Active Immunization with Lipopolysaccharide Pseudomonas Antigen for Chronic Pseudomonas Bronchopneumonia in Guinea Pigs

Pennington, James E.; Hickey, William F.; Blackwood, Linda L.; Arnaut, Marina

doi:10.1172/jci110358

Cited by 56 publications

(25 citation statements)

References 34 publications

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“…The activity of the three quinolones in persistent, nonfatal bronchopulmonary infection by P. aeruginosa was evaluated in guinea pigs by using inocula of agar beads impregnated with a mucoid strain of P. aeruginosa, 2192 M, as described previously (20). Agar bead slurries containing approximately 1.5 x 107 CFU of Pseudomonas organisms per lung inoculum at a volume of 0.2 ml were instilled intratracheally.…”

mentioning

confidence: 99%

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia

Kemmerich¹,

Small²,

Pennington³

1986

Antimicrob Agents Chemother

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The therapeutic activity of ciprofloxacin, enoxacin, and ofloxacin was evaluated in guinea pigs with acute and chronic experimental Pseudomonas aeruginosa pneumonia. Ciprofloxacin, enoxacin, and ofloxacin are three newly developed quinoline carboxylic acid derivatives with excellent in vitro activity against Pseudomonas aeruginosa (1,2,4,7,9,15,16,29,33). These compounds also offer interesting therapeutic alternatives for the treatment of P. aeruginosa infections because of their prolonged half-life and high tissue penetration (5,6,10,14,17,28,34,35). The high rate of absorption after oral administration (6, 14, 17, 34) might be particularly useful in the treatment of chronic P. aeruginosa bronchopulmonary infections, such as those seen in patients with cystic fibrosis.Ciprofloxacin was shown recently to be as active as tobramycin and superior to ticarcillin in experimental P. aeruginosa pneumonia in guinea pigs (31). No such information is available for enoxacin and ofloxacin. Also, information about the oral treatment of experimental lung infections and about combination therapy of quinolones with ,-lactams or aminoglycosides for respiratory infection is not available. The objectives of the present study were (i) to investigate the comparative efficacy of ciprofloxacin, enoxacin, and ofloxacin in acute and chronic P. aeruginosa pneumonia, (ii) to provide an in vivo evaluation of monotherapy with ciprofloxacin versus combination with a Pseudomonasactive 1-lactam or an aminoglycoside, and (iii) to compare oral and parenteral administration of ciprofloxacin in chronic P. aeruginosa bronchopneumonia.MATERIALS AND METHODS Animals. Disease-free Hartley strain guinea pigs weighing 350 to 400 g each were obtained from the Charles River Breeding Laboratories, Inc., Wilmington, Mass. The animals were housed in standard cages and fed guinea pig chow (Ralston-Purina, St. Louis, Mo.) and water.Antibiotics. Antibiotics used in this study were ciproflox- Ciprofloxacin, azlocillin, and ceftazidime were supplied as a powder and reconstituted in water to a final concentration of 20, 250, and 250 mg/ml, respectively. Powdered ofloxacin was dissolved in 0.1 N NaOH to a concentration of 10 mg/ml and thereafter titrated with concentrated HCl to a neutral pH. Enoxacin, supplied as a solution of 200 mg/ml, was diluted in water to a concentration of 40 mg/ml, and tobramycin was diluted with isotonic saline to a final concentration of 4 mg/ml. Bacteria. Three clinical isolates of P. aeruginosa were used for infections. Strains 220 and A-5 were used in the acute pneumonia experiments, and the mucoid strain 2192M was used in the chronic model. The origins and characteristics of these strains were described previously (21,22,31). Maintenance and preparation of the bacteria for experimental infections were done as reported elsewhere (24). The MICs and MBCs of the antibiotics used in this study against the three challenge strains were determined by a microdilution method in Mueller-Hinton broth supplemented with calcium (50 ,ug/ml) and magn...

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mentioning

confidence: 99%

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia

Kemmerich¹,

Small²,

Pennington³

1986

Antimicrob Agents Chemother

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“…Previous studies with this model have established the relative efficacies of tobramycin and ticarcillin (11,12,17), and these two agents were included in the present study for comparative purposes. In addition, because an oral anti-Pseudomonas agent might be useful in the treatment of chronic forms of respiratory infections caused by P. aeruginosa, such as that seen in patients with cystic fibrosis, the therapeutic efficacy of ciprofloxacin was also evaluated in a more chronic form of experimental P. aeruginosa pulmonary infection (10). Throughout these studies, ciprofloxacin was administered in dosages designed to produce levels in the sera of guinea pigs similar to those achieved by oral administration of this agent to humans (6).…”

mentioning

confidence: 99%

“…To duplicate more closely the persistent bronchopulmonary infection caused by P. aeruginosa and commonly seen among patients with cystic fibrosis, Pennington et al have developed a guinea pig model of nonfatal, persistent Pseudomonas bronchopneumonia (10). For the present study, strain 2192M, a mucoid P. aeruginosa isolate, was prepared in an agar bead slurry as previously described (10) and was used to inoculate guinea pig lungs via the trachea. Approximately 6 x 107 CFU of P. aeruginosa were contained in each lung inoculum.…”

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Comparative activities of ciprofloxacin, ticarcillin, and tobramycin against experimental Pseudomonas aeruginosa pneumonia

Schiff¹,

Small²,

Pennington³

1984

Antimicrob Agents Chemother

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The therapeutic efficacy of ciprofloxacin, an investigational quinoline derivative, was compared with those of ticarcillin and tobramycin in guinea pigs with experimental Pseudomonas aeruginosa pneumonia. Guinea pigs challenged with tracheal instillations of 10(8) CFU of P. aeruginosa developed acute pneumonia, for which survival rates were: controls, 0%; ticarcillin treatment, 37%; ciprofloxacin treatment, 57%; and tobramycin treatment, 69%. Intrapulmonary killing of P. aeruginosa was greater (P less than 0.05) in animals treated with ciprofloxacin or tobramycin than in groups treated with ticarcillin. A more chronic, nonfatal form of bronchopneumonia caused by P. aeruginosa was induced with agar beads impregnated with bacteria for pulmonary challenge. In this model, ciprofloxacin treatment resulted in significantly (P less than 0.001) greater intrapulmonary killing than did any other therapy. These data suggest that ciprofloxacin may be useful in the treatment of acute and more-chronic forms of pulmonary infection caused by P. aeruginosa.

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“…Involvement with LPS in either of these ways has often resulted in frustration. A heptavalent LPS vaccine, based on the 7 immunotypes of Fisher et al [8], was prepared by Hanessian et al [9] and tested in animal models [10][11][12][13] and patients [14,15], The vaccine proved to be immunogenic and pro tective in many of these trials [10,12,14,15]; however, the problems resulting from its tox icity [14][15][16] have prevented its development into an acceptable, widely useful vaccine. Numerous efforts aimed at detoxification of LPS have been reported [17,18]; neverthe less, an effective vaccine consisting solely of detoxified LPS from P. aeruginosa has yet to be developed.…”

Section: Experimental Vaccinesmentioning

confidence: 99%

Protective Mechanisms of Experimental Vaccine-Induced Immunity to <i>Pseudomonas aeruginos</i><i>a</i>

Lieberman¹

1985

Pathol Immunopathol Res

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Active Immunization with Lipopolysaccharide Pseudomonas Antigen for Chronic Pseudomonas Bronchopneumonia in Guinea Pigs

Cited by 56 publications

References 34 publications

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia

Comparative activities of ciprofloxacin, ticarcillin, and tobramycin against experimental Pseudomonas aeruginosa pneumonia

Protective Mechanisms of Experimental Vaccine-Induced Immunity to <i>Pseudomonas aeruginos</i><i>a</i>

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