Development of immunotherapy for infections due to Pseudomonas aeruginosa.
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Biomedical subjects
Publications and source records attributed to M W Fisher.
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Butirosin (BTN) (P. W. K. Woo, G. L. Coffey, H. W. Dion, S. A. Fusari, and G. D. Senos, U. S. Patent 3,541,078, 1970) is a new aminoglycoside antibiotic notably active against opportunist bacterial species within Pseudomonas, Klebsiella, Enterobacter, Serratia, and Proteus. Numerous comparative tests were carried out with BTN and gentamicin (GTM) in vitro and in experimental infections in mice. BTN was more active in Mueller-Hinton broth than in agar, but its activity was lessened at acid pH or under anaerobiosis, as has been observed with other aminoglycosides. In standard agar diffusion tests, inhibition zones greater than 12 mm around 30-mug BTN disks generally denoted susceptibility, equivalent to minimal inhibitory concentrations [Formula: see text] 25 mug/ml. Cross-resistance between BTN and GTM occurred in a variable manner, with a number of bacterial strains strongly resistant to GTM being moderately susceptible to BTN. In mice, after a single subcutaneous injection, absorption of both antibiotics was rapid, with peak serum levels occurring in 15 min; this was followed by rapid elimination with estimated serum half-lives of about 20 min for each. After peroral administration of high doses in mice, there was no appreciable absorption of BTN. Several tests were carried out to compare BTN and GTM with respect to minimal inhibitory concentrations in vitro, acute subcutaneous median mouse protective doses, peak serum levels at such doses, and the therapeutic ratios derived from acute median protective and lethal doses. Although GTM usually proved to be more potent antibacterially on a weight basis, observations on BTN indicated a superior effectiveness in terms of therapeutic ratios.
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Phenazopyridine, at its maximum tolerated dose, did not affect the effectiveness of sulfonamides against uropathogenic bacterial species in mice.
Butirosin is a new aminoglycosidic antibiotic complex which has broad gram-negative and gram-positive inhibitory antibacterial activity, as well as some bactericidal properties. Significantly susceptible bacteria include strains of Staphylococcus aureus and Streptococcus pyogenes, and pathogenic gram-negative species such as Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and P. vulgaris, Salmonella enteritidis and S. typhimurium, Shigella flexneri and S. sonnei. Good activity by parenteral dosing was obtained in various acute mouse infections. Butirosin is especially interesting because of its activity against Pseudomonas aeruginosa in vitro, including gentamicin-resistant clinical isolates, and in experimental mouse infections at relatively low doses.
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A reasonably precise, reproducible, and sensitive microbiological procedure for directly assaying sulfacytine and other sulfonamides as antibacterially active drugs has been developed by appropriately modifying the standard disc-agar diffusion technique. Blood and urine levels as low as 3 mug/ml may be determined through the use of a strain of Escherichia coli and a chemically defined agar medium devoid of sulfonamide antagonists. Results indicate that this assay method should be a useful adjunct to the Bratton-Marshall colorimetric procedure, by permitting the direct measurement of antibacterially active drug in clinical specimens.
Tests were performed on 64 strains of Pseudomonas pseudomallei to compare rifampin, various tetracyclines, and other antibiotics for inhibitory activity in vitro. Rifampin minimum inhibitory concentration (MIC) values generally fell between 25 to 50 mug/ml. For deoxycycline, methacycline, tetracycline, and minocycline, MIC means ranged from 1.3 to 2.7 mug/ml. Delayed treatment tests in subacute mouse infections revealed a better rifampin activity than was expected from its weak activity in vitro, whereas of the others, minocycline appeared superior. None of these five antibiotics demonstrated fully curative effectiveness in terms of mouse survival or eradication of residual infection in organs.
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