Studies on Leptospira Icterohaemorrhagiae. Ii. a Critical Study of the Effect of Penicillin on Leptospira Icterohaemorrhagiae in Vitro and in Leptospirosis in Guinea Pigs.

Observations on the therapeutic effect of penicillin in both experimental and clinical leptospirosis have not been in full agreement. Heilman and Herrel (1) reported that of 32 guinea pigs which, 17 to 24 hours after the inoculation with L. icterohaemorrhagiae, received a total of 800 oxford units (hereafter abbreviated as o.u.) of penicillin daily for 7 days, 23 showed a complete suppression of leptospirosis, while 9 gave evidence of relapse 3 to 7 days after treatment. These 9 animals became normal after an additional 3 to 4 days of penicillin treatment. On the other hand, Augustine, Weinman, and MacAllister (2) of this Department found that a course of penicillin, begun after the appearance of jaundice and amounting to 24,000 o.u. daily for about 3 days, failed to alter the fatal course of the infection in 5 guinea pigs. In another group of 4 guinea pigs in which the treatment, consisting of 30,000 o.u. daily for 2 days, was begun 38 hours after inoculation, none was patently ill, although 3 died between the 7th and 11th days after inoculation. At autopsy these 3 animals showed no severe lesions, but leptospirae were found in the liver and kidneys. These authors (Augustine et al.) thought that the death of the 5 animals in the first group might have been due to penicillin toxicity, and that penicillin might have some suppressive, but not curative, effect in leptospirosis. Working with L. icterohaemorrhagiae in mice and L. canicola in hamsters, Larson and Griffiths (3) reported that the administration of penicillin to a total of 400 o.u. per mouse, and 1600 o.u. per hamster, produced a marked beneficial effect when the treatment was begun 48 to 52 hours after inoculation with leptospirae, less favorable results after 66 to 78 hours, and no apparent effect after 88 hours. These results suggest that the success of penicillin therapy in leptospirosis depends on its early administration. Alston and Broom (4) found that the presence of 0.4 to 50 o.u. of penicillin in 3.5 ml. of culture medium stopped the multiplication of both L. icterohaemorrhagiae and L. canicola introduced in a rich inoculum. The addition of as much as 240 o.u. of penicillin per 10 ml. of a well grown culture of L. icterohaemorrhagiae greatly reduced the number of leptospirae after 12 days of incubation as compared with a control culture, although motile leptospirae were present even after 3 weeks of incubation. On this observation, they based their belief that penicillin has some lethal effect on leptospirae. Alston and Broom (4) also confirmed the results of Heilman and Herrel (1) that penicillin treatment, if started 18 hours after inoculation with leptospirae, exerted a favorable therapeutic action in guinea pigs. It is worth mentioning that these authors (4) observed no suppressive effect of penicillin on the development of serum antibodies in the treated animals. Cross (5) infected 2 guinea pigs with L. icterohaemorrhagiae, and treated 1 animal 6 days after inoculation with 3000 o.u. of penicillin daily for 4 days. The treated animal showed no illness, whereas the untreated one died of leptospirosis 10 days after inoculation. Information on the therapeutic effect of penicillin in human leptospirosis has been very scanty, and very few cases have been studied. Hart (6) reported a case of leptospirosis which recovered spontaneously, although the patient discharged leptospirae in the urine. Upon administration of 90,000 o.u. of penicillin daily for 3 days, the number of leptospirae in the urine diminished on the 2nd, and the organisms disappeared on the 3rd day of treatment. Cross (5) noted the recovery of a patient with leptospirosis after a combined treatment of 20 ml. of antiserum on the 9th, 10th, and 11th days of the illness, and 120,000 o.u. of penicillin daily beginning on the 14th day, and