Rat-Bite Fever: A Clinical Overview for Health Care Providers

Rat-bite fever (RBF) is an infectious disease caused by two bacteria, Streptobacillus moniliformis and Spirillum minus, which people catch from rodents that carry them.

Overview

RBF is rare in the United States, and it is not reportable in any state or territory or nationally notifiable. Recent case reports point to a growing risk for infants, children and teenagers, who are more likely to handle pet rodents. Cases are sometimes reported in pet stores and animal research laboratories.

The two bacteria

• S. moniliformis causes most RBF in North America. It is a slow-growing, gram-negative, pleomorphic rod — non-spore-forming, unencapsulated, non-motile and facultatively anaerobic — that forms tangled filaments with bulbous swellings.
• S. minus more often causes RBF in Asia. It is a short, thick, motile spirochete with tufts of flagella at both ends.

How it spreads

Both bacteria live harmlessly in rodents, in their mouth, nose and eye secretions and in their urine. People can be infected through broken skin, a bite or a scratch, or by close contact with an infected rodent even without a bite or scratch. Food or drink contaminated with the bacteria can also cause RBF.

Signs and symptoms

S. moniliformis

• Incubation usually 3 to 10 days.
• First symptoms are non-specific: fever, chills, muscle aches, headache and vomiting.
• About 2 to 4 days after the fever starts, a maculopapular rash may appear on the arms and legs; half of patients then develop arthritis in several joints.
• Haverhill fever, a form of S. moniliformis infection seen mainly in North America, differs slightly, with more severe nausea, vomiting and sore throat.

S. minus

• Symptoms usually begin 7 to 21 days after exposure to an infected animal; the patient has probably travelled abroad, especially to Asia.
• After the bite has partly healed: fever, an ulcer at the bite, inflamed lymph vessels, swollen lymph nodes, and a distinctive rash of purple or red plaques.

Complications, if RBF goes untreated or is treated wrongly: abscesses in soft tissue and solid organs, septic arthritis, pneumonia, hepatitis, nephritis, meningitis, and endocarditis, myocarditis or pericarditis. Endocarditis carries the highest risk of death.

Testing and diagnosis

Consider RBF in a patient who has been around rodents and has its symptoms — commonly fever, nausea, vomiting, joint pain and rash.

• S. moniliformis is diagnosed by culturing it from blood, joint (synovial) fluid, other body fluids, affected tissue such as abscesses, or the original wound. Without a positive culture, pleomorphic gram-negative rods on a Gram stain of a suitable specimen can support a first diagnosis. Whole blood and joint fluid are the best specimens, and they should be taken before antibiotics are started. Because protocols have changed, contact CDC's Bacterial Special Pathogens Branch at (404)-639-1711 about testing.
• S. minus does not grow on artificial media. It is diagnosed by seeing the characteristic spirochetes in specimens under darkfield microscopy or with special stains.

When RBF is suspected in a severe illness or a death but no diagnosis has been made, physicians can ask their state public health laboratory or CDC for help.

Treatment

Research on which antibiotics work best is limited, but S. moniliformis is generally susceptible to many: penicillins, cephalosporins, carbapenems, aztreonam, clindamycin, erythromycin, nitrofurantoin, bacitracin, doxycycline, tetracycline, teicoplanin and vancomycin.

• Usual treatment: intravenous penicillin G for 7 days or more, then oral penicillin. Patients can have adverse reactions to penicillin, which the page says usually improve quickly once antibiotics are started.
• Penicillin allergy: doxycycline or streptomycin.
• When Rocky Mountain spotted fever is also possible: RBF can look like RMSF and other fevers with rash. If both are in the differential diagnosis, consider doxycycline first, because both need rapid treatment and diagnostics for both are limited — including in children under 8. Doxycycline used for less than 14 days does not risk staining teeth.
• Endocarditis, a rare complication, may need intravenous penicillin G combined with streptomycin or gentamicin, though no recent studies have tested the combination.

Sources

• Centers for Disease Control and Prevention, "Clinical Overview of Rat Bite Fever (RBF)." https://www.cdc.gov/rat-bite-fever/hcp/clinical-overview/index.html
• CDC Infectious Disease Laboratories, specimen submission: https://www.cdc.gov/laboratory/specimen-submission/index.html
• Corrected: the page lists "solid-green abscesses" among the complications; the context is abscesses of soft tissue and solid organs. It also spells the bacterium "moniliformisn."
• A stock photograph on the page is not reproduced here.