01Approach to the Critical Patient/attcp64

Immediate priorities

›Airway and breathing assessment

›Respiratory status evaluation

›Oxygen saturation on room air

›Respiratory rate trend

›Oxygenation failure triggers

›SpO2 < 90% on room air

›Rising work of breathing

›Secondary pneumonia concern

›Any new respiratory symptoms in confirmed tularemia mandate urgent chest imaging

›Hematogenous spread can occur in any clinical form

›Circulation and sepsis assessment

›Shock physiology markers

›SBP < 90 mmHg

›MAP < 65 mmHg

›Lactate >= 2 mmol/l

›Sepsis screening

›Suspected tularemia with organ dysfunction

›Typhoidal form or untreated ulceroglandular progressing to systemic illness

›If septic shock, initiate aminoglycoside within 1 hour

›Gentamicin 5 mg/kg/day IV preferred for severe disease

›Blood cultures prior to antibiotics when feasible

›Key decision branching

›Ulceroglandular pattern identification

›Cutaneous ulcer at inoculation site

›Painful regional lymphadenopathy

›Exposure history to ticks, rabbits, or wild game

›Systemic progression concern

02History/hx56

Exposure and timeline

›Tick exposure

›Most common US vector accounting for approximately 69% of cases

›Peak incidence in summer months (June through September)

›Ixodes, Dermacentor, and Amblyomma species implicated

›Animal contact

›Handling rabbits, hares, or rodents

›Skinning or butchering wild game without gloves

›Cat bites or scratches as increasingly recognized route

›Dead animal sightings or mowing over animal carcasses

›Incubation and onset

›Incubation period typically 3 to 5 days

›Range 1 to 21 days

›Patients typically seek care after median of 3 days of illness

Symptom characterization

›Systemic symptoms

›Abrupt onset fever 38 to 40 C

›Rigors and chills

›Headache

›Myalgia

›Malaise and anorexia

›Local symptoms

›Skin lesion or ulcer at inoculation site

›Develops after initial febrile period

›May be overlooked in hair-bearing areas

›Painful swollen regional lymph nodes

›Inguinal or femoral for lower extremity bites

›Axillary for upper extremity inoculation

03Physical Exam/exam52

Vitals and general appearance

›Vital sign pattern

›Temperature 38 to 40 C in most patients

›Hyperpyrexia above 40 C in severe cases

›Lack of fever does not exclude disease in immunocompromised

›Pulse-temperature dissociation

›Relative bradycardia for degree of fever in up to 42% of patients

›Shared feature with typhoid fever, Legionella, and brucellosis

›Blood pressure

›SBP < 90 mmHg or MAP < 65 mmHg indicates hemodynamic compromise

›General appearance

›Toxic appearing with systemic illness

›Prostration in severe forms

›Mental status alteration in typhoidal conversion

Skin and lymph node examination

›Inoculation site ulcer

›Classic ulcer characteristics

›Well-demarcated punched-out ulcer with raised edges

›Central eschar formation

›Surrounding erythema

›Location reflects exposure route

›Lower extremities for tick bites

›Hands for direct animal contact

›May be hidden in scalp, axilla, or groin

›Regional lymphadenopathy

›Painful tender enlarged nodes

›Typically unilateral

›Nodes range 1 to 5 cm or larger

04Differential Diagnosis/ddx46

Life-threatening diagnoses

›Cannot-miss diagnoses

›Bubonic plague

›ICD-10 A20.0

›Bubo formation with more rapid progression and higher mortality

›Exposure to rodent fleas; absence of ulcer at inoculation site

›Cutaneous anthrax

›ICD-10 A22.0

›Painless black eschar with surrounding gelatinous edema

›No significant regional lymphadenopathy initially

›Necrotizing soft tissue infection

›ICD-10 M72.6

›Rapidly progressive systemic toxicity disproportionate to local findings

›Surgical emergency distinguishes from tularemia

›Septic tularemia complication

›Tularemia septicemia

›ICD-10 A21.7

›Bacteremia with multiorgan dysfunction

›Untreated ulceroglandular can progress to typhoidal form

Common mimics

›Infectious mimics

›Cat scratch disease (Bartonella henselae)

›ICD-10 A28.1

›Cat exposure with lymphadenopathy but typically less systemic toxicity

›No ulcer at inoculation site distinguishes from tularemia

›Staphylococcal or streptococcal lymphadenitis

›ICD-10 L04.9

›Responds to beta-lactams unlike tularemia

05Laboratory Tests/lt55

Serology and confirmatory testing

›Serology (primary diagnostic method)

›Agglutination antibody titer

›Single titer >= 1:160 supports diagnosis

›Fourfold rise in paired sera confirms diagnosis

›Paired sera collected 2 to 4 weeks apart

›Antibodies detectable by second week of illness

›May remain positive for years after infection

›ELISA IgM and IgG

›Earlier IgM rise than agglutination in some series

›Combined IgM and IgG ELISA improves sensitivity

›Limitations

›Cross-reactivity with Brucella species

›Early illness serology may be negative; repeat at 2 to 4 weeks

›Culture

›Blood culture

›Low yield in ulceroglandular form

›Bacteremia more common in typhoidal form

›Alert laboratory to suspected F. tularensis due to BSL-2 handling requirements

›Lymph node aspirate or ulcer swab culture

›Requires BSL-2 facility; notify laboratory before submitting

›Sensitivity enhanced by special media (BCYE agar or modified Thayer-Martin)

›Laboratory safety

›F. tularensis is classified as a select agent requiring special handling

›Laboratory notification essential to prevent occupational exposure

Molecular diagnostics

›PCR testing

›Ulcer swab or lymph node aspirate PCR

06Diagnostic Tests/dt70

Scoring Systems

›Tularemia clinical probability assessment

›No validated formal scoring system specific to tularemia

›Diagnosis remains clinically and epidemiologically driven

›Exposure history plus compatible syndrome is primary framework

›Key diagnostic criteria combination

›Tick or animal exposure in endemic area

›Fever with ulcer and regional lymphadenopathy

›Failure to respond to beta-lactam antibiotics

›Severity stratification

›Mild to moderate: ulceroglandular without systemic toxicity, suitable for outpatient fluoroquinolone

›Severe: systemic toxicity, hypotension, respiratory compromise — parenteral aminoglycoside

›Typhoidal: no localizing signs, high fever, sepsis — ICU level care

›Bioterrorism assessment scoring

›Epidemiologic clues suggesting intentional release

›Cluster of febrile patients without identifiable exposure

›Large number of pneumonia cases in non-endemic urban area

›Unusual strain or exposure route identified

›Action threshold

›Any concern for intentional release triggers immediate public health notification

›FBI and CDC notification in bioterrorism scenario

MRI

›MRI role in tularemia

›Limited routine utility

›Not indicated for initial diagnosis of ulceroglandular form

›Availability and time constraints in febrile infectious workup

›Problem-solving indications

›Lymph node characterization when CT equivocal for lymphoma versus infection

07Disposition/dispo41

Admission and level of care

›Outpatient management criteria

›Mild to moderate ulceroglandular tularemia

›No systemic toxicity or hemodynamic instability

›Able to tolerate oral medications and fluids

›Reliable follow-up within 48 to 72 hours

›Oral antibiotic regimens suitable for outpatient

›Ciprofloxacin 500 to 750 mg PO BID for 10 to 14 days

›Levofloxacin 500 mg PO daily for 10 to 14 days

›Doxycycline 100 mg PO BID for 14 to 21 days

›Inpatient admission indications

›Systemic toxicity or high fever with prostration

›Inability to tolerate oral intake

›Respiratory symptoms suggesting secondary pneumonia

›Immunocompromised host

›Diagnostic uncertainty requiring workup

›Suppurative lymphadenopathy requiring drainage

›ICU level care indications

›Septic shock with vasopressor requirement

›Respiratory failure requiring supplemental oxygen escalation

›Altered mental status or meningitis concern

›Typhoidal tularemia with multiorgan involvement

Transfer and public health

›Transfer criteria

›Lack of BSL-2 or reference laboratory capability for confirmatory testing

›Surgical drainage expertise unavailable

›ICU capability exceeded at receiving facility

›Public health obligations

08Treatment/t79

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

09Special Populations/sp67

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

10Background/b73

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

11Patient Discharge Instructions/pdi34

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

12References/r26

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

Evidence & Review

Evidence & Review