Doxycycline Prophylaxis for Leptospirosis
For high-risk, time-limited exposures to leptospirosis, administer doxycycline 200 mg orally starting one week before exposure, then 200 mg once weekly during the exposure period, with a final 200 mg dose at completion of exposure. 1
Dosing Regimen
- Pre-exposure initiation: Begin doxycycline 200 mg orally one week before anticipated exposure to leptospirosis 1
- During exposure: Continue 200 mg orally once weekly throughout the exposure period 1
- Post-exposure: Administer a final 200 mg dose after the last exposure 1
- Maximum daily dose: Do not exceed 200 mg in any 24-hour period to minimize photosensitivity reactions and gastrointestinal side effects 1
This weekly dosing regimen is specifically designed for high-risk, time-limited exposures such as military personnel training in endemic areas, disaster relief workers in flood zones, or occupational exposures during monsoon seasons.
Evidence Quality and Context
The CDC guideline recommendation 1 is supported by two randomized controlled trials demonstrating efficacy of doxycycline prophylaxis. The highest quality evidence comes from a trial of 940 soldiers showing a risk difference of -4.1% (95% CI -5.9% to -2.3%) for symptomatic, verified leptospirosis, with a number needed-to-treat of 24 2. However, a more recent meta-analysis from 2021 found that weekly 200 mg doxycycline did not show statistically significant benefit versus placebo (OR 0.20; 95% CI 0.02-1.87; p = 0.16), though a single dose at flood water exposure showed potential benefit (OR 0.23; 95% CI 0.07-0.77; p = 0.02) 3.
Despite this conflicting evidence, the CDC maintains its recommendation for the weekly regimen based on the military trial data and the biological plausibility of sustained prophylactic coverage 1, 2.
Pediatric Dosing
- Children <45 kg: Use 2.2 mg/kg every 12 hours if daily dosing is required for treatment (prophylactic pediatric dosing not specifically established) 1
- Children ≥45 kg: Use adult dosing of 100 mg every 12 hours for treatment 1
Note that the weekly prophylactic regimen has primarily been studied in adults, particularly military populations 2.
Special Populations and Contraindications
- Pregnancy: Use doxycycline with extreme caution in pregnant women and only when the risk of leptospirosis clearly outweighs the risks of tetracycline exposure to the fetus 1
- Children <8 years: Tetracyclines carry risk of permanent tooth discoloration and enamel hypoplasia; use only when other options are exhausted 4
Administration Guidelines
- Take doxycycline on a full stomach with at least 200 mL of water 5
- Remain upright for at least 1 hour after taking to prevent esophagitis 5
- Separate dosing by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 5
Common Pitfalls
The most significant compliance issue with doxycycline prophylaxis is drug-induced gastritis, which can be mitigated by taking the medication with food 6. The weekly dosing schedule improves compliance compared to daily regimens while maintaining protective drug levels 2.
Adverse Effects
Adverse effects occurred in 3% of participants receiving doxycycline versus 0.2% receiving placebo (number needed-to-harm 39) 2. The most common adverse effects include:
- Photosensitivity reactions 1, 5
- Gastrointestinal symptoms (nausea, vomiting, diarrhea) 5
- Esophagitis if not taken properly 5
Alternative Exposure Scenarios
For single high-risk exposures (such as flood water contact), some evidence suggests a single 200 mg dose may provide benefit 3, 7, though this is not the primary CDC recommendation for sustained prophylaxis 1. A pilot study in São Paulo showed a protective association (RR = 2.3) for a single 200 mg dose after flood exposure, though this did not reach statistical significance due to small sample size 7.