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Serum concentrations of penicillin were measured in children with rheumatic fever. The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable. The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.

A 3-year old girl had localized lipoatrophy after an intragluteal injection of benzathine penicillin G. No associated abnormalities were found.

Because of published data suggesting the inadequacy of once-every-4-weeks intramuscular injections of benzathine penicillin G for secondary rheumatic fever prevention, serum penicillin levels were determined at 1, 3, 10, 21, and 28 days after administration of 1,200,000 units of this repository penicillin. A total of 193 samples were studied. Mean serum penicillin levels remained greater than or equal to 0.02 micrograms/ml for 21 days, but by 28 days only 44% of the serum samples had detectable levels of penicillin and only 36% had levels greater than or equal to 0.02 micrograms/ml. Patients weighing more than 45 kg had significantly lower serum penicillin levels than did those who weighed less. There were similar correlations with body surface area and with age. These data indicate that a significant percentage of patients receiving benzathine penicillin G prophylaxis for prevention of recurrent attacks of rheumatic fever are not protected during the fourth week. More frequent administration of benzathine penicillin G should be considered in instances of high risk of recurrence of rheumatic fever.

In studies involving 531 children with streptococcal skin lesions, with or without penicillin-resistant staphylococci also present, intramuscular benzathine penicillin G provided the most effective treatment. Streptococci, when present in the respiratory tract, were also eradicated. Neither topical bacitracin nor a single injection of penicillin in oil gave satisfactory results. Six of 54 siblings of children with nephritis, all of whom were infected with nephritogenic streptococci, developed acute glomerulonephritis within one week after initiation of therapy, suggesting that treatment came too late to prevent this complication. It is uncertain how often benzathine penicillin G therapy prevented nephritis in other patients. Such therapy does provide a means for prompt eradication of streptococci, effective clearing of clinical infection, and limiting the spread of organisms to others. Significant untoward reactions to penicillin were not observed.

Summary Five types of penicillin, for intramuscularinjection were evaluated for intensity of local reaction: (1) benzathine penicillin G suspension, 600,000 units in 1 c.c.; (2) benzathine penicillin G suspension, 600,000 units, with 5 mg. of cortisone in 1 c.c.; (3) benzathine penicillin G suspension, 600,000 units, with 2 mg. of 9-alphafluoro-hydrocortisone alcohol in 1 c.c.; (4) benzathine penicillin G, 300,000, units plus aqueous procaine penicillin, 300,000 units in 1 c.c.; and (5) aqueous procaine penicillin, 600,000 units in 1 c.c. A total of 244 children were evaluated at twenty-four hours after injection and the following percentages of local reaction were recorded for the five penicillin suspensions listed: (1) 44 per cent, (2) 77 per cent, (3) 50 per cent, (4) 12 per cent and (5) 5 per cent. The addition of steroids to benzathine penicillin G did not alter the high rate of local muscle soreness in this group of children. A mixture of 300,000 units of benzathine penicillin G and 300,000 units of aqueous procaine penicillin gave the lowest local reaction rate for both intensity and duration when compared with other repository preparations containing benzathine penicillin G. Although many of the children complained of pain for twelve hours following the injection of such a mixture, when evaluated at twenty-four hours most of the symptoms had subsided.

Summary 1. One thousand, one hundred three intramuscular injections of 1,200,000 units of benzathine penicillin to fortysix patients with recent rheumatic fever were given for an average of twenty-four months without a single recurrence. Two patients with old failure and enlarged hearts continue to smoulder but are still living. 2. A similar group of forty-six patients on sulfonamides showed a recurrence rate of 4.3 per cent in an average period of 38.6 months. One child in this group died from what we believe to have been an intercurrent infection and three others had vague aches but no clear-cut recurrences. 3. When added to the previous studies, the evidence is increasingly strong for large-scale use of benzathine penicillin G intramuscularly for prevention of rheumatic recurrences.

Erythromycin, phenoxymethyl penicillin, and intramuscularly administered benzathine penicillin G were compared in the treatment of 708 patients with bacteriologically proved streptococcal skin infection. All forms of therapy were highly effective in eradicating skin streptococci. However, benzathine penicillin G proved more effective than the oral preparations in preventing early recurrences or new cases of impetigo and in reducing streptococcal respiratory carrier rates. Acute nephritis developed in 5 of 91 children known to be infected with nephritogenic streptococci.

We evaluated the efficacy of rifampin in eradicating chronic pharyngeal carriage of group A streptococci. Carriers were defined as healthy children whose throat cultures showed persistence of group A streptococci 3 weeks after receiving benzathine penicillin G intramuscularly. Subsequent M and T typing of group A streptococcal isolates and limited serologic studies confirmed that enrolled patients were carriers. Thirty-eight carriers (37 completed the study) were randomly assigned to three groups: group 1 (13 patients) received no treatment; group 2 (10) received benzathine penicillin intramuscularly; group 3 (14) received benzathine penicillin intramuscularly plus rifampin orally (10 mg/kg twice a day for eight doses). Throat cultures were obtained every 3 weeks for at least 9 weeks. Group 2 and 3 patients who still had positive cultures 3 weeks after treatment were crossed to the opposite group. Cultures became negative in 93% (13 of 14) of patients in group 3, compared with 23% in group 1 and 30% in group 2 (P less than 0.001 and P less than 0.01, respectively). Including patients crossed over, the penicillin plus rifampin regimen was effective in 17 (89%) of 19 treatment courses and was significantly superior to no therapy or to penicillin alone (P less than 0.0005 and P less than 0.005, respectively). We conclude that rifampin plus benzathine penicillin intramuscularly is an effective regimen for those selected patients in whom eradication of group A streptococcal carriage is judged to be desirable.

T n E I N C ! D E N C E of congenital syphili s has increased in recent years, 1 prompting renewed interest in the treatment of this entity. One recommended form of therapy is benzathine penicillin G, 100,000 units per kilogram of body weight given in a single intramuscular injection. ~ Few data exist in respect to the achievable levels of penicillin within the cerebrospinal fluid space in neonates following administration of BPG? A study was therefore undertaken to measure penicillin levels in the CSF at varying time intervals after the administration of BPG.