An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis

Clin Infect Dis. 2004 Nov 15;39(10):1417-24. doi: 10.1086/425001. Epub 2004 Oct 26.


Background: Leptospirosis is an important cause of fever in the rural tropics. Since 1996, there has been a marked increase in the incidence of leptospirosis in northeastern Thailand. Although leptospirosis generally is susceptible to antibiotics, there is no consensus regarding the optimal treatment for severe leptospirosis.

Methods: An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium (hereafter known as "penicillin G"), and doxycycline for the treatment of suspected severe leptospirosis was conducted. The study involved 540 patients admitted to 4 hospitals in northeastern Thailand.

Results: A total of 264 patients (48.9%) had leptospirosis confirmed by serologic testing or culture. The overall mortality rate was 5%. There were no significant differences between the antibiotics with regard to associated mortality, defervescence, or time to resolution of abnormal findings of laboratory tests either among all study participants or among the subgroup of patients with confirmed leptospirosis. A total of 132 patients had rickettsial infection diagnosed, and, for these patients, treatment with doxycycline was superior to treatment with penicillin G.

Conclusions: Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Cefotaxime / therapeutic use*
  • Doxycycline / therapeutic use*
  • Female
  • Humans
  • Leptospirosis / drug therapy*
  • Male
  • Middle Aged
  • Penicillins / therapeutic use*
  • Severity of Illness Index


  • Anti-Bacterial Agents
  • Penicillins
  • Doxycycline
  • Cefotaxime