Treating and Preventing Tularemia: CDC's 2025 Recommendations

Tularemia — also called rabbit fever or deer fly fever — is a rare but potentially serious disease caused by the bacterium Francisella tularensis. About 200–300 cases are reported in the United States each year, from every state except Hawaii. Because so few bacteria can cause infection (as few as 10 organisms), it is also classed as a potential bioterrorism agent. In 2025 CDC issued new recommendations for treating and preventing it, updating guidelines last published in 2001. They are aimed at U.S. clinicians, public health practitioners and first responders.

The disease

Two subspecies cause human illness in the United States. Type A (F. tularensis subspecies tularensis) is found only in North America; its A1 (eastern) group is more virulent. Type B (subspecies holarctica) occurs across the Northern Hemisphere and causes most cases worldwide. Overall, about 2%–3% of Type A infections and under 1% of Type B infections are fatal, though Type B can cause long illness and disability.

How people are infected: bites from ticks, deer flies and mosquitoes; skin contact while butchering or handling infected animals; contaminated food or water; contaminated soil or hay; and breathing in the bacteria. Transmission from person to person is exceedingly rare, and has never been reported through the air.

How it shows up depends on the route:

Rarer but potentially severe manifestations include meningitis, septic arthritis, osteomyelitis, endocarditis, otitis media and mastoiditis. Tularemia responds to aminoglycosides, fluoroquinolones and tetracyclines; beta-lactams (penicillins, cephalosporins, carbapenems) and several other classes don't work, even when lab tests suggest they might. No tularemia vaccine is licensed in the United States.

War, disaster and bioterrorism

Tularemia has flared where war or disaster disrupts daily life: hundreds of thousands of cases in the former Soviet Union during World War II, outbreaks in Finland and after the wars in Bosnia and Kosovo (over 900 suspected cases in 1999–2000, traced to a postwar surge in rodents contaminating food and water), and a cluster of more than 130 cases in Turkey years after a 1999 earthquake damaged water systems.

Since 2012 F. tularensis has been a Tier 1 Select Agent, the highest-risk category. The United States and the Soviet Union stockpiled it as a weapon in the 1950s and 1960s. A World Health Organization assessment estimated that releasing 50 kg in aerosol form over a city of 5 million could, under certain conditions, incapacitate about 250,000 people and kill 19,000. The 21st Century Cures Act requires CDC to keep evidence-based guidelines for the medical countermeasures the government stockpiles.

How the guidelines were built

CDC systematically reviewed 870 published human cases treated with antibiotics (1993 to March 2023), analyzed 1,153 U.S. surveillance cases from 2006–2021, held two topic sessions in September 2022 and an expert forum in February 2024 with about 85 clinical and public health experts, and rated the evidence using the GRADE approach.

What's new since 2001

• Recommendations are now organized as treatment and prophylaxis, replacing the old split between "contained casualty" (all intravenous or intramuscular) and "mass casualty" (all oral) scenarios.
• Ciprofloxacin and doxycycline moved up to first-line treatment, and levofloxacin was added as first-line for treatment and prophylaxis.
• Streptomycin dropped to a third-tier option: it works well but carries more risk of side effects than gentamicin, is hard to get, and is prone to dosing errors because it is rarely used.
• Azithromycin was added for prophylaxis and as a third-tier treatment (except against Eastern European Type B biovar II strains, which resist macrolides).
• Chloramphenicol was downgraded to third-tier because of serious risks such as aplastic anemia; rifampin was added as a third-tier prophylaxis option.
• Alternatives within each drug class were added — for example moxifloxacin, ofloxacin, amikacin, tobramycin and plazomicin — to widen supply in a large emergency.
• New recommendations cover neonates, breastfeeding infants, lactating mothers and older adults.

Treatment

First-line drugs for adults and children aged 1 month or older are ciprofloxacin, levofloxacin, gentamicin or doxycycline; for neonates (28 days or younger), ciprofloxacin or gentamicin; and for pregnant women, ciprofloxacin, levofloxacin or gentamicin. The choice depends on how severe the illness is, what is available, and a shared decision about route and side effects.

These drugs are not FDA-approved for tularemia but are widely used off-label. Children's, neonatal and pregnancy doses, and the alternative drugs, are set out in the full report.

Clinical points:

• All forms can be treated with the same drugs; only meningitis needs a different regimen — gentamicin plus ciprofloxacin or levofloxacin, with gentamicin for at least 10 days and 21 days of treatment in total.
• For severe illness (hemodynamic instability, end-organ dysfunction, need for respiratory support, or other signs of sepsis), start with an aminoglycoside if possible; a combination of two effective classes, such as gentamicin plus ciprofloxacin, can also be used.
• If treatment has been delayed by more than 2 weeks, a bactericidal drug (ciprofloxacin, levofloxacin or gentamicin) is preferred over doxycycline, or two drugs together. In one Spanish outbreak with long delays, ciprofloxacin succeeded in 95.5% of patients, streptomycin in 76.6% and doxycycline in 57.1%.
• Patients can switch from IV or IM to oral drugs once their fever has resolved and they have improved.
• Take tetracyclines with a glass of water and stay upright for 30 minutes; avoid taking tetracyclines and fluoroquinolones with milk, yogurt or calcium-fortified juice.

Prophylaxis

• After a deliberate release, people likely exposed should start prophylaxis as soon as possible, ideally within 48 hours, with one drug: ciprofloxacin or levofloxacin for 7 days, or doxycycline for 10–14 days (ciprofloxacin or levofloxacin first-line in pregnancy). Adult doses: ciprofloxacin 500 mg every 12 hours, levofloxacin 500 mg every 24 hours, doxycycline 100 mg every 12 hours, all by mouth. Don't wait for the preferred drug — start an available alternative.
• Before exposure, prophylaxis is not recommended for the public, first responders or health workers.
• Health workers who used standard precautions don't need it; those with a breach and substantial exposure may take it or monitor for fever. The same applies to lab workers after an accidental exposure.
• After natural exposures (tick bites, mowing, skinning animals), prophylaxis is generally not recommended because the risk is low — 0.064 cases per 100,000 people — but it can be considered for people who handled an animal known to be infected.

If an attack is suspected

Clinicians and local health departments should alert state and federal authorities immediately. Responders must identify the source, distinguish tularemia from diseases caused by other potential bioweapons such as Yersinia pestis or Bacillus anthracis, test the strain for engineered drug resistance, and deploy treatment fast. Until susceptibility is known, treat symptomatic patients with two drug classes, at least one first-line. Who receives prophylaxis would be decided by public health agencies.

Protective equipment

Standard precautions are enough for routine care; add eye, nose and mouth protection for procedures that may splash, and a full face shield, a mask with shield, or mask and goggles for aerosol-generating procedures. N95 respirators aren't needed for routine care of pneumonic tularemia. Labs should be warned when tularemia is suspected, because cultures are highly infectious, and environmental response teams should follow EPA guidance.

Gaps

Much of the evidence comes from case reports with high risk of bias; no randomized trials have been run in recent decades. CDC calls for better vaccines, faster diagnostic tests, rapid resistance testing, and more research on treatment and on special populations.

Sources

• Nelson CA, Meaney-Delman D, Fleck-Derderian S, Winberg J, Mead PS. "Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response — United States, 2025." MMWR Recommendations and Reports 74(2), Centers for Disease Control and Prevention.
• The report's conclusion describes two-drug treatment for severe disease as recommended, while its clinical guidance says it can be considered; this page follows the clinical guidance's wording.