What is the recommended treatment approach for children diagnosed with leptospirosis, based on Clinical Practice Guidelines (CPG)?

Treatment of Leptospirosis in Children

Children with suspected leptospirosis should be treated with antibiotics upon clinical suspicion, using penicillin or tetracyclines during the bacteraemic phase, despite limited evidence of benefit in severe disease. 1

Initial Treatment Approach

Treatment should be initiated based on clinical suspicion alone, given the non-specific nature of initial laboratory investigations. 1 The decision to treat should not await serological confirmation, as the earliest positive results appear 6-10 days after symptom onset. 1

Mild Disease (Outpatient)

• Early mild disease is generally self-limiting, but penicillin and tetracycline antibiotics are thought to be effective during the bacteraemic phase (first 4-7 days of illness). 1
• Crystalline penicillin is the drug of choice for treatment of leptospirosis in children. 2
• Macrolides (such as azithromycin or erythromycin) are also sensitive antimicrobial options. 3

Severe Disease (Inpatient/Weil's Disease)

• Patients presenting with jaundice, hepatorenal syndrome, or hemorrhagic manifestations require parenteral penicillin therapy despite limited evidence of mortality benefit. 1
• Most infectious disease specialists continue to recommend antibiotics for severe disease, while accepting that severe disease is probably immunologically mediated. 1
• Antimicrobial therapy has been shown to reduce the extent of renal failure and thrombocytopenia in children with late, severe leptospirosis. 4
• Patients may require renal or liver support despite antibiotic therapy. 1

Evidence Limitations and Clinical Reality

A systematic review of antibiotic effectiveness in established leptospirosis showed no benefit for antibiotic treatment based on three trials. 1 However, this evidence has important limitations:

• The mortality analysis only included two trials (403 patients total), showing no statistically significant difference: 8.0% mortality with antibiotics versus 5.4% with placebo (OR 1.56,95% CI 0.70 to 3.46). 5
• Antibiotics may decrease the duration of clinical illness by 2-4 days in survivors, though this result was not statistically significant. 5
• The benefit of antibiotic therapy remains unclear, particularly for severe disease, and further clinical research is needed. 5

Despite this equivocal evidence, pending further evidence, most infectious disease specialists continue to recommend antibiotics because:

1. Early treatment during the bacteraemic phase (first 5 days) is theoretically most effective 1, 3
2. Antibiotics benefit children with late, severe leptospirosis by reducing renal failure and thrombocytopenia 4
3. The disease can progress to severe multiorgan failure with mortality exceeding 10% in some settings 6, 2

Antibiotic Selection

When choosing between antibiotics, selection of penicillin, doxycycline, or cephalosporin does not appear to impact mortality or duration of fever. 5 Specific options include:

• Penicillin (parenteral): Standard choice for hospitalized children 1, 2
• Cephalosporins: No mortality difference compared to penicillin (3.4% vs 5.2%, OR 0.65,95% CI 0.23 to 1.87) 5
• Doxycycline: Comparable to penicillin for mortality (2.5% vs 4.5%, OR 0.54,95% CI 0.10 to 3.02) 5
• Macrolides: Alternative option, though may require long-term therapy with large doses 3

Streptomycin provides short-term treatment that exterminates leptospires, while penicillin, cephalosporins, tetracyclines, and macrolides may require long-term therapy with large doses from the early stage until antibody appearance. 3

Critical Timing Considerations

Blood cultures should be obtained within the first 5 days of symptom onset, before antibiotics are started, and kept at room temperature prior to dispatch to the reference laboratory. 1 Urine is not a suitable sample for isolation of leptospira. 1

Common Pitfalls

• Delaying treatment while awaiting serological confirmation: Treat on clinical suspicion, as serology may not be positive until 6-10 days after symptom onset 1
• Assuming antibiotics will prevent severe complications: Severe disease is probably immunologically mediated, and patients can become very unwell despite therapy 1
• Failing to provide supportive care: Renal or liver support may be required regardless of antibiotic therapy 1
• Not considering leptospirosis in the differential diagnosis of severe febrile illness in children: Severe disease occurs in children and should be considered, particularly with appropriate epidemiologic exposure 4