The overall mortality of an untreated tularemia infection is 5–15% [50]. The prevailing connection to a fatal outcome is in the pulmonary form of the disease. Nevertheless, other forms may lead to terminal consequences, too. Timely diagnosis with specific antibiotic treatment significantly lowers life-threatening complications, often leaving patients entirely symptom-free. In the pre-antibiotic area, around 30% of patients with tularemia died in the USA. In infection with the more pathogenic type A, nowadays, even with prompt and appropriate antibiotic treatment, the mortality of the disease caused by this subtype is 4%. In Europe, with the less virulent subtype prevailing, however, death following tularemia is much less frequently encountered [13,27].

The antibiotic of choice depends mainly on the severity of the disease and the patient’s age (Table 1). The best minimal inhibitory concentration is streptomycin or gentamycin when taken orally for 7–14 days [28]. Ciprofloxacin, doxycycline, and chloramphenicol are also effective and should be administered for at least 14 days. Antibiotic testing of F. tularensis is not routinely performed in a clinical setting as antibiotic resistance of the bacterium has never been reported [82]. Thus, aminoglycosides streptomycin, gentamicin, fluoroquinolone ciprofloxacin, and tetracycline antibiotic doxycycline are most commonly used in tularemia. First-line drugs for mild to moderate tularemia cases, which predominate in Europe, are ciprofloxacin and doxycycline. Gentamicin has been reported to result in higher relapse rates, though it is often used in patients with systemic diseases and children. In younger patients, fluoroquinolones are contraindicated owing to possible damage to the muscles and skeletal system. Ciprofloxacin is a safer choice for children 1–10 years. Streptomycin or chloramphenicol are the antibiotics of choice in pregnant women with milder forms of the disease. However, gentamicin should be used in pregnant women with severe tularaemia. Possible side effects of the medication should be weighed against the severity of the disease [5,28].

In milder forms of the disease, the recommendations are to opt for treatment with ciprofloxacin or doxycycline. While fluoroquinolones such as ciprofloxacin have been reported to have a lower relapse rate (5–10%, in contrast to 10–15% in tetracyclines), several factors contribute to choosing doxycycline in cases of the disease following a tick-bite [73]. Doxycycline empirically treats other possible tick-related illnesses (e.g., Lyme disease), which is useful in the setting of a tick bite, especially before final microbiological investigations. Additionally, doxycycline is associated with fewer side effects than ciprofloxacin. In 2018, the European Medicines Agency finalised a review of severe, disabling and potentially permanent side effects of quinolone and fluoroquinolone antibiotics, endorsing new recommendations to restrict further fluoroquinolone use. Physicians are instructed to use other antimicrobials if possible. The side effects of ciprofloxacin have proven to be long-lasting, disabling, and potentially permanent, involving tendons, muscles, joints, and the nervous system [83].

Nevertheless, doxycycline is contraindicated in children and pregnancy owing to teeth discolouration and impairment of foetal bone growth [84]. The recommended duration of treatment with tetracyclines varies in the literature. According to Maurin et al. (2016), the suggested regime for doxycycline in tularemia is three weeks long to avoid disease relapses [13]. The WHO guidelines from 2007 recommend a daily dose of 200 mg of doxycycline for at least 15 days [28].

In lymphadenitis cases, surgical drainage of a colliquative lymph node is commonly indicated besides specific antibiotic treatment. However, in the experience of Atmaca et al. (2008), as reported in their study, complete surgical removal of tularemia-affected lymph nodes is often challenging, with adherent tissue preventing the dissection from the surrounding tissues [61]. Hence, as with other inflammatory swellings in the neck, tularemia-associated-lymphadenitis should be managed by a staged therapeutic approach. Therefore, the first point of reference for physicians in planning the surgical treatment of lymphadenopathy is for the lymph nodes in the neck area to be greater than 1 cm or 1.5 cm in the jugulodigastric nodes [85]. The decision to excise or drain the affected lymph node relies on colliquation in the lymph nodes, cellulitis over the skin, or sepsis. In those cases, immediate surgical drainage is required. Thus, conservative treatment with antibiotics is sufficient in the absence of liquefaction in the lymph nodes [86]. Nevertheless, even in lymphadenopathy cases without colliquation, surgical intervention in tularemia is usually performed to acquire tissue and pus samples to confirm a diagnosis and warrant antibiotic treatment.