MASSIVE DOSES OF PENICILLIN IN THE TREATMENT OF SUBACUTE BACTERIAL ENDOCARDITIS

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Abstract
A patient with Streptococcus viridans, subacute bacterial endocarditis failed to respond to 3,200,000 U of penicillin given between Nov. 1943 and Aug. 1944. The organism''s resistance to penicillin increased from .5 to 1.4 Oxford units from Nov. 1944 to March 1945 when 39,880,000 additional units were given without benefit. In an attempt to obtain blood levels several times the in vitro lethal requirements, 3,000,000 units of penicillin were given by continuous intraven. drip for 17 days, but the blood level did not exceed 1.0 units. Renal blockade was then started. As a control 1,500,000 units of penicillin were given by continuous intravenous drip for 3 days securing a blood level of .4 unit. Upon the addition of diodrast for the purpose of renal blockade, the blood level rapidly increased and in 70 hrs. was 3.2 units or 8 times the control level. Because of unexplained fever, diodrast was stopped. The penicillin blood level then dropped to .5 unit. p-Aminohippurate was then given for 8 days to produce renal blockade. Penicillin blood level increased to 2.0 units which was 4 times the control level. Following the high penicillin blood levels all evidence of active bacterial infection disappeared. During the following 6 mos. observation period the patient appeared well. In the treatment of these cases, first establish the organism''s sensitivity to penicillin, give adequate dosage to secure, blood levels several times the in vitro requirement, employing renal blockade, if necessary. Increasing resistance to penicillin is avoided and a small effective dose suffices with better opportunity for recovery.

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