Rat bite fever is a rare but potentially fatal systemic zoonotic infection caused by Streptobacillus moniliformis (predominant in the US/Western world) or Spirillum minus (predominant in Asia), with a 7–13% mortality rate if untreated. [1-3] The classic triad is fever, migratory polyarthritis, and rash, though the triad is incomplete in over half of cases. [4]
1. History
- Exposure: Direct rat bite or scratch, handling of rats (pet or wild), contact with rat urine/feces/saliva, or ingestion of contaminated food/water (Haverhill fever variant) [1][5]
- Incubation period: Typically 2–10 days after exposure; can extend to 3 weeks [3][6]
- Symptom onset: Abrupt fever, rigors, myalgias, headache, vomiting [3]
- Rash timing: Appears after fever onset; erythematous macules, papules, pustules, or petechiae predominantly on extremities (hands and feet) [1][5]
- Joint symptoms: Migratory polyarthralgia/polyarthritis, often asymmetric [4][6]
- Key question: "Do you have any pet rats, work with rodents, or recall any rodent bite/scratch?" — rodent exposure is not volunteered by patients in ~1/3 of cases [4]
- Important negatives: No tick exposure (helps distinguish from rickettsial disease), no pharyngitis (helps distinguish from rheumatic fever), no drug changes (rules out drug reaction)
2. Alarm Features
- Sepsis/septic shock: High fevers with hemodynamic instability [1][3]
- Endocarditis: New murmur, embolic phenomena (splenic/renal infarcts), especially in patients with pre-existing valvular disease [7-8]
- Meningitis: Altered mental status, nuchal rigidity [9]
- Osteomyelitis/discitis: Back pain, neurologic deficits [10]
- Rapidly progressive rash with petechiae/purpura (consider meningococcemia in differential)
- Untreated mortality: 7–13% — early antibiotic initiation is critical [2-3]
3. Medications
First-line treatment
- IV Penicillin G: 12–20 million units/day divided q4h for 3–4 weeks (uncomplicated); for endocarditis: 4 weeks [11]
- Pediatric dosing: 150,000–250,000 units/kg/day divided q4h [11]
- Step-down: Oral penicillin V or amoxicillin to complete 7–14 days total for uncomplicated cases [1]
Penicillin allergy alternatives
- Doxycycline: 100 mg PO/IV q12h (avoid in children <8 years and pregnancy) [1][12]
- Streptomycin [1]
- Ceftriaxone or cephalexin have been used successfully in case reports [9-10]
Contraindicated/cautions
- Macrolides: Variable activity, generally avoided [13]
- SMP-TMP: Not reliable monotherapy for S. moniliformis
- Antibiotics render cultures negative rapidly — obtain cultures before starting treatment [4]
4. Diet
- No specific dietary triggers or restrictions
- Ensure adequate hydration, especially in febrile/septic patients
- If Haverhill fever variant (ingestion-related): counsel on food/water contamination prevention in rodent-infested environments
5. Review of Systems
- Constitutional: Fever (often high/relapsing), rigors, malaise, weight loss
- MSK: Migratory joint pain/swelling (knees, ankles, wrists, hands)
- Dermatologic: Rash on extremities — macules, papules, pustules, petechiae, hemorrhagic pustules [5]
- GI: Nausea, vomiting, abdominal pain (especially Haverhill fever)
- Neurologic: Headache, altered sensorium (if meningitis)
- Cardiac: Dyspnea, chest pain (if endocarditis/myocarditis)
- Back pain: Consider osteomyelitis/discitis [10]
6. Collateral History and Family History
- Pet ownership: Rats, mice, gerbils, hamsters — all rodents can carry S. moniliformis [2][14]
- Occupational exposure: Laboratory workers, pet store employees, pest control workers [1]
- Living conditions: Urban crowding, homelessness, rodent-infested housing [1]
- Family history: Not hereditary, but household members with shared rodent exposure may also be at risk
- Immunocompromised contacts: Higher risk of severe disease
7. Risk Factors
- Children (>50% of reported cases) [1]
- Pet rat/rodent ownership (increasing with exotic pet popularity) [2]
- Laboratory animal handlers [1]
- Inner-city/urban residents with rodent exposure [1]
- Pre-existing valvular heart disease (risk for endocarditis) [7]
- Immunocompromised states
- Handling rat feces/urine without gloves [5]
8. Differential Diagnosis
The differential for the fever + rash + polyarthritis triad is broad: [1][15]
- Disseminated gonococcal infection — sexually active patients, tenosynovitis, pustular rash
- Meningococcemia — petechial/purpuric rash, rapid deterioration (cannot miss)
- Rocky Mountain spotted fever / rickettsial diseases — tick exposure, centripetal rash spread
- Lyme disease — erythema migrans, tick exposure, geographic risk
- Rheumatic fever — preceding pharyngitis, Jones criteria
- Reactive arthritis — preceding GI/GU infection, conjunctivitis, urethritis
- Leptospirosis — water exposure, conjunctival suffusion, jaundice
- Infective endocarditis — Osler nodes, Janeway lesions, murmur
- Drug reaction — temporal relationship to new medication
- ANCA-associated vasculitis — RBF can mimic and even induce ANCA positivity [15]
- EBV / viral exanthem — pharyngitis, lymphadenopathy, atypical lymphocytes
- Septic arthritis (other organisms) — typically monoarticular
9. Past Medical History
- Valvular heart disease: Significantly increases risk of S. moniliformis endocarditis (most reported cases occur on previously damaged valves, often from rheumatic heart disease) [7]
- Prosthetic heart valves: Prosthetic valve endocarditis has been reported [16]
- Prior episodes of RBF: Recurrence possible with ongoing exposure [8]
- Immunosuppression: May alter presentation and increase severity
- Recent dental procedures/jaw hardware: Can confound diagnosis [8]
10. Physical Exam
- Vitals: High fever (often >39°C), tachycardia; hypotension if septic
- Skin: Erythematous maculopapular rash on palms, soles, and extremities; hemorrhagic pustules, petechiae, purpuric lesions [1][5]
- Bite wound: May be healed or show a dry, non-purulent crust by the time systemic symptoms appear [6]
- Joints: Swelling, warmth, effusion — typically large joints (knees, ankles, wrists); migratory pattern [4]
- Cardiac: Auscultate for new murmurs (endocarditis)
- Abdomen: Hepatosplenomegaly (rare complication) [1]
- Lymph nodes: Regional lymphadenopathy near bite site
- Neuro: Meningeal signs if CNS involvement [9]
11. Lab Studies
- Blood cultures: Essential — notify lab to hold cultures for extended incubation (S. moniliformis is fastidious, requires enriched media with serum/ascitic fluid, 5% blood, yeast extract) [1][4]
- CBC: Leukocytosis (often with left shift); anemia in prolonged cases
- CRP/ESR: Elevated
- BMP/CMP: Assess renal function (nephritis is a known complication)
- LFTs: May be elevated (hepatitis reported) [9]
- Joint fluid analysis: If arthritis present — send for culture on enriched media; 90% detection rate on joint fluid when properly cultured [4]
- Procalcitonin: May help differentiate bacterial from viral etiology
- 16S rRNA PCR: Alternative when cultures are negative (especially if antibiotics already started) [4][6][17]
- mNGS (metagenomic next-generation sequencing): Emerging diagnostic tool, can identify pathogen even with negative cultures [17]
12. Imaging
- Joint imaging: X-rays of affected joints to rule out osteomyelitis; MRI if discitis/osteomyelitis suspected [10]
- Echocardiography: TTE (or TEE if high suspicion) if endocarditis is a concern — vegetations demonstrated in reported cases [7-8]
- CT abdomen: If splenic/renal infarcts suspected (embolic endocarditis) [8]
- Chest X-ray: If pneumonitis suspected
- Imaging is unnecessary in straightforward, uncomplicated presentations responding to antibiotics
13. Special Tests
- PCR (16S rRNA gene sequencing): From blood, joint fluid, or bite-site crust — highly valuable when cultures are negative or antibiotics have been started [4][6]
- Bite-site crust PCR: Can detect S. moniliformis DNA even weeks after exposure [6]
- Metagenomic next-generation sequencing (mNGS): Detected S. moniliformis genome in <72 hours in one case with negative blood cultures [17]
- Warthin-Starry/Steiner stain: Can identify rod-shaped bacteria in tissue specimens [8]
- No validated serologic test is widely available for routine clinical use
14. ECG
- Obtain ECG if: Endocarditis is suspected, new murmur, or hemodynamic instability
- Findings in endocarditis: New conduction abnormalities (AV block, intraventricular conduction delays) — associated with invasive infection and 2-fold higher mortality [18]
- Myocarditis: ST-segment changes, arrhythmias (rare but reported at autopsy) [19]
- Routine ECG not required for uncomplicated RBF without cardiac symptoms
15. Assessment
- RBF is a clinical diagnosis supported by exposure history — the classic triad of fever, rash, and migratory polyarthritis arising days to weeks after rodent exposure is highly suggestive [1-2]
- The triad is incomplete in >50% of cases, particularly in adults where rash is frequently absent [4]
- Rodent exposure is not volunteered in ~1/3 of cases — active inquiry is essential [4]
- Severity stratification: Uncomplicated (fever, rash, arthritis) vs. complicated (endocarditis, meningitis, osteomyelitis, sepsis)
- Complications: Endocarditis (most feared), septic arthritis, osteomyelitis/discitis, meningitis, hepatitis, pneumonitis, myocarditis, nephritis [1][7][9-10]
- Atypical presentations: Monoarticular septic arthritis mimicking inflammatory arthritis, vasculitis mimicking ANCA-associated disease, vertebral osteomyelitis [10][15][20]
16. Treatment Plan
Initial stabilization
- IV fluid resuscitation and hemodynamic support if septic
- Obtain blood cultures (and joint fluid if applicable) before antibiotics
Uncomplicated RBF
- IV Penicillin Goral penicillin Vamoxicillin[1][11]
Complicated RBF (endocarditis)
- IV Penicillin G 12–20 million units/day divided q4h for 4 weeks [11]
- Pediatric: 150,000–250,000 units/kg/day divided q4h for 4 weeks [11]
- Valve replacement may be necessary in severe cases [8][16]
Penicillin allergy
- Doxycycline 100 mg PO/IV q12h [1][12]
- Ceftriaxone 2g IV daily (if non-anaphylactic penicillin allergy) [9]
Adjunctive
- NSAIDs for arthritis symptom management [15]
- Joint drainage if septic arthritis with significant effusion [4]
17. Disposition
Admit if
- Sepsis or hemodynamic instability
- Endocarditis (new murmur, embolic phenomena, positive echocardiogram)
- Meningitis or altered mental status
- Inability to tolerate oral medications
- Significant comorbidities or immunosuppression
- Complicated osteoarticular infection requiring IV antibiotics or surgical drainage
Discharge if
- Clinically stable, well-appearing
- Able to tolerate oral antibiotics
- Reliable follow-up ensured
- No signs of endocarditis or other complications
Observation
Consult
- Infectious disease: All confirmed or strongly suspected cases
- Cardiology/cardiac surgery: If endocarditis suspected
- Orthopedics: If septic arthritis requiring drainage or osteomyelitis
18. Follow Up / Return Precautions
- Follow-up: Within 48–72 hours of ED discharge to reassess clinical response to antibiotics; repeat at 1–2 weeks to confirm resolution
- Blood culture follow-up: Ensure final culture results are reviewed (S. moniliformis may take 5–7+ days to grow) [1][4]
- Return immediately for: Worsening fever, new rash, joint swelling, chest pain, dyspnea, confusion, syncope, or any signs of clinical deterioration
- Expected recovery: Fever typically resolves within 24–48 hours of appropriate antibiotic therapy; arthritis may take longer to fully resolve
- Patient counseling:
- Complete the full antibiotic course
- Minimize direct contact with rodents; use gloves when handling cages/excreta
- RBF is not nationally notifiable, but local health departments may be interested in cases from wild rat exposure [1]
- Counsel on safe pet rodent handling practices to prevent recurrence
References
1. Rat Bite Fever: Fever, Arthritis, and Rash in a 4‐Year‐Old Boy. — Lewis BK, Vanderhooft S. Pediatric Dermatology. 2011.
2. Rat Bite Fever and Streptobacillus Moniliformis. — Elliott SP. Clinical Microbiology Reviews. 2007.
3. Fatal Rat-Bite Fever--Florida and Washington, 2003. — MMWR. Morbidity and Mortality Weekly Report. 2005.
4. Septic Arthritis Complicating Streptobacillus Moniliformis Rat Bite Fever: A Case Report and Review of Its Pathophysiology and Diagnosis. — Giraudon E, Larranaga Lapique E, Wallemacq S, et al. Frontiers in Medicine. 2023.
5. Rat Bite Fever, a Diagnostic Challenge: Case Report and Review of 29 Cases. — Kämmerer T, Lesmeister T, Wollenberg A, et al. Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2021.
6. Rat-Bite Fever Diagnosed by Polymerase Chain Reaction of a Bite-Site Crust Specimen Three Weeks After Exposure: A Case Report. — Yoshida K, Saito M, Sumiyoshi A, et al. Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2026.
7. Streptobacillus Moniliformis Endocarditis: Case Report and Review. — Rupp ME. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 1992.
8. Severe Recurrent Streptobacillus Moniliformis Endocarditis in a Pregnant Woman, and Review of the Literature. — Crofton KR, Ye J, Lesho EP. Antimicrobial Resistance and Infection Control. 2020.
9. Rat Bite Fever Due to Streptobacillus Notomytis Complicated by Meningitis and Spondylodiscitis: A Case Report. — Pongsuttiyakorn S, Kamolvit W, Limsrivanichakorn S, Phothisirisakulwong A, Wangchinda W. BMC Infectious Diseases. 2021.
10. Rat Bite Fever With Osteomyelitis and Discitis: Case Report and Literature Review. — Adams SH, Mahapatra R. BMC Infectious Diseases. 2021.
11. FDA Drug Label. — Updated date: 2020-05-27. Food and Drug Administration.
12. FDA Drug Label. — Updated date: 2025-07-25. Food and Drug Administration.
13. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. — Stevens DL, Bisno AL, Chambers HF, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2014.
14. Multiplex Serology for Streptobacillus Moniliformis and Other 'Rat Bite Fever-Like' Microorganisms for Seroprevalence Studies in Rodents. — Schmidt K, Butt J, Matt U, et al. PloS One. 2025.
15. Rat Bite Fever Mimicking ANCA-associated Vasculitis. — Błaż A, Zalewski J, Masiak A, et al. Rheumatology International. 2023.
16. Prosthetic Valve Endocarditis Caused by Streptobacillus Moniliformis: A Case of Rat Bite Fever. — Chen PL, Lee NY, Yan JJ, et al. Journal of Clinical Microbiology. 2007.
17. Rat Bite Fever Caused by Streptobacillus Moniliformis Infection in a Chinese Patient. — Zhang WW, Hu YB, He GX, et al. BMC Infectious Diseases. 2019.
18. Update to Practice Standards for Electrocardiographic Monitoring in Hospital Settings: A Scientific Statement From the American Heart Association. — Sandau KE, Funk M, Auerbach A, et al. Circulation. 2017.
19. The Etiology of Rat-Bite Fever. — Blake FG. The Journal of Experimental Medicine. 1916.
20. Septic Polyarthritis Caused by Streptobacillus Moniliformis. — Uddin A, Phan T, Yassin M. Emerging Infectious Diseases. 2021.