Lack of BSL-2 or reference laboratory capability for confirmatory testing
Surgical drainage expertise unavailable
ICU capability exceeded at receiving facility
Public health obligations
Mandatory reporting to local and state health department
Tularemia is a nationally notifiable condition in the United States
Report all suspected and confirmed cases
Bioterrorism scenario management
Immediate public health and law enforcement notification
Cluster investigation initiation
Post-exposure prophylaxis coordination for contacts
Discharge and follow-up
Discharge criteria
Tolerating oral antibiotics without difficulty
Fever trending down and systemic symptoms improving
Stable or improving lymphadenopathy without suppuration
Follow-up timing
Recheck in 48 to 72 hours after initiating antibiotics
Repeat serology at 2 to 4 weeks for paired sera confirmation
Two-week follow-up for ulcer healing and lymph node regression assessment
Treatment
First-line antibiotics for mild to moderate disease
Fluoroquinolones (preferred oral regimen per 2025 CDC guidelines)
Ciprofloxacin
500 to 750 mg PO BID
Duration 10 to 14 days
2025 CDC MMWR designation as first-line for outpatient naturally acquired infections
Low relapse rate compared to doxycycline
Levofloxacin
500 mg PO daily
Duration 10 to 14 days
Alternative fluoroquinolone when ciprofloxacin unavailable
Doxycycline (bacteriostatic alternative)
Dosing
100 mg PO BID
Duration 14 to 21 days
Longer courses required due to bacteriostatic mechanism
Limitations
Higher relapse rate than aminoglycosides or fluoroquinolones
Courses shorter than 14 days associated with treatment failure
Not preferred for severe disease
Parenteral antibiotics for severe disease
Gentamicin (first-line parenteral agent)
Dosing
5 mg/kg/day IV as once-daily dosing
Alternative 1.5 mg/kg IV q8h (traditional dosing)
Duration until clinical improvement (typically 7 to 10 days)
Monitoring
Renal function monitoring every 48 to 72 hours
Trough levels if using traditional dosing
Audiologic monitoring for prolonged courses
Evidence
Class I recommendation for severe tularemia based on clinical experience
CID guidelines endorse as first-line parenteral agent
Streptomycin (historical gold standard)
Dosing
15 mg/kg IM q12h
Maximum 2 g per day
Duration 10 days for most patients
Limitations
Intramuscular route less practical in severely ill patients
Limited availability in many centers
Ototoxicity and nephrotoxicity monitoring required
Step-down therapy
Parenteral aminoglycoside until clinical improvement
Typically 3 to 7 days of IV therapy
Clinical improvement defined as defervescence and systemic symptom resolution
Complete course with oral fluoroquinolone or doxycycline
Total duration 10 to 14 days from initiation
Fluoroquinolone preferred for step-down to minimize relapse
Contraindicated and ineffective antibiotics
Beta-lactams
Penicillins, cephalosporins, and carbapenems ineffective
F. tularensis intrinsically resistant due to beta-lactamase production
Empiric beta-lactam use is a common and dangerous cause of treatment failure
Clinical implication
Failure to improve on beta-lactams for presumed lymphadenitis should trigger tularemia consideration
Other ineffective agents
Most macrolides generally ineffective
Anti-tuberculosis agents ineffective
Trimethoprim-sulfamethoxazole historically used but unreliable
Adjunct management
Lymph node management
Suppurative node incision and drainage or aspiration
Indicated for fluctuant nodes not resolving with antibiotics
Required in approximately 30% of cases
Culture aspirate for diagnostic confirmation if not already confirmed
Avoid premature drainage of non-fluctuant nodes
May increase risk of sinus tract formation
Supportive care
Antipyretics for symptom control
Acetaminophen 500 to 1000 mg PO q6h as needed
NSAIDs for myalgia and lymph node pain
Fluid resuscitation
IV fluid for dehydration or inability to maintain oral intake
Lactated Ringer's or normal saline 1 to 2 L bolus for hemodynamically unstable patients
Post-exposure prophylaxis
Indications
High-risk laboratory exposure to F. tularensis
Bioterrorism exposure scenario
Regimen per 2025 CDC MMWR
Ciprofloxacin 500 mg PO BID for 14 days
Doxycycline 100 mg PO BID for 14 days as alternative
Begin within 24 hours of exposure for maximum efficacy
Special Populations
Pregnancy
Antibiotic selection in pregnancy
Fluoroquinolone considerations
Ciprofloxacin and levofloxacin: limited human data; animal studies show musculoskeletal effects
Generally avoided in pregnancy unless benefits clearly outweigh risks
May be used if no safer alternative in life-threatening infection
Doxycycline contraindication in pregnancy
Tetracyclines cause fetal dental staining and skeletal abnormalities
Contraindicated in second and third trimester
Avoid in first trimester if possible
Aminoglycoside use in pregnancy
Gentamicin preferred parenteral agent if parenteral therapy required
Fetal renal and ototoxicity risk with prolonged aminoglycoside use
Use lowest effective dose with renal and audiologic monitoring
Disease course in pregnancy
Severe tularemia with sepsis may precipitate preterm labor
Fetal loss reported with untreated septic tularemia
Infectious disease and obstetric co-management recommended
No specific data on vertical transmission of F. tularensis
Geriatric
Age-specific epidemiology
Second incidence peak in men over 55 years
Reflects continued occupational and recreational exposures (hunting, farming)
Bimodal distribution with childhood peak
Modified assessment in older adults
Atypical presentations more common
Minimal or absent fever despite significant infection
Delirium as presenting feature rather than focal findings
Pulse-temperature dissociation may be more pronounced
Comorbidities may mask localizing features
Treatment modifications
Aminoglycoside dosing adjustment
Gentamicin dosing based on actual body weight and creatinine clearance
Age-related decline in renal function increases toxicity risk
Daily monitoring of renal function with parenteral aminoglycosides
Fluoroquinolone considerations
Increased tendon rupture risk in older adults
QTc prolongation risk with concomitant QT-prolonging medications
Increased risk of severe disease and complications
Lower threshold for admission and parenteral therapy
More frequent reassessment during outpatient treatment
Pediatrics
Age-specific epidemiology
Highest incidence in children aged 5 to 9 years
Outdoor play and animal contact primary exposures
Tick exposure during outdoor activities in endemic areas
Pediatric tularemia: case series and literature review support (Kossadoum et al., Pediatr Infect Dis J, 2025)
Clinical features in children
Similar presentation to adults
Fever, ulcer, regional lymphadenopathy
Cervical lymphadenopathy more prominent in children
Reflects head and neck tick exposure during outdoor play
Atypical presentations include oropharyngeal form from contaminated water or undercooked game
Antibiotic dosing in children
Ciprofloxacin (preferred oral agent despite age caution)
15 mg/kg/dose PO BID (maximum 500 mg per dose)
Duration 10 to 14 days
Risk-benefit favors use over untreated tularemia in children
Doxycycline
2.2 mg/kg/dose PO BID (maximum 100 mg per dose)
Contraindicated in children under 8 years except for life-threatening infection
Duration 14 to 21 days
Gentamicin
2.5 mg/kg IV q8h for severe disease
Renal and auditory monitoring required
Duration until clinical improvement then oral step-down
Immunocompromised pediatric patients
Children on anti-TNF therapy (e.g., infliximab for IBD) at increased risk for severe pulmonary tularemia
Case reported by Schwarzova et al. (Pediatr Pulmonol, 2023)
Lower threshold for parenteral therapy and infectious disease consultation
Background
Epidemiology
Incidence and distribution
United States incidence approximately 100 to 200 cases per year in recent surveillance
MMWR 2013 reported 1208 cases between 2001 and 2010 (average 120 per year)
Wu et al. (CID, 2024) analyzed US surveillance data 2006 to 2021
Geographic concentration
Endemic US states: Arkansas, Missouri, Oklahoma, South Dakota, Montana
Global: Scandinavia, former Soviet Union, parts of Europe and Asia
Seasonal pattern
Peak June through September corresponding to tick activity
Secondary winter peak associated with rabbit hunting
Transmission routes
Tick bites most common US exposure (approximately 69% of cases)
Direct animal contact: rabbits, hares, squirrels, muskrats
Cat bites or scratches as increasingly recognized route
Inhalation: mowing over infected carcasses or laboratory aerosol
Contaminated water ingestion
No person-to-person transmission documented
Mortality
Overall mortality for ulceroglandular form less than 2% with appropriate treatment
Untreated fatality rate for all forms can reach up to 60%
Ulceroglandular carries the best prognosis among tularemia clinical forms
Typhoidal and pneumonic forms carry higher mortality
Pathophysiology
Causative organism
Francisella tularensis
Gram-negative intracellular coccobacillus
Extremely low infectious dose of approximately 10 organisms for inhalation route
Type A (F. tularensis tularensis): North America; highest virulence
Type B (F. tularensis holarctica): Europe and Asia; milder disease
Infection mechanism
Entry through skin, mucous membranes, or respiratory tract
Inoculation site ulcer forms at entry point
Organism evades phagolysosomal killing in macrophages
Intracellular survival and replication
Replicates within macrophages and monocytes
Escapes phagosome into cytoplasm for replication
Local and systemic spread
Drains to regional lymph nodes causing lymphadenitis
Bacteremia with dissemination to liver, spleen, lungs, and other organs
Host immune response
Granuloma formation
Histology shows caseating granulomas similar to tuberculosis
Explains mimicry of mycobacterial infection on biopsy
Suppuration
Caseous necrosis and liquefaction in lymph nodes in approximately 30%
Cell-mediated immunity critical for clearance
Immunocompromised patients especially susceptible to severe disease
Therapeutic Considerations
Antibiotic mechanism and evidence
Aminoglycosides (gentamicin, streptomycin)
Bactericidal; penetrate intracellular compartments sufficiently for F. tularensis
Historical gold standard with proven efficacy in clinical series
Class I recommendation for severe disease based on clinical experience and expert consensus
Fluoroquinolones (ciprofloxacin, levofloxacin)
Bactericidal; excellent oral bioavailability
2025 CDC MMWR designates as first-line for outpatient naturally acquired infections
Lower relapse rate than doxycycline in retrospective studies
Doxycycline (tetracycline class)
Bacteriostatic mechanism; higher relapse rates especially with short courses
Courses of 14 to 21 days reduce but do not eliminate relapse risk
Treatment failure and relapse
Beta-lactam use as primary cause of treatment failure
Must be recognized early and regimen changed promptly
Short course doxycycline associated with relapse
Delayed treatment beyond 2 to 3 weeks from onset increases failure risk
Bioterrorism preparedness considerations
F. tularensis is CDC Category A bioterrorism agent
Extremely low infectious dose and ease of aerosolization
Pneumonic tularemia would be primary presentation after intentional aerosolization
Mass casualty antibiotic formulary
Stockpiled ciprofloxacin and doxycycline under Strategic National Stockpile
Post-exposure prophylaxis regimens defined by 2025 CDC MMWR guidelines
Laboratory safety
Select agent regulations apply to F. tularensis cultures
BSL-3 for aerosol-generating procedures; BSL-2 for routine culture handling
Patient Discharge Instructions
copy discharge instructions
Your diagnosis and treatment
You have been diagnosed with tularemia (rabbit fever), a bacterial infection
It is caused by a bacterium called Francisella tularensis
It is spread by tick bites, handling infected animals, or contaminated water — not from person to person
You have been prescribed an antibiotic
Take every dose exactly as directed for the full prescribed duration
Do not stop early even if you feel better — stopping early can cause the infection to return
Complete the full 10 to 21 days as prescribed
What to expect during recovery
Fever and symptoms should begin improving within 48 to 72 hours of starting antibiotics
If you are not improving after 2 to 3 days, contact your doctor immediately
The skin ulcer may take several weeks to months to fully heal
Swollen lymph nodes may remain enlarged for weeks to months even with successful treatment
If the lymph node becomes more painful, fluctuant, or begins draining, seek evaluation
Return to emergency department immediately if
Worsening fever or fever returning after initial improvement
New cough, shortness of breath, or chest pain
Increasing swelling or redness around the skin ulcer or lymph node
The lymph node becomes very tender, fluctuant, or starts draining pus
Confusion, severe headache, or stiff neck
Inability to keep antibiotics or fluids down
Feeling much sicker despite being on antibiotics for 48 hours
Prevention of future exposure
Use DEET-based insect repellent when outdoors in wooded or grassy areas
Wear permethrin-treated clothing
Perform daily tick checks on yourself, children, and pets after outdoor activities
Remove attached ticks promptly with fine-tipped tweezers
Wear gloves when handling wild animals or their carcasses
Ensure thorough cooking of wild game meat
Avoid drinking untreated water from natural sources in endemic areas
Follow-up instructions
See your doctor in 48 to 72 hours to confirm you are improving
Blood tests may be repeated in 2 to 4 weeks to confirm the infection
Contact your doctor promptly if any new or worsening symptoms develop
References
Guidelines and key sources
Primary guidelines
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 Recomm Rep. 2025.
Designates fluoroquinolones and doxycycline as first-line outpatient treatment
Post-exposure prophylaxis regimens defined
Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. 2001;285(21):2763-2773.
Consensus statement on bioterrorism preparedness and management
Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. IDSA and ASM. Clin Infect Dis. 2024.
PCR recommended as preferred rapid diagnostic when available
Landmark clinical studies
Weber IB, Turabelidze G, Patrick S, et al. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. Clin Infect Dis. 2012.
Tick exposure in 69% of cases; patients sought care after median 3 days of illness
Wu HJ, Bostic TD, Horiuchi K, et al. Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021. Clin Infect Dis. 2024.
Contemporary US surveillance outcomes data
Maurin M, Gyuranecz M. Tularaemia: Clinical Aspects in Europe. Lancet Infect Dis. 2016;16:113-124.
Suppuration in approximately 30% of cases; lymphadenopathy may persist months
Maurin M, Pondérand L, Hennebique A, et al. Tularemia Treatment: Experimental and Clinical Data. Front Microbiol. 2023.
Relapse rates with doxycycline; beta-lactam inefficacy mechanism
Reviews and epidemiology
Antonello RM, Giacomelli A, Riccardi N. Tularemia for Clinicians: An Up-to-Date Review on Epidemiology, Diagnosis, Prevention and Treatment. Eur J Intern Med. 2025.
Comprehensive up-to-date clinical review
Kossadoum RF, Baron A, Parizot M, et al. Tularemia in Pediatric Patients: A Case Series and Review of the Literature. Pediatr Infect Dis J. 2025.
Pediatric dosing and clinical features
Schwarzova V, Schwarz J, Mitrova K, et al. Pulmonary tularaemia in a female adolescent with inflammatory bowel disease receiving infliximab. Pediatr Pulmonol. 2023.
Immunocompromised pediatric case
Özan Köse S, Erdem H, Köse ÖC, Yilmaz Ertürk F. A Clinical Pitfall in Caseating Necrotizing Granulomatous Lymphadenitis: Tularemia. Diagn Microbiol Infect Dis. 2025.
Lymphoma and TB misdiagnosis pitfall
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.