Morton S. Bryer

The clinical use of polymyxin.

Polymyxin is an antibacterial agent uniquely active against several species of gram-negative microorganisms. Adequate protection of experimentally infected animals was demonstrated with doses of the antibiotic far smaller than those a t which any toxic manifestations were noted. Trial in patients, therefore, appeared warranted. These early cases cannot be considered therapeutic trials to establish the clinical use of this antibiotic, but rather as eariy explorations into the pharmacology and human hostdrug relationships. The small series of patients treated thus far, the varied types of infections, and the great age range of these patients render any generalization or statistical treatment untenable. Gram-negative infections differ markedly from many gram-positive infections in that complications often exist which aid in the initiation of the disease or its maintenance. Many of the cases treated were suffering from an underlying dermatitis, neoplasm, burn, etc. Thus, the clinical course of the untreated case is more difficult to predict, and that of the treated case, to evaluate. Reçort to bacteriological procedures coupled with objective and subjective clinical observations of each case is necessary. The observations on these patients will be presented, and data as to tolerance, blood levels attained, urinary excretion, untoward reactions, and cultural examinations reported. The coune of the patient while on polymyxin therapy may be followed, but no definite deductions as to cause and effect will be attempted. Some cases were treated with a daily dose of 3 mg./kg. per day, divided into 8 equal amounts and given a t 3-hour intervals. Others were given a daily dose of 7 mg./kg./day. In these patients, an initial dose of 3 mg./kg. followed by two doses of 2 mg./kg. at 8-hour intervals was employed, and thereafter the drug was continued at equal amounts given three times a day. This dosage was not tolerated for more than three to four days and then was oftea reduced to 3 mg./kg. per day. A few cases have been treated with doses of 4 mg./kg. per day, given as four divided doses at 6 hour intervals. AI1 dmg was dissolved in a phosphate buffer pH 7.4 and administered via the intramuscular route. A concentration of 60 to 120 mg. in two cubic centimeters was tolerated locally. At the higher concentrations, dull drawing pain was noted for several minutes following the injection. In several individuals, after repeated injections, small, reddened, tender areas persisted a t the injection site. However, almost a11 patients preferred this discomfort to two doses of more dilute material. The injections were not discontinued in any patient because of local reactions. On m e occasion, The dosages of polymyxin employed in these trials varied.

An Evaluation of Aureomycin Therapy in Primary Atypical Pneumonia

AUREOMYCIN has been reported as an effective agent in the therapy of primary atypical pneumonia.1 2 3 4 5 6 Most observers have noted a consistent pattern of response, but only one study in which c...

PHARMACOLOGY OF POLYMYXIN

_ _ 250 11 45 275 I 5 ~ 2; I 5 1 50 300 10 50 10 50 350 1 7 I 70 I 3 I 30 Polyrnyxin (B-71) is an antibiotic derived from cultures of Bacillus polymyxa?-* Its activity appears to be restricted to certain gram-negative species of bacteria. Aero~porin~-~ is a similar antibiotic derived from B. aerosporus Greer. It is the purpose of this presentation to describe some of. the pharmacological studies which have been performed on experimental animals. Toxicity. The acute toxicity of polymyxin was determined for albino Swiss mice by single subcutaneous injection and the L.D.W was 250 to 300 mg./kg. A one per cent solution of drug was used and occasional loss of fur and skin irritation a t the injection site was noted with doses above 200 mg./kg. Deaths occurred within 6 hours with scratching of the head, ataxia, convulsions, paralysis, and respiratory arrest. Intraperitoneal injection of 250 to 275 mg./kg. produced convulsions followed by paralysis and death in 5 to 20 minutes. Stansly, Shepherd, and White2 also recorded an L.D.60 of 300 mg./kg. in mice receiving a single subcutaneous dose. TABLE 1 reveals, in the outlined area, the doses of polymyxin in mg./kg.

The chemotherapy of bacterial infections refractory to the common antibiotics

Abstract Since the introduction and widespread use of antibiotics, organisms such as B. proteus, Ps. aeruginosa, coli-aerogenes, Staph. aureus and the enterococcus have emerged as common etiologic agents of refractory infections. With proper precautions and careful observation, more toxic antibiotics such as polymyxin, neomycin and bacitracin may be successfully employed in the treatment of these infections. In addition, erythromycin, carbomycin and furadantin are more recent chemotherapeutic agents which are of some assistance in combating organisms resistant to the older antibiotics. Of course, it must be stressed that the successful treatment of a refractory bacterial infection depends on the early and proper evaluation of the diagnosis and the host factors involved, as well as consideration of the chemotherapeutic and bacterial agents. The answer to eradication of these infections will most frequently be found in sound clinical judgment, application of longestablished principles of general medical and surgical therapy, and in carefully standardized and controlled laboratory sensitivity determinations.