01Approach to the Critical Patient/attcp33

Immediate recognition

›High-risk presentation triggers

›High fever >39 C with hemodynamic instability

›Suggests progression to typhoidal or septic tularemia

›Immediate IV access and fluid resuscitation

›Altered mental status, confusion, or meningeal signs

›Rare but documented complication: meningitis and brain abscess

›Urgent lumbar puncture consideration if meningism present

›Vision loss or rapidly worsening vision

›Corneal ulceration or severe orbital inflammation

›Emergent ophthalmology consultation

›Cough, dyspnea, or pleuritic chest pain

›Hematogenous spread to lungs (secondary pneumonic tularemia)

›Chest imaging and expanded antibiotic planning

Stabilization priorities

›Hemodynamic assessment

›SBP <90 mmHg or MAP <65 mmHg

›IV fluid resuscitation 30 ml/kg crystalloid

›Norepinephrine if refractory to fluids

›Sepsis screening

›Lactate target <2 mmol/l

›Broad-spectrum antibiotics within 1 hour if septic shock

›Escalation to ICU level care for organ dysfunction

›Class I recommendation for early goal-directed sepsis management

›Blood cultures x2 before antibiotics

Consult triggers

›Mandatory early consultations

›Ophthalmology for all cases

02History/hx57

Exposure and mechanism

›Conjunctival inoculation mechanism

›Handling infected animals (rabbits, hares, rodents)

›Touching eyes after contact with infected carcass

›Splash of contaminated water into eyes

›Arthropod vector

›Tick bite followed by self-inoculation (touching bite site then eyes)

›Deerfly bite near periocular area

›Aerosol or laboratory exposure

›Working with F. tularensis cultures without biosafety precautions

›Exposure to contaminated soil or vegetation aerosol

Symptom onset and timeline

›Incubation and progression

›Incubation period 3-5 days (range 1-21 days)

›Sudden onset of eye pain, redness, and tearing

›Fever developing concurrently with ocular symptoms

›Lymph node involvement

›Painful preauricular or submandibular swelling days after ocular symptoms

›Suppuration of nodes in approximately 30% of cases

›Mean time to diagnosis approximately 41 days

›Delayed diagnosis drives complication rate of 31.5%

›High clinical suspicion needed to avoid delays

Core symptoms

›Ocular symptoms

›Unilateral eye burning and pain

›Photophobia

›Excessive lacrimation

›Blurred vision

03Physical Exam/exam47

Vitals

›Hemodynamic and temperature assessment

›Fever often >38.5 C

›Tachycardia as systemic marker

›Hypotension if systemic or septic progression

›Respiratory rate

›Tachypnea if pulmonary involvement

›Oxygen saturation screen for pneumonic spread

Ocular exam

›Conjunctival findings

›Unilateral conjunctival injection with chemosis

›Conjunctival ulceration (pathognomonic when present)

›Vasculitis pattern on slit-lamp exam

›Granulomatous nodules on palpebral conjunctiva

›Yellow-white follicular lesions

›Differentiated from bacterial purulent conjunctivitis

›Corneal involvement

›Fluorescein exam for ulceration

›Corneal involvement suggests severity and risk of vision loss

Lymph node exam

›Regional lymphadenopathy

›Preauricular nodes (most common regional site)

›Tender, enlarged, firm nodes

›Parinaud's oculoglandular syndrome definition

›Submandibular and cervical nodes

›Secondary nodal involvement from drainage

›Fluctuance indicating suppuration requiring drainage

›Suppuration assessment

04Differential Diagnosis/ddx35

Parinaud's oculoglandular syndrome causes

›Infectious mimics of oculoglandular tularemia

›Cat scratch disease (Bartonella henselae)

›Most common cause of Parinaud's oculoglandular syndrome

›History of cat scratch or bite near eye; Bartonella serology positive

›ICD-10: A28.1

›Sporotrichosis (Sporothrix spp.)

›Ocular inoculation from contaminated plant material or cat scratch

›Diagnosed by culture

›Tuberculosis

›Chronic granulomatous conjunctivitis; PPD or IGRA positive

›ICD-10: A18.59

›Yersinia enterocolitica or pseudotuberculosis

›Rare cause of Parinaud's syndrome; associated GI symptoms

›ICD-10: A04.6

Conjunctivitis mimics

›Common conjunctivitis differential

›Adenoviral conjunctivitis

›Typically bilateral and follicular

›No suppurative lymphadenopathy

›Chlamydial inclusion conjunctivitis

›Mucopurulent, often bilateral

›Sexually active young adults; urogenital symptoms

›Herpes simplex keratoconjunctivitis

›Dendritic ulcer on fluorescein exam

›Vesicular eyelid lesions

›ICD-10: B00.53

05Laboratory Tests/lt45

Serology

›Tularemia serology (primary confirmatory test)

›Tube agglutination or microagglutination titer

›Single titer >=1:160 supportive of diagnosis

›4-fold rise between acute and convalescent sera (2-4 weeks apart) confirms diagnosis

›Convalescent sample at 2-4 weeks post-infection

›ELISA for IgM and IgG

›IgM appears by week 1-2 of illness

›IgG persists for years (may indicate past exposure)

›Cross-reactivity limitation

›False positives with Brucella, Yersinia, and Proteus OX-19

Microbiological testing

›Culture and molecular diagnostics

›Blood culture (low yield, but obtain in systemic disease)

›Requires biosafety level 3 handling

›Notify laboratory of suspected tularemia before sending

›Conjunctival swab culture

›Requires special media (cysteine-enriched agar)

›Sensitivity limited; negative culture does not exclude diagnosis

›PCR (most rapid confirmatory test)

›Conjunctival swab, lymph node aspirate, or blood

›High sensitivity and specificity; result in 24-48 hours

›Preferred for early diagnosis before serologic response

Routine supporting labs

›Inflammatory and organ function markers

›Complete blood count

›Leukocytosis with left shift in systemic disease

›Thrombocytopenia possible in severe infection

06Diagnostic Tests/dt44

Scoring Systems

›Clinical diagnostic framework

›No validated point-based scoring system for tularemia

›Diagnosis based on clinical syndrome plus exposure history

›Parinaud's oculoglandular triad: unilateral granulomatous conjunctivitis + regional lymphadenopathy + systemic fever

›Epidemiologic criteria supporting diagnosis

›Compatible exposure within 21 days of symptom onset

›Endemic region or season

›Occupation or activity with animal or vector contact

›CDC case definition

›Confirmed: culture-positive or 4-fold titer rise or positive PCR

›Probable: compatible clinical illness with single titer >=1:160 or positive DFA

MRI

›MRI indications in tularemia

›Orbital MRI for suspected orbital cellulitis or abscess

›Differentiates preseptal from postseptal inflammation

›Indicates if surgical drainage required

›Brain MRI for neurologic complications

›Meningitis: leptomeningeal enhancement

›Brain abscess: ring-enhancing lesion

›Encephalitis pattern: T2/FLAIR signal abnormality

›MRI neck for deep space lymph node assessment

›Suppurative lymphadenitis versus abscess

›Guides drainage planning

CT

›CT applications for tularemia complications

›CT chest for pulmonary involvement

›Hilar lymphadenopathy as marker of systemic spread

07Disposition/dispo30

Admission criteria

›Indications for inpatient admission

›Systemic toxicity

›High fever with hemodynamic instability

›Lactate elevation or organ dysfunction

›Complicated local disease

›Suspected or confirmed lymph node suppuration requiring drainage

›Vision-threatening corneal involvement

›Orbital cellulitis or abscess

›Requirement for IV antibiotics

›Unable to tolerate oral medications

›Severe disease requiring aminoglycoside therapy

›Host factors

›Immunocompromised patients

›Elderly or frail with high systemic burden

Discharge criteria

›Eligibility for outpatient management

›Hemodynamically stable and afebrile or defervescing

›Tolerating oral antibiotics without GI intolerance

›No vision-threatening findings on ophthalmology exam

›Reliable follow-up arranged

›Ophthalmology within 48-72 hours

›Primary care or infectious disease at 1-2 weeks

›Clear return precautions provided

›Patient understands worsening symptoms requiring ED return

Transfer and escalation

›Transfer triggers

›Suspected secondary pneumonic tularemia

08Treatment/t58

Antibiotic therapy - first line

›Mild to moderate oculoglandular tularemia (oral outpatient)

›Ciprofloxacin 500 mg PO BID x 10-14 days

›First-line per 2025 CDC guidelines for naturally acquired infection

›Lower relapse rate 5-10% compared to doxycycline

›Fluoroquinolones designated first-line for outbreaks of any size (MMWR 2025)

›Doxycycline 100 mg PO BID x 14-21 days

›Alternative first-line oral agent

›Relapse rate approximately 10-15%

›Minimum 14 days to reduce relapse risk

Antibiotic therapy - severe disease

›Severe or systemic tularemia (IV regimen)

›Gentamicin 5 mg/kg/day IV daily (or divided q8h) x minimum 10 days

›Preferred IV agent for severe disease

›Adjust dose for renal impairment using creatinine clearance

›Monitor trough levels (<1 mg/l) and peak levels (5-10 mg/l)

›Streptomycin 1 g IM BID x minimum 10 days

›Historically first-line aminoglycoside

›Availability limited in many centers

›Preferred in pregnancy for severe disease

Contraindicated and ineffective agents

›Antibiotics to avoid

›Beta-lactams (penicillins, cephalosporins, carbapenems)

›F. tularensis is intrinsically resistant

›Do not use as monotherapy or empiric coverage

›Most macrolides

›Generally ineffective against F. tularensis

›Azithromycin has limited role only in type B strains

09Special Populations/sp43

Pregnancy

›Pregnant patients with tularemia

›Preferred antibiotic selection

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

›Azithromycin may be considered for mild type B infections in select settings

›Ciprofloxacin: use with caution (musculoskeletal concerns, limited data)

›Agents to avoid in pregnancy

›Doxycycline: avoid in all trimesters (fetal bone and tooth development)

›Streptomycin: potential fetal ototoxicity

›Maternal-fetal considerations

›Maternal fever and sepsis increase risk of preterm labor and fetal loss

›Aggressive antipyretic management with acetaminophen

›Obstetric consultation mandatory

›Fetal monitoring in viable pregnancy

›Multidisciplinary infectious disease and obstetrics team

Geriatric

›Older adults with tularemia

›Increased risk of systemic disease

›More frequent typhoidal presentation in older age

›Higher risk of organ dysfunction and sepsis

›Aminoglycoside dosing adjustments

›Renal function decline with age requires dose reduction

›Creatinine clearance-based dosing for gentamicin

›Extended-interval dosing with level monitoring

›Drug interactions and tolerability

›Fluoroquinolone QTc prolongation in polypharmacy

›Doxycycline photosensitivity with outdoor activity history

›Delayed presentation recognition

10Background/b62

Epidemiology

›Epidemiologic data for tularemia

›Overall tularemia incidence in the US

›Approximately 100-200 cases reported annually in the United States

›Oculoglandular form accounts for approximately 3% of all tularemia cases

›Demographic distribution

›Male sex predominates (65% of US cases)

›Peak incidence in summer months correlating with tick and deerfly season

›Geographic distribution

›South-central US most affected: Arkansas, Missouri, Oklahoma

›Endemic in Northern Hemisphere: Scandinavia, Turkey, Central Europe

›Sporadic cases on all continents except Australia

›Transmission modes

›Tick bite most common route (69% of US cases; Dermacentor, Amblyomma)

›Animal contact (rabbits, hares, rodents): key route for oculoglandular form

›Deerfly bite, contaminated water, inhalation, laboratory exposure

›Complication and mortality data

›Complication rate approximately 31.5% largely from delayed diagnosis

›Mean time to diagnosis approximately 41 days

›Overall case fatality rate <2% with appropriate treatment; higher without

Pathophysiology

›Francisella tularensis biology and disease mechanism

›Organism classification

›Francisella tularensis: small gram-negative coccobacillus

›Type A (tularensis): highly virulent, North America

›Type B (holarctica): less virulent, North America and Europe

›Conjunctival inoculation and local infection

›F. tularensis enters via conjunctival mucosa after direct inoculation

11Patient Discharge Instructions/pdi30

copy discharge instructions

›Tularemia (oculoglandular form) discharge instructions

›What is tularemia

›Bacterial infection caused by Francisella tularensis acquired from animals or insect bites

›Your form affects the eye and nearby lymph nodes

›Not contagious person-to-person; your family is safe

›Your medications

›Take all antibiotic doses exactly as prescribed (10-21 days depending on antibiotic)

›Do not stop antibiotics early even if you feel better; relapse is common with incomplete courses

›Ciprofloxacin: take with plenty of water; avoid dairy products or antacids within 2 hours

›Doxycycline: take with full glass of water; stay upright for 30 minutes after dose; avoid sun exposure

›Eye care at home

›Artificial tears for discomfort 4-6 times daily

›Cool compresses to eye for swelling

›Do not touch or rub your eye

›Wear sunglasses outdoors if sensitive to light

›Follow-up appointments

›Ophthalmology appointment within 48-72 hours for eye check

›Return to your doctor in 1-2 weeks to confirm improvement

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

›Return to emergency department immediately for

›Worsening eye pain, vision changes, or new eye symptoms

›Increasing swollen lymph node size, redness, or drainage from node

›Persistent or recurrent fever after 48-72 hours of antibiotics

›New cough, chest pain, or shortness of breath

›Confusion, severe headache, or neck stiffness

›Prevention for the future

›Wear gloves when handling wild animals or carcasses

12References/r21

Guidelines and key sources

›Primary guidelines and landmark references

›Nelson CA et al. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response - United States, 2025. MMWR. 2025. PMID: 41026652

›2025 CDC MMWR guidelines: fluoroquinolones and doxycycline as first-line for tularemia

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

›Comprehensive clinical review including oculoglandular form epidemiology and outcomes

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

›Landmark bioterrorism preparedness guidelines for F. tularensis

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

›Comprehensive treatment evidence review including MIC data and relapse rates

›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

›2025 comprehensive clinician-focused review

›Copur B, Surme S. Water-Borne Oculoglandular Tularemia: Two Complicated Cases and a Review of the Literature. Travel Med Infect Dis. 2022. PMID: 36334909

›Oculoglandular-specific review with complication data and timeline to diagnosis

›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

›WMS tick-borne illness guidelines including tularemia management

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

›Comprehensive tick-borne disease reference including tularemia

›Weber IB, Turabelidze G, Patrick S et al. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. CID. 2012. PMID: 22911645

›Large US case series informing epidemiology and clinical features

›Adalja AA, Toner E, Inglesby TV. Clinical Management of Potential Bioterrorism-Related Conditions. NEJM. 2015

›Bioterrorism framework for tularemia and other Category A agents

Evidence & Review

Evidence & Review