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At least 1,171 records · Page 65Linked to original sources
PubMed1981

Azlocillin and gentamicin in respiratory tract infections with Pseudomonas aeruginosa in patients with cystic fibrosis.

Azlocillin, 200 mg/kg bodyweight every 8 h, and gentamicin, 2.5-4 mg/kg bodyweight every 12 h, in combination were given intravenously to 10 patients with cystic fibrosis for at least 10 days. The patients were colonized with Pseudomonas aeruginosa and were hospitalized due to symptoms of lower respiratory tract infections. Using an agar well diffusion method the antibiotic concentrations were followed in serum and sputum. The individual sputum concentration of azlocillin varied during 4 h after administration from less than 1.5 to 38 micrograms/ml. The sputum concentration of gentamicin varied from 0.3 to 1.1 micrograms/ml. P. aeruginosa was apparently eliminated in 3 patients. The concentration of the antibiotics in sputum could not predict the outcome of treatment. All patients improved subjectively. No adverse effect was seen.

Adolescent↗
PubMed1981

Antibiotic treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The retrospective bacteriological results of 322 courses of anti-Pseudomonas aeruginosa chemotherapy in a cohort of 57 cystic fibrosis (CF) patients are reported. Tobramycin given as mono-therapy eradicated P. aeruginosa from the lungs of CF patients in 9% of the courses, whereas a combination therapy consisting of carbenicillin + tobramycin eradicated P. aeruginosa in 55% of the courses. However, the efficacy of the chemotherapy diminished successively when repeated courses of treatment were given. The efficacy of the carbenicillin + tobramycin combination in eradicating P. aeruginosa from the lungs of CF patients was compared with the efficacy of azlocillin + tobramycin and piperacillin + tobramycin in a prospective study. P. aeruginosa was eradicated in 78% of CF patients treated with carbenicillin + tobramycin, in 28% of CF patients treated with azlocillin + tobramycin, and in 33% of CF patients treated with piperacillin + tobramycin. However, the two latter groups of patients had on an average significantly higher numbers of P. aeruginosa precipitins in serum, indicating more severe infections. In CF patients where P. aeruginosa was not eradicated, a significant increase of MIC against carbenicillin, azlocillin and piperacillin was observed. There was a significant improvement of lung function and laboratory parameters reflecting diminished inflammation as a result of the treatment. 40% of the CF patients treated with azlocillin or piperacillin developed serum sickness-like symptoms.

Adolescent↗
PubMed1995

In vivo bacterial protease production during Pseudomonas aeruginosa corneal infection.

PURPOSE: To establish if active pseudomonal proteases are present in vivo during corneal infection with Pseudomonas aeruginosa and to determine if the mouse strains used in these and previous studies have the ability to mount a nonocular antibody response to the purified proteases because antibodies to the bacterial proteases were not detected previously during in vivo ocular infection. METHODS: At certain times after corneal infection with P. aeruginosa, corneas were harvested and supernatants from the corneal homogenates were analyzed for proteolytic activity by zymography and immunoreactivity by immunoblotting. The efficiency of the extraction procedures used in these studies was determined by incubating uninfected corneal homogenates with the purified proteases. The resultant supernatants were analyzed for alkaline protease and elastase activity. Additionally, mice were immunized intraperitoneally with the purified proteases with and without adjuvant to determine if the animals could mount a nonocular antibody response. RESULTS: Corneas infected with P. aeruginosa demonstrated the presence of alkaline protease, but not elastase, by the two methods examined. The kinetics of the in vivo alkaline protease response closely parallels previously reported bacterial clearance studies in that peak alkaline protease activity was detected in corneal tissue when peak bacterial numbers also were observed in the eye, and it was absent when the eyes were sterile or nearly sterile. In addition, C57BL/6J mice were capable of mounting a nonocular antibody response to microgram quantities of both proteases only in the presence of adjuvant. CONCLUSIONS: In the model described, enzymatically active alkaline protease, but not elastase, was demonstrated in corneal tissues during in vivo infection. Concentrations of these proteases were much lower than those required to stimulate an antibody response.

Animals↗
PubMed2006

Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.

For efficacious vaccine development against Pseudomonas aeruginosa (P. aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three different plasmids each targeting a fusion of outer membrane proteins (OprF/OprI), a protein regulating type III secretion system (PcrV), or an appendage (PilA) were prepared and mice were immunized with single (monovalent) or a combination of these plasmids (multivalent) via intramuscular electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine via imEPT induced the most potent protection against lethal pneumonia. Although the serum levels of IgG binding to whole bacteria cells were comparable between groups, the strongest immune protection was associated with the serum levels of Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and macrophages in the bronchoalveolar lavage following intranasal challenge. These results implied the possible clinical application of multivalent DNA vaccine against P. aeruginosa.

Animals↗
PubMed1983

Pharmacokinetics and clinical aspects of azlocillin in paediatrics.

A pharmacokinetic and clinical study was done in 25 newborn infants suffering predominantly from pseudomonas infections treated with azlocillin. After a single iv dose of 50 mg azlocillin per kg bodyweight in biphasic concentration time course suggested an open two compartment body model. There was a rapid diffusion between the peripheral and the central compartment. The elimination half life calculated from the beta-slope was 2.5-2.6 h, and differences between premature neonates with more than 2000 g body weight and mature neonates were absent. To maintain a median steady state concentration of 50-80 mg/l in the serum 100-200 mg azlocillin/kg body weight per day must be given. Using this dosage non-linear kinetics and an accumulation of the drug would not occur. Bacteriological and clinical results confirm that in neonatal reinfection, and bronchopulmonary and local infection caused by pseudomonas strains, azlocillin has favourable properties.

Azlocillin↗
PubMed1996

Pathogenesis of corneal infection: binding of Pseudomonas aeruginosa to specific phospholipids.

Clinical isolates of Pseudomonas aeruginosa were examined for binding interactions with phospholipids of corneal epithelium. Thin-layer chromatography (TLC) of lipids extracted from corneal epithelia followed by staining with an ammonium molybdate spray reagent revealed three phospholipid components, PL1, PL2, and PL3. The chromatographic mobility of PL1 was similar to that of the phospholipid standards phosphatidylinositol (PI) and phosphatidylserine (PS), which were not well resolved from one other; PL2 and PL3 comigrated with the standards phosphatidylcholine and phosphatidylethanolamine, respectively. By use of a TLC-bacterial overlay procedure, 35S-labeled P. aeruginosa organisms were shown to bind to PL1 but not to PL2 or PL3. P. aeruginosa binding to PL1 was concentration dependent. Alkaline methanolysis abolished the binding. PL1 was separated into two components, PL1-I and PL1-S, by chromatography on borate-treated TLC plates. Both PL1-I and PL1-S contained binding sites for P. aeruginosa. Mass spectral analysis identified PL1-I and PL1-S as PI and PS, respectively. Radiolabeled P. aeruginosa organisms were subsequently shown to bind to commercially available bovine PI and PS and synthetic dipalmitoyl-PS but not to other phospholipid standards, including bovine SM and PC or synthetic dioleoyl- and distearoyl-PC. A control Escherichia coli strain did not bind to either PS or PI. Tetramethylurea, a disrupter of hydrophobic associations, did not influence the binding of P. aeruginosa to PS or PI. P. aeruginosa bound to the monolayers of corneal epithelial cells. P. aeruginosa binding to the monolayer cultures as well as to rabbit corneas pretreated with exogenous PS and PI was significantly higher than that to those preincubated with PC or medium alone. The data suggest that phospholipids PS and PI present in mucus or on the cell surface may function as P. aeruginosa receptors and contribute to selective bacterium-host interactions responsible for initial colonization.

Animals↗
PubMed2004

Toll-like receptor 2 represses nonpilus adhesin-induced signaling in acute infections with the Pseudomonas aeruginosa pilA mutant.

Expression of pili and associated proteins is an important means of host invasion by bacterial pathogens. Recent evidence has suggested that the binding of Pseudomonas aeruginosa through nonpilus adhesins may also be important in respiratory diseases, since adhesins bind mucins. Using wild-type C57BL/6 and TLR2KO mice, we compared the induction levels of the host response to P. aeruginosa that either expressed pili or lacked pilus expression due to a mutation in the structural gene pilA. In C57BL/6 mice, deletion of pili led to a decreased immune response, evidenced by a lower secretion of cytokines and a lack of neutrophil chemotaxis. By contrast, the P. aeruginosa pilA mutant induced a hyperresponsive phenotype in TLR2KO mice. TLR2KO mice showed an increased number of neutrophils in lavage fluid compared to the levels seen when either mouse strain was exposed to wild-type P. aeruginosa. Further analysis indicated that the increased neutrophil influx was associated with an increased expression of calgranulins, possibly through an induction of Toll-like receptor 4 (TLR4) expression. The hyperresponsive phenotype of TLR2KO mice exposed to the P. aeruginosa pilA mutant was associated with TLR4 induction and indicated that nonpilus adhesin-induced signaling was repressed by TLR2 function and, if not blocked by the host, could induce airway hyperresponsiveness.

Acute Disease↗
PubMed2000

Outbreak of infections caused by Pseudomonas aeruginosa producing VIM-1 carbapenemase in Greece.

Resistance to imipenem and meropenem was observed in 211 (16.5%) isolates of Pseudomonas aeruginosa recovered in a Greek university hospital during 1996 to 1998. In six isolates selected from throughout this period, high-level resistance to both carbapenems (MICs >/= 128 microg/ml) was associated with production of the class B beta-lactamase VIM-1. bla(VIM)-bearing isolates belonged to serotype O:12 and were indistinguishable by pulsed-field gel electrophoresis.

Anti-Bacterial Agents↗
PubMed1982

Pseudomonas aeruginosa corneal infections in seriously ill children.

Bacterial corneal ulcers can destroy vision if not treated early. Two seriously ill patients developed corneal infections with Pseudomonas aeruginosa while in the pediatric intensive care unit. In one patient the eye was destroyed. The other patient was treated successfully, but early intervention was crucial.

Child, Preschool↗
PubMed1979

Chemotherapy of chronic infections with mucoid Pseudomonas aeruginosa in lower airways of patients with cystic fibrosis.

The bacteriological effect of chemotherapy against Pseudomonas aeruginosa (Ps.ae.) in lungs of patients with cystic fibrosis is reviewed. During a 5-year period 49 children and adults were treated with 190 courses of different antibiotics. The mucoid strains of Ps.ae. disappeared in 72.0% of the courses in which a combination of tobramycin and carbenicillin was employed. Tobramycin given alone had only bacteriological effect in 26.6% of the courses. Colimycin alone or in combination with carbenicillin had no effect. In 18 patients who received subsequent courses of tobramycin and combination of tobramycin and carbenicillin a significant difference in favour of the combination therapy was found, also in cases with many precipitins against Ps.ae. in serum. In 74.5% of the initially successful courses the patients were recolonized with Ps.ae. within 1 month. No nephrotoxic or ototoxic side effects were demonstrated in spite of the high doses of tobramycin (10 mg/kg/24 h) emmployed and the repeated courses.

Adolescent↗