What is the recommended treatment and prophylaxis for leptospirosis in adults, including first‑line oral doxycycline (or amoxicillin if contraindicated), intravenous penicillin G or ceftriaxone for severe disease, regimens for pregnant women and children, and alternative antibiotics for patients with drug allergies?

Treatment and Prophylaxis of Leptospirosis in Adults

First-Line Treatment for Mild-to-Moderate Leptospirosis

For outpatient management of mild leptospirosis, oral doxycycline 100 mg twice daily for 7 days is the treatment of choice, reducing illness duration by approximately 2 days and favorably affecting fever, malaise, headache, and myalgias. 1

• Doxycycline prevents leptospiruria and has demonstrated efficacy in randomized controlled trials for non-severe disease 1
• Alternative oral agents include amoxicillin (dosing not specified in guidelines but used for non-severe forms) and azithromycin, both of which are acceptable for mild cases 2, 3
• Oral beta-lactams (amoxicillin) are appropriate when doxycycline is contraindicated 2

Severe Leptospirosis Requiring Hospitalization

For severe leptospirosis with icterohaemorrhagic manifestations (Weil's disease), respiratory involvement, or multi-organ dysfunction, intravenous ceftriaxone or cefotaxime are the preferred agents, with penicillin G as an alternative. 2, 3

• Ceftriaxone and cefotaxime have demonstrated acceptable efficacy in recent trials and may be preferred over penicillin for severe disease 3
• Injectable beta-lactams (mainly cephalosporins) are recommended for severe forms with significant mortality risk 2
• Penicillin has long been considered standard treatment but shows no mortality benefit over placebo in meta-analysis (OR 1.65; 95% CI 0.76-3.57; p=0.21), and does not reduce time to defervescence, hospital stay, or prevent oliguria/anuria 4
• No differences exist between penicillin, cephalosporins, and doxycycline in comparative trials 4

Treatment in Pregnant Women

Pregnant women with leptospirosis should receive amoxicillin or a cephalosporin (ceftriaxone or cefotaxime), avoiding doxycycline due to pregnancy category D classification and fetal risk. 2, 3

• Doxycycline is contraindicated in pregnancy because of potential tooth discoloration and bone growth effects in the fetus 5
• Amoxicillin provides safe and effective coverage during pregnancy 2
• For severe disease in pregnancy, intravenous ceftriaxone or cefotaxime should be used 2, 3

Pediatric Treatment Regimens

Children with leptospirosis should receive amoxicillin or azithromycin for mild disease, with ceftriaxone or cefotaxime reserved for severe cases; doxycycline must be avoided in children younger than 8 years. 2, 3

• Doxycycline causes permanent tooth discoloration and impaired bone growth in children under 8 years 5
• Amoxicillin is the preferred oral agent for pediatric mild-to-moderate leptospirosis 2
• Azithromycin appears promising for less severe pediatric disease 3

Alternative Antibiotics for Drug Allergies

For patients with penicillin or cephalosporin allergies, doxycycline 100 mg twice daily for 7 days is the primary alternative; azithromycin may be considered for mild disease, though fluoroquinolones lack adequate human trial data. 3, 1

• Doxycycline is a reasonable alternative to beta-lactams but should not be used in pregnant women or children under 8 years 3, 1
• Azithromycin is acceptable for less severe disease in allergic patients 3
• Fluoroquinolones show promise but lack sufficient human trials to fully support their use 3
• Leptospira are highly susceptible to a wide variety of antimicrobials in vitro, but optimal clinical choices remain penicillin, doxycycline, cefotaxime, ceftriaxone, and azithromycin 3

Chemoprophylaxis Considerations

Weekly doxycycline 200 mg does not prevent symptomatic leptospirosis (OR 0.20; 95% CI 0.02-1.87; p=0.16), but a single dose at flood water exposure may have benefit (OR 0.23; 95% CI 0.07-0.77; p=0.02); routine prophylaxis is not recommended. 4

• Prophylactic antibiotics have not been confirmed effective in clinical trials 6
• Exposure control through behavioral modifications and personal protective measures are the major preventative strategies 6
• Neither doxycycline, penicillin, nor azithromycin have shown statistically significant differences in preventing symptomatic infection 4

Critical Clinical Recognition Points

Leptospirosis should be suspected in patients with acute fever, myalgias, and conjunctival involvement following freshwater exposure or travel to tropical areas during rainy season, particularly when thrombocytopenia, cholestasis, rhabdomyolysis, or markedly elevated CRP are present. 2

• Initial symptoms are non-specific and may resemble flu-like or dengue-like syndrome 2
• Key clinical clues include muscle pain, cough, conjunctival involvement, and jaundice 2
• Biological markers include thrombocytopenia, cholestasis, rhabdomyolysis, and frank CRP elevation 2
• Early antibiotic therapy is essential before progression to severe icterohaemorrhagic (Weil's disease) or respiratory forms with significant mortality 2

Timing and Duration of Antibiotic Therapy

Antibiotics are most effective when administered during the early phase of infection; late disease with organ dysfunction requires supportive care, and antibiotic benefit during late disease is doubtful. 6

• Treatment duration is typically 7 days for both oral and intravenous regimens 1
• Early treatment prevents progression to severe disease 2
• Supportive care becomes paramount once multi-organ dysfunction develops 6

Common Pitfalls to Avoid

• Do not delay antibiotic therapy while awaiting confirmatory serology, as early treatment is critical 2
• Do not use doxycycline in pregnant women or children under 8 years; substitute amoxicillin or cephalosporins 5, 2, 3
• Do not rely on antibiotics alone for late-stage disease with organ failure; prioritize intensive supportive care 6
• Do not prescribe routine chemoprophylaxis with weekly doxycycline, as efficacy is unproven 4