Paradoxical Synergism and Antagonism Between Serum and the Antibacterial Activity of Colistin

Davis, Starkey D.; Iannetta, Antoinette; Wedgwood, Ralph

doi:10.1093/infdis/123.4.392

Cited by 25 publications

(14 citation statements)

References 13 publications

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“…Bactericidal activity of the polymyxins may be blocked by low concentrations of calcium or serum (9,18). However, endotoxin detoxification by polymyxin B was not inhibited by such treatment in the present study.…”

Section: Resultscontrasting

confidence: 66%

Inactivation of Endotoxin by Polymyxin B

Cooperstock

1974

Antimicrob Agents Chemother

124

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The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 Og of polymyxin B per ml, whereas Bacteroides fragilis endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.Recent studies have demonstrated the capacity of polymyxin B to protect animals from a variety of toxic effects of endotoxin, including the generalized Schwartzman reaction (5, 23), diffuse intravascular coagulation (6, 7), renal cortical necrosis (6, 7), leukopenia (6, 7), and death (6,12,21,23). The limulus gelation test, developed by Levin and others (13,14), has provided a useful in vitro means to assess an endotoxin activity which corresponds with in vivo indices of toxicity (3,15,24). We have previously found this assay to be useful in evaluating endotoxin inactivation processes (4). The present study was designed to evaluate the effect of polymyxin B and other antibiotics upon endotoxin, the conditions of the reaction, and the relative polymyxin susceptibility of endotoxins from a variety of gram-negative bacteria. MATERIALS AND METHODS

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Section: Resultscontrasting

confidence: 66%

Inactivation of Endotoxin by Polymyxin B

Cooperstock

1974

Antimicrob Agents Chemother

124

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“…Studies on the interaction of antibiotic, serum, and other reagents in broth were carried out as described previously (2)(3)(4). Tubes contained 0.4 ml of antibiotic in Mueller-Hinton broth (BBL), 0.4 ml of bacterial inoculum in broth, and 0.8 ml of other reagents in broth.…”

Section: Methodsmentioning

confidence: 99%

Antagonistic Effect of Calcium in Serum on the Activity of Tobramycin Against Pseudomonas

Davis

Iannetta

1972

Antimicrob Agents Chemother

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Physiological concentrations of calcium in serum antagonize the activities of colistin, polymyxin B, and gentamicin against Pseudomonas aeruginosa. Studies were carried out to determine whether tobramycin, a new aminoglycoside antibiotic, is also antagonized by calcium. The activity of tobramycin in vitro was shown to be antagonized by human serum and by physiological concentrations of calcium. The addition of human serum in broth-dilution tests produced a fourfold rise in the minimal inhibitory concentrations of tobramycin for five strains of Pseudomonas. In disc diffusion tests, the addition of calcium to the agar significantly decreased the size of inhibition zones, and the addition of a chelating agent to the agar increased the zone sizes. In a limited comparative study, tobramycin and gentamicin were tested against both light and heavy bacterial inocula of two strains of Pseudomonas. Tobramycin appeared to be antagonized less by serum than was gentamicin at equal antibiotic concentrations.Tobramycin, formerly designated nebramycin factor 6 (6), is a new aminoglycoside antibiotic that has a broad spectrum and high activity against Pseudomonas aeruginosa (1, 8). Physiological concentrations of calcium are known to antagonize the activities of gentamicin, colistin, and polymyxin B against P. aeruginosa (2-4). The present study was designed to determine whether the activity of tobramycin against Pseudomonas is also antagonized by calcium. MATERIALS AND METHODSA group of 21 strains of P. aeruginosa, representing seven immunotypes, were obtained from Myron Fisher of Detroit, Mich. (5). Five strains of Escherichia coli were obtained from the Clinical Microbiology Laboratory of the University Hospital. Tobramycin was supplied by Eli Lilly & Co. as a 1 mg/ml solution and was stored at 4 C. Gentamicin powder, a gift of Schering Corp., was reconstituted in sterile water at 100 mg/ml and was stored at -65 C until used. Serum from healthy adult donors was also stored at -65 C until used.Studies on the interaction of antibiotic, serum, and other reagents in broth were carried out as described previously (2-4). Tubes contained 0.4 ml of antibiotic in Mueller-Hinton broth (BBL), 0.4 ml of bacterial inoculum in broth, and 0.8 ml of other reagents in broth. Bacteria from an overnight culture were grown at 37 C in broth for 2 to 3 hr and then were diluted in broth to give a final concentration of about 3 X 103 organisms per ml. Antibiotic, bacteria, and other reagents were mixed at time zero by agitation, and incubation was begun at 37 C in a shaker-water bath.At time zero and at 3 hr, samples of 0.1 ml were taken and streaked onto the surface of agar plates. The plates were incubated overnight and the colonies were counted.Tests for antibiotic susceptibility were carried out by a twofold dilution technique in Mueller-Hinton broth with and without various concentrations of human serum. Tubes contained 0.4 ml of antibiotic in broth, 0.4 ml of bacterial inoculum in broth, and 0.8 ml of serum diluted in broth. The bacterial inoc...

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“…As previously reported, physiological concentrations of calcium in ser um antagonized the bactericidal effects in vitro of colistin, gentamicin, and tobramycin on Pseudomonas [3][4][5][6]. However, calcium was not anta gonistic to the effects of carbenicillin on Pseudomonas [4].…”

Section: Discussionmentioning

confidence: 88%

“…MIC's were determined by a twofold tube-dilution technique in Mueller-Hinton broth (Baltimore Biological Laboratories) as previously described [5]. The tests were carried out in duplicate and were interpreted 'blindly' by one of us.…”

Section: Methodsmentioning

confidence: 99%

“…Physiological concentrations of calcium in serum have been shown to antagonize the activities of colistin and gentamicin on Pseudomonas aeru ginosa [4][5][6], Tobramycin, formerly nebramycin factor 6, is a new ami noglycoside antibiotic that is active against P. aeruginosa [1,12]. It is also antagonized by calcium [3], Carbenicillin is the only major antibiotic used in treatment of Pseudomonas infections that is not antagonized by calcium [4].…”

mentioning

confidence: 99%

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Relative Antagonism <i>in vitro</i> of Calcium in Serum to the Bactericidal Activities of Gentamicin and Tobramycin on <i>Pseudomonas Aeruginosa</i>

Davis¹,

Iannetta²

1973

Chemotherapy

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Physiologic concentrations of calcium in serum antagonize the activities in vitro of gentamicin and tobramycin on Pseudomonas aeruginosa. The relative antagonism of serum to these antibiotics in vitro was determined on 21 strains of Pseudomonas, representing three each of the seven recognized immunotypes. Serum was more antagonistic to gentamicin than to tobramycin for 14 strains. Serum had little antagonism to either antibiotic for four strains. Serum was highly antagonistic to both antibiotics for three strains. In no instance was serum more antagonistic to tobramycin than to gentamicin. These results suggest that tobramycin may be more active against most strains in vivo than gentamicin at equal concentrations. The relevance in vivo of these in vitro findings remains to be determined.

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Paradoxical Synergism and Antagonism Between Serum and the Antibacterial Activity of Colistin

Cited by 25 publications

References 13 publications

Inactivation of Endotoxin by Polymyxin B

Inactivation of Endotoxin by Polymyxin B

Antagonistic Effect of Calcium in Serum on the Activity of Tobramycin Against Pseudomonas

Relative Antagonism <i>in vitro</i> of Calcium in Serum to the Bactericidal Activities of Gentamicin and Tobramycin on <i>Pseudomonas Aeruginosa</i>

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