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Both an oral and a parenteral form of a 6β-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella, and Haemophilusspecies in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the Staphylococcus aureusinfection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of Escherichia coli.

Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture.

Both an oral and a parenteral form of a 6beta-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella, and Haemophilus species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the Staphylococcus aureus infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of Escherichia coli.

Mersalyl (Salyrgan), an organic mercurial diuretic, was tested against human and animal viruses with in vivo model infections in mice and tissue culture systems. Mersalyl was active against coxsackieviruses A21 and B1 in mice if administered intraperitoneally immediately after infection. No effect was observed if intraperitoneal treatment was delayed 1 or 2 h postinfection, or if treatment was administered either subcutaneously or per os. Topical treatment with a 5% aqueous solution of mersalyl produced a statistically significant effect against herpes simplex dermatitis in mice but the substance was inactive against systemic infections in mice with herpes simplex as well as Columbia SK, influenza, Semliki Forest, and Sendai viruses. Contact inactivation of coxsackieviruses A21 and B1 and herpes simplex virus was observed, but mersalyl was inactive in tissue culture against coxackieviruses A21 and B1, herpes simplex, influenza, rhinovirus, Semliki Forest, Sendai, and vaccinia viruses.

A radioimmunoassay using a 3H- or 125I-labeled morphine antigen has been shown to be of practical value for the rapid detection of nanogram amounts of morphine and morphine analogs in biological fluids [1–3]. A radioimmunoassay for detection of barbiturates by conjugation of a secobarbital derivative to protein was also developed utilizing 14C-labeled pentobarbital or barbital [4,5]. The present report describes our experiences with a practical radioimmunoassay for barbiturates employing a secobarbital derivative labeled with 125I, as the antigen.

The effect of Mg2+and ethylenediaminetetraacetic acid (EDTA) on the in vitro activity of coumermycin A1and novobiocin was determined against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilisgrown in Trypticase Soy Broth or defined synthetic medium. In the presence of EDTA, the activity of coumermycin A1was significantly enhanced (8- to 40-fold) against all four organisms in the synthetic medium lacking Mg2+; novobiocin activity was increased to a lesser extent (4- to 16-fold) against three strains and remained unchanged against P. mirabilis.Addition of 200 μg of Mg2+per ml to the synthetic medium containing EDTA completely reversed the enhancement of activity of both antibiotics by EDTA only against P. aeruginosa.The addition of Mg2+to the synthetic medium appreciably inhibited the activity of novobiocin (sixfold) but not coumermycin A1against E. coli, and had little or no effect on the activity of either antibiotic against the remaining organisms. K. pneumoniaeshowed the greatest susceptibility to both antibiotics, and addition of EDTA enhanced this activity from 4-fold to 20-fold in all of the media tested. Subinhibitory concentrations of both antibiotics induced filament formation by all four organisms in all media. In addition, lysis of K. pneumoniaecells was observed.

Grunberg, E. (Hoffman-La Roche, Inc., Nutley, N.J.), and R. Cleeland. Fluorescence and viability of Proteus mirabilisstained directly with fluorescein isothiocyanate. J. Bacteriol. 92:23–27. 1966.—Washed cell suspensions of Proteus mirabilis, under the proper conditions, stained well with fluorescein isothiocyanate with little or no loss of cell viability. The speed and intensity of the reaction was dependent on both the concentration of dye and pH. Within a range of pH 3.0 to 10.0, staining was most rapid at pH 5.0 to 6.0, with a slower and less intense reaction occurring at the other pH values. As the concentration of dye at either pH 5.0 or 9.0 was increased from 10 to 1,000 μg/ml, there was an increase in the rate of staining but a decrease in cell viability. After 24 hr of incubation at 4 C, pH 5.0, and a dye concentration of 10 μg/ml, all cells were stained, the majority exhibiting intense fluorescence with little or no loss of viability noted. In preliminary experiments with Staphylococcus aureus, similar results were obtained. Of various other fluorescent dyes tested, only rhodamine isothiocyanate was found to give satisfactory staining.