01Approach to the Critical Patient/attcp50

Immediate resuscitation priorities

›Airway and breathing

›Respiratory distress or failure

›SpO2 < 90% on room air

›Respiratory rate > 30 per minute

›Accessory muscle use or inability to speak full sentences

›Oxygen supplementation

›Target SpO2 92-96%

›High-flow nasal cannula if standard O2 insufficient

›Intubation triggers

›Refractory hypoxemia despite supplemental oxygen

›Respiratory fatigue or altered mental status

›Class I recommendation for definitive airway when protection lost

›Circulation and sepsis

›Septic shock triggers

›SBP < 90 mmHg or MAP < 65 mmHg

›Lactate >= 2 mmol/l

›Altered mental status with suspected infection

›Fluid resuscitation

›30 ml/kg isotonic crystalloid within 3 hours

›Reassess fluid responsiveness after initial bolus

›Vasopressors if refractory hypotension

›Norepinephrine first-line vasopressor

›MAP target >= 65 mmHg

Antibiotic urgency

›Time-to-antibiotic mandate

›Septic shock or severe illness

›Antibiotics within 1 hour of recognition

02History/hx59

Exposure and epidemiologic context

›Exposure history

›Animal contact

›Rabbits, hares, rodents, squirrels

›Cats that hunt wildlife

›Tick or deerfly bites in endemic regions

›Occupational and recreational exposure

›Hunting, trapping, or skinning animals

›Veterinary or laboratory work with potential Francisella tularensis

›Rural residence or outdoor activities in endemic areas

›Inhalation route

›Mowing or landscaping over areas with rodent activity

›Laboratory aerosol exposure

›Bioterrorism as rare but life-threatening source

›Geographic and temporal context

›Endemic regions

›North America (Arkansas, Missouri, Oklahoma, Kansas highest burden)

›Northern Europe (Scandinavia, Finland)

›Central Europe and Turkey

›Seasonal pattern

›Summer peak coincides with tick activity

›Secondary peak in winter during hunting season

›Incubation period

›1-14 days after exposure (average 3-5 days)

›Exact exposure date aids diagnosis

Symptom characterization

›Core respiratory symptoms

›Cough

03Physical Exam/exam54

Vital signs and general

›Vital sign findings

›Temperature

›Fever 38.0-41.5 C typical

›Hypothermia indicates septic shock and critical illness

›Heart rate

›Tachycardia present in most cases

›Relative bradycardia occasionally (Faget sign-like)

›Respiratory rate

›>= 30 per minute as severity marker

›Increasing trend more important than single measurement

›Blood pressure

›Hypotension indicates septic shock

›SBP < 90 mmHg triggers immediate resuscitation

›Oxygen saturation

›Room air value baseline

›Ambulatory desaturation increases severity classification

Pulmonary examination

›Auscultation findings

›Crackles

›May be focal or diffuse depending on extent

›Often less prominent than imaging suggests

›Reduced breath sounds

›Pleural effusion when dullness to percussion

›Consolidation with bronchial breath sounds and egophony

›Wheeze

›Less common than in community-acquired pneumonia

›May indicate airway involvement

04Differential Diagnosis/ddx44

Life-threatening pneumonia mimics

›Bacterial pneumonia

›Community-acquired pneumonia

›ICD-10 J18.9

›No specific animal exposure; typical pathogens (Streptococcus pneumoniae, Legionella)

›Legionella pneumophila

›ICD-10 A48.1

›Water exposure; urinary antigen positive; hyponatremia common

›Plague pneumonia (Yersinia pestis)

›ICD-10 A22.1

›Bioterrorism differential; Southwest US exposure; hemoptysis more prominent

›Other zoonotic pneumonias

›Q fever (Coxiella burnetii)

›ICD-10 A78

›Farm animal exposure; headache prominent; serology diagnostic

›Psittacosis (Chlamydophila psittaci)

›ICD-10 A70

›Bird exposure; splenomegaly common

›Hantavirus pulmonary syndrome

›ICD-10 B33.4

›Rodent exposure; rapid ARDS without mediastinal adenopathy

Bioterrorism differentials

›Inhalational anthrax (Bacillus anthracis)

›ICD-10 A22.1

›Widened mediastinum on CXR/CT

›Hemorrhagic mediastinitis; no alveolar infiltrates initially

›Cluster of cases in non-endemic context

›Bioterrorism protocol triggers

05Laboratory Tests/lt64

Core infectious workup

›Complete blood count

›Leukocytosis

›WBC typically elevated but may be normal

›Left shift supports bacterial infection

›Leukopenia

›Possible in severe or typhoidal form

›Associated with worse prognosis

›Thrombocytopenia

›Suggests sepsis or disseminated intravascular coagulation

›Inflammatory markers

›C-reactive protein

›Markedly elevated in active infection

›Useful for treatment response monitoring

›Erythrocyte sedimentation rate

›Elevated but non-specific

›Less useful than CRP for acute management

›Procalcitonin

›Elevated in bacterial infection

›Not validated specifically for tularemia

Microbiologic testing

›Serology (mainstay of diagnosis)

›Tube agglutination or microagglutination

›Titre >= 1:128 or fourfold rise between acute and convalescent sera

›Convalescent serum drawn at 2-4 weeks

›ELISA for anti-Francisella tularensis IgM and IgG

›IgM rises in first week; IgG appears in second week

›Sensitivity 84-100% in convalescent phase

06Diagnostic Tests/dt46

Scoring Systems

›Tularemia-specific severity scoring

›No validated severity scoring system specific to tularemia

›Clinical severity guided by vital signs and organ function

›Sepsis-related Organ Failure Assessment (SOFA) score applicable for septic presentations

›PSI (Pneumonia Severity Index)

›May be applied to stratify pneumonic tularemia

›Variables: age, comorbidities, vital signs, labs, CXR findings

›CURB-65 score

›Confusion, urea > 7 mmol/l, RR >= 30, SBP < 90 or DBP <= 60, age >= 65

›Score >= 2 supports inpatient management

MRI

›MRI chest

›Limited role in acute pneumonic tularemia

›Not indicated as primary imaging modality

›CT preferred for chest parenchyma characterization

›MRI brain if CNS involvement suspected

›Tularemia meningitis or encephalitis rare

›Indicated for altered mental status with negative CT

CT

›CT chest without contrast

›Primary advanced imaging modality for pulmonary evaluation

›Indicated when CXR is non-diagnostic or equivocal

›Superior to CXR for detecting early or subtle infiltrates

›Characteristic findings of pneumonic tularemia

›Peribronchial infiltrates and alveolar consolidation

›Mediastinal and hilar lymphadenopathy (highly characteristic)

›Pulmonary nodules (may mimic malignancy on PET)

07Disposition/dispo42

Admission criteria

›Inpatient admission indications

›Severe pneumonia or respiratory distress

›SpO2 < 92% on room air

›Respiratory rate >= 30 per minute

›CURB-65 score >= 2

›Hemodynamic instability

›SBP < 90 mmHg or MAP < 65 mmHg

›Lactate >= 2 mmol/l

›Inability to tolerate oral medications

›Vomiting or gastrointestinal compromise

›Severe systemic toxicity

›High-risk patient features

›Immunosuppression including anti-TNF therapy

›Age extremes with comorbidities

ICU-level care criteria

›ICU admission triggers

›Septic shock requiring vasopressors

›Norepinephrine initiation

›Persistent hypotension despite 30 ml/kg fluid

›Respiratory failure

›Mechanical ventilation required

›ARDS pattern with bilateral infiltrates

›Multi-organ dysfunction

›AKI with creatinine rise

›Encephalopathy or hepatic dysfunction

›Transfer considerations

›Bioterrorism suspected

08Treatment/t92

Immediate stabilization

›Supportive care

›Oxygen therapy

›Target SpO2 92-96%

›Escalate to HFNC or intubation as required

›Fluid resuscitation for sepsis

›30 ml/kg isotonic crystalloid within 3 hours

›Reassess after each bolus for fluid responsiveness

›Vasopressor initiation for refractory hypotension

›Norepinephrine 0.01-3.0 mcg/kg/min IV

›Titrate to MAP >= 65 mmHg

First-line antibiotics — severe disease

›Gentamicin (preferred aminoglycoside, IV route)

›Adult dose

›1.5 mg/kg IV every 8 hours

›Alternative: 5 mg/kg IV once daily (extended interval dosing)

›Duration

›10-14 days for severe pneumonic tularemia

›Transition to oral fluoroquinolone when clinically improving

›Monitoring

›Trough levels < 1 mg/l for q8h dosing

›Renal function every 48 hours

›Audiologic monitoring for extended courses

›Streptomycin (historical first-line, IM route)

›Adult dose

›7.5-15 mg/kg IM every 12 hours

›Maximum 1 g per dose

›Duration

›10-14 days

›Availability limited in many regions

›Monitoring

›Nephrotoxicity and ototoxicity monitoring

›Renal function dosing adjustment required

First-line antibiotics — mild to moderate disease

›Ciprofloxacin (preferred oral agent)

›Adult dose

›750 mg orally twice daily

›IV formulation: 400 mg IV every 12 hours for hospitalized patients

›Duration

›14-21 days for mild-moderate disease

›MMWR 2025 CDC recommendation

›Considerations

›Avoid in pregnancy and young children (musculoskeletal concerns)

›Relapse rates lower than doxycycline in some series

›Levofloxacin

›Adult dose

›500-750 mg orally or IV once daily

›Emerging evidence for equivalence to ciprofloxacin

›Duration

›14-21 days

›CID 2024 data support fluoroquinolone efficacy for severe Type B tularemia

›Monitoring

›QTc prolongation risk

›Tendinopathy risk especially in elderly

Alternative antibiotics

›Doxycycline

›Adult dose

›100 mg orally or IV twice daily

›Alternative when fluoroquinolones contraindicated

›Duration

›14-21 days minimum

›Higher relapse rate than aminoglycosides or fluoroquinolones (5-15%)

›Contraindications

›Pregnancy (avoid after first trimester)

›Children < 8 years (dental staining)

›CID IDSA guideline basis

›Class IIa recommendation as alternative agent

›Chloramphenicol

›Reserved for meningitis or CNS tularemia

›50-75 mg/kg/day IV in 4 divided doses

›CNS penetration superior to aminoglycosides

›Hematologic toxicity monitoring required

Antibiotics to avoid

›Beta-lactam antibiotics

›Penicillins and cephalosporins

›Francisella tularensis is intrinsically resistant

›Beta-lactamase production mediates resistance

›Frontiers in Microbiology 2023 evidence

›Carbapenems

›Also ineffective; avoid empiric coverage for suspected tularemia

›Most macrolides

›Azithromycin, clarithromycin

›Generally ineffective

›Azithromycin may have activity against European Type B strains only

›Lancet Infectious Diseases 2016 data

›Trimethoprim-sulfamethoxazole

›Variable in vitro activity

›Not recommended as monotherapy

›High clinical failure rates reported

Bioterrorism post-exposure prophylaxis

›Post-exposure prophylaxis protocol

›Confirmed or suspected aerosolized release

›Ciprofloxacin 500 mg orally twice daily for 14 days

›Or doxycycline 100 mg orally twice daily for 14 days

›MMWR 2025 CDC recommendation for post-exposure prophylaxis

›Mass casualty scenario

›Coordinate with public health authorities

›Stockpile medications under Strategic National Stockpile protocols

09Special Populations/sp68

Pregnancy

›Maternal and fetal risks

›Tularemia severity in pregnancy

›Increased severity risk with immunologic changes of pregnancy

›Preterm labour and fetal loss reported with severe infection

›Francisella tularensis can cross placenta

›Antibiotic safety considerations

›Gentamicin: preferred agent in severe disease despite aminoglycoside cautions

›Fetal ototoxicity theoretical but severe maternal disease justifies use

›Contraindicated antibiotics

›Ciprofloxacin and fluoroquinolones: avoid (cartilage toxicity concern)

›Doxycycline: avoid after first trimester (dental staining, hepatotoxicity risk)

›Recommended approach in pregnancy

›Severe disease

›Gentamicin 1.5 mg/kg IV every 8 hours with fetal monitoring

›Infectious disease and maternal-fetal medicine co-management

›Mild disease

›Doxycycline acceptable in first trimester if no alternative

›Individualize based on gestational age and severity

›Notification

›Obstetric team early involvement

›Neonatal team alert if delivery imminent

Geriatric

›Physiologic considerations

›Altered presentation

›Fever may be absent or blunted

›Confusion may be the dominant presenting feature

›Higher mortality risk with pneumonic form

10Background/b90

Epidemiology

›Global and regional burden

›Incidence

›Rare in most countries; United States reports 100-200 cases per year

›Sporadic cases across North America, Europe, and Central Asia

›Mortality up to 30-60% untreated pneumonic form; < 2% with appropriate treatment

›Endemic regions

›North America: Arkansas, Missouri, Oklahoma, Kansas highest reporting states

›Europe: Scandinavia, Finland, Turkey with periodic outbreaks

›Central Asia and Eastern Europe

›Transmission and forms

›Transmission routes

›Tick bites (Dermacentor variabilis and Amblyomma americanum in North America)

›Deerfly bites (Chrysops species)

›Contact with infected animals (rabbits, rodents, cats)

›Inhalation of contaminated aerosols or dust

›Ingestion of contaminated water or food

›Clinical forms

›Ulceroglandular: most common form (75-85% of cases)

›Pneumonic: primary (inhalation) or secondary (hematogenous spread)

›Typhoidal: systemic illness without localizing features

›Oculoglandular, oropharyngeal, glandular forms also described

›Seasonal and occupational patterns

›Summer peak from tick and deerfly activity

›Secondary winter peak from hunting season (rabbit handling)

›Hunters, farmers, veterinarians, landscapers, and laboratory workers at risk

Pathophysiology

›Organism characteristics

›Francisella tularensis microbiology

›Gram-negative, aerobic, intracellular coccobacillus

›Infective dose extremely low: 10-50 organisms by inhalation

›Type A (F. tularensis subsp. tularensis): more virulent, North America

›Type B (F. tularensis subsp. holarctica): less virulent, Europe and North America

›Intracellular survival mechanism

›Survives and replicates within macrophages and other phagocytes

›Escapes phagosomal killing by inhibiting phagosome-lysosome fusion

›Spreads to regional lymph nodes, then hematogenously

›Pulmonary pathology

›Primary pneumonic form

›Direct inhalation of organisms reaches alveoli

›Alveolar macrophages engulf bacteria but fail to kill them

›Neutrophilic and macrophage inflammatory infiltrates develop

›Necrotizing granulomatous inflammation in severe cases

›Secondary pneumonic form

›Hematogenous seeding of lungs from another primary site

›Associated with bacteremia and systemic illness

›Histopathology

›Necrotizing granulomas with central necrosis

›Peribronchial and interstitial lymphocytic infiltrates

›Organizing pneumonia patterns in subacute presentations

›Immune response

›Innate immunity

›Initial inflammatory response; TLR2 and TLR4 activation

›Cytokine storm in severe cases (TNF-alpha, IL-6, IL-1beta)

›Adaptive immunity

›Cell-mediated immunity critical for clearance

›Antibody response (IgM then IgG) forms basis of serologic diagnosis

›Immunosuppression markedly worsens prognosis

Therapeutic Considerations

›Antibiotic mechanism of action

›Aminoglycosides (gentamicin, streptomycin)

›Bactericidal: inhibit 30S ribosomal subunit; protein synthesis disruption

›Penetrate intracellular compartments to reach F. tularensis

›Historical gold standard with extensive clinical evidence

›Fluoroquinolones (ciprofloxacin, levofloxacin)

›Bactericidal: inhibit DNA gyrase and topoisomerase IV

›Excellent intracellular penetration and oral bioavailability

›CID 2024 fluoroquinolone data show high efficacy for severe Type B tularemia

›Doxycycline

›Bacteriostatic: inhibits 30S ribosomal subunit

›Good intracellular penetration but higher relapse rates (5-15%)

›Adequate for mild disease when aminoglycosides and fluoroquinolones unavailable

›Treatment duration considerations

›Severe disease

›10-14 days parenteral aminoglycoside therapy

›Transition to oral fluoroquinolone to complete 14-21 day course

›Mild-moderate disease

›14-21 days oral fluoroquinolone

›Duration extended if slow clinical response

›Relapse risk factors

›Short antibiotic courses < 10 days

›Doxycycline monotherapy

›Immunosuppressed host

›Treatment response monitoring

›Fever defervescence

›Expected within 24-72 hours with appropriate antibiotics

›Persistent fever beyond 5 days suggests treatment failure or complication

›Imaging response

›Radiographic improvement may lag clinical recovery by days to weeks

›Follow-up imaging at 6-8 weeks to exclude malignancy masquerade

›Bioterrorism context

›Strategic National Stockpile medications available for mass casualty

›CDC MMWR 2025 recommendations govern post-exposure prophylaxis protocols

11Patient Discharge Instructions/pdi25

copy discharge instructions

›Discharge instructions for tularemia

›Your diagnosis

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

›This infection is acquired from animals, ticks, deerflies, or contaminated water — not from other people

›Tularemia does not spread person-to-person; no isolation from family is needed

›Medications

›Take all prescribed antibiotic doses for the full course (14-21 days)

›Do not stop antibiotics early even if you feel better; stopping early can cause relapse

›Do not take penicillin or amoxicillin-type antibiotics — they do not work for tularemia

›Activity and recovery

›Rest during the recovery phase; fatigue and weakness may persist for weeks

›Gradually increase activity as strength returns

›Full recovery may take several weeks after completing antibiotics

›Follow-up

›Return to clinic or your doctor in 48-72 hours to assess treatment response

›A follow-up chest X-ray may be needed 6-8 weeks after discharge

›Inform your doctor immediately if symptoms worsen or you develop new symptoms

›Return to emergency department immediately if

›High fever returns or does not improve within 2-3 days of starting antibiotics

›Worsening shortness of breath or difficulty breathing

›Chest pain that is severe or worsening

›Dizziness, fainting, or severe weakness

›Confusion or altered mental status

›Inability to take medications due to vomiting

›Any symptoms that concern you or feel severe

12References/r40

Guidelines and key sources

›CDC MMWR 2025

›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 2025; PMID 41026652

›JAMA Bioterrorism Consensus 2001

›Dennis DT, Inglesby TV, Henderson DA, et al

›Tularemia as a Biological Weapon: Medical and Public Health Management

›JAMA 2001;285(21):2763-2773

›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

›CID Fluoroquinolone Outcomes 2024

›Widerström M, Mörtberg S, Magnusson M, Fjällström P, Johansson AF

›Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones

›Clin Infect Dis 2024; PMID 38294118

›Frontiers in Microbiology 2023

›Maurin M, Pondérand L, Hennebique A, et al

›Tularemia Treatment: Experimental and Clinical Data

›Front Microbiol 2023; PMID 38298538

›Lancet Infectious Diseases 2016

›Maurin M, Gyuranecz M

›Tularaemia: Clinical Aspects in Europe

›Lancet Infect Dis 2016; PMID 26738841

›International Journal of Infectious Diseases 2026

›Zaghdoudi A, Robin F, Moulinie J, et al

›Pulmonary Tularemia: A Diagnosis Not to Overlook

Evidence & Review

Evidence & Review