01Approach to the Critical Patient/attcp57

Immediate priorities

›Sepsis and hemodynamic threats

›Septic shock physiology

›SBP < 90 mmHg or MAP < 65 mmHg

›Tachycardia with cool extremities

›Altered mental status

›IV access, 2 large-bore peripheral lines

›IV crystalloid bolus 30 ml/kg if hypotensive

›Vasopressors if unresponsive to fluids

›Blood cultures x2 before antibiotics

›Notify microbiology lab immediately if tularemia suspected

›BSL-3 precautions for cultures

›Broad-spectrum empiric antibiotics within 1 hour of sepsis recognition

›Gentamicin preferred first-line for severe typhoidal disease

›Class I recommendation for early antibiotic initiation in septic shock

›Respiratory threats

›Secondary pneumonia from hematogenous spread

›Tachypnea, hypoxemia, new infiltrates

›SpO2 target > 94%

›Supplemental oxygen titrated to target

›HFNC if high-flow requirements

›Intubation if respiratory failure

›Chest imaging to detect pleural effusion or pneumonia

›Neurological threats

›Confusion, stupor, or behavioral change indicate severe systemic disease

›GCS assessment on arrival

›If GCS < 13, CT head to exclude abscess or meningitis

›Tularemia meningitis rare but documented

02History/hx51

Exposure history

›Tick or arthropod exposure

›Dermacentor variabilis (American dog tick), Amblyomma americanum (lone star tick)

›Peak season: late spring through summer

›Tick attachment time and location on body

›Deer fly bites in endemic areas

›Animal contact

›Handling rabbits, hares, rodents (skinning, dressing carcasses)

›Hunters, trappers, veterinarians at highest risk

›Cats can transmit from prey (bite or scratch)

›Farm animals less commonly implicated

›Environmental and occupational exposure

›Mowing or landscaping over animal carcasses (aerosolized organisms)

›Laboratory exposure (BSL-2 accidents)

›Ingestion of contaminated water (streams, lakes)

›Undercooked wild game (rabbit, squirrel)

Presenting symptoms

›Onset pattern

›Abrupt onset of high fever (38–40°C) after incubation 3–5 days (range 1–14 days)

›Chills, rigors

›Severe headache

›Progressive constitutional symptoms

›Profound myalgias, especially low back pain

›Malaise, anorexia, weight loss

›Gastrointestinal symptoms

›Nausea, vomiting, diarrhea, abdominal pain

›May dominate presentation and mimic enteric fever

›Hepatosplenomegaly in prolonged disease

03Physical Exam/exam35

Vital signs

›Temperature pattern

›High sustained fever 38–40°C

›Fever without localizing source is hallmark

›Pulse-temperature dissociation (relative bradycardia) in up to 42%

›Tachycardia when fever expected but may be absent (pulse-temperature dissociation)

›Hypotension indicates septic shock

›Tachypnea if secondary pneumonia present

General appearance

›Toxic-appearing, diaphoretic patient

›Cachectic if illness prolonged > 2–3 weeks

›Profound fatigue and weakness

›Night sweats

Head, eyes, ears, nose, and throat

›Pharyngeal assessment

›Erythema may suggest oropharyngeal entry (rare in typhoidal form)

›Tonsillar exudate in oropharyngeal tularemia

›No ulcers or exudate typical in typhoidal form

Lymph node examination

›Absence of regional lymphadenopathy

›Defining feature distinguishing typhoidal from glandular forms

›Diffuse non-tender lymphadenopathy may occur rarely

›Splenomegaly palpable in prolonged infection

Skin examination

›No inoculation ulcer in typhoidal form

›Absence of cutaneous findings is diagnostically significant

›Erythema nodosum (uncommon) — tender nodules on shins

›Non-specific macular or papular rash reported rarely

04Differential Diagnosis/ddx46

Infectious mimics

›Typhoid fever (Salmonella typhi)

›ICD-10: A01.0

›Similar sustained fever, relative bradycardia, GI symptoms

›Travel to endemic region; rose spots on exam; blood/stool culture positive

›Brucellosis (Brucella species)

›ICD-10: A23.9

›Undulant fever, sweats, hepatosplenomegaly

›Animal or dairy exposure; serologic cross-reactivity with tularemia possible

›Q fever (Coxiella burnetii)

›ICD-10: A78

›Fever, headache, pneumonia; livestock exposure history

›Serology distinguishes; atypical pneumonia pattern

›Rocky Mountain spotted fever (Rickettsia rickettsii)

›ICD-10: A77.0

›Tick-borne; high fever, headache, but rash present in most cases

›Cytopenias and elevated transaminases more prominent

›Ehrlichiosis (Ehrlichia chaffeensis)

›ICD-10: A77.40

›Tick-borne; leukopenia, thrombocytopenia, elevated LFTs

›Morulae on peripheral smear; PCR confirms

Systemic and non-infectious mimics

›Lymphoma or hematologic malignancy

›ICD-10: C85.9

›Prolonged fever, weight loss, night sweats

›Hypermetabolic mediastinal nodes on PET-CT may mimic tularemia

›Bone marrow biopsy and LDH distinguish

›Tuberculosis (Mycobacterium tuberculosis)

05Laboratory Tests/lt52

Hematologic studies

›Complete blood count

›Leukocytosis or leukopenia both reported

›Leukopenia more common in early disease

›Relative lymphopenia

›Thrombocytopenia in severe disease

›Anemia if prolonged illness

Metabolic and hepatic studies

›Comprehensive metabolic panel

›Elevated hepatic transaminases (ALT, AST) common

›Hepatitis pattern may be presenting finding

›Hyponatremia in SIADH or severe sepsis

›Renal function baseline

›Creatinine and BUN before aminoglycoside initiation

›Serial monitoring every 48 hours during aminoglycoside therapy

Inflammatory markers

›Erythrocyte sedimentation rate and C-reactive protein

›Markedly elevated in active disease

›Useful for monitoring treatment response

›Not specific for tularemia

›Procalcitonin

›Elevated in bacteremic sepsis

›May help guide antibiotic duration in uncomplicated disease

›Sensitivity and specificity not well validated for tularemia specifically

Microbiologic studies

›Blood cultures

›F. tularensis rarely isolated on standard media

›Requires cysteine-enriched media (chocolate agar, cysteine heart agar)

06Diagnostic Tests/dt51

Scoring Systems

›No validated clinical scoring system for tularemia

›Diagnosis based on clinical suspicion, exposure history, and laboratory confirmation

›SOFA score applicable for severity assessment when sepsis present

›SOFA score >= 2 meets sepsis-3 criteria

›Duke criteria applicable if endocarditis suspected as differential

›Modified Duke criteria validated for culture-negative endocarditis

MRI

›Brain MRI indications

›Neurological tularemia (confusion, seizures, focal deficits)

›Tularemia meningitis: leptomeningeal enhancement

›Tularemia encephalitis: T2 hyperintensity white matter changes

›MRI with contrast superior to CT for posterior fossa and brainstem pathology

›Brain abscess: ring-enhancing lesion with surrounding edema

›Diffusion-weighted imaging for early ischemic changes from emboli

›MRI abdomen indications

›Hepatosplenic abscess detection

›Superior to CT for soft tissue characterization

›Splenic abscess: hypointense on T1, hyperintense on T2

CT

›CT chest indications

›Secondary pneumonia detection

›Hilar lymphadenopathy prominent in some cases

›Consolidation pattern: lobar or multilobar in pneumonic tularemia

›Pleural effusion assessment

›Mediastinal lymphadenopathy

›May mimic lymphoma on CT (hypermetabolic nodes)

›PET-CT can be misleading without microbiologic confirmation

07Disposition/dispo30

Admission criteria

›All typhoidal tularemia patients require hospital admission

›Typhoidal form is by definition severe systemic disease

›Parenteral antibiotics required for severe disease

›Clinical monitoring for deterioration essential

›Infectious disease consultation for all admitted cases

›Public health notification: tularemia is nationally notifiable

Level of care

›ICU admission indications

›Septic shock requiring vasopressors

›Respiratory failure requiring mechanical ventilation

›Neurological compromise (encephalitis, meningitis)

›Standard ward admission for stable patients

›Close monitoring for clinical deterioration

›Telemetry if pulse-temperature dissociation or arrhythmia concern

Transfer criteria

›Transfer to higher-level facility if

›ICU care unavailable at current facility

›Neurosurgical intervention required for abscess

›Mechanical ventilation beyond local capacity

›Reference laboratory access for confirmatory testing

›CDC laboratory testing for bioterrorism confirmation

Discharge criteria

›Afebrile for 24–48 hours

›Hemodynamically stable off vasopressors

›Tolerating oral antibiotics

›Improving clinically and laboratory trends improving

›Step-down to oral fluoroquinolone or doxycycline to complete 10–14 day course

08Treatment/t66

Resuscitation and supportive care

›Fluid resuscitation

›IV crystalloid 30 ml/kg for septic shock

›Reassess hemodynamics after each bolus

›Lactate-guided resuscitation targeting clearance

›Vasopressor therapy if MAP < 65 mmHg after 2 litres IV fluid

›Norepinephrine first-line vasopressor

›Target MAP >= 65 mmHg

›Fever management

›Antipyretics for symptomatic relief

›Acetaminophen 650–1000 mg PO/IV every 6–8 hours

›NSAIDs with caution in renal impairment

›Active cooling if temperature > 40°C with hemodynamic compromise

›Isolation precautions

›Standard precautions only

›No airborne or droplet isolation required

›No person-to-person transmission; contact precautions for wound drainage only

First-line antibiotics for severe/typhoidal tularemia

›Gentamicin (preferred parenteral agent)

›5 mg/kg/day IV in divided doses every 8 hours

›Alternative: once-daily dosing per institutional aminoglycoside protocol

›Duration: 10–14 days

›Monitoring

›Trough level < 1 mg/l (conventional dosing)

›Renal function every 48 hours

›Auditory and vestibular monitoring for prolonged courses

›Dose adjustment required for CrCl < 50 ml/min

›Pharmacist consultation for individualized dosing

›Streptomycin (historical drug of choice)

›15 mg/kg IM every 12 hours (maximum 2 g/day)

›Duration: 10–14 days

›Limited availability in most centres

›Superior outcomes in historical data vs. tetracyclines

›Consider when gentamicin unavailable or failed

Alternative antibiotics

›Ciprofloxacin

›400 mg IV every 12 hours (severe disease)

›Step-down to 750 mg PO twice daily when clinically improving

›Duration: 10–14 days

›2025 CDC MMWR designates fluoroquinolones as first-line for outbreak scenarios

›Effective alternative for severe disease when aminoglycosides contraindicated

›Relapse rate approximately 5–10%

›Levofloxacin

›500–750 mg IV/PO once daily

›Duration: 10–14 days

›Alternative fluoroquinolone when ciprofloxacin unavailable

›Doxycycline

›100 mg IV/PO every 12 hours

›Duration: minimum 14 days (extend to reduce relapse)

›Relapse rate 10–15% (higher than fluoroquinolones)

›Bacteriostatic; risk of relapse higher than aminoglycosides

›Not preferred for severe typhoidal disease

›Option for mild-moderate disease or step-down in stable patients

Antibiotics to avoid

›Beta-lactams (penicillins, cephalosporins, carbapenems)

›F. tularensis intrinsically resistant

›Treatment failure when used as monotherapy

›Do not rely on beta-lactam coverage when tularemia is suspected

›Most macrolides (azithromycin, clarithromycin)

›Generally ineffective; intrinsic resistance

›Exception: azithromycin may be considered in pregnancy for type B mild disease

›Anti-tuberculosis agents

›Not effective against F. tularensis

›Caseating granuloma histology may prompt misdiagnosis and incorrect TB therapy

Bioterrorism mass-casualty prophylaxis

›Post-exposure prophylaxis (bioterrorism scenario)

›Doxycycline 100 mg PO twice daily for 14 days

›Ciprofloxacin 500 mg PO twice daily for 14 days as alternative

›Initiate within 24 hours of confirmed or suspected aerosol exposure

›2025 CDC MMWR recommendations for mass prophylaxis

›Public health coordination required for large-scale distribution

09Special Populations/sp55

Pregnancy

›Maternal risk

›Tularemia in pregnancy carries risk of premature delivery and miscarriage

›Severe maternal sepsis increases fetal compromise risk

›Early aggressive treatment reduces maternal and fetal mortality

›Antibiotic selection in pregnancy

›Gentamicin acceptable for severe disease in pregnancy

›Monitor fetal wellbeing and renal function closely

›Risk-benefit: untreated typhoidal tularemia carries up to 60% mortality

›Azithromycin may be considered for mild type B tularemia in Europe

›Data limited to mild disease; not validated for typhoidal form

›Avoid doxycycline in pregnancy

›Tetracyclines cause fetal bone and tooth discoloration

›Category D teratogen

›Fluoroquinolones generally avoided in pregnancy

›Cartilage toxicity concerns in animal data

›May be considered if no safe alternative available for severe life-threatening disease

›Obstetric consultation

›Fetal monitoring during acute illness

›Multidisciplinary approach with infectious disease and maternal-fetal medicine

Geriatric

›Increased disease severity in older patients

›Systemic typhoidal form more common in age > 50 years

›Higher baseline comorbidity increases complication risk

›Immunosenescence impairs bacterial clearance

›Aminoglycoside considerations

›Age-related decline in GFR increases nephrotoxicity risk

›Baseline creatinine and calculated CrCl before gentamicin

10Background/b60

Epidemiology

›Global and US incidence

›Tularemia reported in the United States at approximately 100–300 cases per year

›Incidence has increased in recent decades; 2006–2021 US surveillance data: peak in summer months

›Overall US case fatality rate with treatment: approximately 2.3%

›Untreated typhoidal and pneumonic forms: up to 30–60% mortality

›Typhoidal form carries the highest fatality rate among all tularemia forms

›Geographic distribution

›South-central United States: Arkansas, Missouri, Oklahoma, Kansas account for majority of US cases

›Endemic in Scandinavia, Turkey, central Europe, and parts of Asia

›European cases predominantly caused by F. tularensis subsp. holarctica (type B)

›Bioterrorism potential

›CDC Category A select agent requiring BSL-3 for culture

›Potential for weaponization via aerosol (historical Cold War programs)

›Demographics

›Male sex approximately 65% of US cases

›Peak incidence in summer months coinciding with tick activity

›Occupationally exposed individuals at highest risk

Pathophysiology

›Causative organism

›Francisella tularensis, gram-negative coccobacillus

›Two main subspecies: F. tularensis subsp. tularensis (type A, North America, more virulent) and subsp. holarctica (type B, Europe)

›Extremely low infectious dose: fewer than 10 organisms sufficient for infection via aerosol

›Intracellular pathogen

›Survives and replicates within macrophages and monocytes

›Escapes phagosomal killing by inhibiting phagosome-lysosome fusion

›Entry routes and form determination

›Skin inoculation (tick bite, animal contact): ulceroglandular or glandular form

›Inhalation: pneumonic form

›Ingestion: oropharyngeal or typhoidal form

›Typhoidal form

›Occurs when infection overwhelms local containment without identifiable portal of entry

›Bacteremia with hematogenous seeding of liver, spleen, lungs, CNS

›Granulomatous inflammation in multiple organs (can be caseating, mimicking TB)

›Immune evasion and tissue injury

›F. tularensis suppresses neutrophil function and prolongs neutrophil lifespan

›Paradoxical delay in neutrophil killing allows dissemination

›Pro-inflammatory cytokine storm contributes to multiorgan dysfunction

›Lipopolysaccharide (LPS) is less immunostimulatory than classic gram-negative LPS

›Attenuated early innate immune response delays diagnosis

Therapeutic Considerations

›Antibiotic mechanism and selection rationale

›Aminoglycosides (gentamicin, streptomycin)

›Bactericidal activity against F. tularensis

›Penetration into macrophages sufficient for intracellular killing

›Preferred for severe typhoidal disease due to bactericidal activity

›Fluoroquinolones (ciprofloxacin, levofloxacin)

›Bactericidal; good intracellular and CNS penetration

›2025 CDC MMWR: first-line for naturally acquired and bioterrorism outbreak scenarios

›Relapse rates 5–10%, lower than tetracyclines

›Doxycycline

›Bacteriostatic mechanism explains higher relapse rate (10–15%)

›Adequate for mild disease but extend duration to minimum 14 days

›Resistance and intrinsic susceptibility

›F. tularensis intrinsically resistant to all beta-lactams

›Produces beta-lactamase; also lacks outer membrane beta-lactam binding targets

›Most macrolides ineffective (azithromycin exception with some activity)

›No acquired antibiotic resistance in wild-type strains reported to date

›Theoretical concern for engineered resistance in bioweapon strains

›Treatment response monitoring

›Clinical improvement expected within 48 hours of appropriate antibiotic therapy

›Failure to improve by 72 hours warrants reassessment of diagnosis and regimen

›Prolonged delayed treatment (> 2–3 weeks from onset) associated with higher failure and relapse rates

11Patient Discharge Instructions/pdi29

copy discharge instructions

›Tularemia discharge instructions

›You were treated for tularemia, a bacterial infection caused by Francisella tularensis

›This infection is acquired from tick bites, animal contact, or exposure to contaminated water or soil

›It is not spread from person to person

›Complete your full course of antibiotics as prescribed

›Do not stop antibiotics early even if you feel better

›Stopping early increases the risk of relapse (return of infection)

›Take your medications as prescribed

›Ciprofloxacin or doxycycline with food if stomach upset occurs

›Stay well hydrated during recovery

›Prevention after discharge

›Use insect repellent (DEET) and protective clothing in tick-prone areas

›Check yourself for ticks after outdoor activities and remove promptly

›Avoid handling wild rabbits, rodents, or other small animals without protective gloves

›Do not drink untreated water from streams or lakes

›Cook wild game thoroughly

›Return to the emergency department immediately if you develop

›Recurrence of high fever after initial improvement

›New or worsening cough, shortness of breath, or chest pain

›Confusion, severe headache, or stiff neck

›Persistent vomiting, diarrhea, or severe abdominal pain

›New skin sores, swollen lymph nodes, or rash

›Weakness or dizziness that prevents normal activity

›Follow-up appointment

›See your physician within 1 week of discharge

›A blood test may be repeated to confirm the infection has resolved

›Full recovery may take several weeks; fatigue may persist

12References/r31

Guidelines and key sources

›2025 CDC MMWR tularemia treatment and prophylaxis 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. PMID: 41026652

›Designates fluoroquinolones as first-line for outbreak scenarios

›Updated prophylaxis dosing for special populations

›Tularemia clinical review (Lancet Infectious Diseases 2016)

›Maurin M, Gyuranecz M. Tularaemia: Clinical Aspects in Europe. Lancet Infect Dis. 2016. PMID: 26738841

›Comprehensive European clinical experience and antibiotic outcomes

›Relapse rates by antibiotic class

›Tularemia as biological weapon (JAMA 2001)

›Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. 2001. PMID: 11368703

›Working group consensus on bioterrorism management

›Clinical features, treatment algorithms, mass prophylaxis

›Tularemia for clinicians — up to date review (European Journal of Internal Medicine 2025)

›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. PMID: 40107886

›Current epidemiology, treatment recommendations, and antibiotic outcomes data

Supporting references

›Tularemia treatment experimental and clinical data (Frontiers in Microbiology 2023)

›Maurin M, Pondérand L, Hennebique A, et al. Tularemia Treatment: Experimental and Clinical Data. Front Microbiol. 2023. PMID: 38298538

›Antibiotic mechanism of action and relapse rates

›Intrinsic resistance to beta-lactams and macrolides

›US surveillance data 2006–2021 (CID 2024)

›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. PMID: 38294115

›National epidemiology, demographic data, case fatality rates

›Tularemia in pediatric patients (Pediatric Infectious Disease Journal 2025)

›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. PMID: 39312633

›Pediatric dosing guidance and diagnostic challenges

›CDC Tickborne Diseases Manual 6th Edition (2022)

Evidence & Review

Evidence & Review