Continuing Education Activity

Tularemia is an acute febrile zoonotic infection caused by the highly infectious organism Francisella tularensis and may present with ulceroglandular, glandular, oculoglandular, oropharyngeal, gastrointestinal, pneumonic, or typhoidal disease, depending on the route of exposure. Because early symptoms may be nonspecific and laboratory confirmation can be delayed, clinicians must promptly recognize exposure risks, clinical syndromes, and treatment considerations. The identified practice gap is inconsistent clinician competence in recognizing tularemia, selecting appropriate diagnostic strategies, initiating timely antimicrobial therapy, and coordinating laboratory and public health communication. This activity addresses the gap by strengthening diagnostic reasoning, improving the selection of evidence-based treatments based on disease severity and patient characteristics, reinforcing prevention and biosafety measures, and promoting coordinated interprofessional care to reduce delayed diagnosis, prevent complications, and improve patient-centered outcomes.

Objectives:

• Identify epidemiologic clues, including zoonotic and environmental exposures, to suggest tularemia as a possible diagnosis.
• Differentiate tularemia from other causes of ulceroglandular, pneumonic, and systemic febrile illnesses based on clinical and epidemiologic features.
• Determine appropriate diagnostic strategies for suspected tularemia, including indications for laboratory testing and public health notification.
• Coodinate as an interprofessional team to manage health care exposures and specify antimicrobial agent selection, route of administration, and duration of therapy based on evidence-based recommendations for tularemia.

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Introduction

Tularemia is an acute febrile zoonotic illness caused by the highly infectious gram-negative bacterium Francisella tularensis. Clinicians should maintain a high degree of clinical suspicion for tularemia infections because symptoms can vary by route of infection. F tularensis is one of the most infectious bacterial agents capable of causing human infection because as few as 10 to 25 organisms can cause illness. Several bacterial subspecies are known, and their virulence and geographic range also vary. Tularemia infections in humans present with a wide range of symptoms, including skin ulcers, lymphadenopathy, oral and gastrointestinal tract symptoms, and pneumonia, depending on the initial route of infection. In the US, tularemia is uncommon, with most cases reported in the South Central states associated with tick or animal exposure. In other parts of the world, waterborne exposure is also reported. Importantly, the organism’s high infectivity and multiple modes of transmission give it significant potential as a bioweapon, as detailed in the Etiology and Treatment and Management sections below.

Etiology

Tularemia is caused by the highly infectious gram-negative intracellular coccobacillus Francisella tularensis.[1] The organism was primarily characterized in the early 1900s in California, where it was associated with many ground squirrel deaths. The first confirmed human case occurred in 1914, presenting with oculoglandular tularemia, characterized by ocular inflammation, fever, and lymphadenopathy. However, similar symptoms had been previously reported in other parts of the world following hare ingestion in the 19th century.[2] Although tularemia is commonly associated with rabbits and hares, which has led to the nickname "rabbit fever," it has been reported in more than 150 animal reservoirs across the Northern Hemisphere.[3] 

Infection can occur with a small number of organisms through various entry sites, including inhalation, direct contact with infected animals or animal tissue through nonintact skin or mucous membranes, ingestion, or the bite of a tick, fly, or mosquito vector.[2] The organism can survive environmental temperature extremes, including in frozen animal carcasses, and may persist in aquatic environments for prolonged periods.[2][4] However, thorough cooking can lessen the risk of transmission. Tularemia has also been rarely associated with animal bites or scratches, particularly from cats.[5][6] Human-to-human transmission is exceedingly rare but theoretically possible through direct contact with infected tissue, such as during autopsy or in other health care settings, or in the setting of an organ transplant.[7]

F tularensis has 4 subspecies, with F tularensis subspecies tularensis (type A) causing the majority of human infections and the most severe disease in North America. Less severe disease is associated with F tularensis subspecies holarctica (type B) in other parts of the Northern Hemisphere, including Europe.[8] In addition to variations in disease severity across subtypes, differences in antibiotic susceptibility may occur, with greater success with fluoroquinolone treatment reported in type B disease.[9] Arthropod vectors also differ: ticks are more common in type A disease, and mosquitoes are more common in type B disease.[10]

Tularemia has multiple potential clinical presentations. The type of tularemia a patient develops depends on the mode of infection. For example, ulceroglandular disease presents with an ulcer at the site of inoculation after either an insect bite or direct contact between skin or other tissue and infected animal tissue. Oropharyngeal and gastrointestinal tract disease can occur after ingestion of infected animal tissue, foods washed in water contaminated with tularemia, or direct ingestion of contaminated water. Pneumonic disease occurs after airborne exposure to the organism, which has been reported in various settings, including lawnmower dispersion of infected animal tissue, animal-facilitated aerosolization of infected animal tissue by rolling or shaking, farm exposures associated with hay or sugar cane handling where plant material is exposed to potentially infected wildlife, aerosol-generating procedures associated with animal processing, and laboratory exposures.[2][7][11][12][13][14] Regional variation in clinical presentation occurs. For example, in the US, where tick-borne illness is common, ulceroglandular syndromes are predominant. In parts of Europe and Turkey, where waterborne infections are most common, oropharyngeal and gastrointestinal tract symptoms are typical.[15] 

The organism is considered a Tier 1 select agent by the United States Federal Select Agent Program, indicating the greatest risk for a potential bioterrorism attack.[7] Multiple reports describe military and other investigations of potential germ warfare using tularemia in the 20th century and beyond, including reports suggesting that tularemia has been used through waterborne dispersion in wartime. Models of airborne tularemia dispersal in a densely populated area, the highest-impact projected bioterrorism scenario, predict thousands of casualties from pneumonic tularemia, with likely delays in diagnosis and treatment and multiple waves of illness over several weeks, given the organism's ability to persist in the environment. An outbreak of severe, atypical pneumonia that does not respond to empiric antibiotics in an urban area should trigger concern for possible intentional tularemia exposure.[16]

Epidemiology

Tularemia infections are reported throughout the Northern Hemisphere and occur in a wide variety of vertebrates, with rabbits and hares historically considered the primary reservoirs.[17] Tularemia is not endemic in the Southern Hemisphere or the tropics but has recently been reported in Australia in rare cases.[4][18] Infection occurs most often during the warmer summer months and early fall through tick or fly bites or the handling of infected animal tissue. In the US, infection is most frequently reported in the South Central states of Arkansas, Missouri, and Oklahoma, with the remainder of cases occurring sporadically elsewhere in the country.[19] Notably, tularemia has been repeatedly reported on Martha's Vineyard, an island in Massachusetts outside the south-central US, following the introduction of rabbits from Arkansas and Missouri in the 1930s, highlighting the importance of animal reservoirs as sources of infection.[20] The known incidence of tularemia in the United States peaked in the 1930s and decreased steadily through the 1950s and 1960s, with only 100 to 200 cases reported annually since the 1960s.[2][20] However, the reported incidence of tularemia increased in the US and parts of Europe through the 2010s, which could be due to either increased diagnostic sensitivity and surveillance or a true increase in infection.[19][21]

In general, tularemia is most commonly reported in men.[19][21] In US reports, tularemia occurs most commonly in children aged 5 to 9 years, followed by men aged 65 to 84 years.[19] Importantly, different patterns of infection across age groups are observed, depending on exposures such as hunting parties or occupational risks. The risk of infection is increased in the following populations:

• Laboratory workers
• Farmers and landscapers
• People who work with animals, including veterinarians and those in the exotic pet trade
• People who handle meat or animal tissue, such as hunters, taxidermists, or those working at animal processing plants [2][4][11][13][20][22]

Tularemia outbreaks may also occur during environmental and societal disruptions associated with natural and other disasters because of increased exposure to animal reservoirs of infection, reduced preventive practices such as insect repellent use or safe food handling, and increased reliance on potentially contaminated water supplies.[7]

Pathophysiology

Exposure to as few as 10 organisms can lead to human infection.[2] Once inside the body, the organism rapidly multiplies, and clinical symptoms typically appear 3 to 6 days after exposure (range, 1 to 21 days).[2][9] Ulceration is common, although not universal, at the site of entry, and local lymphadenopathy usually follows.

F tularensis can infect a wide variety of immune and nonimmune cells, leading to necrosis and microabscess formation at multiple sites.[1][2] Macrophages and other immune cells phagocytose the organism through complement-mediated and other mechanisms. F tularensis then escapes the phagosome and replicates within the cytosol of host cells.[23][24] Upon cell death, the cytosolic bacteria can spread to adjacent host cells.[17] F tularensis has many other immune-evasion adaptations, including an atypical lipopolysaccharide structure that is less inflammatory than that of other gram-negative bacteria.[17][25] The multitude of immune-evasion mechanisms has made the development of effective vaccines challenging.

Histopathology

Microabscesses and necrosis are commonly identified on biopsy. Granuloma formation can also be seen and may be mistaken for tuberculosis or atypical mycobacterial infection in lymph nodes or lung tissue.[2][26]

History and Physical

Patients with tularemia present with a variety of symptoms and physical examination findings, depending on the route of infection.[4] A detailed travel, occupational, and personal activity history may reveal exposures, such as ingestion of game or groundwater, participation in outdoor activities, such as handling carcasses while hunting, or arthropod bites. However, the absence of a history of a tick bite or other definitive exposure does not exclude the diagnosis of tularemia, because an arthropod bite may go unnoticed and environmental exposures are often unrecognized or underreported, particularly in children.[27]

Results from serologic studies suggested that asymptomatic or mild infections can occur, but most patients present with symptoms within 1 week of exposure.[2] Among all syndromes, fever, headache, and malaise are common early in illness. In most endemic areas, glandular and ulceroglandular tularemia are the most common clinical presentations.[13][14][28][29][30][31] Ulceroglandular tularemia presents with an ulcer at the site of inoculation and tender regional lymphadenopathy. Glandular tularemia, in which regional lymphadenopathy occurs without an ulcer, is common after inoculation via various routes. In younger children, both glandular and ulceroglandular tularemia often present with head and neck symptoms, which may reflect tickborne transmission and can be missed in hair or oropharyngeal exposures.[1][27] In adults, symptoms can present in the upper extremities following direct exposure to infected tissue during hunting activities or more diffusely with other exposure risks.[32]

Other clinical tularemia syndromes include:

• Oculoglandular (Parinaud oculoglandular syndrome): unilateral painful exudative conjunctivitis and regional lymphadenopathy; occurs from touching eyes after exposure to contaminated material or aerosol exposure
• Oropharyngeal: severe exudative pharyngitis and usually unilateral regional submandibular or cervical lymphadenopathy; follows ingestion or inhalation, when organisms contact mucous membranes
• Gastrointestinal tract: abdominal pain, diarrhea, and vomiting; follows ingestion
• Pneumonic: severe, potentially hemorrhagic bilateral pneumonia with hilar adenopathy; follows inhalation
• Typhoidal: systemic illness characterized by fever, septic shock, and hepatosplenomegaly; can occur following any route of inoculation [1][9][32]

In all presentations with associated lymphadenopathy, the lymph node may develop fluctuance as the disease progresses, even after the resolution of systemic symptoms. Erythema nodosum or erythema multiforme–like skin lesions can occur with any clinical syndrome of tularemia.[9][32][33] Rare clinical presentations have been reported, likely resulting from systemic or typhoidal tularemia, including endocarditis, meningitis, brain abscess, septic arthritis, osteomyelitis, and others.[32][34][35][36] The presentation of tularemia in pregnant women does not differ substantially from that in the general population. Similarly, presentations in immunocompromised patients are consistent with the syndromes above, with a potentially increased proportion of systemic infections and more invasive syndromes.[37]

Table

A 35-year-old man presents to the emergency department in the South Central US with a 5-day history of cough and shortness of breath. He was diagnosed with bilateral pneumonia by his primary care clinician 3 days ago and has been taking amoxicillin-clavulanate (more...)

Evaluation

Diagnosis of tularemia requires a high degree of clinical suspicion because the disease may be difficult to confirm with laboratory testing. Clinicians should carefully consider clinical syndromes and exposures in all patients. Importantly, because tularemia does not respond to the β-lactam antibiotics typically used as first-line therapy for skin lesions, lymphadenitis, pneumonia, and other clinical syndromes similar to tularemia, a lack of response to empiric β-lactam therapy is a clue for clinicians to consider tularemia in the differential diagnosis.[20][28][27]

Typical evidence of bacterial infection, such as leukocytosis on a complete blood count or elevated inflammatory markers such as the erythrocyte sedimentation rate or C-reactive protein, may or may not be present in tularemia. Laboratory abnormalities are more commonly reported in the early days of illness or in severe disease. However, laboratory values are often normal regardless of clinical symptoms and therefore cannot be relied on to rule out active infection.[10][15][38] 

Necrotic regional adenopathy, including potential abscesses, may be identified on ultrasonography, computed tomography, or other imaging in multiple tularemia syndromes.[39][40] Radiographic findings of pneumonic tularemia are variable and may include diffuse or localized infiltrates and bilateral hilar adenopathy.[2] Bronchoscopic findings typically include local or diffuse hemorrhagic inflammation, with potential granulomatous-appearing foci.[41]   

As noted above in histopathology, inflammation, granulomatous changes, and microabscesses may be observed in tissue samples from lymph nodes, pulmonary lesions, or skin lesions. Phagocytosed bacilli are rarely identified on histopathologic staining.[26] Review findings indicate that tularemia meningitis is associated with lymphocytic pleocytosis in the cerebrospinal fluid rather than the neutrophilic pleocytosis common in other forms of bacterial meningitis.[34]

In most cases, the mainstay of diagnosis is serology, given the limitations of molecular testing and the challenges of direct culture. Serologic diagnosis, with either an initial titer greater than 1:160 or a 4-fold rise between the initial and convalescent serologic samples, is most commonly used to confirm tularemia across all clinical syndromes.[1] Clinicians should recognize that early testing results may be negative because antibodies may take 10 to 20 days to form. Therefore, an initial negative serology result does not rule out tularemia infection, and follow-up confirmatory testing in 2 to 4 weeks is recommended to evaluate for an antibody rise over time.[27] Furthermore, negative serologic testing should not preclude antitularemia treatment when a patient's symptoms are consistent with a tularemia clinical syndrome.

F tularensis can also be cultured from blood, spinal fluid, lymphatic tissue, and skin lesion swabs for definitive diagnosis of tularemia. However, culturing F tularensis should be performed under highly controlled conditions, such as in a biosafety level 3 laboratory within a biological safety hood, because accidental inhalation by laboratory workers poses a significant risk of pneumonic tularemia.[4][42] F tularensis requires cysteine-enriched agar for growth and typically forms smooth, pale, green colonies after 2 to 5 days of incubation under ideal conditions.[2] Because tularemia is a select agent and potential bioweapon, local authorities, such as the Centers for Disease Control and Prevention in the US, must be notified when handling the organism in bacterial culture.[4] Clinical laboratory personnel must be advised of potential tularemia exposure when handling cultures of lymph node tissue, wound exudate, or other potentially infected tissue in endemic areas, or when exposure is suspected, so they can take appropriate protective measures. The laboratory should also be notified, because tularemia culture requires specialized media and longer incubation times. Although not widely available, the organism can be identified by polymerase chain reaction in certain settings and tissues.[1][43]  

Treatment / Management

To date, no randomized controlled trials have defined the optimal antibiotic treatment for tularemia, including the optimal agent, route, or duration, given the disease’s relative rarity in typical settings. Aminoglycosides have long been reported as effective therapy and are historically the drugs of choice. Evidence first established the effectiveness of intravenous streptomycin and was then extended to intravenous gentamicin for 7 to 14 days.[32] With increasing experience using other agents for tularemia, the Centers for Disease Control and Prevention now recommends multiple first-line options for adults with mild or moderate tularemia, including:

• Ciprofloxacin 400 mg intravenously (IV) every 8 hours or 750 mg orally every 12 hours for 10 days
• Levofloxacin 750 mg IV or orally every 24 hours for 10 days
• Gentamicin 6 mg/kg IV or intramuscularly (IM) every 24 hours for 10 days
• Doxycycline 200 mg loading dose then 100 mg IV or orally every 12 hours for 14 to 21 days [7]

For children older than 1 month with mild or moderate tularemia, the following regimens are recommended:

• Ciprofloxacin 10 mg/kg (maximum 400 mg/dose) every 8 to 12 hours IV or 15 mg/kg (maximum 500 mg/dose every 8 hours or 750 mg every 12 hours) every 8 to 12 hours orally for 10 days
• Levofloxacin 10 mg/kg IV or orally every 12 hours (maximum 375 mg/dose) for children younger than 5 years, or 10 mg/kg (maximum of 750 mg/dose) IV or orally every 24 hours for children older than 5 years for 10 days
• Gentamicin 5-7.5 mg/kg IV or IM every 24 hours for 10 days
• Doxycycline 4.4 mg/kg (maximum 200 mg) loading dose followed by 2.2 mg/kg (maximum 100 mg/dose) for 14 to 21 days [7]

For children younger than 1 month of age with mild or moderate tularemia, the following regimens are recommended:

• Ciprofloxacin 10 mg/kg IV every 8 or 12 hours for 10 days
• Gentamicin dosed based on postnatal age for 10 days [7]

For severe disease in all groups, an aminoglycoside is the recommended regimen consistent with other recent recommendations.[7][32] Although no controlled studies support the use of dual therapy, such as a fluoroquinolone and an aminoglycoside, in severe disease, it is used in some cases. Alternatives that may be considered in some groups include moxifloxacin, ofloxacin, minocycline, tetracycline, azithromycin (specifically for type A and susceptible type B), amikacin, and tobramycin.[7] In areas where streptomycin is still available, the drug may also be considered.[32] In pregnant women, ciprofloxacin, levofloxacin, and gentamicin are considered first-line options.[7] These recommendations are based on published clinical experience, even though most of these antibiotics are not approved by the Food and Drug Administration for the treatment of tularemia.

In some cases, incision and drainage of affected lymph nodes may be needed, particularly if the patient has been ill for a prolonged period before treatment.[3][27] Additionally, patients with endocarditis may require valve replacement. In addition to systemic antibiotics, topical antibiotics of a similar class, such as tobramycin or ciprofloxacin, may be helpful in oculoglandular tularemia. However, no clinical trials definitively support this treatment.[44] Based on current evidence, topical antibiotics should be used in addition to systemic antibiotics to speed recovery rather than as monotherapy. In suspected bioterrorism mass-casualty scenarios, oral therapy with a fluoroquinolone (ciprofloxacin or levofloxacin) or doxycycline is recommended to facilitate broad-scale treatment. Oral therapy may also be used as postexposure prophylaxis.[7] 

Differential Diagnosis

The differential diagnosis for tularemia is largely driven by the clinical syndrome present, such as ulceroglandular, glandular, or pneumonic tularemia. General considerations include:

• Bartonellosis
• Tuberculosis
• Sporotrichosis
• Staphylococcal infections
• Streptococcal infections
• Epstein-Barr virus or cytomegalovirus infection
• Legionella pneumonphilia infection
• Psittacosis
• Q-fever
• Plague
• Anthrax

Prognosis

Outcomes, including symptom duration, antibiotic failure, lymph node suppuration, and mortality, are improved with early and effective therapy.[31][45] Ulceroglandular or glandular tularemia is very rarely fatal, but recovery can be prolonged for weeks to months without prompt treatment.[1][16] Fatigue, pain, and malaise may be particularly prolonged in some patients.[46] If pneumonic, typhoidal, or other invasive tularemia syndromes are not treated, mortality rates can reach 30% to 60%.[1][2] Typhoidal tularemia carries the highest mortality. Tularemia during pregnancy may be associated with complications, based on results from human and animal studies that have associated tularemia with early pregnancy loss.[47]

Complications

Abscess formation is common in patients with untreated ulceroglandular or glandular tularemia, or in those with any syndrome involving lymphadenopathy, but it is also reported with pneumonic tularemia, meningitis, and other tularemia syndromes.[10][27][40][48][49][50] Less common complications include:

• Acute respiratory distress syndrome
• Renal failure
• Rhabdomyolysis [51][52][53]

Although not technically complications of tularemia infection, monitoring for adverse effects of antimicrobial treatment is recommended. For example, as in many gram-negative organisms, patients with severe disease may experience a Jarisch-Herxheimer–like reaction characterized by worsening inflammation, fever, and other systemic symptoms following initial doses of aminoglycoside therapy, as organisms are killed and highly inflammatory bacterial components are released into the circulation.[7][54] In addition, the aminoglycosides most commonly used to treat tularemia, gentamicin and streptomycin, may cause ototoxicity and nephrotoxicity in some patients. In general, gentamicin has a more favorable adverse-effect profile than streptomycin and is thus more widely used. The risk of renal injury can be decreased with once-daily dosing and close monitoring of drug levels and renal function (urine output and serum creatinine), particularly in older, high-risk patients or patients with other conditions or medications that affect kidney function.[7][55] Patients should also be monitored for symptoms of vestibulotoxicity, such as dizziness, because vestibulotoxicity is more common than cochlear injury and deafness, but less predictable with respect to dose or treatment duration.[55] Hearing testing is also commonly performed, particularly when treatment is prolonged.[7] Patients treated with tetracycline-class antibiotics should be advised to drink a large glass of water and remain upright for 30 minutes after each dose to reduce the risk of esophagitis.[7] Congenital infection has been rarely reported, but it is a potential complication of tularemia infection in pregnant women.[56] As noted above, pregnancy loss may also be associated with infection in pregnancy.[47]

Postoperative and Rehabilitation Care

Patients should be offered occupational therapy, physical therapy, or both as needed to treat prolonged fatigue, pain, and weakness that may occur.

Consultations

Consultation with an infectious disease specialist is recommended, particularly in pregnancy, immunocompromised states, suspected bioterrorism, and other high-risk situations. Surgical or interventional radiology consultation may be needed to treat suppurative lymph nodes or other complications.

Deterrence and Patient Education

Vaccines against tularemia are not currently widely available or licensed, although vaccine studies are ongoing.[57][58] A live strain–based vaccine has been used at times for high-risk laboratory technicians.[59] Prevention efforts focus on managing exposures and postexposure prophylaxis in rare scenarios.[4] Postexposure prophylaxis is not recommended for close contacts of people with tularemia or for people bitten by ticks in endemic areas.[16] Postexposure prophylaxis may be considered in cases of suspected intentional release of tularemia (bioterrorism), laboratory exposures, or occupational exposures among people who work with infected animals. In these cases, postexposure prophylaxis is generally recommended for 7 days with a fluoroquinolone or for 10 to 14 days with a tetracycline.[7]

Outdoor occupations and hobbies increase the risk of tularemia infection through both vector and direct animal exposures. To decrease the risk of tularemia and other vector-borne illnesses, those engaging in outdoor activities should consistently use control measures such as insect repellent according to the manufacturer's instructions, wear clothing to cover exposed skin, and promptly remove any ticks.[4][60] Tularemia infection from ingestion can be avoided by thoroughly cooking potentially contaminated food products, particularly wild game, and by avoiding the use of freshwater for washing, preparation, or drinking in endemic areas.[4] 

People in high-risk occupations, such as landscaping, game meat handling, laboratory work, and veterinary or other animal handling, should consider protective practices, including contact isolation with handwashing, gloves, and other barriers, and masking to reduce inhalation of potential tularemia organisms.[4][20][60][61] In the US, where most cases of tularemia associated with domestic pets have been reported, pet owners should also be informed about risks and use contact precautions or other precautions when their pet has access to wild animals.[4][62] For landscaping workers, protective skirting on mowers or collection bags can also serve as a barrier, helping minimize inhalation of potentially infected particles.

Any attempts to culture tularemia should occur in a biosafety level 3 laboratory, with workers wearing masks, and all procedures, particularly any potential aerosol-generating procedures, should be conducted within a biological safety hood.[4][27] Clinical laboratory personnel must be advised of potential exposure to tularemia when handling cultures of lymph node tissue, wound exudate, or other potentially infected tissue in endemic areas. Healthcare professionals should use standard precautions to minimize the risk of infection when coming into contact with infected skin lesions or potential aerosols, consistent with precautions for other bacterial infections.[4] Additional specific isolation procedures for patients in clinical settings are not recommended because human-to-human transmission is very unlikely.[16][63]  

Pearls and Other Issues

Pearls regarding tularemia include:

• Prompt treatment is essential to improve outcomes for patients with tularemia. Clinicians in endemic areas should familiarize themselves with the clinical syndromes and modes of transmission associated with tularemia to facilitate early recognition. Symptoms are typically related to the route of infection. 
• Ulcers and lymphadenopathy (ulceroglandular and glandular tularemia) occur following an insect bite or direct contact with infected tissue. Oropharyngeal or gastrointestinal tract symptoms follow ingestion of contaminated food or water. Pulmonary symptoms follow inhalation. Systemic symptoms, termed typhoidal tularemia, as well as other presentations, such as meningitis and endocarditis, can occur. 
• Serology is the most common tool for diagnosing tularemia, but serologic results may be negative early in the course of symptoms.
• If a specimen is cultured for the potential identification of tularemia, such as a wound culture or lymph node aspirate, the laboratory should be notified, because tularemia poses a significant inhalation risk to laboratory workers if not handled in a protected setting.
• Aminoglycosides are the drug of choice in severe disease. Fluoroquinolones and doxycycline may be used for less severe disease.
• Tularemia is a potential bioweapon and would likely present as an increase in the number of patients with bilateral pneumonia who do not respond to typical β-lactam antibiotics in a densely populated area. 
• Vaccines are not generally available. Prevention is achieved by managing exposures, such as masking to prevent inhalation, using insect repellent, and properly handling animal tissues.

Enhancing Healthcare Team Outcomes

Tularemia is an acute febrile zoonotic illness caused by the highly infectious gram-negative intracellular coccobacillus Francisella tularensis, which can infect humans with as few as 10 to 25 organisms. Clinical presentation varies by route of infection and includes ulceroglandular, glandular, oculoglandular, oropharyngeal, gastrointestinal tract, pneumonic, and typhoidal syndromes. Common features across syndromes include fever, headache, malaise, and regional lymphadenopathy. Diagnosis relies primarily on serology because culture requires biosafety level 3 precautions, and molecular testing is not widely available. A lack of response to empiric β-lactam therapy should raise suspicion for tularemia. Treatment includes aminoglycosides for severe disease and fluoroquinolones or doxycycline for milder cases. The organism is classified as a Tier 1 select agent due to its potential for bioterrorism.

Effective treatment of tularemia demands coordinated interprofessional teamwork. Clinicians and infectious disease specialists play a central role in maintaining clinical suspicion, particularly in endemic regions, and in selecting appropriate antibiotic regimens tailored to disease severity, patient age, pregnancy status, and subspecies considerations. Primary care clinicians and advanced practice clinicians in primary care and emergency settings are often the first to encounter patients with nonspecific febrile illness, skin ulcers, or lymphadenopathy, making their awareness of tularemia syndromes and exposure histories essential for early recognition and timely referral.

Nurses contribute to patient safety through careful monitoring for treatment-related complications, including nephrotoxicity and ototoxicity associated with aminoglycoside therapy. Nurses also play a vital role in patient education on tick prevention, safe food handling, and the importance of completing the full course of antibiotics. Pharmacists are essential partners in verifying appropriate dosing, particularly weight-based pediatric dosing and renal-adjusted aminoglycoside dosing, monitoring drug levels, reviewing potential drug interactions, and counseling patients on medication-specific precautions. Laboratory personnel must be promptly notified of suspected tularemia specimens so that cultures are handled under biosafety level 3 conditions, protecting workers from potential inhalation exposure. Public health workers may play a clear role during a natural outbreak or bioterrorism exposure in identifying cases, determining exposures, and coordinating prophylaxis. Clear, proactive communication among all team members, from the initial suspicion of tularemia through laboratory notification, treatment selection, complication monitoring, and rehabilitation, is fundamental to enhancing patient-centered outcomes, ensuring safety, and optimizing team performance in treating this uncommon but potentially life-threatening infection.

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Disclosure: Jessica Snowden declares no relevant financial relationships with ineligible companies.

Disclosure: Tyler Stephen declares no relevant financial relationships with ineligible companies.

Disclosure: Kari Simonsen declares no relevant financial relationships with ineligible companies.