginosa was: ORL infection (4 cases), infection of upper respiratory tract (4 cases), pneumonia (21 cases), infected bronchiectasias (one case), endocarditis (2 cases) and primary bacteremia (3 cases). Most of these infections were community-acquired ones (30 cases [85.7%]). Degree of immunodepression was variable, with 12 cases (34.3%) affecting to patients with more than 200 CD4+lymphocytes x 10(-9)/l. Radiological pattern of pneumonias consisted in alveolar consolidation (18 cases [85.7%]), necrotizing pneumonia (2 cases [9.5%]) and interstitial pattern (one case [4.8%]). More than a 80% of isolates of P. aeruginosa was sensible to ceftazidime, ciprofloxacin, aminoglycosides, ureidopenicillins and imipenem. Recidives of the P. aeruginosa infection were detected in 7 cases (20%): 4 cases of ORL infection (100%) and 3 cases of lower respiratory tract infection (13.6%). Overall mortality was a 20% (7 cases), being directly attributed to P. aeruginosa infection in every one of the cases, all of them pneumonias. Secondary bacteremia was associated to a higher mortality (odds ratio [OR] 18.67; p = 0.0207). CONCLUSIONS: P. aeruginosa affect to the HIV-infected patients, independently of their immunodepression degree, affecting to different localizations. This bacteria continues to be sensible to conventional anti-Pseudmonas treatment. Pneumonia with secondary bacteremia is associated to a higher mortality.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Determinants of the biologic activity of surface slime in experimental Pseudomonas aeruginosa infections.

A purified fraction of the extracellular slime of Pseudomonas aeruginosa, characterized chemically as a glycolipoprotein (GLP), has been identified as responsible for a number of biologic properties of the viable cell. Mice immunized actively or passively against GLP are protected against an otherwise lethal challenge with viable bacteria. GLP is chemically, physically, and antigenically distinct from the lipopolysaccharide of the same strain. An in vivo association of GLP with blood leukocytes has been demonstrated, and the leukopenia in mice following challenge with P. aeruginosa may be accounted for by the subsequent sequestration of a neutrophil-GLP complex in the liver. Anti-GLP serum in the absence of complement mediates the phagocytosis and eventual killing of viable P. aeruginosa by mouse polymorphonuclear leukocytes and unstimulated peritoneal macrophages. A polysaccharide fraction isolated from the GLP is responsible for its protective immunogenicity. Although the lipid moiety governs the leukopenic and lethal capacities, the carbohydrate, specifically the mannose of this moiety, is required for full expression of GLP lethality. Mannose is also an immunodominant sugar.

Animals↗
PubMed1992

Temocillin and cystic fibrosis: outcome of intravenous administration in patients infected with Pseudomonas cepacia.

Twelve courses of intravenous temocillin were given in combination with an intravenous aminoglycoside to five patients with cystic fibrosis (CF) for pulmonary exacerbations associated with Pseudomonas cepacia. All patients were infected concurrently with Pseudomonas aeruginosa in addition to P. cepacia. Improvement occurred after six of seven courses given to three patients in which temocillin was used as first-line therapy and following three of five courses given to two patients after failure of other antipseudomonal agents. All ten pre-treatment isolates of P. cepacia were resistant to aminoglycosides and eight were sensitive to temocillin. Clinical improvement was seen on both occasions in which the pre-treatment isolates were resistant to temocillin.

Adolescent↗
PubMed2000

[When bacteria communicate with each other: the significance of intercellular signals in acute Pseudomonas aeruginosa infections].

In the opportunistic pathogen Pseudomonas aeruginosa a cell-to-cell signaling circuitry regulates the production of several major extracellular virulence factors. This interbacterial communication system allows P. aeruginosa to produce these virulence factors in a coordinated manner that overwhelms the host defense mechanisms. This article gives an overview of our present knowledge of the complex cell-to-cell signaling circuitry of P. aeruginosa and tries to outline its importance in the pathogenesis of acute P. aeruginosa infections. New therapeutic strategies, based on the blockage of this circuitry, are presented.

Acute Disease↗
PubMed2006

Nosocomial outbreak of Pseudomonas aeruginosa infections related to a flexible bronchoscope.

An outbreak of Pseudomonas aeruginosa infections affecting 17 patients was detected in the 27-bed intensive care unit (ICU) of a community hospital from 1 July to 30 September 2003. An ambidirectional cohort study was conducted to identify the risk factors for infection. Nosocomial infections were defined using the criteria of the Centers for Disease Control and Prevention. Random arbitrary polymorphic DNA-polymerase chain reaction was used for genotypic characterization. Logistic regression analyses demonstrated that case patients were more likely than non-cases to have had a longer stay in the ICU, and to have undergone mechanical ventilation and antimicrobial treatment. The multi-variate analysis identified recent bronchoscopy [risk ratio (RR) 3.8, 95% confidence interval (CI) 2.5-3.9] and exposure to an infected patient (RR 2.9, 95% CI 1.1-3.7) as independent risk factors. Molecular analysis showed that of the nine isolates available, four patients had a similar strain. The factor with the strongest influence on the risk of death was infection with P. aeruginosa (RR 2.1, 95% CI 1.0-2.4, P=0.04). A combined infection control strategy was implemented, including strict compliance with isolation precautions and recommendations for cleaning and disinfecting bronchoscopes, and a sharp reduction in the incidence of P. aeruginosa infection followed. It is thought that this outbreak was caused by patient-to-patient transmission and infection from a common source, i.e. the flexible bronchoscope.

Bronchoscopes↗
PubMed1987

Serum IgG antibodies in patients with cystic fibrosis with early Pseudomonas aeruginosa infection.

Serum IgG antibodies to Pseudomonas aeruginosa surface antigens were measured by enzyme linked immunosorbent assay in all patients with cystic fibrosis from whom P. aeruginosa was isolated for the first time during a study period of 18 months. In 15 patients the titre of serum IgG antibodies was greater than control values before or at the time of the first bacteriological isolation of P. aeruginosa. The presence of serum antibodies specific to P. aeruginosa suggests exposure to infection by that organism for some months before its isolation in significant numbers from the respiratory tract. In the other two patients serum titres were within the control range before isolation of P. aeruginosa but had increased to above the control range within the next month. Longitudinal studies on the entire group of patients showed further increases in titre concurrently with further isolations of P. aeruginosa. These results suggest that this assay may be an indicator of the beginning of pulmonary infection by P. aeruginosa and may prove to be a sensitive monitor of the progress of infection, and response to treatment, during the first months of infection by that organism.

Adolescent↗
PubMed2003

An outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes.

BACKGROUND: Endoscopes, including bronchoscopes, are the medical devices most frequently associated with outbreaks of nosocomial infections. We investigated an outbreak of Pseudomonas aeruginosa infections after bronchoscopic procedures. METHODS: Microbiologic results were reviewed to determine the rates of recovery of P. aeruginosa from bronchoalveolar-lavage specimens. Environmental samples from endoscopes and the endoscopy suite were cultured. Medical records were reviewed to identify infections in the 14 days after a bronchoscopy. RESULTS: The rate of recovery of P. aeruginosa from bronchoalveolar-lavage specimens obtained with use of endoscopy-suite bronchoscopes increased from 10.4 percent at base line to 31.0 percent during the outbreak (relative risk, 2.97; 95 percent confidence interval, 2.28 to 3.90). Cultures of samples from three bronchoscopes grew P. aeruginosa, whereas cultures of samples from the environment, instrument-cleaning machines, and gastrointestinal endoscopes did not. The three bronchoscopes had been part of a nationwide recall. A total of 414 patients underwent bronchoscopy during the outbreak, and there were 48 respiratory tract and bloodstream infections among 39 of these patients (9.4 percent). In 32 infections (66.7 percent), P. aeruginosa was confirmed as a potentially causative organism. Exposure to a potentially contaminated bronchoscope may have had a role in the death of three patients. The rate of recovery of P. aeruginosa returned to base line after the instruments were removed from service. CONCLUSIONS: This large outbreak of P. aeruginosa infections related to bronchoscopy was apparently caused by a loose biopsy-port cap in the bronchoscopes. Instrument safety and surveillance methods for bronchoscopy must be improved, and better recall procedures are needed for medical devices.

Academic Medical Centers↗
PubMed2003

Role of elastase in a mouse model of chronic respiratory Pseudomonas aeruginosa infection that mimics diffuse panbronchiolitis.

Pseudomonas aeruginosa frequently colonizes the respiratory tract of patients suffering from cystic fibrosis (CF) and diffuse panbronchiolitis (DPB). However, the relationship between lung inflammation and extracellular products of P. aeruginosa is not well-defined. To assess the role of elastase released by P. aeruginosa in DPB, a murine model of DPB was employed in this study. Mice were inoculated with either P. aeruginosa PAO1 or PAO-E64; the latter produces elastase with greatly reduced enzymic activity. Throughout the 90-day experiments, counts of viable bacteria from the PAO1- and PAO-E64-infected mice were found to be equivalent. However, the number of lymphocytes isolated from the lungs of PAO-E64-infected mice was significantly lower than the number isolated from the lungs of PAO1-infected animals. Histopathological examination of the lungs of mice infected by PAO1 on day 90 revealed an intense accumulation of chronic respiratory cells surrounding the bronchi, in sharp contrast to the more localized inflammatory response found in those mice infected by PAO-E64. These data suggest that P. aeruginosa elastase (PE) is a potent inflammatory factor in a mouse model of DPB and that the control of PE release by P. aeruginosa may be beneficial for patients with DPB.

Animals↗
PubMed2005

Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis.

Cross-infection with Pseudomonas aeruginosa is an emerging issue in the care of patients with cystic fibrosis (CF). This study sought to determine the extent of, and patient factors associated with, cross-infection in a tertiary referral adult CF centre. P. aeruginosa isolates were genotyped into two groups between November 2001 and February 2003, using pulsed-field gel electrophoresis after DNA digestion by the SpeI endonuclease, and identified as clustered if there was >80% homology in the macrorestriction profiles. Patient factors and measures of disease severity were identified a priori. In total, 157 out of 227 patients had a P. aeruginosa isolate genotyped. Of these, 94 patients (60%) were infected with clustered genotypes and 47 (30%) were infected with the newly described "Midlands 1" (Md1) genotype. A further 18 patients were infected with the previously identified "Liverpool" genotype and two with the "Manchester" genotype. Logistic regression analysis revealed that the predominant predictor of infection with Md1 was age at the time of referral to the centre, suggesting that infection may have occurred prior to referral in some patients. Md1 demonstrated a relatively benign anti-biogram and did not appear to be associated with more severe disease. In conclusion, the present study provides further evidence of the emerging importance of Pseudomonas aeruginosa cross-infection in cystic fibrosis.

Adult↗
PubMed1994

Serious Pseudomonas aeruginosa infection in AIDS.

During a 7-year period, 32 patients with Pseudomonas aeruginosa infection were identified on an HIV treatment service at a university-affiliated teaching hospital. The number of cases increased from 2 in 1986 to 13 in 1992. Affected patients had evidence of advanced HIV infection. In those treated with antiretroviral therapy, 96% of infections occurred > 1 year after initial presentation with HIV disease. Eighteen cases of pneumonia and 14 nonpulmonary (central venous access device, soft tissue, middle ear-mastoid, corneal, and peritoneal) infections were seen. Comparison with matched controls identified use of a central venous access device and administration of aerosolized pentamidine, corticosteroids, or ganciclovir as risk factors for infection (odds ratios, 5.3, 6.5, 15.0, and 9.0, respectively; p = 0.004, 0.007, 0.02, and 0.02, respectively). Seventy-five percent of cases had community onset, but time since last hospital discharge was significantly shorter in study patients than in controls (mean difference, -85 days; 95% confidence interval, -24 to -146; p = 0.01). Among evaluable cases, outcome was fatal (survival < or = 30 days) in 2 of 16 (13%) patients in whom initial antibiotic therapy was appropriate and 8 of 14 (57%) patients in whom initial therapy was not appropriate (p = 0.016). Ten recurrent infections were seen in 8 of 21 patients who survived the initial infection. Median survival after onset of infection was only 80 days. Pseudomonas aeruginosa infection is an increasingly frequent, severe complication of advanced HIV disease. Several treatment and prevention strategies used in the management of advanced HIV disease are associated with an increased risk of infection.

AIDS-Related Opportunistic Infections↗
PubMed2006

Chronic Pseudomonas aeruginosa infection reduces surfactant levels by inhibiting its biosynthesis.

Chronic Pseudomonas aeruginosa infection, as occurs in cystic fibrosis, is associated with decreased surfactant phospholipid levels. To investigate mechanisms, we measured synthesis of dipalmitoylphosphatidylcholine (DPPC), the major surfactant phospholipid. Mice received an agarose bead slurry alone, or were infected with beads containing a clinical mucoid isolate of P. aeruginosa. Bacterial infection after 3 days resulted in a approximately 50% reduction in surfactant DPPC content versus control. These changes in surfactant were associated with co-ordinate reductions in mRNAs and immunoreactive levels for CTP: phosphocholine cytidylyltransferase (CCTalpha), the rate-regulatory enzyme required for DPPC synthesis. P. aeruginosa infection of murine lung epithelia decreased CCTalpha gene transcription without altering mRNA stability and by a mechanism other than release of a soluble extracellular inhibitor. Promoter deletional analysis revealed that P. aeruginosa activates a negative response element from -1019 to -799 bp of the CCTalpha proximal 5'-flanking region. Exposure of cells to a P. aeruginosa mutant strain producing alginate reduced CCTalpha promoter activity, whereas these effects were not observed in strains defective in alginate synthesis. Murine type II cells isolated from P. aeruginosa-infected CCTalpha promoter-beta-galactosidase transgenic mice exhibited significantly reduced CCT and beta-galactosidase enzyme activities versus control. Thus, a mucoid P. aeruginosa strain reduces mRNA synthesis of a key biosynthetic enzyme thereby decreasing levels of surfactant.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Pseudomonas aeruginosa infective endocarditis presenting as bacterial meningitis.

Pseudomonas aeruginosa is a rare cause of infective endocarditis. The case of community-acquired P. aeruginosa infective endocarditis reported here is the first described in the literature to present as bacterial meningitis. Furthermore, new risk factors for P. aeruginosa infective endocarditis, including mitral annular calcification and re-use of insulin syringes, are proposed. Treatment of P. aeruginosa infective endocarditis complicated by bacterial meningitis is discussed.

Acyclovir↗
PubMed1982

[Changes in the anti-infection immunity indices of esophageal cancer patients undergoing combined immunization against staphylococcal and Pseudomonas aeruginosa infections].

The method of the complex immunization of patients with esophageal cancer against the main causative agents of purulent infections has been developed. Purified concentrated staphylococcal toxoid and polyvalent corpuscular P. aeruginosa vaccine were used for the immunization of 26 patients. Immunization was carried out in 3 injections (11 patients) and 4 injections (15 patients) made at intervals of 7 days. This resulted in the activation of nonspecific immunity factors (the total bactericidal properties of the blood serum, the phagocytic activity of neutrophils, the increase of the IgG level) and in a considerable increase in the factors of specific protection against staphylococcal and P. aeruginosa infections: the titer of staphylococcal anti-alpha-toxin increased 7- to 11-fold and the titer of antibodies to P. aeruginosa antibodies increased 5- to 6.5-fold. The preoperative vaccination of patients decreased the occurrence of postoperative purulent complications from 71% to 11.5%.

Adult↗