Rat bite fever is a systemic febrile illness caused by infection with the Gram-negative bacillus Streptobacillus moniliformis in North America, or the spirochete Spirillum minus in Asia, following a bite, scratch, or contact with excrement [1, 2]. A third syndrome is Haverhill fever, caused by ingestion of S. moniliformis-contaminated food . Case reports describe exposures among people living in poverty, laboratory technicians, and pet store workers. The affected demographics have broadened, as rats have become more popular pets. S. moniliformis colonizes the nasopharynx of 50–100% of healthy wild, lab, and pet rats, and is also excreted in the urine . It is also found in mice, guinea pigs, gerbils, and squirrels. After a bite or scratch, the wound should be immediately cleaned with soap and warm water, and tetanus prophylaxis administered, if warranted. The efficacy of antibiotic prophylaxis for rat bite is unknown. Some authors suggest administration of amoxicillin/clavulanate at a dosage of 500 mg p.o. every 8 h for 3 days.
S. moniliformis is a pleomorphic (straight, fusiform, or with lateral bulbar swellings), filamentous, Gram-negative, nonmotile, and non-acid-fast rod . However, on Gram stains it can appear as either Gram-negative or Gram-positive rods.
Rat bite fever typically begins with a bite or other exposure, followed by abrupt onset of systemic illness, including intermittent relapsing fever, arthritis, and rash 3 days to 3 weeks later. A maculopapular, petechial, or purpuric rash develops in approximately 75% of those affected in the first symptomatic week [1, 2]. Over half of those affected develop migratory polyarthralgias, with involvement of both large and small joints of the extremities . If untreated, the mortality rate approaches 10% . Endocarditis is a well-described complication, but only 26 cases of native valve endocarditis have been reported to date . We found no reports involving pregnant patients.
Our patient’s presentation was notably atypical in multiple respects. First, the hyperemesis she experienced was likely wrongly attributed to pregnancy and contributed to delayed diagnosis. Second, she denied a history of rash or arthralgias. Third, eroded intra-oral hardware made fastidious Streptococcal spp. or other oral flora equally likely pathogens. Fourth, the diagnosis of the primary infectious agent in this case was further complicated by the positive Bartonella IgG titers. Bartonella IgG titers between 1:64 and 1:256 represent possible active or recent Bartonella infection; our patient’s IgG titers were 1:256. IgM titers > 1:20 strongly suggest current infection; our patients IgM titers were negative. Furthermore, she had no characteristic cutaneous lesions or lymphadenopathy, and there was no Bartonella signal detected on the PCR. Taken together, the above essentially rule out Bartonella endocarditis. Another confounder was the identification of Propionibacterium spp. on the mitral valve specimen. Propionibacterium spp. are a very rare cause of infectious endocarditis, and almost always cause prosthetic valve endocarditis. Here, they were most likely a contaminant. Finally, she suffered septic emboli to the right popliteal artery, spleen, and kidneys - a rare complication of rat bite fever endocarditis .
Diagnosis of S. moniliformis is difficult, requiring a high index of suspicion. It is fastidious, requiring microaerophilic conditions (5–10% CO2 or anaerobic conditions supplemented with 20% normal rabbit serum) . Furthermore, growth is inhibited by 0.05% sodium polyanethol sulfonate (an anticoagulant routinely added to most aerobic blood culture bottles) . When blood cultures remain negative after prolonged incubation, PCR can be used diagnostically. 16sRNA gene sequencing has been used successfully on heart valves, bone, and synovial fluid, but this method is specific only to the Streptobacillus genus and not the species . PCR is effective even after antibiotic treatment has been initiated, even if the blood culture is sterile, as the DNA remains detectable in the infected valve.
In this case, blood and valve cultures were persistently negative, despite repeated anaerobic and aerobic sub culturing on various agars and broths including Chocolate, Charcoal Yeast Extract, Columbia, and serum supplemented media. The initial mitral valve specimen was collected surgically 4 days after initiation of empiric antibiotic therapy, likely contributing to the difficulty in culturing the specimen. Broad range bacterial PCR and sequencing of a segment of 16 s rRNA gene matched to Streptobacillus sp. (genus level) and most closely related to Streptobacillus moniliformis (species level). Speciation of 16 s rRNA gene sometimes can be difficult and erroneous. The patient was counseled about the risks associated with rats especially pertaining to bites.
Recommended treatment of S. moniliformis endocarditis is dual therapy with high-dose penicillin G for 4 weeks in combination with streptomycin or gentamicin for 2 weeks [1, 2]. Ceftriaxone (2gIV daily for 6 weeks) has also been effective . In this case, treatment was limited by the patient’s pregnancy until she underwent dilation and evacuation. Aminoglycosides are pregnancy class D, given several reports of congenital deafness; they are known to cross the placenta.
A literature review was performed by a professional medical librarian using the search strategy presented in the supplemental file. This revealed only two cases, but neither involved endocarditis [6, 7]. One involved a 22 year old woman who developed Streptobacillus moniliformis amnionitis , and the other involved polymicrobial chorioamnionitis with Aerococcus christensenii, Gemella spp., Snethia spp., Parvimonas micra, and Streptobacillus moniliformis in a pregnant woman .
Our report is limited by the usual features of a single case report, and that more and different samples were not available for duplicate and triplicate laboratory testing. Despite these limitations, it includes the key laboratory and management detail useful for providers who may encounter this in the future, and it appears to be a first reported case based on a thorough literature review described in the supplemental material.
This case highlights the diagnostic and management challenges of an infrequent cause culture negative endocarditis that was further complicated by pregnancy, thromboembolic phenomenon, and a patient’s undaunted love of her pets.