There is evidence that an early start of
penicillin reduces the case-fatality rate of
leptospirosis and that
chemoprophylaxis is efficacious in persons exposed to the sources of leptospira. The existent data, however, are inconsistent regarding the benefit of introducing
penicillin at a late stage of
leptospirosis. The present study was developed to assess whether the introduction of
penicillin after more than four days of symptoms reduces the in-hospital case-fatality rate of
leptospirosis. A total of 253 patients aged 15 to 76 years with advanced
leptospirosis, i.e., more than four days of symptoms, admitted to an
infectious disease hospital located in Salvador, Brazil, were selected for the study. The patients were randomized to one of two treatment groups: with intravenous
penicillin, 6 million units day (one million unit every four hours) for seven days (n = 125) and without (n = 128)
penicillin. The main outcome was death during hospitalization. The case-fatality rate was approximately twice as high in the group treated with
penicillin (12%; 15/125) than in the comparison group (6.3%; 8/128). This difference pointed in the opposite direction of the study hypothesis, but was not statistically significant (p = 0.112). Length of
hospital stay was similar between the treatment groups. According to the results of the present randomized clinical trial initiation of
penicillin in patients with severe forms of
leptospirosis after at least four days of symptomatic
leptospirosis is not beneficial. Therefore, more attention should be directed to prevention and earlier initiation of the treatment of
leptospirosis.