Treatment of Tularemia in Patient with Chronic Graft-versus-Host Disease

Jan Weile

, Erik Seibold, Cornelius Knabbe, Martin Kaufmann, and Wolf Splettstoesser

Author affiliations: Heart and Diabetes Centre North Rhine–Westphalia, Bad Oeynhausen, Germany (J. Weile, C. Knabbe); Bundeswehr Institute of Microbiology, Munich, Germany (E. Seibold, W. Splettstoesser); University of Rostock, Rostock, Germany (W. Splettstoesser); Robert-Bosch-Hospital, Stuttgart, Germany (M. Kaufmann)

Abstract

We describe a case of human tularemia caused by Francisella tularensis subsp. holarctica in a stem cell transplant recipient with chronic graft-versus-host disease who was receiving levofloxacin prophylaxis. The infection was characterized by pneumonia with septic complications. The patient was successfully treated with doxycycline.

Tularemia is a zoonotic infection caused by the gram-negative bacterium Francisella tularensis. Humans are accidental hosts; infection occurs after contact with infected animals, contaminated water or soil, or invertebrate vectors (1). Strains of the 2 subspecies F. tularensis subsp. tularensis and F. tularensis subsp. holarctica account for virtually all infections in humans. Only rarely have strains of the subspecies F. tularensis novicida or the closely related species F. philomiragia or F. hispaniensis been cultured from clinical specimens (2).
F. tularensis subsp. tularensis, also referred to as type A, is found almost exclusively in North America and is the most virulent subspecies. F. tularensis subsp. holarctica, also referred to as type B, is found predominantly in Asia and Europe, but also in North America (3). Patients infected with F. tularensis have abrupt onset of fever, chills, headache, and malaise after an incubation period of 2–21 days. Additional signs and symptoms may develop, depending on the portal of entry. The most common signs and symptoms are lymphadenopathy, fever, pharyngitis, appearance of ulcers/eschars/papules, nausea and vomiting, and hepatosplenomegaly.
Antimicrobial drug therapy should be administered to patients with this suspected or confirmed diagnosis, even though spontaneous resolution may occur in 50%–95% of cases (depending on the clinical syndrome) (4). For severe tularemia, gentamicin is the drug of choice (5 mg/kg/d, divided into 2 doses and monitored by analysis of serum drug concentration). If available, streptomycin is a well-suited alternative agent. This approach is based on observational data evaluating frequency of cure and relapse with different antimicrobial drugs (5) and is currently recommended by the World Health Organization (6). Oral agents may be used for treatment of mild illness. Preferred agents are doxycycline or ciprofloxacin. Observational data for tetracycline have found an 88% cure rate and 12% relapse rate (5), although other studies have indicated that relapse might be more common in patients who received tetracycline than in those who received ciprofloxacin or aminoglycosides (6).