Methylprednisolone Pulse Therapy for Severe Leptospirosis (Weil's Disease)
For a 59-kg male with severe Weil's disease, administer methylprednisolone 500 mg intravenously once daily for 3 consecutive days, followed by oral prednisone 30 mg daily (0.5 mg/kg/day) with a gradual taper over 3–6 months, and initiate concurrent antibiotic therapy with intravenous penicillin G or ceftriaxone.
Evidence-Based Dosing Protocol
Pulse Methylprednisolone Regimen
Administer 500 mg IV methylprednisolone once daily for 3 consecutive days. This dose provides adequate immunosuppression for severe leptospirosis while minimizing infection risk 1, 2.
The 500 mg dose (approximately 8.5 mg/kg for a 59-kg patient) falls within the standard pulse therapy range of 250–1000 mg daily recommended for severe inflammatory conditions 1, 3.
Infuse each dose over 30–60 minutes to minimize acute adverse effects such as hypertension and arrhythmias 3.
Clinical Evidence Supporting Corticosteroids in Severe Leptospirosis
A descriptive study from Sri Lanka demonstrated that bolus methylprednisolone 500 mg IV for 3 days reduced mortality from 21.8% to 10.7% (p=0.025) in severe leptospirosis 2.
At severity score 4, survival improved from 38% to 100% with methylprednisolone therapy (p<0.001), suggesting maximal benefit when administered before established multiorgan dysfunction 2.
Early administration is critical—patients who died despite methylprednisolone had severity scores of 5–6 or significant comorbidities (alcohol use disorder, cardiac disease), indicating that therapy must begin before irreversible organ failure develops 2.
Case reports document successful use of methylprednisolone boluses in severe leptospirosis complicated by acute kidney injury, pulmonary hemorrhage, myocarditis, and thrombocytopenia 4, 5.
Transition to Oral Prednisone
On day 4 (immediately after completing the 3-day pulse), start oral prednisone at 30 mg daily (0.5 mg/kg/day for a 59-kg patient). This lower maintenance dose achieves comparable efficacy to historic 1 mg/kg regimens while reducing serious adverse events 1, 6.
Use the conversion ratio: 1 mg IV methylprednisolone = 1.25 mg oral prednisone 1, 3.
Maintain 30 mg daily for the first 4 weeks, then begin tapering 6.
Tapering Strategy
Weeks 1–4: Prednisone 30 mg daily (no taper) 6.
Weeks 5–12: Reduce by 5 mg every 2 weeks (30 mg → 25 mg → 20 mg → 15 mg → 10 mg) 1, 3.
Weeks 13–24: Reduce by 2.5 mg every 2–4 weeks (10 mg → 7.5 mg → 5 mg → 2.5 mg) 1, 6.
Target a dose ≤7.5 mg/day by 4–6 months, ideally ≤5 mg/day or complete discontinuation if clinical recovery permits 6.
Mandatory Concurrent Antibiotic Therapy
Initiate intravenous penicillin G (1.5 million units every 6 hours) or ceftriaxone (1–2 g daily) immediately upon suspicion of severe leptospirosis 7.
Antibiotic therapy is most effective when started within the first several days of illness 7.
Continue IV antibiotics for at least 7 days or until clinical improvement, then consider transition to oral doxycycline 100 mg twice daily to complete a 10–14 day course 7.
Essential Monitoring During Pulse Therapy
Monitor blood glucose before each infusion and every 4–6 hours for 24 hours post-dose, with particular attention to the 6–9 hour window when hyperglycemia peaks 1, 3.
Check serum potassium and sodium daily during pulse therapy, especially in patients with renal impairment (common in Weil's disease) 3.
Assess blood pressure before, during, and after each infusion 3.
Monitor renal function (creatinine, urea) daily, as acute kidney injury is a hallmark of severe leptospirosis 4, 2.
Obtain baseline chest radiograph and repeat if respiratory symptoms develop, as pulmonary hemorrhage occurs in up to 70% of severe cases 8.
Supportive Care and Prophylaxis
Provide gastric protection with a proton pump inhibitor (e.g., omeprazole 20 mg daily) throughout corticosteroid therapy 1.
Administer calcium 1000–1500 mg/day and vitamin D 800–1000 IU/day to prevent corticosteroid-induced osteoporosis 1.
Consider antifungal prophylaxis (e.g., fluconazole 100 mg daily) during high-dose steroid therapy, particularly if prolonged treatment is anticipated 1, 6.
Implement venous thromboembolism prophylaxis with subcutaneous heparin or low-molecular-weight heparin, as high-dose corticosteroids increase thrombotic risk 3.
Critical Pitfalls to Avoid
Do not taper rapidly or discontinue abruptly after the pulse course—a minimum slow-weaning period of 6–14 days is essential to prevent disease rebound 3.
Do not delay methylprednisolone administration—efficacy is highest when given early (severity score ≤4) before multiorgan dysfunction becomes irreversible 2.
Do not omit antibiotic therapy—corticosteroids address the immune-mediated component but do not eradicate the spirochete 7.
Do not continue high-dose prednisone (>30 mg/day) beyond 4 weeks without initiating an aggressive taper, as prolonged high doses markedly increase infection risk 6.
Maintain high suspicion for opportunistic infections—glucocorticoid therapy attenuates the febrile response, masking occult infections 3.
When Methylprednisolone May Not Be Effective
Patients with established multiorgan dysfunction (severity score 5–6) or significant comorbidities (alcohol use disorder, cardiac disease, hypertension) have poor outcomes despite corticosteroid therapy 2.
In such cases, consider plasma exchange as a rescue therapy—case reports document dramatic improvement with two cycles of therapeutic plasma exchange in severe leptospirosis unresponsive to antibiotics and methylprednisolone 4.
Practical Administration Summary for a 59-kg Male
- Days 1–3: Methylprednisolone 500 mg IV once daily (infuse over 30–60 minutes) + IV penicillin G or ceftriaxone.
- Day 4 onward: Prednisone 30 mg PO once daily + continue antibiotics.
- Weeks 1–4: Prednisone 30 mg daily (no taper).
- Weeks 5–24: Gradual taper as outlined above, targeting ≤7.5 mg/day by month 6.
- Throughout: Monitor glucose, electrolytes, renal function, and blood pressure; provide gastric protection, calcium/vitamin D, and VTE prophylaxis.