Penicillin at the late stage of leptospirosis: a randomized controlled trial

Abstract

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.

Clinical presentation of leptospirosis: a retrospective study of 201 patients in a metropolitan city of Brazil

“…44,45 Some reports, however, suggest that penicillin therapy did not provide better clinical outcome in patients with leptospirosis and acute kidney injury, mainly after at least four days of symptomatic disease. 12,46 In the present study, Penicillin G was administered in 131 (65%) of the patients. The majority of these patients, in the last decade, promptly received penicillin as soon as they were admitted in the hospital.…”

“…Costa et al 11 found 14.2% of death among severe leptospirosis cases. Costa et al 12 reported 9% of nonsurvivors among 253 patients. In the present study, death occurred in 15.4% of cases, and the majority of them were due to pulmonary bleeding.…”

“…11,33 Death is also attributed to acute kidney injury in a significant number of cases. 11,12 Jauréguiberry et al 19 reported no deaths among 34 patients. Costa et al 11 found 14.2% of death among severe leptospirosis cases.…”

“…[7][8][9] Pulmonary involvement and acute kidney injury are the main causes of death in leptospirosis. [10][11][12] Renal involvement in leptospirosis is characterized by acute interstitial nephritis that may be associated with acute tubular necrosis. Predisposition to hypokalemia is another particular feature of renal involvement in this disease.…”

Insuficiência renal aguda associada à leptospirose

“…Consensus about the use of antibiotics for treating leptospirosis still lacks. [44][45][46][47][48] A recent meta-analysis has not found sufficient evidence to indicate the use of antibiotics in leptospirosis; however, it concluded that antibiotic therapy in that disease seemed to have more benefits than drawbacks. 44 A recent experimental study has assessed the expression of the NHE3 of the proximal tubule and of the NKCC2 in hamsters with leptospirosis treated or not with ampicillin.…”