Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021.

BACKGROUND: Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. METHODS: Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. RESULTS: Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. CONCLUSIONS: Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia.

Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones.

BACKGROUND: Fluoroquinolones lack approval for treatment of tularemia but have been used extensively for milder illness. Here, we evaluated fluoroquinolones for severe illness. METHODS: In an observational study, we identified case-patients with respiratory tularemia from July to November 2010 in Jämtland County, Sweden. We defined severe tularemia by hospitalization for >24 hours and severe bacteremic tularemia by Francisella tularensis subsp. holarctica growth in blood or pleural fluid. Clinical data and drug dosing were retrieved from electronic medical records. Chest images were reexamined. We used Kaplan-Meier curves to evaluate time to defervescence and hospital discharge. RESULTS: Among 67 case-patients (median age, 66 years; 81% males) 30-day mortality was 1.5% (1 of 67). Among 33 hospitalized persons (median age, 71 years; 82% males), 23 had nonbacteremic and 10 had bacteremic severe tularemia. Subpleural round consolidations, mediastinal lymphadenopathy, and unilateral pleural fluid were common on chest computed tomography. Among 29 hospitalized persons with complete outcome data, ciprofloxacin/levofloxacin (n = 12), ciprofloxacin/levofloxacin combinations with doxycycline and/or gentamicin (n = 11), or doxycycline as the single drug (n = 6) was used for treatment. One disease relapse occurred with doxycycline treatment. Treatment responses were rapid, with median fever duration 41.0 hours in nonbacteremic and 115.0 hours in bacteremic tularemia. Increased age-adjusted Charlson comorbidity index predicted severe bacteremic tularemia (odds ratio, 2.7 per score-point; 95% confidence interval, 1.35-5.41). A 78-year-old male with comorbidities and delayed ciprofloxacin/gentamicin treatment died. CONCLUSIONS: Fluoroquinolone treatment is effective for severe tularemia. Subpleural round consolidations and mediastinal lymphadenopathy were typical findings on computed tomography among case-patients in this study.

[Painful lymphadenopathy after an insect bite-a case report]. / Schmerzhafte Lymphadenopathie nach Insektenstich ­ ein Fallbericht.

Tularemia is a bacterial zoonosis which is commonly transmitted through tick or insect bites or contact with meat of infected animals. We report the case of a 36-year-old man who developed fever, chills, headaches, and a painful, unilateral, inguinal lymphadenopathy with a red-livid skin discoloration after an insect bite on his abdomen. Ulceroglandular tularemia was diagnosed through polymerase chain reaction (PCR) and serology. Treatment with doxycycline for 21 days resulted in an excellent outcome.

Identification of Francisella tularensis in ascites in the context of typhoidal tularaemia.

Tularaemia is a highly infectious, zoonotic disease caused by Francisella tularensis, which has become increasingly prevalent over the past decade. Depending on the route of infection, different clinical manifestations can be observed. We report a case of typhoidal tularaemia presenting as a febrile illness with gastrointestinal symptoms in a patient in her mid-80s. During the acute illness phase and in the context of alcohol-related liver cirrhosis, the patient developed progressive ascites. During paracentesis, spontaneous bacterial peritonitis was consistently reported. Blood culture revealed Gram-negative bacilli identified as F. tularensis upon microscopic examination. Immediate clinical improvement was observed after adaptation to a pathogen-specific antibiotic regime. Typhoidal tularaemia presents general, non-specific symptoms without the local manifestations seen in other forms of the disease, thus representing a diagnostic challenge. In the case of protracted fever and if the epidemiological context as well as possible exposure are compatible, tularaemia should be considered in the differential diagnosis.

[Fever and lymphadenopathy. Report of 4 cases of tularemia]. / Fieber und Lymphadenopathie. Bericht über 4 Tularämiefälle.

We report on 4 patients with different types of tularemia acquired in Switzerland or nearby countries. All patients presented with fever, moderate to highly elevated signs of inflammation, and local lymphadenopathy. Additionally, 3 patients did not respond to empirical antimicrobial therapy with aminopenicillins. A tick bite was identified as mode of transmission in 2 patients, while 1 patient showed a possible connection to a tick bite. The route of transmission for the fourth patient remained unknown. The diagnosis of tularemia was either based on positive serology, on a positive polymerase chain reaction (PCR) from the lymph node samples or on positive blood cultures. The treatment in adult patients was ciprofloxacin 500-750 mg twice daily orally for 3 weeks. The pediatric patient was treated with gentamicin 4 mg/kg i.v. once daily for 1 week and ciprofloxacin 15 mg/kg twice daily orally for another 2 weeks. All patients recovered completely. Due to the increasing incidence of tularemia in Switzerland, this infection should be considered in patients with fever and lymph node enlargement particularly after tick bite. We recommend treatment with ciprofloxacin orally for 14-12 days.

[Glandular tularemia--case report]. / Tularemia wezlowa--opis przypadku.

Tularemia is a rare zoonosis occuring in many clinical forms, including ulceral, glandular, oropharyngeal, pneumonic, and septic form. ENT specialists seeing their patients in ambulatory and emergency settings are most likely to encounter oropharyngeal and glandular form. Tularemia became widely discussed clinical entity in recent years due to its potential to being used as a biological weapon in acts of terrorism. Authors present a case of a 75 yrs old woman treated for atypical tonsillitis with suppurative cervical lymphadenitis. As infection with typical pathogens was ruled out and no improvement with antibiotics was observed, further evaluation was initiated. Malignancies and tuberculosis were excluded. Final diagnosis was established based on a serological test. Epidemiology, clinical manifestations, diagnostic procedures and treatment of tularemia, as well as diagnostic pitfalls are briefly discussed.

Francisella tularensis as a potential agent of bioterrorism?

Francisella tularensis is a category A bioterrorism agent. It is the etiological agent of tularemia, a zoonotic disease found throughout the northern hemisphere. The intentional spread of F. tularensis aerosols would probably lead to severe and often fatal pneumonia cases, but also secondary cases from contaminated animals and environments. We are not ready to face such a situation. No vaccine is currently available. A few antibiotics are active against F. tularensis, but strains resistant to these antibiotics could be used in the context of bioterrorism. We need new therapeutic strategies to fight against category A bioterrorism agents, including development of new drugs inhibiting F. tularensis growth and/or virulence, or enhancing the host response to infection by this pathogen.

Prevention and treatment of bacterial diseases caused by bacterial bioterrorism threat agents.

There is general consensus that the bacterial agents or products most likely to be used as weapons of mass destruction are Bacillus anthracis, Yersinia pestis, Francisella tularensis and the neurotoxin of Clostridium botulinum. Modern supportive and antimicrobial therapy for inhalational anthrax is associated with a 45% mortality rate, reinforcing the need for better adjunctive therapy and prevention strategies. Pneumonic plague is highly contagious, difficult to recognize and is frequently fatal. Therefore, the development of vaccines against this agent is crucial. Although tularemia is associated with low mortality, the highly infectious nature of aerosolized F. tularensis poses a substantive threat that is best met by vaccine development. Safer antitoxins and a vaccine are required to meet the threat of the use of botulinum toxin as a weapon of mass destruction. In this article, the current status of research in these areas is reviewed.

Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room.

Bioterrorism has become a potential diagnostic consideration in infectious diseases. This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed. Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint. In addition to the clinical features of the infectious diseases mentioned, the article discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents. The review concludes with suggestions for postexposure prophylaxis and therapy.

[Tularemia, a potential bioterrorism weapon]. / La tularémie, arme potentielle de bioterrorisme.

A POTENTIAL WEAPON: Because of its highly contagious nature with a low inoculum, principally with the biovar A, F. tularensis is considered as an agent that could be used by terrorists, notably when sprayed. Any epidemic of tularemia, essentially in its respiratory form, particularly in areas of low incidence of this infection, should be suspected to be a biowarfare attack. The voluntary contamination of water with this bacteria could also be used as a biological weapon. THE DIFFERENT FORMS OF THE DISEASE: Depend on the mode of contamination, the dose of inoculum and the virulence of the strains. The forms are pulmonary, ulcerous-glandular, typhoid, glandular, ocular-glandular, oropharyngeal and septicemic. IN GENERAL PRACTICE: Tularemia is a disease that requires official notification. Many guidelines exist for the treatment and prophylaxis of patients having been exposed to F. tularensis.

[A patient with a fever and an eschar caused by tularemia]. / Een patiënt met koorts en een eschar door tularemie.

A 38-year-old man presented at the first-aid department complaining of fever, general malaise and a painful left groin. The complaints had started shortly after an active holiday in Finland. Physical examination showed enlarged left sided inguinal lymph nodes and a marked eschar on the left lower leg. In terms of differential diagnosis a Rickettsia or a tularemia infection were considered. The pathogen for tularemia, Francisella tularensis subspecies holarctica, was isolated in wound discharge from the patient. Serology also indicated infection with F. tularensis. The patient was treated at home with oral doxycycline and recovered fully in a few days. In patients presenting with an eschar, rickettsiosis is often the first and only disease that is considered. This case report clearly emphasizes that a differential diagnosis of an eschar can be made and that this includes tularemia.