Laboratory studies on oxacillin. I. In vitro activity against staphylococci and some other bacterial pathogens II. Absorption and urinary excretion in normal young men.

Tests of the new susceptibility of some common bacterial pathogens to oxacillin indicate that this new, semisynthetic penicillin is active against both penicillinase-producing staphylococci and those that do not produce penicillinase, being appreciably more active than methicillin against the former and less active than penicillin G against the latter. It is also highly active against other Gram-positive cocci, except enterococci. Oxacillin appears to be bound to serum protein to a greater extent than penicillin G or methicillin. Studies of the absorption and excretion in normal young men indicated that single oral doses of 1.0 g. were well absorbed and yielded useful levels of activity in the serum for at least 2 hr. after a dose given on a fasting stomach or 4 hr. after breakfast. When given immediately after breakfast, absorption was delayed, peak levels were lower and achieved later, but significant activity persisted somewhat longer in the serum. About one-fifth of the administered oral doses was accounted for in the urine when oxacillin was given on a fasting stomach or 4 hr. after breakfast, and a somewhat smaller proportion (about one-seventh) was recovered when the oral dose was given promptly after the meal. A single dose of 0.5 g. of oxacillin, given i.m. to normal young men, provided levels of activity in the serum equivalent to those achieved by twice that amount given orally on a fasting stomach and the same was true of the amount of active oxacillin recovered in the urine after these doses. A dose of 0.5 g. of oxacillin given i.m. during the oral administration of probenecid resulted in levels of antibacterial activity in the serum approximating those obtained with an i.m. dose of 1.0 g. without probenecid. However, an appreciably smaller proportion of the i.m. administered oxacillin was recovered in the urine when it was given during oral probenecid. These properties of oxacillin suggest that it should prove useful in oral treatment of staphylococcal infection and that oral probenecid may be a useful adjunct to intramuscular therapy in serious deep-seated infections.