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Table 1 Literature review summary of nine RBF cases associated with osteomyelitis or discitis, 2008 through 2019

From: Rat bite fever with osteomyelitis and discitis: case report and literature review

Year

Country

Study

Age/sex

Exposure

Clinical history and findings

Significant biochemical findings

Site of osteomyelitis/discitis

Identification method of Streptobacillus moniliformis

Cultures

Imaging findings

Surgical treatement

Histological findings

Diagnosis

Antibiotic treatment

Outcome

##

France

Dubois et al.

80-year/male

Rooster scratch

History: One week of shaking chills and back pain radiating to both legs on awakening. The pain subsided by time of presentation.

On exam: Afebrile. Physical examination was without specific signs. Over following days developed disorders of consciousness and fever (Tmax 39 °C).

WBC 19, neutrophil count 18, CRP 488 mg/liter, fibrinogen 8.9 g/liter, procalcitonin 13 ng/ml.

Later, CRP level lowered to 240 mg/liter, then to 163 and 115 mg/liter.

T5-T6 and L2-L3

16S rRNA PCR assay from psoas abscess fluid

Blood specimens inoculated into paired aerobic and anaerobic bottles gave positive results after 1–5 days.

Gram-staining of psoas abscess and blood smears showed pleomorphic fusiform gram-negative rods.

CT thorax revealed pericardial and pleural effusions.

CT abdomen showed right iliac psoas abscess communicating with a prosthesis screw.

Bone scan showed increased signal at L3.

MRI lumbar spine revealed psoas abscess and of spondylodiscitis at T5 and T6, and at L2 and L3.

(Imaging details not provided).

none

n/a

Spondylodiscitis and psoas abscess

Began with empirical antibiotic therapy parenteral amoxicillin-clavulanic acid (1 g, Q8H) and ofloxacin (200 mg, Q12H). Switched to imipenem-cilastatin (1 g, Q12H), ciprofloxacin (400 mg, Q12H), and teicoplanin (600 mg, QD).

Then an additional 9-week treatment with i.v. ofloxacin (200 mg, Q12H), i.v. clindamycin (600 mg, Q8H), and metronidazole (500 mg, Q8H).

In good health at 8 month follow-up.

##

United States

Flannery et al.

22-month/male

Two pet rats

History: Two days of URI symptoms, then 5 days of fever, malaise, with a worsening and blistering rash on all extremities, including palms and soles. Irritability.

On exam: Mild hypertension, tachycardia, T 38.0 °C. Scattered tender, erythematous, pustular rash on hands, feet, ankles without joint swelling or tenderness on initial exam. Fevers persisted for several days with worsening rash and pain. On day 5, refused to bear weight on feet; pain with right-hip range of motion exam.

Day 1: WBC 10,200/μl, Hb 10.9 g/dl, plt 217,000/μl

Day 5: WBC 18,100/μl (neutrophilic predominance), Hb 10.0 g/dl, plt 523,000/μl, CRP 5.4 mg/dl, ESR 94 mm/h.

Right-hip joint

16S RNA sequencing and DNA mapping

Blood, left-foot pustule fluid, synovial fluid, and femoral bone cultures grew Gram-negative rods (though bone culture may have been contaminated).

Ultrasound of right hip revealed joint effusion.

MRI: bone marrow edema in the right proximal femoral epiphysis with edema in the surrounding muscles and fascial planes (possibly post-op changes)

Open irrigation and debridement of hip joint

n/a

Septic arthritis and possible osteomyelitis

Started on vancomycin and ceftriaxone for empirical bacterial coverage. Switched to i.v. penicillin (250,000 units/kg of body weight/day divided every 4 h).

Total of 8 weeks of antibiotics, with 4 weeks of intravenous penicillin and 4 weeks of oral amoxicillin.

At one-month follow-up patient remained afebrile with normal inflammatory markers. X-rays of hips and pelvis were normal. Improved weight bearing with physical therapy. Thereafter lost to follow-up.

##

United Kingdom

Adizie et al.

29-year/male

Owner of three rats

History: Five days of malaise, feverishness, headache, sore throat, joint swellings with rash.

On exam: Pustular, maculopapular and petechial rash of the extremities including palms and soles. Right knee and left ankle effusions, right second MCPJ swelling.

CRP 211, ESR 36, ferritin 417, neutrophils 7.89

Left ankle

16S rRNA PCR molecular sequencing

Blood cultures and joint aspirate were initially negative.

Repeat joint aspirate showed S. moniliformis on 16S rRNA molecular testing.

Left ankle MRI: considerable marrow edema, moderate thick walled effusion consistent with septic arthritis and associated osteomyelitis.

none

Rash skin biopsy: mild non-specific perivascular inflammation within the subcutis

Septic arthritis and associated osteomyelitis

Initially treated with a broad spectrum antibiotic; changed to i.v. benzylpenicillin; then switched to oral penicillin after 2 weeks.

Good recovery

##

Japan

Nei et al

72-year/female

Denied any direct contact with rodents. Possibility of contact with contaminated water and/or food.

History: 8 days of fever and chills.

On exam: T 38 C. Subsequent worsening severe lower back pain which limited ability to ambulate.

WBC 13.3 (95% neutrophils), alkaline phosphatase 1035 IU/L, γ-glutamyl transferase 239 IU/L, CRP 26.92 mg/dL

L3-L4 vertebrae and intervertebral disc

16S rRNA genotyping

At 2 days of incubation in aerobic culture with 5% CO2 on 5% sheep blood agar, highly pleomorphic, filamentous gram-negative bacilli are visualized.

Colonies described as very tiny, transparent and slightly white.

MRI: Vertebral bodies L3 and L4 with low signal on T1WI, high signal on STIR. Low intervertebral disk with linear T2 high signal.

Vertebral endplates at L3, L4 were destroyed with visible high-signal-intensity bone marrow edema.

none

n/a

Vertebral spondylodiscitis

Initially treated with cefazolin (2.0 g, Q8H) and NSAIDs. Switched to ampicillin (2.0 g/every 6 h). Switched again to sulbactum/ampicillin (3.0 g/Q6H) due to failed antimicrobial susceptibility tests.

Gradual improvement of lower back pain; gradual recovery of exercise and walking capacity. Discharged on 71st day of hospital stay.

##

Japan

Sato et al.

52-year/male

Rats infestation in his home; suspicion of bite during sleep.

History: Four days of diffuse arthralgias beginning in knees and back. Found immobile due to severe arthralgia and was taken to hospital.

On exam: Afebrile, HR 110, RR 24. Scars on his fingers and feet. Warm, swollen, and tender joints with pain with passive motion. Tenderness at L5/S1 vertebrae.

Day 4 of admission: systolic fell to 70 mmHg, septic shock.

WBC 10,300/mL (88% neutrophils). Creatinine kinase 789 U/L. CRP 34.6 mg/dL.

L5, S1 vertebrae; L5-S1 disc

MALDI-TOF MS suggested S. moniliformis DSM 12112 T (score value was 1.588 – unreliable).

16S rRNA molecular sequencing.

Blood cultures positive for gram-negative bacilli at 25 h/ 35 C/ 5% CO2.

T2-weighted MRI: high signal intensity in L5 and S1, destruction of L5-S1 disc space supporting diagnosis of diagnosis of vertebral osteomyelitis

Surgical debridement. Cultures from site were negative.

n/a

Vertebral osteomyelitis

Ceftriaxone, 1 g per 24 h, 6 weeks

Complete resolution of arthralgia and back pain; no long-term sequelae.

##

Canada

Akter et al.

46-year/female

Pet rat scratch

History: One-week of fever and symmetric polyarthritis of the distal extremities with morning stiffness. One day nausea, vomiting, and diarrhea.

On exam:

Day 1 of presentation: T 38 °C, HR 130 beats/min, BP 96/64 mmHg. Effusions in wrists, ankles, and MTPJ.

Day 2 of presentation: T 39 °C. Worsening synovitis, new onset lumbar spinal pain.

Day 1: WBC 11.1, ESR 76 mm/hr., CRP 149 mg/L.

Day 2: AST 105, ALT 114, ESR 124, CRP 170.

L5-S1 intervertebral disc

Cultures. (Further info not reported).

Initial blood culture was negative. Repeat cultures grew S. moniliformis.

Right ankle synovial fluid sample culture negative.

MRI lumbosacral spine: enhancement of the vertebral end plates; T1WI showed markedly reduced signal at the L5-S1 level, while T2WI showed increased T2 signal.

none

n/a

Discitis

Initially treated with prednisone, methotrexate, sulfasalazine, and hydroxychloroquine due to erroneous diagnosis of rheumatoid arthritis. When correct diagnosis was realized these were discontinued and was started on i.v. ceftriaxone. Was discharged with 3-month course of i.v. ceftriaxone.

Complete resolution of arthritis, marked improvement of back pain, normal inflammatory markers, and resolution of discitis on repeat MRI at 3 months follow-up.

##

Germany

Eisenberg et al.

59-year/male

Snake keeper who bred rats for snake food.

History: 15 days of fever and arthralgia without rash. Inability to stand and acute progressive onset of dyspnea.

On exam: T 39 °C. Was initially sedated and placed on ventilator.

With discontinuation of sedation, exam showed cervical pain, flaccid tetraplegia, sensitivity at the T4 level. Knees and left wrist swollen with joint effusions.

WBC 15 (predominantly neutrophils); C-reactive protein 125 mg/L.

C5–T1 vertebrae

16S rRNA gene sequencing from synovia

Blood cultures showed negative results.

Culture-negative inflammatory liquid and uric acid crystals found in joint effusions.

Fat-saturated, contrast-enhanced T1-weighted MRI spine: Sagittal view of the cervical spine shows spondylodiscitis; epidural absess with C5–T1 compression.

none

n/a

Vertebral osteomyelitis and an epidural abscess with consecutive compression of the spinal cord (C5–T1)

Amoxicillin and cloxacillin

Not reported.

##

United Kingdom

Abusalameh et al

62-year/female

Denied history of rat bite; acknowledged exposure to live rats and rats droppings.

History: Four-days of diarrhea and vomiting followed by acute onset of diffuse hot, swollen joints with severe lower back pain. Hx of seropositive RA (positive anti-CCP), controlled with MTX and tocilizumab.

CRP 218 mg/l, creatinine 2.37

L5/S1 intervertebral disc

16S rRNA PCR

Knee, ankle, wrist, and L5/S1 disc needle aspirates grew a gram-negative organism.

MRI spine: edema of L5/S1 intervertebral disc.

none

n/a

Discitis

Initially on benzyl penicillin and clindamycin. Later changed to 12-week course of oral amoxicillin and clindamycin.

Disc edema improvement after weeks of antibiotic treatment.

##

Portugal

Pena et al.

75-year/female

Rat bite

History: Four-day history of fever, myalgias, headache.

On exam: Subfebrile, hypotensive, incised wounds on two fingers of left hand. Neck stiffness. On day 3 of admission patient developed worsening neck pain and quadriparesis.

WBC 14,670/μL (86.3% neutrophils), CRP 334 mg/dL, normal LP

C5, C6, and C7 vertebrae, left SC joint

16S rRNA PCR and Sanger sequencing

Two blood cultures (BD BACTEC Plus Aerobic/F medium) grew gram-negative bacteria after 3 days incubation.

Normal CT brain.

MRI T2WI: high signal intensity in C5, C6, and C7 vertebrae with meningeal enhancement and high signal intensity the left SC joint, consistent with diagnosis of vertebral osteomyelitis and septic arthritis

none

n/a

Vertebral osteomyelitis and septic arthritis

Empirically treated on day 1 of hospitalization with i.v. ceftriaxone (2 g/day); completed 26 days of i.v. ceftriaxone followed by 8 months of oral amoxicillin-clavulanate after discharge.

Complete resolution of neck pain and tetraparesis.