01Approach to the Critical Patient/attcp35

Immediate priorities

›Sepsis and systemic toxicity recognition

›Fever >39 C with rigors and systemic collapse

›Assess for typhoidal or pneumonic tularemia progression

›Initiate sepsis bundle within 1 hour of recognition

›Hemodynamic instability triggers

›SBP < 90 mmHg

›MAP < 65 mmHg

›Lactate >= 2 mmol/l

›If septic shock, parenteral aminoglycoside within 1 hour

›Gentamicin 5 mg/kg/day IV divided q8h as first line

›Blood cultures before antibiotics when feasible

Escalation triggers

›Progression to severe or non-glandular form

›New respiratory symptoms (cough, dyspnea, pleuritic pain)

›Raises concern for hematogenous pneumonic tularemia

›Chest imaging and ICU consultation

›Neurological deterioration (confusion, stupor)

›Assess for meningitis or typhoidal form

›CT head and lumbar puncture consideration

›Rapidly enlarging or fluctuant lymph nodes

›Surgical drainage consultation

›~23% of patients require surgical intervention

›Failure to improve on beta-lactam antibiotics

›Classic clinical clue to tularemia diagnosis

›Switch to fluoroquinolone or aminoglycoside

Key consults and reporting

›Mandatory reporting and specialist triggers

02History/hx61

Exposure history

›Vector and animal contact

›Tick bite exposure (Dermacentor variabilis, D. andersoni, Amblyomma americanum)

›Accounts for >50% of US cases

›Peak exposure in spring and summer months

›Deerfly or horsefly bites

›Important vector in Wyoming and Western US

›Mosquito bites

›Common vector in Scandinavia and Finland

›Direct animal contact

›Handling rabbits, hares, rodents, or carcasses

›Hunting, skinning, or butchering wild game

›Domestic cat bites or scratches

›Cats can transmit F. tularensis

Symptom characterization

›Core syndrome

›Tender enlarging lymph node(s) without visible skin ulcer

›Distinguishes glandular from ulceroglandular tularemia

›Ulcer may be present but healed or inconspicuous

›Incubation period

›Typically 3-5 days (range 1-14 days)

›Patients seek care median 3 days after illness onset

›Constitutional symptoms

›Fever, chills, rigors, headache, malaise, myalgias

›Adenopathy location clues

›Inguinal/femoral: lower extremity tick bite

›Axillary: upper extremity exposure

›Cervical: oropharyngeal route less common in glandular form

03Physical Exam/exam54

Vital signs

›Hemodynamic and fever assessment

›Temperature

›Fever nearly universal in tularemia

›Hyperpyrexia >39 C marker of systemic disease

›Heart rate

›Tachycardia proportional to fever and systemic illness

›Blood pressure

›SBP < 90 mmHg triggers resuscitation

›Respiratory rate

›Elevated rate raises concern for pneumonic progression

›Oxygen saturation

›Desaturation warrants chest imaging urgently

Lymph node examination

›Regional adenopathy characteristics

›Location mapped to inoculation site

›Inguinal/femoral nodes: lower extremity tick bite

›Axillary nodes: upper extremity bite or scratch

›Cervical nodes: head, neck, or oropharyngeal exposure

›Node characteristics

›Tender, enlarged, firm or rubbery

›Overlying erythema and warmth common

›Fluctuance suggests suppuration (occurs in ~30% of cases)

›Solitary vs conglomerate adenopathy

›Conglomerate nodes more likely to require drainage

›Spontaneous drainage assessment

›Sinus tract formation possible in late disease

04Differential Diagnosis/ddx38

Life-threatening diagnoses

›Serious infections with lymphadenopathy

›Plague (Yersinia pestis)

›ICD-10 A20.0 bubonic plague

›Painful inguinal/axillary adenopathy; epidemiologic context differs

›Requires immediate isolation and reporting

›Typhoidal tularemia (progressive form)

›ICD-10 A21.7

›Systemic sepsis without localizing lymphadenopathy

›Pneumonic tularemia

›ICD-10 A21.2

›Hematogenous pulmonary seeding; high mortality without treatment

›Lymphoma

›ICD-10 C85.90

›Tularemia can mimic malignancy on imaging and histopathology

›B symptoms (fever, night sweats, weight loss) overlap

Common mimics

›Infectious mimics

›Cat scratch disease (Bartonella henselae)

›ICD-10 A28.1

›Regional lymphadenopathy after cat scratch or bite

›Typically self-limited; Warthin-Starry stain positive

›Staphylococcal or streptococcal lymphadenitis

›ICD-10 L04.9

›Responds to beta-lactam antibiotics (failure = tularemia clue)

›Tuberculosis lymphadenitis

›ICD-10 A18.2

›Caseating granulomas; histopathology indistinguishable from tularemia

05Laboratory Tests/lt49

Serology

›Serum agglutination test (SAT)

›Most commonly used diagnostic test for tularemia

›Single titer >=1:160 or fourfold rise between acute and convalescent is diagnostic

›Sensitivity increases to >90% by 2-3 weeks after symptom onset

›May be negative in first week of illness

›Paired acute and convalescent serology

›Obtain acute sample at presentation

›Convalescent sample at 2-3 weeks

›Fourfold rise confirms diagnosis

Microbiologic tests

›Blood cultures

›Low sensitivity in glandular form (<5%)

›Obtain in febrile patients with systemic toxicity

›Alert lab to biosafety concern before plating (BSL-3 organism)

›Lymph node aspirate or tissue culture

›Higher yield than blood cultures

›Requires biosafety notification

›Slow-growing organism requiring enriched media

›PCR for Francisella tularensis

›Rapid and sensitive in early disease

›Available at state public health or reference labs (IDSA/ASM 2024 guideline)

›Preferred when available in first 7 days before seroconversion

Core inflammatory and metabolic labs

›Infection and inflammation markers

›Complete blood count

›Leukocytosis common but non-specific

›Leukopenia seen in severe or typhoidal form

06Diagnostic Tests/dt62

Scoring Systems

›Tularemia scoring and risk stratification

›No validated emergency department scoring system exists for tularemia

›Clinical diagnosis relies on exposure history and clinical syndrome

›National Notifiable Disease Surveillance System used for epidemiologic tracking

›Severity classification (clinical)

›Mild-moderate: hemodynamically stable, tolerating PO, localized disease

›Severe: systemic toxicity, inability to take PO, pneumonic or typhoidal form

›Critical: septic shock, respiratory failure, neurological involvement

›Bioterrorism risk assessment

›Multiple simultaneous cases without epidemiologic link raise concern

›JAMA consensus: pneumonic form with aerosol exposure is highest bioterrorism risk

MRI

›MRI applications in tularemia

›MRI of lymph nodes (limited role in routine ED workup)

›Necrotic lymph nodes appear hypointense on T1, hyperintense on T2

›Ring-enhancing pattern with gadolinium in suppurative adenopathy

›Preferred over CT for soft tissue characterization pre-operatively

›MRI brain

›Indicated if neurological signs (confusion, focal deficits) present

›Assess for tularemia encephalitis or meningitis

›Diffusion-weighted imaging for acute cerebral ischemia mimics

›Limitations

›Not a first-line tool in the ED for tularemia

›CT and ultrasound provide sufficient initial characterization

CT

›CT chest

›Indicated when respiratory symptoms present

07Disposition/dispo36

Discharge criteria

›Outpatient management criteria

›Hemodynamically stable

›SBP >90 mmHg without vasopressor support

›Tolerating oral medications

›No nausea or vomiting limiting oral antibiotic intake

›No signs of systemic toxicity

›Absence of confusion, respiratory distress, or severe rigors

›Reliable follow-up

›Follow-up in 48-72 hours arranged

›Appropriate antibiotic initiated

›Oral fluoroquinolone or doxycycline prescribed

›Most glandular tularemia cases qualify for outpatient management

›CID: outpatient oral therapy appropriate for mild-moderate glandular form

Admission criteria

›Inpatient admission indications

›High fever with systemic toxicity

›Rigors, confusion, or hemodynamic instability

›Inability to tolerate oral medications

›Nausea, vomiting, or dysphagia requiring IV therapy

›Suspected progression to pneumonic or typhoidal form

›New respiratory or neurological symptoms

›Immunocompromised host

›HIV, transplant, high-dose immunosuppressive therapy

›Suppurative lymph nodes requiring IV antibiotics or surgical drainage

›Fluctuant nodes with systemic illness

Transfer and escalation

›ICU-level indications

08Treatment/t51

First-line antibiotic therapy — mild to moderate disease

›Fluoroquinolones (preferred outpatient)

›Ciprofloxacin

›500 mg PO BID for 10-14 days

›Relapse rate approximately 5-10%

›2025 CDC MMWR: fluoroquinolones designated first-line for naturally acquired infections

›Levofloxacin

›500 mg PO daily for 10-14 days

›Alternative if ciprofloxacin not tolerated

›Doxycycline (alternative)

›100 mg PO BID for 14-21 days

›Longer duration required compared to fluoroquinolones

›Higher relapse rate ~10-15% vs ~5-10% with fluoroquinolones

›Bacteriostatic mechanism accounts for higher relapse risk

First-line antibiotic therapy — severe disease

›Aminoglycosides (preferred parenteral)

›Gentamicin

›5 mg/kg/day IV divided q8h for 10 days

›Adjust dose for renal function (monitor levels)

›Trough goal <2 mcg/ml; peak goal 5-10 mcg/ml

›Audiometric monitoring for prolonged courses

›Streptomycin (alternative parenteral)

›30 mg/kg/day IM divided q12h for 10 days

›Maximum 2 g/day

›Preferred in pregnancy with severe disease per 2025 CDC recommendations

›Step-down therapy

›Parenteral aminoglycoside until clinical improvement

›Defined as afebrile >24-48 hours, tolerating PO

09Special Populations/sp57

Pregnancy

›Antibiotic considerations in pregnancy

›Avoid fluoroquinolones if possible

›Risk of arthropathy; however benefit may outweigh risk in severe disease

›2025 CDC MMWR: discuss risks and benefits with patient

›Avoid doxycycline in pregnancy

›Risk of fetal bone and tooth discoloration

›Contraindicated in second and third trimester

›Preferred severe disease agent

›Gentamicin 5 mg/kg/day IV in divided doses

›Monitor maternal renal function and fetal wellbeing

›Streptomycin noted in CDC guidance but higher ototoxicity risk to fetus

›Fetal and obstetric considerations

›Tularemia bacteremia may cause intrauterine infection

›Risk of preterm labor, fetal loss in severe maternal illness

›Obstetric consultation for any pregnant patient with systemic tularemia

›No known teratogenicity of F. tularensis itself

›Maternal fever and hypoxia pose greatest fetal risk

Geriatric

›Age-related management modifications

›Altered pharmacokinetics

›Reduced creatinine clearance requires aminoglycoside dose adjustment

›Monitor gentamicin levels more frequently in elderly

›Risk of nephrotoxicity and ototoxicity increased

›Atypical presentations in older adults

›Fever may be blunted or absent

›Lymphadenopathy may be less prominent

›Confusion may be first or only presenting feature

10Background/b69

Epidemiology

›Incidence and distribution

›US annual incidence

›Approximately 100-200 reported cases per year in the US

›Glandular form represents 14-25% of all tularemia cases (CID)

›Ulceroglandular and glandular forms together account for ~80% of cases

›Geographic distribution

›South-central US highest burden: Arkansas, Missouri, Oklahoma

›Also present across Northern Hemisphere broadly

›Re-emerging in Europe, particularly Scandinavia and Central Europe

›Seasonal pattern

›Peak in summer months (June-September) in US

›Correlates with tick and insect vector activity

›Demographic distribution

›Male sex predominance

›Occupational and recreational outdoor exposure groups

›CDC surveillance 2006-2021 (Wu et al. CID 2024): reviewed outcomes in US cases

›Mortality and morbidity

›Overall case fatality rate <2% with appropriate treatment

›Untreated typhoidal and pneumonic forms can exceed 30-60% mortality

›Complications

›Lymph node suppuration in ~30% of glandular cases

›Surgical drainage required in ~23%

›Relapse rate 5-15%, higher with bacteriostatic agents or delayed treatment

Pathophysiology

›Organism and virulence

›Francisella tularensis classification

›Gram-negative facultative intracellular coccobacillus

›Subspecies tularensis (Type A): North America, higher virulence

›Subspecies holarctica (Type B): Europe and North America, lower virulence

›Infectious dose as low as 10-50 organisms via skin or aerosol route

›Intracellular survival mechanism

›Survives and replicates inside macrophages and neutrophils

›Evades phagolysosomal killing

›Neutrophil functional impairment described (Immunological Reviews 2016)

›Glandular form pathogenesis

›Inoculation via skin

›Tick bite, insect bite, or direct animal contact

›Bacteria invade via skin, travel via lymphatics to regional nodes

›Primary skin ulcer may heal before lymphadenopathy manifests

›Lymph node response

›Granulomatous inflammation with necrosis

›Caseating necrotizing granulomas indistinguishable from TB histologically

›Suppuration and abscess formation in severe cases

›Systemic spread

›Bacteremia can seed lungs, liver, spleen, meninges

›Hematogenous pneumonic tularemia can complicate glandular form

›Typhoidal form results from widespread hematogenous dissemination

Therapeutic Considerations

›Antibiotic mechanism and resistance

›Aminoglycosides (bactericidal)

›Gentamicin and streptomycin are bactericidal against F. tularensis

›Preferred for severe disease due to killing kinetics

›No acquired aminoglycoside resistance reported in natural strains

›Fluoroquinolones (bactericidal)

›Ciprofloxacin and levofloxacin are bactericidal

›Lower relapse rate than doxycycline (~5-10%)

›2025 CDC MMWR designation as first-line for natural infections

›Doxycycline (bacteriostatic)

›Effective but higher relapse rate 10-15%

›Longer treatment duration required (14-21 days)

›Intrinsic beta-lactam resistance

›F. tularensis produces beta-lactamase

›Penicillins and cephalosporins universally ineffective

›Evidence base and guideline evolution

›IDSA/ASM 2024 laboratory guidelines on PCR testing

›2025 CDC MMWR update on antimicrobial treatment and prophylaxis

›Frontiers in Microbiology 2023 (Maurin et al.): comprehensive treatment evidence review

›Bioterrorism preparedness context

›JAMA 2001 (Dennis et al.): classified as Category A bioterrorism agent

›NEJM 2015 (Adalja et al.): clinical management of bioterrorism conditions

›Aerosol release would cause pneumonic form with high mortality

11Patient Discharge Instructions/pdi34

copy discharge instructions

›Diagnosis and illness explanation

›Glandular tularemia (rabbit fever) is a bacterial infection spread by tick bites, insect bites, or contact with infected wild animals

›It causes painful swollen lymph nodes and fever

›It is not spread from person to person

›Most people recover fully with antibiotic treatment

›Medications

›Take your antibiotic as prescribed for the full course even if you feel better

›Do not stop antibiotics early — this increases relapse risk

›Ciprofloxacin: take every 12 hours with or without food; avoid antacids within 2 hours

›Doxycycline: take every 12 hours with plenty of water; avoid sun exposure

›Follow-up instructions

›Return to clinic in 48-72 hours to check response to antibiotics

›Bring list of current medications

›A follow-up blood test at 2-3 weeks may confirm the diagnosis

›Return to emergency department immediately for

›Worsening or new swollen lymph nodes or drainage from a lymph node

›Especially if fever persists beyond 48-72 hours of antibiotics

›New cough, difficulty breathing, or chest pain

›May indicate spread of infection to the lungs

›Confusion, severe headache, or stiff neck

›Inability to keep antibiotics down due to vomiting

›Worsening fever or new shaking chills despite antibiotics

›Prevention counseling

›Tick avoidance measures

›Use DEET-containing insect repellent on exposed skin

›Apply permethrin to clothing and gear

›Conduct full-body tick checks after outdoor activities

12References/r24

Guidelines and key sources

›Primary guidelines

›Nelson CA, Meaney-Delman D, Fleck-Derderian S, et al. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response — United States, 2025. MMWR Recomm Rep. 2025.

›2025 CDC MMWR: designates fluoroquinolones as first-line for natural infections

›Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. 2001;285(21):2763-2773.

›Foundational bioterrorism management framework

›Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by IDSA and ASM. Clin Infect Dis. 2024.

›PCR and laboratory diagnostic guidance

›CDC. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers, 6th Edition. 2022.

›Comprehensive tick-borne disease management

Key clinical studies

›Landmark studies and reviews

›Maurin M, Gyuranecz M. Tularaemia: Clinical Aspects in Europe. Lancet Infect Dis. 2016.

›Epidemiology, clinical presentation, and management in European context

›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.

›US clinical series defining glandular form characteristics

›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.

›National surveillance outcomes data

›Maurin M, Pondérand L, Hennebique A, et al. Tularemia Treatment: Experimental and Clinical Data. Front Microbiol. 2023.

›Comprehensive antibiotic evidence review including relapse rates

›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 presentation and management guidance

›Adalja AA, Toner E, Inglesby TV. Clinical Management of Potential Bioterrorism-Related Conditions. N Engl J Med. 2015.

›Bioterrorism preparedness and clinical management

›Çakır Kıymaz Y, Bolat S, Katırcı B, et al. Evaluation of Clinical Characteristics, Laboratory Parameters, and Antibiotic Treatment in Patients Diagnosed With Tularemia. J Infect Chemother. 2025.

›Recent clinical data on characteristics and treatment outcomes

Evidence & Review

Evidence & Review