Wilfred F. Jones

Development of Resistance and Cross-Resistance in vitro to Erythromycin, Carbomycin, Spiramycin, Oleandomycin and Streptogramin.∗

Summary and conclusions Four strains of M. aureus were rendered resistant to erythromycin, carbomycin, oleandomycin, spiramycin and streptogramin by repeated subcultures in the presence of increasing concentrations of these antibiotics. Cross-resistance to about the same degree developed to all of these agents except to streptogramin; the latter produced homologous resistance at a slower rate than the others, but this was associated with a corresponding increase in cross-resistance to the other 4 antibiotics.

STAPHYLOCOCCAL INFECTIONS CURRENTLY ENCOUNTERED IN A LARGE MUNICIPAL HOSPITAL: SOME PROBLEMS IN EVALUATING ANTIMICROBIAL THERAPY IN SUCH INFECTIONS

The topic originally designated for this paper, “The Effect of Present Antimicrobials in Staphylococcal Infections” was presumably chosen in order to present in this monograph a clear picture of the status of antimicrobial therapy as applied to the kinds of staphylococcal infections now being encountered. This topic proved to be rather difficult, and neither profitable nor even capable of clear definition, either from our own experience or from data readily available in the literature. Much of the difficulty seemed to stem from the lack of any large body of basic data on the occurrence of various types of staphylococcal infections. Because 1 important objective of this monograph was interpreted to be the definition of some of the major problems involved in staphylococcal infections and an exploration into possible methods of coping with them, it seemed proper to deviate somewhat from the assigned topic in order to present some data and observations arising out of an attempt to evaluate antibiotic therapy. These will concern 2 general topics: first, the magnitude of the problem of staphylococcal infections as encountered at the Boston City Hospital in recent months and, second, some problems involved in evaluating the effectiveness of antibiotics in the management of severe staphylococcal infections.

Sulfamethoxypyridazine: preliminary observations on absorption and excretion of a new, long-acting antibacterial sulfonamide.

Summary and conclusions Concentrations of sulfamethoxypyridazine in blood and urine of 6 normal adult males were determined after a single oral dose of 4 g. The drug was well absorbed, yielding high levels of free drug and only small amounts in acetylated form in the plasma. Little if any of the drug diffuses into the blood cells. The drug is cleared slowly from the plasma, the acetylated form being cleared by the kidney about 11 times as fast as the free drug. Urine concentrations varied up to about 200 mg %, between 35 and 60% being in the conjugated form. Significant levels were still present in the blood and urine 105 hours after the dose. This prolonged action should be of clinical interest and suggests that further exploration of the potentialities of this new sulfonamide drug is warranted.

Plasma Penicillin Levels from Oral Penicillins V and G and Intramuscular Penicillin G.

Summary Oral penicillin V gave higher and better sustained levels of penicillin activity in the plasma than oral buffered potassium penicillin G at each of 3 dosage levels, viz. 200000, 400000 and 1 million units. Intramuscular penicillin G yielded higher and better sustained levels than oral penicillin V in equivalent doses given at levels of 400000 or 1 million units. An i. m. dose of 200000 units of penicillin G produced higher peak levels and these occurred earlier but they were less well sustained than with this amount of oral penicillin V; the total amount of penicillin absorbed from this amount of penicillin was not significantly different for these 2 dosage forms. Persons over 60 years of age attained peak levels later; in general they had higher and better sustained levels of penicillin in the plasma from any given dose than did younger individuals.

Absorption and Excretion of Sulfachloropyridazine

Summary Sulfachloropyridazine is rapidly absorbed and rapidly excreted in the urine, in contrast to sulfamethoxypyridazine which is also absorbed fairly rapidly but is excreted much more slowly.