THE MODE OF ACTION OF p-AMINOBENZENESULPHONAMIDE AND PRONTOSIL IN HqMOLYTIC STREPTOCOCCAL INFECTIONS

Colebrook, Leonard

doi:10.1016/s0140-6736(00)48181-x

Cited by 94 publications

(21 citation statements)

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“…Although sulfonamides are classically bacteriostatic (1), under appropriate conditions they have been shown to exert a bactericidal effect (5,12). Thus, the observation here of a bactericidal effect by sulfamethoxazole alone is neither a new finding nor at variance with some previous observations.…”

Section: Methodsmentioning

confidence: 99%

Technique for Determining the Bactericidal Effect of Drug Combinations

Lorian

Fodor

1974

Antimicrob Agents Chemother

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Two paper strips, each containing different antimicrobial agents, were placed on plates on Mueller-Hinton agar to permit antibiotic to enter the agar. A filter membrane was placed on this plate, and the microorganisms were planted on the membrane. After 6 h of incubation at 37 C, the membrane was transferred to antibiotic-free Mueller-Hinton agar containing triphenyltetrazolium hydrochloride and incubated for 18 h at 37 C. Specific growth patterns were indicative of additive (indifferent), synergistic, or antagonistic effects of the drug combination used. Trimethoprim and sulfamethoxazole proved to act synergistically against 85% of Escherichia coli, 86% of Klebsiella, and 89% of Proteus mirabilis strains tested. A few strains resistant to either drug were susceptible to their combination. The technique was useful against organisms with widely differing susceptibilities to the two antimicrobial agents tested.A number of methods have been devised to establish the bactericidal effect of antibacterial agents against pathogenic organisms (8,9,11,13). The replica transfer method was introduced by Lederberg and Lederberg (10). Elek et al. (6,7) and Streitfeld (14) applied this method using a velvet replicator for the study of antibiotic combinations. Chabbert and Waterworth (4) applied the same principle using a cellophane membrane for the study of synergistic effects of antibiotics. They used filter paper strips impregnated with antibiotics placed at right angles to diffuse the drugs into the agar.In this paper we report the usefulness of a modified cellophane technique in which the cellophane has been replaced by a filter membrane. The technique was tested with the association of trimethoprim plus sulfamethoxazole. MATERIALS AND METHODSOne hundred strains each of Escherichia coli, Proteus mirabilis, and Klebsiella, isolated from specimens submitted to this laboratory, were tested for susceptibility to trimethoprim and sulfamethoxazole singly or in combination.Media and reagents. Media used were as follows: (i) Mueller-Hinton agar (MHA) (BBL) with 0.25% dextrose and 0.04% triphenyltetrazolium hydrochloride (TTC) (Biological Products, N.J.) (after the agar was autoclaved and cooled at 52 C [in a 52 C water bath ], 1 ml of a 4% solution of TTC in 20% alcohol was added to 100 ml of MHA with 0.25% dextrose); Trypticase soy broth (TSB) (BBL). Filter membranes #PHWPO9025, 9 cm in diameter (Millipore Corp., Bedford, Mass.), and filter paper grade #740E (Schleicher and Schuell, Inc. Keene, N.H.) were used. Trimethoprim and sulfamethoxazole were from Hoffman-La Roche, Inc., N.J. Trimethoprim (10 mg) was dissolved in 100 ml of boiling water containing 0.2 ml of hydrochloric acid p.a., and sulfamethoxazole (200 mg) was dissolved in 98 ml of boiling water containing 2 ml of a 4% sodium hydroxide solution.Antibiotic-impregnated plates were prepared in the following manner. Strips 4 cm long and 0.9 cm wide were cut from the filter paper (water absorption per strip was 0.29 ml). One strip was soaked in the trimethoprim solution (pr...

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Section: Methodsmentioning

confidence: 99%

Technique for Determining the Bactericidal Effect of Drug Combinations

Lorian

Fodor

1974

Antimicrob Agents Chemother

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“…In haemolytic streptococcal infection, Colebrook et al (1936) demonstrated that, although the addition of prontosil itself to the blood was without effect on bactericidal action, after administration of this drug to animals and man the bactericidal power of the blood for small numbers of organisms was increased. This action was considered to be due to the reduction of the inactive prontosil to p-aminobenzenesulphonamide, which had feeble bactericidal powers.…”

Section: Part V-the Effect Of Prontosil Therapy On the Anti-streptolmentioning

confidence: 99%

Haemolytic Streptococcal Infections and Acute Rheumatism

Green¹

1942

Annals of the Rheumatic Diseases

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“…in Mice and in Other Species Successful results have been recorded by various workers in the treatment of other experimental infections in mice-for example, with meningococci (Buttle et al., 1936;Proom, 1937), certain salmonella and coliform bacilli (BLIttle et al, 1937a ;Mayer, 1938); but not others (Gross et al, 1938b). These organisms tend not to be highly virulent, and the device has been employed of introducing the inoculum along with mucin into the peritoneum.…”

Section: Effect Of Sulphanilamide Drugs On Various Infectionsmentioning

confidence: 99%

“…The chemotherapeutic property of prontosil could not have been discovered except by trial in infected subjects, because the drug lacks antiseptic action in the test-tube. But in the case of sulphanilamide certain observers noted that in vitro, provided the number of organisms used as the inoculum was small enough, streptococci were inhibited or even killed by considerable dilutions of the drug in ordinary media, human blood (with leucocytes present or removed), or serum (Colebrook et al, 1936;Buttle, 1937;Hoare, 1938;Britton, 1938). This influence exerted by the size of the inoculum is manifest, however, with various other antiseptics-for example, mercuric chloride or acriflavine (Garrod, 1935; personal observations).…”

Section: Mode Of Action Of Sulphanilamide Drugsmentioning

confidence: 99%

“…For example, acriflavine, or especially proflavine, is little toxic for the mammalian body while at the same time an enormously more potent antiseptic than sulphanilamide, and its rate of excretion is not significantly different from that of the latter; nevertheless it fails to cure a general infection. Colebrook et al (1936) remark: " It is somewhat surprising that the low bactericidal power of the blood of mice treated with the sulphonamide should be associated with suLch a notable therapeutic effect." Therefore it must be concluded that the weak anti-bacterial property demonstrable int vitro is not likely to be more than a subsidiary factor contributing to the chemotherapeutic action of the sulphanilamide group.…”

Section: Mode Of Action Of Sulphanilamide Drugsmentioning

confidence: 99%

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