Laboratory studies on methicillin. with special reference to patients treated for staphylococcal infections.

Nearly all the pathogenic staphylococci tested in this study were susceptible to 3.1 mug. per ml. of methicillin or within a 2-fold range of this concentration. Resistant strains were not encountered and did not develop during treatment. Staphylococci were not regularly eradicated during methicillin therapy and the time required to eradicate some of them varied with the lesion. Staphylococci isolated from the same patient during or soon after methicillin therapy were usually of the same phage pattern and had the same anttbiogram. but staphylococci differing in these respects were isolated in some cases either from different lesions or at longer intervals after the end of methicillin therapy. Other species of bacteria frequently repopulated the staphylococcal lesions during and soon after methicillin treatment; most frequent were the various Gram-negative bacilli, particularly Ps. seruginosa and organisms of the Klebsiella-Aerobacter group. The latter were especially prominent in the sputum of patients with lower respiratory tract infections, and caused serious superinfections in soms of them. Mehticillin is rapidly and well absorbed after intramuscular injection but. although several times the concentrations required to inhibit the staphylococci were usually achieved, inhibitory concentrations for these organisms were usually maintained for less than 4 hr. after a single dose of 1.0 g. in normal adults. About two-thirds or more of the intramuscular dose was recovered in the urine, and about four-fifths of the total amount excreted was recovered within 4 hr. Probenecid enhanced and prolonged the blood levels but did not increase the total amount excreted in the urine. Patients with impaired renal function when not given probenecid sustained high levels of methicillin better and longer than did patients or normal individuals with unimpaired renal function even when probenecid was used. Very low, and usually insignificant concentrations are achieved in the serum after oral administration of methicillin, but although only a small proportion of the dose is recovered in the urine, the urinary concentrations achieved are considerable.