01Approach to the Critical Patient/attcp55

Airway and severe disease priorities

›Airway threat from lymphadenopathy

›Retropharyngeal or parapharyngeal node extension

›Stridor as warning sign

›Drooling or inability to swallow

›Trismus limiting airway examination

›Muffled or hot potato voice

›Inability to open mouth fully

›If airway compromise suspected, immediate ENT and anesthesia involvement

›Anticipate difficult airway

›CT neck with contrast before intubation attempt if time permits

›Sepsis and systemic toxicity

›Sepsis screening

›Temperature above 38.5 C or below 36 C

›Heart rate above 90 per minute

›MAP below 65 mmHg

›If septic shock, broad spectrum antibiotics within 1 hour

›Include gentamicin 5 mg/kg IV for severe tularemia

›Class I recommendation for sepsis bundle

›Lactate measurement

›Above 2 mmol/l as organ hypoperfusion marker

›Repeat within 2 hours if elevated

›Bioterrorism and public health alert

›Tularemia is a CDC Tier 1 select agent and bioterrorism category A pathogen

›Cluster cases without clear natural exposure source should prompt alert

›Immediate notification to public health authorities required

›Notify local health department for all confirmed or suspected cases

›Nationally notifiable disease in the United States

02History/hx56

Presentation pattern

›Core symptoms

›Severe sore throat

›Abrupt onset

›Odynophagia often severe enough to limit oral intake

›Neck swelling and pain

›Tender cervical lymphadenopathy

›Submandibular or posterior cervical region common

›Fever

›Abrupt onset 38 to 41.5 C

›Chills and rigors

›Associated symptoms

›Constitutional

›Headache

›Myalgia and arthralgia

›Malaise and fatigue

›Gastrointestinal

›Nausea and vomiting

›Diarrhea and abdominal pain

›Oropharyngeal

›Oral ulcers occasionally

›Ear pain from otitis media complication

Exposure and risk history

›Ingestion exposure

›Untreated or unchlorinated water

›Wells, springs, or streams in endemic areas

›Waterborne outbreaks predominant source for oropharyngeal form

›Undercooked wild game

03Physical Exam/exam63

Vitals and general appearance

›Vital sign pattern

›Temperature

›High fever 38 to 41.5 C typical

›Hypothermia as severe sepsis marker

›Heart rate

›Relative bradycardia (pulse-temperature dissociation) in up to 42% of patients

›Tachycardia suggests sepsis or secondary pneumonia

›Blood pressure

›Hypotension indicates sepsis requiring immediate intervention

›MAP below 65 mmHg as resuscitation trigger

›General appearance

›Toxic appearance and degree of distress

›Severe odynophagia limiting swallowing

›Drooling suggesting airway threat

›Voice quality

›Muffled or hot potato voice

›Stridor on inspiration

Oropharyngeal and neck exam

›Oropharyngeal findings

›Pharyngeal erythema and exudate

›Unilateral or bilateral tonsillar exudate

›Pseudomembrane formation possible

›Oral ulcers

›Shallow ulcerations on tonsils or soft palate

›Distinguish from herpangina or aphthous ulcers

›Trismus

›Jaw opening limitation from parapharyngeal involvement

04Differential Diagnosis/ddx41

Infectious mimics

›Bacterial pharyngitis

›Streptococcal pharyngitis

›ICD-10 J02.0

›Rapid strep positive distinguishes; tularemia negative

›Peritonsillar abscess

›Uvular deviation and fluctuance

›Fever with unilateral tonsillar fullness

›Diphtheria

›Pseudomembrane adherent to posterior pharynx

›ICD-10 A36.0

›Rare in vaccinated populations

›Lymphadenopathy-predominant infections

›Infectious mononucleosis

›Heterophile antibody positive

›Atypical lymphocytes and splenomegaly

›Cat scratch disease

›Bartonella henselae serology and PCR

›Cat exposure history

›Cervical tuberculosis (scrofula)

›ICD-10 A18.2

›Caseating granulomas on biopsy histologically identical to tularemia

Malignant mimics

›Lymphoma

›Hodgkin lymphoma

›Constitutional B symptoms

›Hypermetabolic nodes on PET-CT overlap with tularemia

›Non-Hodgkin lymphoma

05Laboratory Tests/lt57

Microbiology and serology

›Serology (primary diagnostic tool)

›Tube agglutination or microagglutination

›Titre above 1:160 presumptive positive

›Single titre greater than or equal to 1:128 supportive in endemic context

›Paired acute and convalescent titres confirm seroconversion

›Four-fold rise in titre

›Convalescent sample at 2 to 4 weeks

›ELISA serology

›IgM and IgG detection

›Sensitivity improves after 7 to 10 days of illness

›PCR

›Real-time PCR on pharyngeal swab or lymph node aspirate

›High sensitivity in early disease

›Reference laboratory submission required

›Rapid result within 24 to 48 hours

›Culture

›Biosafety level 3 laboratory required

›Alert microbiology laboratory before submission

›Throat swab or lymph node aspirate as specimen

›Growth on cysteine enriched media

›Slow growing organism

›3 to 5 days for visible colonies

Inflammation and infection markers

›Complete blood count

›Leukocyte count variable

›Normal or mildly elevated early

›Leukocytosis with left shift in severe disease

06Diagnostic Tests/dt79

Scoring Systems

›Tularemia severity stratification

›Mild disease

›Pharyngitis with reactive cervical lymph nodes

›Stable vital signs

›Able to tolerate oral intake

›Moderate disease

›Exudative tonsillitis with prominent lymphadenopathy

›High fever and systemic symptoms

›Borderline oral tolerance

›Severe disease

›Suppurative or conglomerate lymphadenopathy

›Retropharyngeal extension or airway compromise

›Signs of systemic dissemination (pneumonia, sepsis, meningitis)

›Bioterrorism classification relevance

›CDC category A agent designation

›High potential for deliberate dispersal

›Significant public health impact

›Cluster of unexplained pharyngitis unresponsive to beta-lactams

›Epidemiologic alert threshold

›Coordinate with public health immediately

MRI

›MRI neck indications

›Limited acute utility due to availability and time constraints

›Not first-line in emergency setting

›CT preferred for acute evaluation

›Problem-solving indications

›Complex soft tissue plane assessment

07Disposition/dispo44

Admission indications

›Criteria requiring inpatient care

›Inability to tolerate oral intake or medications

›Severe odynophagia

›Persistent vomiting

›Airway concern

›Stridor or voice change

›Bulky retropharyngeal adenopathy on imaging

›Severe systemic illness

›Hemodynamic instability

›Sepsis or septic shock

›Need for parenteral antibiotics

›Severe disease requiring gentamicin or streptomycin

›Immunocompromised host

›ICU indications

›Septic shock

›Vasopressor requirement

›Lactate above 4 mmol/l despite resuscitation

›Respiratory failure from secondary pneumonia

›Intubation or HFNC requirement

›Altered mental status

›Typhoidal tularemia or meningitic complication

Discharge criteria

›Outpatient management criteria

›Stable vital signs

›Afebrile or low-grade fever trending down

›Normal heart rate and blood pressure

›Tolerating oral antibiotics and fluids

08Treatment/t67

Initial stabilization

›Supportive measures

›IV fluid resuscitation

›Normal saline or lactated Ringer 500 mL bolus for dehydration

›Target MAP above 65 mmHg in septic patients

›Antipyretics and analgesia

›Acetaminophen 1000 mg PO or IV every 6 hours for fever and throat pain

›Ibuprofen 400 to 600 mg PO every 6 to 8 hours as alternative if renal function adequate

›Oral hygiene and care

›Warm saline gargles for comfort

›Soft or liquid diet as tolerated

Antibiotic therapy — mild to moderate disease

›First-line oral regimens (2025 CDC recommendations)

›Ciprofloxacin

›500 mg PO BID for 10 to 14 days

›Lower relapse rate compared to tetracyclines (5 to 10%)

›Monitor for tendon rupture and QT prolongation

›Avoid in patients with prolonged QTc

›Levofloxacin

›500 mg PO daily for 10 to 14 days

›Alternative fluoroquinolone when ciprofloxacin not tolerated

›QT prolongation monitoring required

›Doxycycline

›100 mg PO BID for 14 to 21 days

›Higher relapse rate (10 to 15%) compared to fluoroquinolones

›Photosensitivity counseling required

›Avoid prolonged sun exposure

09Special Populations/sp67

Pregnancy

›Antibiotic selection in pregnancy

›Fluoroquinolones (relative avoidance)

›Potential cartilage toxicity in fetal animal models

›Used when benefits outweigh risks in severe disease

›Doxycycline (avoid especially after 15 weeks)

›Fetal bone and tooth staining

›Avoid after mid-second trimester

›Gentamicin (preferred for severe disease in pregnancy)

›5 mg/kg IV once daily with fetal monitoring

›Renal and audiologic monitoring in mother

›Risk of fetal eighth nerve toxicity with prolonged use

›Maternal management considerations

›Hydration and fever control

›Fever above 38.5 C associated with fetal risk

›Acetaminophen preferred for antipyresis

›Fetal monitoring

›Continuous electronic fetal monitoring if gestational age viable

›Obstetric consultation for all pregnant patients

›Imaging approach

›Neck ultrasound preferred to avoid radiation

›CT neck only when airway assessment critical and benefits outweigh risks

Geriatric

›Atypical presentation features

›Blunted fever response

›Temperature below 38 C may still represent significant infection

›Afebrile presentation possible in frail older adults

›Delirium as presenting symptom

10Background/b77

Epidemiology

›Global distribution

›Northern Hemisphere endemic zones

›North America: south-central United States especially Missouri, Arkansas, Oklahoma

›Europe: Scandinavia, Turkey, Kosovo, Balkan peninsula

›Russia and Central Asia

›Re-emerging zoonosis

›Increased European incidence since 1990s

›Waterborne outbreaks in Kosovo and Turkey

›United States burden

›Approximately 100 to 200 cases reported annually

›Actual incidence likely higher due to underdiagnosis

›MMWR 2001 to 2010: 1,208 reported cases

›Seasonal pattern

›Late summer to autumn peak in tick-borne transmission

›Waterborne outbreaks variable across seasons

›Oropharyngeal form prevalence

›Predominant form in waterborne outbreaks

›Accounts for majority of cluster cases

›Associated with poor sanitation and water quality

›Represents approximately 10 to 30% of all tularemia cases in endemic areas

›Proportional increase during outbreaks

Pathophysiology

›Organism characteristics

›Francisella tularensis subspecies

›Type A (tularensis): North America, higher virulence

›Type B (holarctica): Europe and Asia, typically less severe

›Extremely low infectious dose

›Fewer than 10 organisms required for infection by inhalation

›Ingestion requires higher inoculum (greater than 10 to the 8th organisms)

›Environmental survival

›Survives for weeks in cold water, mud, and animal carcasses

›Explains waterborne outbreak potential

›Mechanism of infection in oropharyngeal form

›Entry via mucosal surfaces of oropharynx

›Ingestion of contaminated water or undercooked meat

›Local mucosal invasion and replication

›Intracellular pathogen

›Survives and replicates within macrophages and neutrophils

›Inhibits phagosome-lysosome fusion

›Lymphatic dissemination

›Regional lymph node invasion and intense inflammatory reaction

›Granuloma formation with central necrosis

›Histologically identical to tuberculosis

›Systemic dissemination pathway

›Bacteremia from lymph node breakdown

›Hematogenous spread to lung, liver, spleen

›Secondary pneumonia most common systemic complication

›Inflammatory response

›Granulomatous inflammation in multiple organs

›Suppuration and abscess formation in affected nodes

Therapeutic Considerations

›Antibiotic mechanism and rationale

›Aminoglycosides (gentamicin, streptomycin)

›Intracellular penetration adequate for bactericidal effect

›Historical standard of care with low relapse rates

›Toxicity limits outpatient use

›Fluoroquinolones (ciprofloxacin, levofloxacin)

›Excellent intracellular penetration

›2025 CDC designation as first-line for naturally acquired and outbreak management

›Relapse rate 5 to 10%

›Tetracyclines (doxycycline)

›Bacteriostatic mechanism results in higher relapse rate 10 to 15%

›Second-line to fluoroquinolones

›Longer course required (14 to 21 days)

›Treatment failure considerations

›Overall treatment failure rate approximately 15%

›Higher with delayed treatment beyond 2 to 3 weeks of illness

›Fluoroquinolones associated with lower failure rates

›Suppurative lymphadenopathy

›Occurs in approximately 30% of patients with lymphadenopathy

›May develop weeks after antibiotic initiation

›Surgical drainage required in approximately 23% of these cases

›Public health and bioterrorism context

›Bioterrorism preparedness protocol

›Stockpile of ciprofloxacin and doxycycline for mass prophylaxis

›Rapid laboratory identification protocols at reference centers

›No person-to-person transmission

›Standard precautions adequate for hospital management

›Contact tracing focuses on shared water or food source

11Patient Discharge Instructions/pdi41

copy discharge instructions

›Tularemia (oropharyngeal) home care instructions

›Take all antibiotics exactly as prescribed

›Ciprofloxacin or doxycycline for the full course (10 to 21 days)

›Do not stop early even if feeling better

›Manage throat pain and fever

›Acetaminophen or ibuprofen as directed

›Soft diet or liquids until swallowing improves

›Drink adequate fluids

›At least 2 litres of water per day

›Avoid dehydration from difficulty swallowing

›Warning signs requiring immediate return to emergency department

›Airway red flags

›Difficulty breathing, stridor, or noisy breathing

›Inability to swallow or drooling

›Significant worsening of neck swelling

›Infection worsening signs

›Fever continuing after 72 hours of antibiotics

›New confusion or unusual behaviour

›New cough, chest pain, or shortness of breath

›Antibiotic side effects

›Severe tendon pain or rupture (ciprofloxacin)

›Severe skin rash or photosensitivity reaction

›Follow-up instructions

›Recheck appointment in 5 to 7 days

›Clinical response assessment

›Convalescent blood tests at 2 to 4 weeks if diagnosis not confirmed

›Lymph node monitoring

12References/r22

Guidelines and key sources

›CDC and government guidelines

›Nelson CA et al. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response — United States, 2025. MMWR Recomm Rep. 2025. https://pubmed.ncbi.nlm.nih.gov/41026652

›CDC Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers, Sixth Edition. 2022. https://www.cdc.gov/ticks/media/pdfs/2025/03/tickborne-diseases-manual-508.pdf

›MMWR Tularemia — United States, 2001–2010. 2013. https://pubmed.ncbi.nlm.nih.gov/24280916

›Key clinical reviews

›Dennis DT et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. 2001. https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.285.21.2763

›Maurin M, Gyuranecz M. Tularaemia: Clinical Aspects in Europe. Lancet Infect Dis. 2016. https://pubmed.ncbi.nlm.nih.gov/26738841

›Antonello RM et al. Tularemia for Clinicians: An Up-to-Date Review on Epidemiology, Diagnosis, Prevention and Treatment. Eur J Intern Med. 2025. https://pubmed.ncbi.nlm.nih.gov/40107886

›Maurin M et al. Tularemia Treatment: Experimental and Clinical Data. Front Microbiol. 2023. https://pubmed.ncbi.nlm.nih.gov/38298538

›Outbreak and clinical studies

›Esmaeili P et al. Oropharyngeal Tularemia Outbreak Linked to Drinking Contaminated Tap Water in North-Western Iran. Diagn Microbiol Infect Dis. 2024. https://pubmed.ncbi.nlm.nih.gov/39146636

›Weber IB et al. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. Clin Infect Dis. 2012. https://pubmed.ncbi.nlm.nih.gov/22911645

›Cakir Kiymaz Y et al. Evaluation of Clinical Characteristics, Laboratory Parameters, and Antibiotic Treatment in Patients Diagnosed With Tularemia. J Infect Chemother. 2025. https://pubmed.ncbi.nlm.nih.gov/39481537

›Kossadoum RF et al. Tularemia in Pediatric Patients: A Case Series and Review of the Literature. Pediatr Infect Dis J. 2025. https://pubmed.ncbi.nlm.nih.gov/39312633

›Diagnostic and microbiology references

›Miller JM et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by IDSA and ASM. Clin Infect Dis. 2024. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciae104

›Ho BM et al. Wilderness Medical Society Clinical Practice Guidelines for Prevention and Management of Tick-Borne Illness. Wilderness Environ Med. 2021. https://journals.sagepub.com/doi/10.1016/j.wem.2021.09.001

›ICD-10 coding

›ICD-10 A21.2 Pulmonary tularemia

›ICD-10 A21.3 Gastrointestinal tularemia

›ICD-10 A21.8 Other forms of tularemia (including oropharyngeal)

›ICD-10 A21.9 Tularemia unspecified

Evidence & Review

Evidence & Review