Clinical History
A 27 year old male with past medical history of mixed connective tissue disease was transferred from an outside hospital where he had initially presented for 6 days of progressively worsening lumbar pain preceded by 1 day of fevers up to 104 F, as well as chills and rigors. Also noted was pain and swelling in his left thumb and a mild rash present on the hands and feet. It is notable that the patient has multiple pets, including a rat.
Workup at the outside hospital included and MRI showing facet arthrosis and effusions at L4-L5 with mass effect on the S1 nerve root. Neurosurgery recommended biopsy of the lumbar spine by Interventional Radiology.
Laboratory Findings
Two sets of blood cultures at the outside hospital showed no growth at 5 days. Two sets of blood cultures obtained at our institution were positive at 15 and 29 hours, with a smear showing gram negative bacilli. The blood culture media was tested by nucleic acid hybridization and no targets were detected. When subcultured, there was only significant growth on the blood plate, with very small gray-green colonies that were not well appreciated
A sample was sent to a reference lab for testing, which identified Streptobacillus moniliformis.
Discussion
In the United States, Streptobacillus moniliformis is the most common causative agent of rat bite fever, a relatively rare infectious systemic illness. This syndrome is also caused by infection with Spirillum minus, primarily seen in Asia, and rarely by Streptobacillus notomytis.1,2
S. moniliformis is a fastidious pleomorphic gram negative rod which grows slowly; in cases where there is clinical suspicion for rat bite fever, cultures can be held up to seven days. It is part of the normal nasal and oropharyngeal flora of rodents, with carriage rates of up to 100% in some rat populations. It can be found in oral, nasal, and conjunctival secretions, as well as urine, and can be transmitted to humans via bites, scratches, or oral contact. This includes kissing a pet rat or ingesting food or water that is contaminated with rat secretions.1,2
S. minus is a gram negative spirochete. It cannot be cultured on synthetic media, but may be visualized by Giemsa or Wright stain, or by using dark-field microscopy. Transmission of S. minus is similar to that of Steptobacillus spp., but has not been documented to be associated with contaminated food or water. (1, 2)
The clinical presentation of rat bite fever ranges from a mild case with only a flu-like illness to cases of severe sepsis. In untreated cases, the mortality rate is approximately 10 to 13 percent. Initial symptoms typically begin within 7 days of exposure for S. moniliformis and in 1 to 3 weeks for S. minus. These initial symptoms can include fever, myalgias, vomiting, pharyngitis, headache, and migratory arthralgias. If exposure was through a wound, it is typically resolved by the time symptoms develop, although it may reappear with ulceration, edema, and regional adenopathy in cases caused by S. minus. Cases associated with ingestion may have more severe vomiting and increased likelihood of developing pharyngitis.1,2
Symptoms may further develop to include a maculopapular rash on the extremities, and asymmetric polyarthralgias. The rash is seen most commonly on the extensor surfaces but can involve the palms and soles. Spontaneous remission may occur, but without treatment the fever can show a relapsing course, and the arthritis may last for several years. Possible complications include bacteremia, endocarditis, myocarditis, pneumonia, abscesses, septic arthritis, osteomyelitis, multiorgan failure, fulminant sepsis and death.1,2
Rat bite fever is usually diagnosed empirically based on consistent symptoms and history of rat exposure, because it is difficult or impossible to culture the causative organisms in the lab and there is no serologic test available. 16S rRNA sequencing can be used for definitive diagnosis, but only for certain sample types, and it is not always available.1,2
The empiric treatment of choice is penicillin, with the dose and duration being dependent on the clinical presentation. Ceftriaxone is also commonly used due to better ease of use in the outpatient setting, and tetracyclines are used in patients with beta-lactam allergies. For uncomplicated cases, most patients are treated for a total of 14 days; initially with IV antibiotics, and then transitioned to oral agents after 5 to 7 days if there is sufficient clinical improvement.1,2
Also remarkable in the patient’s history was a note indicating that they had been known to share drinks with his pets and instances of the pet rat licking the patient’s face. Initial treatment was vancomycin and cefepime, with vancomycin discontinued after the gram stain results. The patient was discharged before a definitive identification of the organism was made, with a plan for 6 weeks of outpatient treatment with ceftriaxone via infusion.
References
1. King, Katherine Yudeh, MD, PhD “Rat Bite Fever.” UpToDate, Wolters Kluwer, 1 Jun. 2020. https://www.cdc.gov/rat-bite-fever/index.html
2. “Rat-bite Fever (RBF).” Centers for Disease Control and Prevention, 1 Jun. 2020. https://www.uptodate.com/contents/rat-bite-fever?search=rat%20bite%20fever&source=search_result&selectedTitle=1~17&usage_type=default&display_rank=1
-Tom Koster, DO is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.
-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.
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