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PubMed1984

[Azlocillin treatment of Pseudomonas aeruginosa bronchopulmonary infections in children with cystic fibrosis].

From April, 1980 to December, 1981 ten children aged from 2 to 14 years presenting with cystic fibrosis were admitted to hospital for exacerbation of their chronic bronchial infection. Mucous Pseudomonas aeruginosa was present in sputum. Seven of the 10 strains isolated were susceptible to azlocillin and 3 were classified as intermediate. Eight children were treated with azlocillin alone in doses of 200-300 mg/kg/day and two with combined azlocillin 300 mg/kg/day and amikacin 16 and 23 mg/kg/day respectively. In both groups the antibiotics were administered 8-hourly by short (30 min) intravenous infusions and the duration of treatment ranged from 8 to 21 days (mean 14 days). Both drugs were well tolerated. Antibacterial activity was assessed as "cure" when Pseudomonas could not be isolated in sputum for at least 2 weeks after the end of the treatment, as "relapse" when that organism reappeared in sputum within the same period of time, and as "failure" when it persisted in sputum. On this account, among the 8 children treated with azlocillin alone 3 were cured, one relapsed and 4 failed. One of the two children treated with the azlocillin-amikacin association was cured, the other failed. Clinical results correlated roughly with antibacterial activity. Five distinct improvements were observed: 2 were associated with bacteriological cure, 2 with transient eradication followed by relapse and 1 occurred although the responsible organism persisted in bronchial secretions. Two children showed poor clinical results; 2 with failure and 1 with bacteriological cure. In two other children treatment was ineffective both clinically and bacteriologically. This study confirms that high parenteral doses of azlocillin have a beneficial effect on exacerbations with Ps. aeruginosa of chronic bronchial infection in cystic fibrosis. Clinical improvement usually correlates with antibacterial activity when the organism is eliminated, even temporarily, from bronchial secretions. The synergistic azlocillin-aminoglycoside association should probably be recommended, at least to reduce the risk of emergence of resistant strains.

Adolescent↗
PubMed2003

Oral administration of specific yolk antibodies (IgY) may prevent Pseudomonas aeruginosa infections in patients with cystic fibrosis: a phase I feasibility study.

Respiratory infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Chronic Pseudomonas aeruginosa (PA) infections ultimately occur in virtually all patients. It is impossible to eradicate PA when a patient has been chronically colonized. Immunotherapy with specific egg-yolk antibodies (IgY) may be an alternative to antibiotics for the prevention of PA infections. We wanted to determine if treatment with specific IgY can prolong the period between the first and the second PA colonization? And long-term, can the treatment diminish the number of positive PA cultures and postpone the onset of chronic colonization? CF patients gargled daily with an IgY-antibody preparation, purified from eggs of hens immunized with PA bacteria. They were compared to a group of patients who did not gargle with the preparation. Both groups had their first colonization with PA eradicated by antibiotics. The basic treatment was essentially the same in both groups. In the initial study, the period between the first and second colonization with PA was significantly prolonged for the treated vs. the control group (Kaplan-Meier P = 0.015, Breslow test). In the prolonged study, the treated group had only 2.5 sputum cultures positive for PA per 100 months of observation, and none of these patients became chronically colonized with PA. No adverse events were reported. In the control group, 13.7 cultures per 100 months of observation were positive for PA, and 5 (24%) patients became chronically colonized with PA. This feasibility study shows that antipseudomonal IgY has the potential to effectively prevent PA colonization without any severe adverse effects. A phase III study should be initiated.

Adolescent↗
PubMed2000

Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive.

PURPOSE: Mice favoring Th1 (C57BL/6, C57BL/10, and B10.D2/nSn) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) response development were evaluated for their response to infection with Pseudomonas aeruginosa. This study addresses the question of whether Th1 versus Th2 response propensity affects the pathogenesis of bacterial keratitis in mice. METHODS: Ocular disease was determined by mean clinical score, slit lamp, plate counts, and histopathology, and antigen-specific cellular responses were assessed by immunostaining and measurement of delayed type hypersensitivity (DTH). RESULTS: Strains of mice favoring Th1 (B6, BL10, and B10.D2) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) responsiveness were infected with P. aeruginosa. Mice favoring Th1 response development exhibited a similar course of disease and the infected eyes of all mice perforated by 7 days postinfection (p.i.). Strains (BALB/c, BALB/cBy, BALB.B, and BALB.K) favoring Th2 response development exhibited a milder course of disease, and none of the infected corneas perforated at 7 days p.i. In a Th1-responsive strain (B10.D2), positive immunostaining for CD4+ and CD8+ T cells was observed in the cornea by 3 days p.i. and by 5 days p.i., respectively, some cells stained positively for IL2-R, indicating that the cells were activated. In contrast, in a Th2 responder strain (BALB/c), there was no detectable positive immunostaining in cornea for any of the T-cell markers tested and DTH was significantly elevated in B10.D2 versus BALB/c mice. CONCLUSIONS: These studies are the first to provide evidence that in P. aeruginosa ocular infection, mouse strains favoring development of a Th1-type response are susceptible (cornea perforates), whereas strains favoring Th2 response development are resistant (no corneal perforation).

Animals↗
PubMed2001

A non-surgical rat model of foreign body-associated urinary tract infection with Pseudomonas aeruginosa.

This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder without surgical manipulation, followed by transurethral inoculation with Pseudomonas aeruginosa. The persistence of P. aeruginosa in the kidneys and bladder was significantly enhanced by placement of the PT, whereas the bacteria were eliminated rapidly from the urinary tract in the animals without the PT. Scanning electron microscopy revealed a thick biofilm on the surface of the PT from the early stage of infection. Histopathologically, acute pyelonephritis was followed by chronic renal inflammation as well as continuous and sporadic polymorphonuclear leukocyte accumulation and hemorrhage in the pelvis and adjacent tissues, suggesting continuous ascending introduction of the bacteria from the biofilm adhering to the PT. We believe our model simulates the pathophysiology of foreign body-associated urinary tract infection characterized by biofilm formation on the surface of a foreign body.

Animals↗
PubMed2005

Unusual implication of biopsy forceps in outbreaks of Pseudomonas aeruginosa infections and pseudo-infections related to bronchoscopy.

Between January and April 2003, a sudden increase in positive respiratory tract specimens for Pseudomonas aeruginosa was observed in an intensive care unit of the University Teaching Hospital of Montpellier, France. Most of the strains were cultured from bronchoalveolar lavage fluid samples, suggesting that bronchoscopic procedures could be implicated. The relationships between isolates were investigated by antibiotyping and pulsed-field gel electrophoresis. Both phenotypic and molecular markers allowed identification of two consecutive nosocomial outbreaks of respiratory infections related to two different bronchoscopes. These two outbreaks implicated nine and seven patients, respectively. Four of these 16 patients had true infections and recovered with antibiotic therapy. Inspection of both bronchoscopes revealed a damaged internal channel caused by defective biopsy forceps. These defects led to improper cleaning and disinfection of the bronchoscopes despite adherence to all current reprocessing procedures. The two outbreaks were controlled after replacing the inner channels of the bronchoscopes and switching from use of re-usable to disposable biopsy forceps. These outbreaks emphasize the need to establish surveillance procedures for detecting contamination of bronchoscopes, and the importance of recording each endoscopic procedure to facilitate further investigations if needed.

Bronchoalveolar Lavage Fluid↗
PubMed1978

The role of hemolysin in corneal infections with Pseudomonas aeruginosa.

Cultures of Pseudomonas aeruginosa considered to be of proven virulence were found to have higher titers of extracellular hemolysin than cultures of lesser virulence. Intracorneal injection of purified hemolysin produced extensive corneal opacification with extensive leukocytic infiltration of the tissue. It is suggested that the hemolysin plays a role in the pathogenesis of P. aeruginosa infections by effecting lysis of host cells and/or subcellular organelles, leading to the release of enzymes destructive to corneal tissue.

Animals↗
PubMed1992

Protective effect of ren-shen-yang-rong-tang (Ninjin-youei-to) in mice with drug-induced leukopenia against Pseudomonas aeruginosa infection.

When 200 mg/kg of cyclophosphamide (CY) or 5-fluorouracil (5-FU) were given subcutaneously to mice, severe reduction of leukocyte numbers in the peripheral blood was observed on day 4 and from day 4 to day 8 after the treatment, respectively. Daily administration of ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), (1 g/kg/day) and recombinant human granulocyte-colony stimulating factor (rhuG-CSF, 2 micrograms/mouse/day) either from day 0 to day 4 after treatment with CY or from day 0 to day 8 after treatment with 5-FU accelerated the recovery of peripheral leukocytes. Administration of NYT and rhuG-CSF inhibited decreases in the number of colony forming units in the spleen (CFU-S) in drug-treated mice. In mice infected intraperitoneally with a virulent strain of Pseudomonas aeruginosa 4 days and 8 days after treatment with CY and 5-FU, respectively, lethal doses were much lower (approximately 1/1000) than that in normal mice. Administration of NYT and rhuG-CSF to drug-treated mice inhibited the enhanced bacterial growth in the peritoneal cavity. Administration of NYT or rhuG-CSF to drug-treated mice enhanced the recovery of accumulation of leukocytes into the infected peritoneal cavity from their depressed state. Administration of NYT was more effective for improving the host resistance of 5-FU-treated mice than for improving that of CY-treated mice in contrast to rhuG-CSF which exhibited stronger effect in CY-treated mice than in 5-FU treated mice.

Animals↗
PubMed2005

Interleukin-4 is not critical to pathogenesis in a mouse model of Pseudomonas aeruginosa corneal infection.

PURPOSE: To determine the contribution of interleukin-4 (IL-4) to the initial host response during corneal infection with Pseudomonas aeruginosa in a mouse model. METHODS: Corneas of 6- to 8-week-old IL-4(-/-) and wild-type mice were topically challenged with P. aeruginosa. Ocular tissue was collected 24 hr and 7 days postchallenge. Viable bacterial counts, myeloperoxidase assays, cytokine levels, and clinical and histological examinations were performed. RESULTS: During challenge with P. aeruginosa, no differences were observed clinically, histologically, or in bacterial load between IL-4(-/-) and wild-type mice at either time point. However, differences in cytokine levels of IL-6, KC, and IL-10 were observed. CONCLUSIONS: The data presented indicate that IL-4, a central Th2 cytokine, may not be critical to the pathogenesis or bacterial clearance in this model of P. aeruginosa bacterial keratitis during the early stages of the infectious process.

Animals↗
PubMed2003

Delivery of CFTR by adenoviral vector to cystic fibrosis mouse lung in a model of chronic Pseudomonas aeruginosa lung infection.

In cystic fibrosis (CF) there is an excessive inflammatory response to lung infections with Pseudomonas aeruginosa, which causes significant morbidity and mortality. Mice deficient in the cystic fibrosis conductance transmembrane regulator homolog (Cftr) have exaggerated production of proinflammatory cytokines in epithelial lining fluid and increased mortality in response to chronic bronchopulmonary infection with mucoid P. aeruginosa, compared with infected wild-type littermates. Whether delivery of CFTR to CF airways by an adenoviral vector (Ad2/CFTR-16) decreases cytokine production and mortality in response to chronic bronchopulmonary infection with mucoid P. aeruginosa was tested. CF mice [stock Cftrtm1Unc-TgN(FABPCFTR)#Jaw] were anesthetized with isoflurane and inoculated intranasally with either Ad2/CFTR-16, diluent (sucrose), or empty vector (Ad2/EV). Two weeks later, mice were anesthetized with 2.5% Avertin and inoculated transtracheally with P. aeruginosa-laden agarose beads (PA M57-15). The cumulative 10-day survival of mice pretreated with Ad2/CFTR-16 was significantly higher compared with mice pretreated with sucrose but not significantly higher than mice pretreated with Ad2/EV. After adjusting for differences in experiment, we found weight loss at 3 days for mice treated with Ad2/CFTR-16 to be significantly less than for the sucrose- or Ad2/EV-treated groups. However, cytokine responses were similar in all groups 3 days after infection. In conclusion, the observed survival advantage of adenoviral delivery of CFTR to the CF lung may be due either to CFTR expression or possibly to proinflammatory effects of the adenoviral vector, or both.

Adenoviridae↗
PubMed1978

[Hospital infections with pseudomonas aeruginosa. II. Intensive care units (author's transl)].

72 newly admitted patients of three surgical intensive care units of the Medical School Hannover were examined bacteriologically for pseudomonas aeruginosa for a period of 7 months. A total of 810 specimens was examined during therapy. 95 strains of pseudomonas aeruginosa were isolated in 32 of 72 patients, taken either at the time of admission or during the stay of the patients in the hospital. The frequency of contamination increased with the duration of the stay of the patients in the hospital as follows: 20 per cent at the time of admission, 71 per cent after 8 to 10-day stay and up to 100 per cent for a duration of stay exceeding 14 days. The germs were mainly localized in the nose-throat region and in the respiratory tract. The results of phage typing suggested a hospital infection in about 50 per cent of the patients. The relationship between infection and infectious disease was discussed with respect to the epidemiologic characteristics of intensive care units. Furthermore, it was attempted to formulate recommendations for interrupting or abolishing the infection chains.

Cross Infection↗
PubMed1994

Pseudomonas stutzeri infection. A review of hospital isolates and a review of the literature.

Pseudomonas stutzeri is uncommonly isolated from patients and rarely causes disease. Clinical isolates of P. stutzeri from a university hospital were reviewed over a 16-year period. In the hospital review, only three patients were identified with P. stutzeri infection, and in only one of these was the organism present as the sole isolate. A review of the literature shows that P. stutzeri is most frequently isolated from blood, wounds, the respiratory tract, and urine. Patients with P. stutzeri infections often have serious underlying disease but generally respond to treatment with antibiotics including the aminoglycosides, the antipseudomonal penicillins, trimethoprim-sulfamethoxazole, and the third-generation cephalosporins.

Adult↗
PubMed1991

Vegetables as a source of infection with Pseudomonas aeruginosa in a University and Oncology Hospital of Rio de Janeiro.

Samples of fresh vegetables fed to patients in an Oncology and a University Hospital were examined for frequency of recovery and counts of Pseudomonas aeruginosa. Thirty-eight isolates from vegetables as well as 98 clinical isolates recovered during the same period of vegetable collection were serotyped and assayed for pyocin production in order to evaluate the role of vegetables as a source of microorganisms. Pseudomonas aeruginosa was recovered from 19.0% of the vegetable samples. Although 1% hypochlorite solution was used as a sanitizer, 50% of the positive samples were found to harbour more than 100 colony-forming units (cfu) g-1. Lettuce, chicory and watercress yielded the highest frequencies of isolation (P less than 0.05). The pyocin typing and serotyping of clinical strains revealed some types identical to those recovered from vegetables. Among those found in the University Hospital, serotype O4 and pyocin type PT10/b were detected in vegetables and in clinical specimens whereas types O1-PT22/e, O2a-PT10/a, O2a-PT10/b, O4-PT10/a, O11-PT10/a and O11-PT10/b were common in both groups of strains isolated in the Oncology Hospital. Our results strongly suggest that vegetables represent a source of endemic infection with P. aeruginosa for hospitalized patients.

Bacterial Typing Techniques↗
PubMed2004

Therapeutic efficacy of "nubiotics" against burn wound infection by Pseudomonas aeruginosa.

"Nubiotics" are a novel class of proprietary protonated nucleic acid-based drugs shown to have potent in vitro antibacterial activities against a number of gram-positive and gram-negative bacteria. These nubiotics are evaluated here for their in vivo therapeutic efficacy for the treatment of burn wound infection caused by Pseudomonas aeruginosa. To achieve this, a burn wound infection model was established in mice by using a highly pathogenic burn wound clinical isolate of P. aeruginosa. Lethal doses of the bacteria were determined for two routes of infection (subcutaneous and topical), representing systemic and local forms of infection, respectively. Using this infection model, treatment with nubiotics by various routes of drug administration was evaluated and optimized. A total of 12 nubiotics and their analogues were tested and of these, Nu-2, -3, -4, and -5 were found to be extremely efficacious in the postexposure treatment of burn wound infection (60 to 100% survival rates versus 0% for untreated control [P < 0.05]). These nubiotics were effective when given either systemically by intravenous and/or subcutaneous administration or given locally to the affected site in the skin by topical application. Treatment by these two routes resulted in almost 100% survival rates and complete eradication of the bacteria from infection sites in the livers, spleens, and blood. These nubiotics were found to be as effective as intravenously administered ciprofloxacin, a potent and broad-spectrum fluoroquinolone. These results suggest that nubiotics may be a promising and effective approach for the treatment of burn wound infection caused by P. aeruginosa.

Administration, Topical↗
PubMed1987

Pseudomonas aeruginosa infection in cystic fibrosis: nucleotide sequence and transcriptional regulation of the algD gene.

Pulmonary infection by mucoid, alginate producing, Pseudomonas aeruginosa is a major complication in patients suffering from cystic fibrosis (CF). To analyze the mechanisms leading to the emergence of mucoid P. aeruginosa in CF lungs, control of the algD gene coding for GDPmannose dehydrogenase was studied. Transcriptional activation of algD was shown to be necessary for alginate production. Sequencing of algD and its promoter revealed multiple direct repeats upstream of the transcription start and throughout the promoter region. Using the algD-xy1E transcriptional fusion the algD promoter was demonstrated to be under positive control by the algR gene. This gene has previously been shown to undergo antibiotic promoted chromosomal amplification resulting in the emergence of the mucoid phenotype. These findings provide a basis for better understanding the control of mucoidy in P. aeruginosa.

Alginates↗
PubMed1988

Iontophoretic application of tobramycin to uninfected and Pseudomonas aeruginosa-infected rabbit corneas.

Pseudomonas aeruginosa keratitis was induced in rabbits to study the effects of corneal infection on the delivery of tobramycin by iontophoresis. Some rabbits were treated by use of an eye cup with no current as a control for iontophoresis, and others were treated with fortified drops (1.36%) delivered topically for comparison with results of earlier studies. One hour after treatment with tobramycin, the concentration of drug in the infected corneas was compared with that achieved in mock-infected and uninfected eyes. Iontophoresis of 25 mg of tobramycin per ml at 0.8 mA for 10 min delivered significantly more drug (P = 0.0001) to corneal tissue than did drops or use of an eye cup without current in P. aeruginosa-infected eyes mock-infected eyes, or uninfected eyes. Tobramycin concentrations in the infected corneas (605.9 micrograms/g) were not significantly different (P = 0.815) from the concentrations in mock-infected eyes (641.4 micrograms/g), but were lower (P = 0.007) than those obtained by iontophoresis in uninfected corneas (853.6 micrograms/g). Use of an eye cup without current delivered tobramycin equally to infected, mock-infected, and normal eyes, i.e., 176.5, 171.0, and 163.1 micrograms/g, respectively (P greater than 0.709). Tobramycin delivered by use of fortified drops delivered topically was detectable in mock-infected corneas (20 micrograms/g) and P. aeruginosa-infected corneas (6.0 micrograms/g). These results suggest that iontophoresis has value as an ocular drug delivery system and that an eye cup could also be useful in a therapeutic regimen for ocular infections.

Animals↗