Treatment of Moderate Leptospirosis
For moderate leptospirosis, initiate treatment with oral doxycycline 100 mg twice daily for 7 days, or alternatively use intravenous penicillin G or ceftriaxone if oral therapy is not feasible or the patient has contraindications to tetracyclines. 1, 2
First-Line Treatment: Doxycycline
Oral doxycycline 100 mg twice daily for 7 days is the preferred first-line agent for moderate leptospirosis based on proven efficacy in reducing illness duration by 2 days and favorably affecting fever, malaise, headache, and myalgias. 3
Doxycycline effectively prevents leptospiruria (5% vs 40% with placebo) and has demonstrated no adverse effects in clinical trials. 3
Treatment should be initiated as soon as possible without waiting for laboratory confirmation, as early antibiotic administration (within the first 4 days of symptoms) is critical for optimal outcomes. 1
Alternative Treatment Options
Penicillin-Based Regimens
Intravenous penicillin G remains an acceptable alternative, particularly when oral therapy cannot be administered or in settings where doxycycline is contraindicated (pregnancy, children under 8 years). 1, 2
Penicillin has been considered the traditional treatment of choice for decades, though recent evidence suggests no clear superiority over other agents. 2, 4
Cephalosporins
Ceftriaxone or cefotaxime are reasonable alternatives and may be preferred agents in some clinical scenarios, particularly when broader gram-negative coverage is desired. 2
These third-generation cephalosporins have demonstrated acceptable efficacy in recent trials and offer convenient once or twice-daily dosing. 2
Azithromycin
- Azithromycin appears promising for less severe disease, though it should be reserved as a secondary alternative. 2
Treatment Duration and Monitoring
The standard antibiotic course is 7 days, but may need extension to 10 days in patients with slow clinical response. 1
Clinical improvement should be evident within 4-7 days (the septicemic phase duration), with resolution of high fever (≥39°C), diffuse myalgias (especially calf pain), headache, and conjunctival suffusion. 1
Do not discontinue antibiotics prematurely even with clinical improvement; complete the full course to prevent relapse. 1
Important Clinical Caveats
Diagnostic Considerations
Moderate leptospirosis may be misdiagnosed as viral hepatitis when patients present with fever and jaundice—maintain high clinical suspicion in endemic areas or with appropriate exposure history. 1
Suggestive clinical findings include conjunctival suffusion (a highly suggestive sign), fever with chills, diffuse myalgias, headache, and jaundice. 1
Laboratory findings supporting the diagnosis include proteinuria, hematuria, leukocytosis with polymorphonuclear predominance, elevated bilirubin with mild transaminase elevation, and altered renal function. 1
Treatment Initiation
Never delay antibiotic therapy while awaiting serological confirmation, as treatment initiated after 4 days of symptoms may be less effective and increases mortality risk. 1
IgM titers of 1:80 to 1:160 are consistent with early infection, while titers >1:320 are highly suggestive; however, treatment should begin on clinical suspicion alone. 1
Contraindications and Special Populations
Avoid doxycycline in pregnant women and children under 8 years of age due to concerns about tooth discoloration and bone development—use penicillin or cephalosporins instead. 2
Fluoroquinolones may be considered as alternatives, though adequate human trial data are lacking to fully support their routine use. 2
Evidence Quality Note
The evidence base for leptospirosis treatment remains limited, with very low-certainty evidence regarding mortality benefits and optimal antibiotic selection. 4, 5 However, the consistent clinical practice of early antibiotic administration, supported by biological plausibility and observational data showing reduced illness duration, justifies empiric treatment in suspected cases. 1, 3 The choice between doxycycline and penicillin-based regimens should be guided by route of administration feasibility, patient-specific contraindications, and local antimicrobial availability. 2