Often healed with dry crust at time of systemic illness
May show regional lymphadenopathy
Spirillum minus causes local ulceration and eschar (sodoku variant)
Musculoskeletal exam
Joint examination
Swelling and warmth
Knees most commonly involved
Ankles and wrists
Effusion assessment
Fluctuance on palpation
Consider aspiration for culture
Migratory pattern
One joint improves while another worsens
Distinguishes from septic arthritis which is typically monoarticular
Cardiac and abdominal exam
Cardiac auscultation
New murmur
Regurgitant murmur suggesting valve destruction
Friction rub suggesting pericarditis
Muffled heart sounds
Pericardial effusion concern
Abdominal exam
Hepatosplenomegaly
Rare but reported complication
Right upper quadrant tenderness
Hepatitis association
Neurologic and lymph node exam
Meningeal signs
Nuchal rigidity
Kernig and Brudzinski signs
CNS involvement reported
Altered mental status
New confusion or agitation
Lymphadenopathy
Regional nodes near bite site
Cervical, axillary, or inguinal depending on bite location
Generalized lymphadenopathy in some cases
Differential Diagnosis
Immediate life threats
Cannot miss diagnoses
Meningococcemia
ICD-10 A39.2
Petechial or purpuric rash with rapid deterioration
Immediate empiric coverage required
Septic shock from other source
ICD-10 A41.9
Requires broad empiric coverage until source identified
Infective endocarditis
ICD-10 I33.0
Duke criteria application
TEE if high suspicion with negative TTE
Fever rash and arthritis mimics
Disseminated gonococcal infection
ICD-10 A54.49
Sexually active patients
Tenosynovitis and pustular rash on extremities
Positive cervical or urethral cultures
Rocky Mountain spotted fever
ICD-10 A77.0
Tick exposure history
Centripetal rash spread from extremities
Doxycycline empiric treatment if suspected
Lyme disease
ICD-10 A69.20
Erythema migrans rash
Tick exposure in endemic area
Reactive arthritis
ICD-10 M02.9
Preceding GI or GU infection
Triad of arthritis, conjunctivitis, urethritis
Rheumatic fever
ICD-10 I00
Preceding streptococcal pharyngitis
Jones criteria application
No rodent exposure
Drug reaction
ICD-10 L27.0
Temporal relationship to new medication
Drug rash with eosinophilia and systemic symptoms
Additional mimics
Leptospirosis
ICD-10 A27.9
Water exposure or animal urine contact
Conjunctival suffusion and jaundice
Viral exanthem
EBV or other viral syndrome
Lymphadenopathy and pharyngitis
Atypical lymphocytes on smear
Rat bite fever organism itself
Streptobacillus moniliformis
ICD-10 A25.1
Americas and Europe
Spirillum minus
ICD-10 A25.0
Asia predominantly (sodoku)
ANCA-associated vasculitis
Rat bite fever can mimic and induce ANCA positivity
Anti-MPO or anti-PR3 serology may be positive
Clinical context and culture essential for differentiation
Laboratory Tests
Blood cultures and organism-specific testing
Blood cultures
Essential before starting antibiotics
Notify lab to hold cultures for extended incubation
S. moniliformis is fastidious and requires enriched media
Media requirements
Enriched with serum, ascitic fluid, 5% blood, or yeast extract
Incubate up to 7 to 14 days
Antibiotics render cultures negative rapidly
Cultures before treatment is critical
Molecular diagnostics
16S rRNA PCR gene sequencing
From blood, joint fluid, or bite-site crust
Highly valuable when cultures are negative or antibiotics already started
Bite-site crust can yield DNA weeks after exposure
Metagenomic next-generation sequencing
Emerging diagnostic tool
Identified S. moniliformis genome within 72 hours with negative blood cultures
Core laboratory panel
Inflammatory and infection markers
Complete blood count
Leukocytosis with left shift
Anemia in prolonged or severe cases
CRP and ESR
Elevated in active infection
Trend useful for treatment response
Procalcitonin
Bacterial infection support
Helpful to differentiate from viral syndrome
Metabolic and organ function
Basic metabolic panel
Renal function for antibiotic dosing
Nephritis is a known complication of rat bite fever
Liver function tests
Hepatitis association reported
Baseline before prolonged antibiotic therapy
Lactate
>= 2 mmol/l as organ hypoperfusion marker
Repeat in 2 to 4 hours if elevated
Joint fluid analysis
Arthrocentesis when joint effusion present
Culture on enriched media
90% detection rate on joint fluid when properly cultured
Notify lab of clinical suspicion
Cell count and differential
Inflammatory fluid with high WBC
Distinguishes from crystal arthropathy
PCR on joint fluid
Alternative when culture sensitivity is uncertain
Send 16S rRNA PCR if available
Serology and ancillary tests
ANCA serology
Anti-MPO and anti-PR3
May be positive due to molecular mimicry
Do not diagnose vasculitis without clinical correlation
Blood smear
Spirillum minus (sodoku) detectable on darkfield microscopy or Giemsa stain
Spiral organisms with characteristic morphology
More useful in Asian cases or travel history
Diagnostic Tests
Scoring Systems
Diagnostic scoring
No validated clinical decision rule specific to rat bite fever
Diagnosis relies on clinical triad plus exposure history
Classic triad present in fewer than 50% of cases
Duke criteria for endocarditis
Applied when endocarditis is suspected complication
S. moniliformis endocarditis reported with Duke criteria application
Sepsis criteria
SOFA score for organ dysfunction assessment
qSOFA as bedside screening tool
MRI
MRI indications in rat bite fever
Osteomyelitis or discitis suspected
Back pain with neurologic deficits
MRI spine with contrast
More sensitive than plain radiographs for early osteomyelitis
CNS involvement suspected
MRI brain with contrast for meningitis or abscess
Gadolinium enhancement patterns
Joint complications
MRI of affected joint if destructive arthritis suspected
Assess for osteomyelitis adjacent to septic joint
CT
CT indications in rat bite fever
Endocarditis with embolic complications
CT abdomen and pelvis for splenic or renal infarcts
CT chest for septic pulmonary emboli
CNS involvement
CT head before lumbar puncture in altered patients
Non-contrast first then contrast for abscess
Abdominal complications
Hepatosplenomegaly assessment
Peritoneal abscess if suspected
Chest imaging
CT chest if pneumonitis suspected
Parapneumonic complications
Ultrasound
Echocardiography
Transthoracic echo
Vegetations on native or prosthetic valves
Valvular regurgitation assessment
Pericardial effusion
Transesophageal echo
Superior sensitivity for small vegetations
Recommended if TTE negative but suspicion high
Preferred for prosthetic valve endocarditis assessment
Point-of-care ultrasound
Joint effusion detection
Guide arthrocentesis
Identify fluid for culture
Abdominal POCUS
Hepatosplenomegaly assessment
Free fluid detection
Vascular ultrasound
Septic thrombophlebitis near bite site
Rare complication
Doppler assessment of regional veins
Disposition
Admission indications
Hospitalization criteria
All confirmed or suspected cases requiring IV antibiotics
Inability to take oral medications
Sepsis or hemodynamic instability
Endocarditis concern
Admit for IV penicillin G 4 to 6 weeks
Cardiac surgery consultation if valve destruction
CNS involvement
Meningitis requires prolonged IV antibiotics
ICU level care if altered mental status
Immunocompromised patients
Lower threshold for admission
Prolonged or complicated course anticipated
ICU criteria
Critical care indications
Septic shock
Vasopressor requirement
Lactate > 2 mmol/l despite resuscitation
Endocarditis with hemodynamic instability
Acute severe valvular regurgitation
Heart failure from valve destruction
Meningitis with neurologic compromise
GCS <= 13
Seizures
Discharge criteria and follow-up
Discharge criteria for uncomplicated presentations
Reliable oral intake
Able to complete oral antibiotic course
Stable vitals
Afebrile or improving fever trend
Normal hemodynamics
No endocarditis or CNS concern
No new murmur
No altered mental status
Follow-up plan
Primary care or infectious disease within 48 to 72 hours
Blood culture results review
Antibiotic tolerance assessment
Repeat clinical evaluation
Ensure complete resolution of fever and arthritis
Relapse monitoring
Treatment
First-line antibiotic therapy
IV penicillin G for moderate to severe disease
Standard dosing
12 to 20 million units per day IV divided every 4 hours
Duration 3 to 4 weeks for uncomplicated disease
Endocarditis dosing
4 weeks minimum duration
Infectious disease guidance for valve involvement
Pediatric dosing
150,000 to 250,000 units per kg per day IV divided every 4 hours
Duration based on severity
Step-down oral therapy
Oral penicillin V step-down
After clinical improvement on IV penicillin
To complete 7 to 14 days total for uncomplicated cases
500 mg PO every 6 hours in adults
Amoxicillin alternative oral step-down
500 mg PO every 8 hours
Well tolerated for outpatient completion
Duration targets by severity
Uncomplicated rat bite fever
7 to 14 days total course
Minimum 7 days after fever resolution
Endocarditis
4 to 6 weeks IV penicillin G
Surgical valve repair or replacement if indicated
Meningitis or osteomyelitis
4 to 6 weeks depending on response
Imaging-guided reassessment
Penicillin allergy alternatives
Doxycycline
100 mg IV or PO every 12 hours
Adults and children over 8 years
Avoid in children under 8 years
Avoid in pregnancy
Duration 7 to 14 days for uncomplicated disease
Ceftriaxone
2 g IV every 24 hours
Supported by case reports
Useful in penicillin-intolerant patients
Duration based on severity
Streptomycin
Historical alternative
7.5 to 15 mg per kg IM every 12 hours
Limited contemporary use due to toxicity
Aminoglycoside monitoring required
Agents to avoid
Macrolides
Variable activity against S. moniliformis
Generally not recommended as primary agents
May be used as last resort with susceptibility testing
Trimethoprim-sulfamethoxazole
Not reliable monotherapy for S. moniliformis
Resistance patterns unpredictable
Obtain cultures before any antibiotics
Antibiotics render cultures negative within hours
Even one dose significantly reduces culture yield
Supportive and adjunctive treatment
Sepsis resuscitation
IV fluid resuscitation
30 mL per kg crystalloid for septic shock
Reassess frequently for fluid overload
Vasopressors if refractory hypotension
Norepinephrine first-line
Target MAP >= 65 mmHg
Pain and fever management
NSAIDs for arthritis symptoms
Useful adjunct for joint pain and swelling
Avoid in renal impairment
Acetaminophen for fever and pain
Safe across most populations
Dose adjust for hepatic impairment
Wound care
Tetanus prophylaxis
Assess immunization status after bite
Tetanus toxoid if not up to date
Wound cleansing
Thorough washing with soap and water
Wound debridement rarely required
Special Populations
Pregnancy
Pregnancy considerations
Antibiotic safety
Penicillin G is safe in all trimesters
Amoxicillin safe as oral step-down
Doxycycline contraindicated in pregnancy
Infection risk
S. moniliformis bacteremia can cause placental infection
Risk of miscarriage, preterm labor, stillbirth reported
Imaging guidance
Echocardiography preferred over CT when possible
MRI without gadolinium preferred for CNS assessment
CT when benefit clearly outweighs risk
Fetal monitoring
When fetal viability reached
Obstetrics consultation for co-management
Geriatric
Older adult considerations
Atypical presentation
Rash may be absent or subtle
Arthritis may be attributed to pre-existing joint disease
Diagnosis delayed more often in older patients
Endocarditis risk
Pre-existing valvular disease increases risk
Aortic stenosis and mitral regurgitation common in older adults
Lower threshold for echocardiography
Antibiotic dosing adjustments
Renal function often reduced
Creatinine clearance-guided dosing for renally cleared drugs
Monitor closely for adverse effects
Functional and cognitive considerations
Delirium risk during febrile illness
Frailty may indicate lower threshold for hospital admission
Post-illness rehabilitation needs
Pediatrics
Pediatric considerations
Epidemiology
Children represent over 50% of reported rat bite fever cases
Pet rat ownership most common exposure in children
Younger children most at risk due to close handling of rodents
Antibiotic dosing
Penicillin G IV 150,000 to 250,000 units per kg per day divided every 4 hours
Amoxicillin PO 40 to 50 mg per kg per day divided every 8 hours for oral step-down
Doxycycline avoided in children under 8 years due to dental staining
Ceftriaxone alternative in penicillin allergy
50 to 100 mg per kg per day IV in children
Maximum 2 g per dose
Clinical differences
Arthritis may be mistaken for juvenile idiopathic arthritis
Rash may be subtle or atypical in young children
Parent and caregiver education on rodent exposure prevention
Background
Epidemiology
Incidence and distribution
Rare but underdiagnosed condition
Exact incidence unknown due to underreporting
Estimated hundreds of cases annually in the US
Geographic distribution of causative organisms
Streptobacillus moniliformis predominant in Americas, Europe, Australia
Spirillum minus predominant in Asia (sodoku)
Demographic patterns
Children most commonly affected, > 50% of reported cases
Pet rodent ownership increasing incidence in urban settings
Laboratory animal workers and pet store employees at risk
Mortality and morbidity
Untreated mortality 7 to 13%
Death from septic shock, endocarditis, or meningitis
Early diagnosis and treatment dramatically improves outcomes
Morbidity
Endocarditis occurs in subset of cases, especially with valvular disease
Arthritis may persist if treatment delayed
Pathophysiology
Causative organisms
Streptobacillus moniliformis
Gram-negative pleomorphic rod
Fastidious, requires enriched media for culture
Normal oral flora of rats and other rodents
Spirillum minus
Gram-negative spiral organism
Darkfield microscopy or Giemsa stain for identification
Causes sodoku variant in Asia
Transmission and inoculation
Direct inoculation via bite or scratch
Rat normal oral flora enters tissue
Local wound often heals before systemic illness
Haverhill fever variant
Ingestion of contaminated food or water
Outbreaks in rodent-infested settings described
GI symptoms more prominent
Indirect contact
Fomites, rodent excreta without direct bite
Disease mechanism
Bacteremia after local inoculation
Organism spreads hematogenously
Tropism for joints and cardiac valves
Joint involvement
Immune-mediated synovitis predominant mechanism
Migratory pattern due to ongoing bacteremic seeding
Endocarditis mechanism
Pre-existing valve damage as nidus
Vegetation formation on damaged endothelium
Embolic complications from vegetations
Therapeutic Considerations
Antibiotic principles
Penicillin G remains drug of choice
Highly susceptible organism
IV route for moderate to severe disease
Oral penicillin or amoxicillin for uncomplicated step-down
Duration guided by clinical syndrome
Uncomplicated cases 7 to 14 days
Endocarditis 4 to 6 weeks
Osteomyelitis or meningitis 4 to 6 weeks
Culture and susceptibility testing
Perform susceptibility when possible given fastidious growth
No standardized breakpoints for S. moniliformis
Diagnostic strategy
Awareness of exposure history critical
Exposure history is primary diagnostic trigger
Classic triad absent in majority of cases
Extended culture incubation
Standard incubation protocols miss diagnosis
Must communicate suspicion to microbiology laboratory
Molecular testing as complement
16S rRNA PCR valuable when cultures negative
Metagenomic sequencing emerging option
Prevention
Wound management after rodent bite
Thorough washing immediately
Tetanus prophylaxis
Prophylactic antibiotics considered in immunocompromised or high-risk hosts
Rodent exposure reduction counseling
Gloves when handling rodents
Avoiding bare-hand contact with feces or urine
Household rodent control measures
Patient Discharge Instructions
copy discharge instructions
Rat bite fever home care instructions
Take all prescribed antibiotics exactly as directed until the full course is complete
Do not stop early even if feeling better
Take with food if stomach upset occurs
Rest and stay well hydrated
Drink plenty of fluids daily
Wound care if bite site present
Keep clean and dry
Watch for increasing redness or discharge
Warning signs requiring immediate return to emergency department
High fever returning or worsening after starting antibiotics
New rash or worsening of existing rash
Severe joint swelling or inability to move a joint
Difficulty breathing or chest pain
Racing or irregular heartbeat
Severe headache or stiff neck
Confusion or difficulty waking up
Weakness or numbness
Follow-up instructions
See your doctor within 2 to 3 days of discharge
Blood culture results may become available
Antibiotic adjustment may be needed
Complete all follow-up appointments as scheduled
Report any new symptoms promptly
Prevention after discharge
Wear gloves when handling pet rodents
Wash hands thoroughly after contact
Avoid allowing rodents to lick open wounds or cuts
Keep pet rodent enclosures clean
Seek medical attention promptly after any future rodent bite or scratch
References
Guidelines and key sources
Primary references
Centers for Disease Control and Prevention rat bite fever guidance
Clinical diagnosis and management recommendations
Hagelskjaer LH et al. systematic review of rat bite fever
Clinical features and outcomes in reported cases
Elliott SP. Rat bite fever and Streptobacillus moniliformis
Clinical Microbiology Reviews 2007
Comprehensive organism and disease review
Case series and reports
Endocarditis case series
Valve involvement patterns and outcomes
Duke criteria application to S. moniliformis endocarditis
Molecular diagnostics in rat bite fever
16S rRNA PCR and metagenomic sequencing case reports
Culture-negative diagnosis facilitated by molecular methods
Diagnostic coding
ICD-10 A25.1 Streptobacillosis
Rat bite fever due to S. moniliformis
ICD-10 A25.0 Sodoku
Rat bite fever due to Spirillum minus
SNOMED CT rat bite fever disorder
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.