Treatment of gonococcal urethritis with single injections of 2-4 mega units of aqueous procaine penicillin.

Owing to the emergence of more resistant strains of gonococci the position of penicillin is seriously threatened; streptomycin, with a failure rate exceeding 30 per cent. in London (Spitzer and Willcox, 1968) has ceased to be a useful drug in this condition; and the writing is already on the wall for the tetracyclines and some other antibiotics. Even after penicillin had been in widespread use for 6 to 7 years the minimal recommended dose for gonorrhoea was only 100,000 units (Hogan, Johnwick, Hanchett, Harb, and Adar, 1950), and at St. Mary's Hospital at that time over 90 per cent. of cases were cured with a single injection of 150,000 units procaine penicillin in oil with aluminium monostearate (PAM). Indeed, it was largely the observation that 300,000 units of PAM might cure four out of five cases of early syphilis (Wright, Nicholson, and Arnold, 1950) which led to the first increases in dosage for gonorrhoea so as to be more sure of aborting the more serious disease if it were also present. In time, in spite of increased dosage (Streitmann and Krassnigg, 1957; Knight, 1958; Willcox, 1958), failure rates to penicillin began to mount, particularly in Europe, although by no means simultaneously in all areas (Schmidt, 1961). If laboratory evidence of increased numbers of less sensitive strains of gonococci was at first inconclusive (Hawks and Greey 1948; Del Love and Finland, 1955), this too in time was provided from the USA (Thayer, Field, Magnuson, and Garson, 1957) and from Denmark (Reyn, Korner and Weis Bentzon, 1958) and elsewhere. The clear demonstrations from London (Curtis and Wilkinson, 1958; Cradock-Watson, Shooter, and Nicol, 1958) of the direct association of the strains of gonococci less sensitive to penicillin with cases showing clinical failure to the antibiotic have since been amply confirmed by many other workers (see for example Juhlin and Krook, 1965). To-day strains of gonococci requiring 2 units of penicillin per ml. or more for inhibition are being encountered in Europe (Aepinus, 1965; Hejzlar and Vymola, 1965) and incidences of less sensitive strains as high as 30 to 50 per cent. have been reported from Denmark (Reyn, 1963), Finland (Rantasalo, 1962), Greenland (Lomholt and Berg, 1966), Norway (Gjessing, 1963), and Yugoslavia (Grin and Karlovac, 1965), while figures of from 12 to 30 per cent. have been noted in other areas (see Willcox, 1967). However, lack of standardization of methods of sensitivity measurement and of definition of a "less sensitive" strain have made exact comparison difficult. Nevertheless strains less sensitive to penicillin are usually completely resistant to streptomycin and vice versa (Reyn, 1963; Thayer, Samuels, Martin, and Lucas, 1965; Grin and Karlovac, 1965). With mounting failure rates in some areasparticularly in the Far East (Bodenbender, 1960; Smedley, 1960; Sabath and Kivlahan, 1961)-the first adjustment to the situation was to abandon the use of repository penicillins, especially benzathine penicillin, and to give larger doses of shorter-acting penicillins; a regime consisting of single doses of 1 2 mega units aqueous procaine penicillin is still widely used for male cases in this country. By increasing the dosage not only have failure rates been at least temporarily reduced but the incidence of less sensitive strains has been noted to decline in the clinics concerned (Letchner and Nicol, 1961; Morton, 1963; Morton and Higson, 1966). Nevertheless, even with 1 -2 mega units procaine penicillin, failure rates of 8 to 12 per cent. have been reported (Tiedemann, Hackney, Simpson, and Price, 1962; Willcox, 1964) and further dosage increases to 1 -8-2-4 mega units have been recommended by the International Union against the Venereal Diseases (Brit. J. vener. Dis., 1961) and by