PAM plus probenecid and procaine penicillin plus probenecid in gonorrhoea.

In 1944, when gonorrhoea responded to 100,000 units of crystalline penicillin given in divided doses, Miller, Scott, and Moeller (1944) observed that the gonococcus was cleared from the urethral secretions within 1 to 6 hours. 23 years later, Holmes, Johnson, and Floyd (1967), in the Far East, noted that only one case, a therapeutic failure, out of twenty treated with 2-4 m.u. procaine penicillin with probenecid, continued to yield gonococci from the urethra after 9 hours. Supporting this evidence of rapid bacterial eradication are the results of treatment with sodium penicillin and probenecid, producing a very high but relatively short-lived penicillinaemia (Jensen, Kvorning, and Norredam, 1963; Olsen and Lomholt, 1969). The straightforward 'one-shot' treatment has still much to commend it; it deals with the problem of those who default from a second injection and prevents the hoarder of tablets from masking his next infection. In keeping with this tradition, Cobbold, Morrison, Spitzer, and Willcox (1970) prescribed 1 2 m.u. procaine penicillin alone or with 1 g. probenecid; the addition of the latter reduced the recurrence rate from 13 to 7-2 per cent. The renal-blocking agent probenecid has had a good record (Boger and Strickland, 1955). Some nausea and vomiting may occur, anaphylaxis is a rare complication, and uric acid crystalluria with deleterious effects on the kidney is a very remote possibility. When the emergence of relatively resistant gonococci first presented a significant problem, Curtis and Wilkinson (1958) suggested that a preparation of penicillin should be devised to yield a blood concentration of not less than 1 unit penicillin per ml. persisting for 24 hours. This principle implies a high initial concentration of penicillin, probably the most important requirement to attack the more resistant organisms (Krook and Juhlin, 1965), and a rapid 'tailing off'. To match this proposition, Hilton (1959) used 1-2 m.u. procaine penicillin in arachis oil with