By Stan Deresinski, MD
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Tularemia is seen in all U.S. states other than Hawaii. Therapy with tetracyclines, aminoglycosides, and fluoroquinolones is effective.
SOURCE: Wu HJ, Bostic TD, Horiuchi K, et al. Tularemia clinical manifestations, antimicrobial treatment, and outcomes: An analysis of US surveillance data, 2006-2021. Clin Infect Dis 2024;78(Supplement_1):S29-S37.
Investigators from the U.S. Centers for Disease Control and Prevention (CDC) reviewed available data from submitted case report forms of 1,163 individuals with tularemia in the United States reported during 2006-2021. The cases were considered confirmed (positive culture or more than four-fold increase in antibiotic titer between acute and convalescent serum specimens) in 57.6% and probable (detection by non-culture method or single elevated antibody titer) in the remainder. While the patients’ median age was 51 years, the distribution was bimodal, with peaks among children younger than 9 years of age and adults 50-59 years of age. Only 11.3% were considered immunocompromised; one was pregnant.
Of the multiple designated clinical forms of tularemia, those identified in this cohort were ulceroglandular (46.7%), glandular (17.9%), typhoidal (14.0%), oculoglandular (2.0%), oropharyngeal (1.6%), and meningitis (0.1%). Of the 908 patients for whom outcomes were known, 27 (3.0%) died. Of 256 patients with an invasive form of infection (pneumonic, typhoidal, meningitic), 10 (3.9%) died, while only nine (1.6%)of 573 with a noninvasive form did so. Among the minority of patients for whom the information was available, approximately two-thirds of those infected with Type A strains died, while this was true for only approximately one-third of those with Type B (tularemia holarctica) infections. There was no difference in mortality between the two groups (4.8% vs. 4.7%).
Of the cohort of 1,163 patients, 905 (77.8%) had evidence of having received one or more antibiotics considered high efficacy, with 536 (62.8%) having received a tetracycline, while 338 (39.6%) received a fluoroquinolone, and 203 (23.8%) were treated with an aminoglycoside — approximately one-fourth received combinations of high-efficacy agents. The median interval from symptom onset to receipt of a high-efficacy antibiotic was 11-13 days depending on the specific antibiotic type. Administration of high-efficacy antibiotics was associated with a significantly greater likelihood of survival. Multivariable analysis (after controlling for culture status) found that the survival odds were 10 times higher with receipt of high-efficacy antibiotics.
COMMENTARY
Francisella is an intracellular pathogen that, on staining, appears as small, gram-negative coccobacilli with fastidious growth characteristics with relatively prolonged incubation times of as many as five to seven days in blood cultures and two to 14 days on solid media. It is considered a potential bioterrorism agent, and the clinical microbiology laboratory should be notified of suspicion of its presence when specimens for culture are submitted. The Gram stain characteristics are typical of some other dangerous pathogens, such as Brucella, and also should alert laboratory personnel.
Infection can occur at very low inocula and may result from a variety of exposures, including direct contact with infected animal tissues, ingestion of contaminated food or water, inhalation, and arthropod bites. Tularemia is present worldwide and is acquired in all U.S. states except Hawaii.
The diagnosis of tularemia depends on knowledge of its multiple clinical manifestations together with a high index of suspicion. Even when it is suspected, the fastidious nature of the organism and slow growth may necessitate empiric therapy prior to disease confirmation.
