S. Stanley Schneierson

Infections Caused by Microorganisms of the Genus Erwinia

Abstract Isolates belonging to the genusErwiniawere recovered from 17 outpatients and 14 hospitalized patients during a 15-month period. Only three of the isolates from the outpatients were in pure...

A Rapid Method for Determination of the Aureomycin Concentration of the Blood

Summary A rapid method for the determination of the aureomycin concentration of the blood is described. Sterile specimens and sterile technic are not required. The procedure is based upon the inhibition of the test organism, Proteus vulgaris OX-19 by the antibiotic, thereby preventing the reaction and color change produced in the urea-phenol red medium when urea is split to ammonia by the test strain. The minimum assayable level is 0.8 μg per ml of serum. A high degree of correlation was found between the actual value and the results of assays with 36 prepared specimens.

Toxicity of Penicillin for the Syrian Hamster

Summary A single injection of crystalline penicillin G potassium administered subcutaneously or intraperitoneally is toxic for hamsters in proportion to amount administered. Toxicity is of the delayed type, the vast majority of deaths occurring on 3rd, 4th and 5th days following injection. This parallels the reported experience with guinea pigs and is in contrast to Swiss mice who easily tolerate very large doses of this antibiotic. In the light of these findings, reevaluation of experimental data concerned with Syrian hamsters either treated with or injected with material sterilized with penicillin would seem to be indicated.

Spheroplasts of Haemophilus influenzae Induced by Cell Wall-Active Antibiotics and Their Effect upon the Interpretation of Susceptibility Tests

The interpretation of in vitro susceptibility tests of Haemophilus influenzae performed by the agar or broth dilution methods with Levinthal enrichment was found to be markedly influenced by the production of spheroplasts by this species. Using an inoculum of 107 organisms/ml, this phenomenon was frequently evident macroscopically as a haziness on agar substrates and in broths containing cell wall-acting agents, such as ampicillin, cephalothin, and penicillin, but was not noted with chloramphenicol. Phase-contrast microscopic examination of the haze from these sources revealed numerous spherical bodies in contrast to the typical cocco-bacillary forms observed in growth controls. With this inoculum size, minimal bactericidal concentrations could not be determined since subculture of 0.1 ml of the hazy broths or the surface haze onto chocolate agar resulted in most instances in the development of a small number of colonies which, upon smear and gram stain, revealed typical Haemophilus morphology. An inoculum of 104 organisms/ml abolished the haziness on agar surfaces and in broths and resulted in clear-cut end points. Also, although spherical bodies were still present, they were distinctly less in number as contrasted to tests performed with an inoculum of 107 organisms/ml. It is recommended that minimal inhibitory concentration end points in antibiotic susceptibility tests be determined by microscopic, rather than macroscopic, observation of the growth milieu to determine the presence or absence of morphologically typical bacilli which, when observed, is indicative of true in vitro resistance. Images

Mucin-Like Enhancement of Microbial Virulence for Mice by Bile Salts and Certain Surfactants

Summary Intraperitoneal injection of bile salts and certain surfactants into mice followed by adjusted, non-lethal inocula of a variety of different microbes results in significant enhancement of latters virulence for mice. With few exceptions, mortality induced with these adjuvants is associated with high incidence of bacteremia involving intraperitoneally injected microorganisms.

Enhancement of Penetration of Penicillin into Inflamed and Normal Mucous Membrane by Hyaluronidase.

Summary The instillation of 200,000 units of crystalline penicillin G into We diseased and normal paranasal antrum is well tolerated and except for the development of an allergic reaction in one patient, was without any adverse effect. In 24 out of 26 patients with chronic suppurative disease of the sinuses and in all 5 normal subjects, a significant penicillin level in the blood was found after the intra-antral instillation. In both groups, the addition of hyaluronidase to the instilled penicillin resulted in even higher blood levels than those found without its use, with one exception. In two patients in whom no blood level could be demonstrated, the addition of hyaluronidase resulted in a significant concentration of penicillin in the blood. It is postulated that the increased blood penicillin level following hyaluronidase is due to greater diffusion and penetration of the penicillin as a result of the spreading action of hyaluronidase.

Inactivation of Amphotericin B, Chlorquinaldol, Gentian Violet and Nystatin by Bile Salts

Summary One per cent bile salts inactivates amphotericin B, chlorquinaldol, gentian violet and nystatin to a considerable but variable degree depending upon the antimycotic agent. A number of factors possibly involved in the mechanism of this inactivation have been studied and are discussed.

INHIBITION OF THE PHENOMENON OF LOCAL TISSUE REACTIVITY BY CORTICOSTEROIDS, SALICYLATES, AND COMPOUNDS RELATED TO SALICYLATES

The phenomenon of local tissue reactivity is a profound vascular damage and necrobiosis elicited by combined local preparatory and intravenous provocative injections of certain bacterial filtrates or combined local preparatory injection of bacterial filtrates and intravenous provocative injection of antigen antibody complexes or certain colloidal agents. The reaction can only be elicited when the provocative injection is made into the general circulation. No satisfactory explanation is yet available concerning the necessity of introducing the provocative agent into the vascular system. The following long list of substances tested failed to modify the phenomenon; namely, acetylcholine, adenosine-5-phosphoric acid, alypin, antiplatelet serum, amino acids in various combinations, ascorbic acid, atropine, benadryl, biotin, calcium chloride, calcium gluconate, casein hydrolysate, choline, cocaine, congo red, curare, DCA, dicumarol, distilled water, estradiol, ether general anesthesia, folic acid, glucose, heparin, hesperidin, histaminase, histamine, india ink, inositol, lemon “citrin,” milk, Niagara sky blue, nicotinic acid, pantothenic acid, paraminobenzoic acid, physostigmine hydrochloride, pilocarpine, progesterone, pyribenzamine, pyridine in doses reducing significantly the blood platelet count, pyridoxal, pyridoxamine, pyridoxine, rat-liver extract, rat-spleen extract, riboflavin, sodium oxalate, sulfadiazine, sulfanilamide, sulfathiazole, thiamine, atocopherol, toluidine blue, trypan blue, trypsin, urethane, vitamin K water-soluble and oil-soluble preparations, wheat-germ oil, yeast extract, BAL, mapharsen, partial exsanguination, thyroidectomy, and anthisan. The negative results obtained with the substances just mentioned seem to exclude several possible mechanisms; namely, alteration of blood coagulation, release of histamine, and modification of the response of the peripheral and central nervous systems.’ There are, however, a few substances that can effectively suppress the phenomenon. As shown by Becker? and corroborated by Schlang3 and by Stetson and Good: nitrogen mustard, benzol, and x-ray irradiation are capable of inhibiting the phenomenon. Becker postulated that these agents produce the suppression by rendering the vascular endothelium of the prepared skin site nonreactive, thus preventing it from reacting to the provocative agent. In studying the mechanism of this inhibition, Schlang and Stetson and Good found that protection of the prepared site from the effect of nitrogen mustard failed to’influence the inhibition of the reaction. In contrast, protection of the lower limbs from the action of nitrogen mustard by aortic occlusion decreased or prevented the inhibition. They concluded justly that the effect of nitrogen mustard was the result of systemic rather than local action. We found that ACTH and cortisone in large doses administered at a suitable time may suppress

A method for producing sustained high penicillin levels in the blood.

Summary A method for obtaining high sustained blood levels of penicillin is described. This consists in repeated large intravenous doses of crystalline penicillin, injected rapidly, in patients receiving caronamide. Clinical applications are suggested. We wish to thank Miss Beatrice Toharsky for capable technical assistance.

Relationship Between Penicillin Susceptibility and Virulence of Staphylococcus aureus.

Summary No distinct correlation was established between penicillin susceptibility and virulence of 80 coagulase positive, hemolytic, mannitol fermenting strains of Staphylococcus aureus. Both penicillin-resistant and penicillin-sensitive strains vary considerably in their mouse pathogenicity but a significantly higher proportion of the former proved to be virulent as compared to the latter which were fairly evenly divided between virulent and avirulent strains. No definite pattern with respect to change in virulence was observed with 4 originally penicillin-sensitive strains following artificial induction of resistance to the antibiotic.