01Approach to the Critical Patient/attcp62

Immediate priorities

›Airway and breathing assessment

›Respiratory distress from pneumonic tularemia

›Tachypnea, use of accessory muscles

›SpO2 < 90% on room air

›Hemoptysis indicating severe pulmonary involvement

›If severe hypoxia unresponsive to supplemental O2, early intubation

›Pneumonic tularemia carries 30-60% mortality untreated

›Rapid sequence intubation preparation

›Oxygen supplementation target SpO2 92-96%

›High-flow nasal cannula for moderate hypoxia

›Non-invasive ventilation for selected patients without hemoptysis

›Circulation and sepsis threats

›Sepsis physiology from typhoidal or pneumonic form

›SBP < 90 mmHg

›MAP < 65 mmHg

›Lactate >= 2 mmol/l

›Septic shock resuscitation

›IV crystalloid 30 ml/kg bolus

›Norepinephrine if fluid-unresponsive hypotension

›Empiric antibiotics within 1 hour for sepsis

›Do NOT use beta-lactams — intrinsic resistance of F. tularensis

›Gentamicin or doxycycline as first empiric choice

Bioterrorism recognition

›CDC Category A agent recognition criteria

›Cluster of pneumonia cases without clear epidemiologic link

›Especially if no tick or animal exposure history

›Abrupt onset febrile illness with pleuropneumonia

02History/hx73

Exposure history

›Tick and arthropod exposure

›Tick bite within prior 14 days

›Dermacentor variabilis (American dog tick)

›Dermacentor andersoni (Rocky Mountain wood tick)

›Amblyomma americanum (lone star tick)

›Deer fly bite

›Outdoor activity in endemic region

›South-central US: Missouri, Arkansas, Oklahoma

›Great Plains states

›Parts of Massachusetts

›Animal contact

›Handling, skinning, or butchering rabbits, hares, or rodents

›Most common animal reservoir: cottontail rabbit

›Squirrels, muskrats, beavers also implicated

›Cat bite or scratch

›Mowing over animal carcasses (aerosol risk)

›Contact with sick or dead animals in the area

›Water and food exposure

›Untreated or natural water source ingestion

›Undercooked wild game consumption

Symptom onset and timeline

›Incubation period

›Typical 3-5 days from exposure

›Range 1-14 days

›Important for exposure dating

›Abrupt onset of constitutional symptoms

›High fever 38-40°C

03Physical Exam/exam59

Vital signs

›Temperature pattern

›Fever 38-40°C typical

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

›Key distinguishing feature from other febrile illnesses

›Tachypnea if pneumonic form

›Respiratory rate > 20 as indicator of pulmonary involvement

›Hypotension or tachycardia signaling sepsis

›Escalate to resuscitation bay

›MAP < 65 mmHg threshold for vasopressor consideration

Skin exam

›Inoculation site inspection

›Papule or ulcer with eschar

›Typically extremities (tick bite), hands/arms (animal handling)

›May be healed or inconspicuous at time of presentation

›Eschar characteristics

›Punched-out 1-3 cm ulcer with raised edges

›Central necrotic eschar

›Rash assessment

›Erythema nodosum on lower extremities (uncommon)

›Macular or papular rash in systemic disease

Lymph node exam

›Regional lymphadenopathy

›Tender, enlarged regional nodes correlating with inoculation site

›Inguinal/femoral for lower extremity bites

›Axillary for upper extremity contact

›Cervical for oropharyngeal form

›Suppurative or fluctuant nodes

04Differential Diagnosis/ddx68

Ulceroglandular mimics

›Cat scratch disease (Bartonella henselae)

›ICD-10: A28.1

›Cat contact, positive Bartonella serology

›Skin papule then axillary/cervical adenopathy

›Cutaneous anthrax

›ICD-10: A22.0

›Black eschar without pain (painless)

›Agricultural exposure, spore contact

›Plague (Yersinia pestis)

›ICD-10: A20.0

›Bubo more painful and tender

›Southwestern US flea exposure

›Sporotrichosis

›ICD-10: B42.9

›Gardening injury, rose thorn exposure

›Lymphocutaneous spread along lymphatics

›Staphylococcal or streptococcal lymphadenitis

›ICD-10: L04.9

›Local skin break as entry point

›No systemic constitutional features initially

Glandular and lymphadenopathy mimics

›Tuberculosis lymphadenitis

›ICD-10: A18.2

›Caseating necrotizing granulomas on biopsy (identical to tularemia)

›AFB stain and culture required for differentiation

›Lymphoma

›ICD-10: C85.90

05Laboratory Tests/lt61

Initial workup

›Complete blood count

›Leukocytosis with neutrophilia in most bacterial forms

›WBC typically 10-15 x10^9/L

›Leukopenia in severe typhoidal form (poor prognostic sign)

›Thrombocytopenia in septic presentations

›Platelet < 100 x10^9/L warrants close monitoring

›Metabolic panel

›Elevated transaminases (hepatitis in systemic form)

›ALT/AST 2-5x upper limit of normal

›Elevated creatinine

›Renal function critical for aminoglycoside dosing

›Hyponatremia (SIADH in severe pulmonary or CNS disease)

›Na < 130 mmol/l warrants fluid restriction

›Inflammatory markers

›C-reactive protein markedly elevated

›Often > 100 mg/L in pneumonic form

›Erythrocyte sedimentation rate elevated

›Nonspecific but supports systemic inflammatory process

›Procalcitonin

›Elevation supports bacterial etiology

›May guide antibiotic therapy duration

Microbiologic testing

›Blood cultures

›Two sets aerobic and anaerobic prior to antibiotics

›Bacteremia present in < 5% of cases

›Low yield but critical for severe disease

›Notify laboratory of suspected tularemia

06Diagnostic Tests/dt78

Scoring Systems

›Tularemia clinical severity classification

›Mild disease

›Ulceroglandular or glandular form

›Immunocompetent, no systemic toxicity

›Able to tolerate oral antibiotics

›Moderate disease

›Systemic symptoms but hemodynamically stable

›Oropharyngeal or early pneumonic form

›Severe disease

›Pneumonic or typhoidal form

›Sepsis criteria met

›Altered mental status

›Bioterrorism risk stratification

›Cluster of unexplained pneumonia cases

›No clear epidemiologic link to animals or ticks

›Rapid onset with high mortality

›Point score systems from CDC mass-casualty planning

›Not validated for individual patient use

›Guide public health response, not individual treatment

›IDSA sepsis criteria overlap

›SOFA score >= 2 with suspected tularemia infection

›Organ dysfunction triggers IV antibiotic escalation

›ICU-level care

MRI

›MRI brain for neurologic complications

›Indications

›Altered mental status with nuchal rigidity

›Seizures or focal neurologic deficits

›Suspected tularemia meningitis or encephalitis

›Findings in tularemia meningitis

›Leptomeningeal enhancement on gadolinium T1 sequences

›Cortical signal changes in encephalitis

›White matter hyperintensities on T2/FLAIR

›MRI musculoskeletal for suppurative lymphadenopathy

›Fluid collection characterization

›Rim enhancement indicating abscess formation

›Extension to adjacent structures

›Guides surgical drainage planning

›Preferred over CT for soft tissue delineation

CT

›CT chest for pneumonic tularemia

›Indications

›Suspected pneumonic form

›Abnormal chest radiograph requiring characterization

›Failure to improve on antibiotics

›Classic chest CT findings

›Bilateral peribronchial consolidations

›Ground-glass opacities

›Pleural effusions (25-30% of pneumonic cases)

›Mediastinal or hilar lymphadenopathy

›Pulmonary nodules (may mimic malignancy on PET/CT)

›Pulmonary tularemia on PET/CT

›Hypermetabolic mediastinal nodes and nodules

›May be misdiagnosed as lung cancer or lymphoma

›CT abdomen for systemic complications

›Hepatosplenomegaly with hypodense foci

›Granulomatous nodules in liver and spleen

›Mesenteric lymphadenopathy

›Abdominal pain and diarrhea context

›CT head before lumbar puncture

›Exclude mass lesion or elevated ICP prior to LP

›Mandatory if papilledema or focal deficits

Ultrasound

›Point-of-care ultrasound for lymph node assessment

›Suppurative lymphadenopathy evaluation

›Hypoechoic center with posterior enhancement indicates abscess

›Guides aspiration for diagnostic and therapeutic purposes

›Avoid aspiration of buboes without antibiotic coverage

›Differentiation from solid lymphoma nodes

›Lymphoma: homogeneous, well-defined, hypoechoic

›Tularemia: heterogeneous with central necrosis

›Pleural ultrasound for effusion

›Fluid volume assessment

›Anechoic or hypoechoic effusion

›Guides thoracentesis planning if needed

›Loculation assessment

›Septations suggest complicated parapneumonic effusion

›Hepatosplenic ultrasound

›Organomegaly measurement

›Splenic enlargement in typhoidal form

›Focal lesions suggesting abscess or granulomas

07Disposition/dispo43

Admission criteria

›Indications for inpatient admission

›Pneumonic or typhoidal tularemia

›IV aminoglycoside therapy required

›High mortality if undertreated

›Sepsis or hemodynamic instability

›ICU-level admission for septic shock

›Vasopressor requirement

›Immunocompromised status

›HIV with low CD4 count

›Active chemotherapy or transplant recipient

›Diagnostic uncertainty with concerning features

›Pending culture and serology

›Unable to exclude alternative severe diagnosis

›Inability to tolerate oral medications

›Nausea, vomiting, altered consciousness

ICU criteria

›Escalation to ICU for

›Septic shock refractory to initial resuscitation

›Ongoing vasopressor requirement

›Respiratory failure requiring intubation

›Pneumonic tularemia with progressive hypoxia

›Altered mental status or coma

›Typhoidal or meningitic form

›Multiorgan dysfunction

›Renal failure, hepatic failure, coagulopathy

Discharge criteria

›Outpatient management appropriate for

08Treatment/t77

Antibiotic therapy — severe disease

›Gentamicin (preferred first-line for severe disease)

›Adult dosing

›5 mg/kg/day IV as single daily dose

›Alternative: 1.5 mg/kg IV every 8 hours

›Duration 10-14 days

›Continue until 5-7 days afebrile

›Therapeutic drug monitoring

›Trough < 1 mg/L to minimize nephrotoxicity

›Peak 5-10 mg/L for bactericidal efficacy

›Renal function monitoring every 48 hours

›Dose adjustment for creatinine clearance < 50 ml/min

›Streptomycin (alternative if gentamicin unavailable)

›15 mg/kg IM every 12 hours

›Maximum 2 g per dose

›Duration 10 days

›Preferred historically but limited availability

›Ototoxicity and nephrotoxicity monitoring required

›Class I recommendation: IDSA and CDC guidelines

Antibiotic therapy — mild to moderate disease

›Ciprofloxacin (first-line oral for mild-moderate disease)

›500-750 mg PO twice daily

›Duration 14-21 days (2025 CDC recommendation)

›Preferred for lower relapse rate vs. doxycycline

›Relapse rate 5-10% with fluoroquinolones

›Lower than doxycycline (10-15%)

›IV formulation if unable to take PO

›400 mg IV every 12 hours

›Levofloxacin (alternative fluoroquinolone)

›500 mg PO once daily

›Duration 14-21 days

›Equivalent efficacy to ciprofloxacin

›Convenience of once-daily dosing

›Doxycycline (alternative when fluoroquinolone contraindicated)

›100 mg PO twice daily

›Duration 14-21 days

›Higher relapse rate 10-15% vs. fluoroquinolones

›Extended to 21 days to reduce relapse

›Contraindicated in pregnancy and children < 8 years

Step-down therapy

›IV to oral transition

›Switch from aminoglycoside to oral fluoroquinolone or doxycycline

›After clinical improvement: afebrile 48-72 hours, tolerating PO

›Complete total 14-21 day course with oral agent

›Step-down from IV ciprofloxacin to oral

›When hemodynamically stable and GI function restored

Drugs to avoid

›Beta-lactam antibiotics — intrinsic resistance

›Francisella tularensis produces beta-lactamases

›Penicillins, cephalosporins, carbapenems ineffective

›Key pitfall: failure of empiric beta-lactam therapy should prompt tularemia consideration

›IDSA guideline: do not use beta-lactam monotherapy

›Most macrolides — largely ineffective

›Azithromycin has limited activity (exception: mild type B in pregnancy)

›Clarithromycin, erythromycin: not recommended

›Chloramphenicol

›Higher relapse rates than aminoglycosides or fluoroquinolones

›Use only when no alternatives available

›Reserved for tularemia meningitis when IV penetration required

Post-exposure prophylaxis

›Prophylaxis for intentional exposure (bioterrorism)

›Ciprofloxacin 500 mg PO twice daily for 14 days

›Or doxycycline 100 mg PO twice daily for 14 days

›Initiate within 24 hours of exposure

›2025 CDC recommendation: fluoroquinolone preferred for prophylaxis

›Prophylaxis for accidental laboratory exposure

›Same regimen as bioterrorism prophylaxis

›Consult infectious disease and occupational health

›Monitor for symptom development

Supportive care

›Fever management

›Acetaminophen 650 mg PO every 6 hours

›NSAID caution in renal impairment

›Active cooling measures for hyperpyrexia > 40.5°C

›Fluid management

›IV crystalloid for sepsis and dehydration

›Lactated Ringer's or normal saline 30 ml/kg initial bolus

›Nutritional support for prolonged illness

›Weight loss and anorexia common in extended illness

›Surgical management of lymphadenopathy

›Needle aspiration or incision and drainage for fluctuant buboes

›Typically required weeks after antibiotic initiation

›Culture aspirate for resistance testing

09Special Populations/sp64

Pregnancy

›Antibiotic selection in pregnancy

›Severe disease: gentamicin preferred

›Despite aminoglycoside ototoxicity risk, benefit outweighs risk

›5 mg/kg/day IV with close fetal monitoring

›Renal function monitoring mandatory

›Mild type B tularemia (Francisella tularensis subsp. holarctica)

›Azithromycin may be considered as alternative

›Limited evidence; infectious disease consultation required

›Doxycycline contraindicated in pregnancy

›Risk of fetal tooth discoloration and skeletal effects

›Fluoroquinolones relatively contraindicated (cartilage risk)

›Obstetric considerations

›Tularemia bacteremia may cause spontaneous abortion

›Fetal monitoring for intrauterine growth restriction

›Placental transmission not well-documented but possible

›Neonatal surveillance if maternal infection near term

›Standard infection control precautions adequate

›No vertical transmission documented in breastfeeding

Geriatric

›Pharmacokinetic adjustments

›Aminoglycoside dosing

›Reduced creatinine clearance requires dose reduction

›Use Cockcroft-Gault equation for GFR estimation

›Enhanced monitoring for nephrotoxicity and ototoxicity

›Fluoroquinolone caution

›QTc prolongation risk in elderly with cardiac comorbidities

›Obtain baseline ECG before starting

10Background/b77

Epidemiology

›Incidence and distribution

›United States epidemiology

›Approximately 100-200 cases reported annually in the US

›South-central states account for majority: Missouri, Arkansas, Oklahoma

›Also endemic in Great Plains and parts of Massachusetts

›All states except Hawaii have reported cases

›Global distribution

›Northern hemisphere: US, Canada, Europe, Russia, Japan

›Highest incidence in Scandinavia and Russia

›European cases predominantly Francisella tularensis subsp. holarctica (type B)

›Demographics

›Bimodal age distribution

›Peak 1: children 5-9 years

›Peak 2: men > 55 years

›Male predominance (hunting and outdoor activity)

›Seasonal peaks

›Summer (June-August): tick and deer fly transmission

›Winter (November-December): hunting-related cases

›Mortality and morbidity

›Overall case fatality rate 1-3% with appropriate treatment

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

›Delayed treatment > 2-3 weeks: significantly worse outcomes

›Relapse rates 5-15% depending on antibiotic class

Pathophysiology

›Organism characteristics

›Francisella tularensis — gram-negative coccobacillus

›Extremely low infectious dose: as few as 10 organisms by inhalation

›10-50 organisms by skin or mucous membrane inoculation

›Two major subspecies

›Francisella tularensis subsp. tularensis (type A)

›North America

›More virulent; higher mortality

›Francisella tularensis subsp. holarctica (type B)

›Europe, Asia, North America

›Less virulent; milder disease

›Immune evasion mechanisms

›Intracellular pathogen

›Survives and replicates within macrophages and neutrophils

›Escapes phagolysosomal killing

›Inhibits neutrophil apoptosis prolonging intracellular survival

›Suppresses pro-inflammatory cytokine response early in infection

›Delays innate immune activation

›Granuloma formation as host response

›Caseating necrotizing granulomas mimic tuberculosis

›Lymph node histology may be indistinguishable from TB

›Transmission routes

›Vector-borne: tick bite, deer fly bite

›Direct contact: handling infected animals or carcasses

›Inhalation: mowing, lab accidents, bioterrorism aerosol

›Ingestion: contaminated water or undercooked meat

›No person-to-person transmission documented

Therapeutic Considerations

›Antibiotic mechanism and rationale

›Aminoglycosides (bactericidal)

›Inhibit bacterial 30S ribosomal subunit protein synthesis

›Penetrate intracellular compartments

›Gold standard for severe disease

›Fluoroquinolones (bactericidal)

›Inhibit DNA gyrase and topoisomerase IV

›Excellent intracellular penetration

›Preferred for oral step-down and mild disease

›Tetracyclines (bacteriostatic)

›Inhibit 30S ribosomal subunit

›Higher relapse rate due to bacteriostatic mechanism

›Adequate for mild disease with full 21-day course

›Beta-lactam resistance mechanism

›Francisella tularensis produces class A beta-lactamase (BlaB)

›Hydrolyzes penicillins and early cephalosporins

›Class C beta-lactamase also present

›Treatment failure with beta-lactams is a diagnostic clue

›Evidence base

›Gentamicin vs. streptomycin: equivalent efficacy

›Gentamicin preferred due to wider availability and IM/IV flexibility

›Fluoroquinolones vs. doxycycline: fluoroquinolones superior

›Lower relapse rate 5-10% vs. 10-15%

›2024 CID surveillance data supports fluoroquinolone preference

›2025 CDC MMWR recommendations: most current guidance

›Fluoroquinolone first-line for mild-moderate naturally acquired disease

›Aminoglycoside first-line for severe disease and bioterrorism response

11Patient Discharge Instructions/pdi37

copy discharge instructions

›Discharge instructions for tularemia

›Your diagnosis

›You have been diagnosed with tularemia, a bacterial infection caused by Francisella tularensis

›It is typically acquired from tick bites, handling wild animals, or outdoor exposures

›It is NOT contagious from person to person

›Your medications

›Take your prescribed antibiotic exactly as directed

›Complete the full course: 14-21 days as prescribed

›Do not stop early even if you feel better

›Take ciprofloxacin with a full glass of water

›Avoid antacids, calcium, iron within 2 hours of ciprofloxacin

›Take doxycycline with food and a full glass of water to reduce stomach upset

›Expected recovery

›Symptoms typically improve within 48-72 hours of starting antibiotics

›Complete recovery may take several weeks

›Fatigue and weakness may persist during recovery

›Lymph nodes may remain swollen or drain for weeks to months

›Follow-up appointments

›Return to your doctor within 1 week to assess response

›Repeat blood tests may be needed at 2-4 weeks (serology)

›Report any new or worsening symptoms to your doctor immediately

›Preventing future infections

›Wear long sleeves and pants in tick-endemic areas

›Use DEET-based insect repellent

›Check for ticks after outdoor activity and remove promptly

›Wear gloves when handling wild animals or carcasses

›Avoid untreated water from natural sources

12References/r17

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. PMID 41026652

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

›Maurin M, Gyuranecz M. Tularaemia: Clinical Aspects in Europe. Lancet Infect Dis. 2016;16(1):113-124. PMID 26738841

›Epidemiology and surveillance

›Tularemia - United States, 2001-2010. MMWR Morb Mortal Wkly Rep. 2013. PMID 24280916

›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

›Clinical management references

›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

›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. PMID 22911645

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

›Special topics

›Widerström M, Mörtberg S, et al. Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones. Clin Infect Dis. 2024. PMID 38294118

›Adalja AA, Toner E, Inglesby TV. Clinical Management of Potential Bioterrorism-Related Conditions. N Engl J Med. 2015. PMID 26200985

›Ho BM, Davis HE, Forrester JD, et al. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States. Wilderness Environ Med. 2021

›Zaghdoudi A, Robin F, Moulinie J, et al. Pulmonary Tularemia: A Diagnosis Not to Overlook. Int J Infect Dis. 2026. PMID 41482246

›Evans ME, Gregory DW, Schaffner W, McGee ZA. Tularemia: A 30-Year Experience With 88 Cases. Medicine. 1985. PMID 3892222

Evidence & Review