II. Epidemiology

  1. Incidence: 2-10 per 100,000 cases/year (16,000) of Monoarticular Arthritis in the Emergency Department (U.S., 2018)
  2. Age
    1. Bimodal distribution peaks <15 years old and over 55 years old
    2. Young children <18-24 months are more susceptible to Septic Arthritis
      1. Bridging veins between metaphysis and epiphysis allow spread of infection to joint
      2. Bridging veins close after age 18-24 months

III. Causes

  1. See Septic Joint Causes
  2. Most common causes of Septic Joint
    1. Streptococcus
    2. Staphylococcus (including MRSA or Methicillin Resistant Staphylococcus Aureus)
      1. MRSA is associated with more severe infection and subperiostal abscess
    3. Gonorrhea is the most common cause of Septic Arthritis in young adults

IV. Risk Factors

  1. No risk factor present in up to 22% of cases
  2. Systemic comorbidity
    1. Immunosuppression
    2. HIV Infection
    3. Diabetes Mellitus
    4. Intravenous drug use (unusual joints affected)
    5. Alcoholism
    6. Sickle Cell Anemia
    7. Elderly patients over age 80 years old
    8. Tobacco Abuse
  3. Joint disorders (47% of cases have previously deranged affected joint)
    1. Rheumatoid Arthritis (14% of cases)
      1. Higher mortality risk with Immunosuppressants (TNF agents, Systemic Corticosteroids)
      2. TNF agents predispose atypical and virulent infections (e.g. Salmonella, Actinobacillus, Listeria)
      3. Higher risk of Oligoarticular infection
    2. Osteoarthritis
    3. Inflammatory Bowel Disease
    4. Prosthetic joint (1-2% risk at 2 years, >2% at 10 years; nearly half occur in the first 3 months after surgery)
      1. Prosthetic Hip Joint
      2. Prosthetic Knee Joint
    5. Other Joint surgery
  4. Overlying skin disruption
    1. Chronic dermatitis
    2. Skin Ulceration
    3. Skin Infection such as Cellulitis
    4. Large vein catheterization (unusual joints affected)
  5. Fungal Arthritis Risk Factors (esp. Candida, also Aspergillus, Coccidioides, Histoplasma, Blastomyces, Cryptococcus)
    1. Diabetes Mellitus
    2. HIV Infection
    3. Immunosuppression
    4. Organ Transplantation
    5. Parenteral Hyperalimentation
    6. Indwelling Catheter
    7. Substance Abuse
    8. Broad Spectrum Antibiotics
    9. Bariteau (2014) J Am Acad Orthop Surg 22(6): 390-401 [PubMed]
  6. Periprosthetic Joint Infection Risk Factors
    1. Obesity (highest risk)
    2. Cardiac disease
    3. Immunocompromised
    4. Peripheral Vascular Disease
    5. Inflammatory Arthritis
    6. Prior joint infection
    7. Renal disease
    8. Liver disease
    9. Malnutrition
    10. Alcohol Abuse
    11. Tobacco Abuse
    12. Diabetes Mellitus
    13. Anemia
    14. Tubb (2020) J Am Acad Orthop Surg 28(8): e340-8 [PubMed]

V. Pathophysiology

  1. Hematologic seeding in most cases from Occult Bacteremia
    1. Once joint seeding occurs, infection progresses rapidly
    2. Joint is susceptable to hematogenous spread
      1. Synovial lining lacks a protective basement membrane
    3. Sources
      1. Pneumonia
      2. Skin or soft tissue infection
      3. Pyelonephritis
  2. Other, less causes of joint infection
    1. Trauma
    2. IV Drug Abuse
    3. Iatrogenic Infection (e.g. Joint Injection, arthroscopy)

VI. Precautions

  1. Septic Arthritis has a high inpatient mortality (approaches 15%)
    1. Delayed diagnosis significantly increases morbidity and mortality
  2. Examination is unreliable in ruling out Septic Arthritis
    1. Poor reliability in distinguishing from Gouty Arthritis
    2. Crystals in Synovial Fluid does not exclude Septic Joint (actually increases its risk)
  3. Lab testing (outside of Joint Aspiration) is unreliable
    1. No lab value (e.g. CRP, ESR, WBC) outside of Joint Fluid examination excludes Septic Joint
  4. Joint infection leads to rapid joint destruction
    1. Inflammatory reaction directly associated with infection
    2. Intra-articular pressure with secondary vascular compromise
    3. Risk of permanent joint injury increases when appropriate antibiotics are delayed >24-48 from onset
  5. Gout or Pseudogout exacerbation does NOT exclude Septic Arthritis
    1. Septic Arthritis occurs concurrent with gout or Pseudogout in 1.5 to 5% of cases

VII. Differential Diagnosis

VIII. History

  1. Fever (<60% of cases)
  2. Recent joint surgery
  3. Pain with joint range of motion
  4. Reduced ability to ambulate on affected joint (e.g. hip)
  5. Sexually Transmitted Disease exposures or history (especially Gonorrhea)

IX. Symptoms: Presentations in newborns

  1. Fever only present in 24-50% of cases
  2. Ill appearance
  3. Decreased use of the affected extremity

X. Findings: Signs and symptoms

  1. Rapid onset monoarticular joint inflammation
    1. Joint Pain with motion (Test Sensitivity 100%, but poor Specificity)
    2. Joint Swelling with effusion
    3. Joint warmth (unreliable)
    4. Joint erythema
    5. Significantly decreased joint range of motion (limited by pain)
    6. Significantly decreased weight bearing on infected joints
    7. Limb paralysis from inflammatory neuritis
    8. Joint with overlying Cellulitis (significantly increased risk of Septic Joint)
  2. Native Joints affected in Bacterial Infection
    1. Septic Arthritis is Polyarticular in 10-20% of cases (evaluate for endocarditis when multiple joints involved)
      1. Oligoarticular infection, often with fever, most commonly affects Shoulder, wrist and elbow
    2. Septic Knee (40-50% of cases)
    3. Septic Hip (15-20% of cases, especially in young children)
    4. Septic Shoulder (10-15% of cases, although some studies list 5%, more often associated with bacteremia)
    5. Septic Ankle (6-9% of cases)
    6. Septic Wrist (5-8% of cases)
    7. Septic Elbow (3-8% of cases)
  3. Joints affected with Intravenous Drug Abuse
    1. Sacroiliac joint
    2. Sternoclavicular joint
    3. Symphysis Pubis
    4. Vertebral disc spaces (e.g. Spinal Epidural Abscess, Diskitis)
  4. Risks for subtle presentations of Septic Joints
    1. Periprosthetic Joint Infections
    2. Small joint infections
    3. Atypical infections (fungal infection, Lyme Disease, Tuberculosis)
    4. Immunosuppression

XI. Labs: General

  1. Precaution
    1. Arthrocentesis is the only accurate method to exclude Septic Arthritis
    2. None of these labs (CBC, ESR nor CRP) absolutely excludes Septic Arthritis at any level
      1. These labs may all be normal or even low despite Septic Arthritis
      2. Lab markers are useful as baseline to follow response to therapy
  2. Erythrocyte Sedimentation Rate (ESR)
    1. Children
      1. ESR typically > 25 mm/hour in pediatric Septic Arthritis
    2. Adults
      1. ESR >10 mm/hour (Test Sensitivity 98%) or ESR >15 mm/hour (Test Sensitivity 94%)
      2. Hariharan (2011) J Emerg Med 40(4): 428-31 [PubMed]
  3. C-Reactive Protein (C-RP)
    1. C-RP typically >20 mg/L in pediatric Septic Arthritis
      1. Closely mirrors infectious, inflammatory process
      2. Test Sensitivity: 95% in children
    2. C-RP >2 mg/dl has Test Sensitivity >92% in adults
      1. Hariharan (2011) J Emerg Med 40(4): 428-31 [PubMed]
  4. Complete Blood Count
    1. WBC Count typically >12,000 in pediatric Septic Arthritis
  5. Other tests in severe cases or as directed by history
    1. Blood Culture
      1. Bacteremia is present in up to one third of cases of Septic Arthritis
    2. Comprehensive Metabolic Panel
      1. Typically obtained in severe Septic Arthritis, to establish end-organ injury, Renal Dosing of antibiotics
      2. May also evaluate Pseudogout
    3. Uric Acid
      1. Evaluate for gout in differential diagnosis
    4. STD Testing
      1. Gonorrhea (PCR from Urethra or Cervix, or Throat Culture)
      2. Syphilis
    5. Procalcitonin
      1. Procalcitonin >0.5 ng/ml has Positive Likelihood Ratio approaching 11
        1. Zhao (2017) Am J Emerg Med 35(8): 1166-71 [PubMed]

XII. Labs: Synovial Fluid Exam via Arthrocentesis

  1. Approach: Synovial Fluid Testing
    1. Synovial Fluid White Blood Cell Count
      1. Non-inflammatory Arthritis: 200-2000 White Blood Cells
      2. Inflammatory Arthritis: 2000 to 50,000 White Blood Cells
      3. Infectious Arthritis: >50,000 White Blood Cells (LR+ 3.6)
        1. However Exercise caution, as Septic Arthritis may occur at lower WBC Counts
    2. Synovial FluidGram Stain
      1. Falsely negative in 20-40% of Septic Arthritis patients
    3. Synovial Fluid culture
      1. Imperative to obtain (Gram Stain alone is insufficient)
      2. Best inoculated into Blood Culture medium (less contamination, better yield than solid plating)
    4. Synovial Fluid Crystal Exam
      1. Evaluates for the alternative, inflammatory Arthritis (e.g. gout, Pseudogout)
      2. However, crystalline Arthritis (e.g. gout) does not exclude Septic Joint
        1. Patients with underlying crystalline Arthritis are at a higher risk for Septic Joint
    5. Avoid Joint FluidGlucose and Protein (not useful)
    6. Synovial Fluid Lactate
      1. Lactic Acid >10 mmol/L consistent with Septic Arthritis
      2. Lactic Acid 5-10 mmol/L is suspicious for Septic Arthritis
  2. Bacterial Arthritis
    1. Opaque to turbid Synovial Fluid
    2. Synovial Fluid WBC
      1. Non-prosthetic joint: >50,000 White Blood Cells (or >90% PMNs)
        1. Likelihood Ratio: 4.7 for Septic Arthritis
      2. Prosthetic joint: >1700 White Blood Cells per mm3 (or >65% PMNs)
    3. Gram Stain
      1. Test Sensitivity: 29-60%
    4. Bacterial Culture
      1. Test Sensitivity: 30-50% (75% if Polyarticular)
      2. Guides antibiotic therapy when positive
    5. Synovial lactate
      1. Synovial lactate >10 mmol/L has a very high Likelihood Ratio for Septic Arthritis (rules in Septic Arthritis)
  3. Gonococcal Arthritis
    1. Clear to opaque Synovial Fluid
    2. Synovial Fluid WBC: 30,000 to 100,000 (>80% PMNs)
    3. Gram Stain Positive in <25% of cases
    4. Culture positive in <50% of cases
    5. Also obtain other Gonorrhea testing (e.g. PCR from urine or Cervix, culture of Cervix, throat or Rectum
  4. Tuberculous Arthritis
    1. Opaque Synovial Fluid
    2. Synovial Fluid WBC: 10,000 to 20,000 (>50% PMNs)
    3. Gram Stain Positive in <20% of cases
    4. Culture positive in 80% of cases
  5. Prosthetic Joint
    1. Synovasure Lateral Flow Test
      1. Detects human alpha defensins released by activated Neutrophils
      2. Positive test suggestive of Bacterial periprosthetic infection

XIII. Imaging

  1. Joint Xray
    1. Early changes
      1. Distention of joint capsule
      2. Joint Dislocation
    2. Late changes
      1. Joint space destruction
      2. Epiphyseal cartilage resorption
      3. Metaphysis erosion
  2. Joint Ultrasound
    1. Bedside Ultrasound using high frequency linear probe (9-15 MHz)
    2. Identifies effusion
      1. Have patient move joint to distinguish effusion (re-distributes) from synovial thickening (static)
    3. Guides aspiration
      1. Especially helpful in Hip Joint evaluation and needle aspiration
      2. See Hip Ultrasound (Anterior Hip in Long Axis or LAX)
  3. Advanced imaging
    1. CT or MRI joint for unclear diagnosis
      1. Perform MRI with and without contrast to evaluate for Osteomyelitis and soft tissue involvement
    2. CT-guided aspiration may also be considered if Ultrasound-guided aspiration results in dry tap

XIV. Imaging: Possibly Infected Prosthetic Joint

  1. Nuclear scan
    1. Negative Nuclear scan excludes septic prosthetic joint
  2. Pet Scan
  3. Avoid CT Scan or MRI in infected prosthetic joint
    1. Does not distinguish infected prosthetic joint from other causes of pain

XV. Management: General

  1. Obtain early Consultation
  2. Septic Arthritis management requires two components
    1. Thorough Joint Fluid drainage of purulent fluid
    2. Antimicrobial management to cover the causative organisms
  3. Antibiotics are started after obtaining joint culture and Blood Culture
    1. See Septic Arthritis Causes for antibiotic considerations
    2. Gram Stain of fluid may assist antibiotic selection
    3. Empirically antibiotics based on age and risk factors (see below) until culture results available
      1. Initial antibiotic coverage for Gram Positive Cocci (Staphylococcus and Streptococcus)
      2. Additional Gram Negative coverage indications (if not otherwise directed by Gram Stain)
        1. Older age
        2. Immunosuppression
        3. Suspected bacteremia from genitourinary source
      3. Consider other coverage based on risk factors and history
        1. See Septic Joint Causes
        2. See Gonococcal Arthritis
        3. See Lyme Disease (Late Disseminated Lyme Disease)
        4. See Tuberculous Arthritis
    4. Antibiotics do not need to be injected into joints
    5. Joint cultures are recommended before antibiotics in most cases even if 24-48 hour antibiotic start delay
    6. Antibiotics may be considered prior to Arthrocentesis ONLY if
      1. Septic Shock (hemodynamically unstable) OR
      2. Strong suspicion of Septic Arthritis AND
      3. Consultant agrees that antibiotics should be started before the culture has been obtained AND
      4. Procedure is delayed >24-48 hours
        1. Difficult Arthrocentesis requiring Intervention Radiology or rheumatology
  4. Intraarticular Anesthetic injection
    1. Consider at time of Arthrocentesis, after aspiration of diagnostic studies
    2. Ropivacaine (up to 3 mg/kg)
  5. Adjunctive Corticosteroids (only if directed by speciality care)
    1. Do not inject intraarticular Corticosteroids in suspected Septic Arthritis
    2. Discuss with consultant (orthopod)
    3. Associated with decreased duration and Disability in studies of pediatric Septic Arthritis
    4. Odio (2003) Pediatr Infect Dis J 22(10): 833-8 [PubMed]

XVI. Management: Surgical

  1. Urgent orthopedic Consultation is indicated in all cases of suspected Septic Arthritis
  2. Serial Joint Aspiration
    1. Repeat for reaccumulation of fluid as needed up to once to twice daily
    2. Consider saline lavage
  3. Arthroscopy
    1. Preferred in Shoulder and Knee Joints (better visualization and irrigation, less post-op morbidity)
  4. Open Surgical drainage indications
    1. Difficult Joint Aspiration access (e.g. hip)
    2. Persistent fever and symptoms >24 hours
    3. Leukocytosis persists beyond 48 to 72 hours
    4. Repeat blood or joint cultures positive >48 hours
    5. Infected joint prosthesis
      1. Prosthesis may be salvaged if infection <1-2 weeks
        1. Many infected prostheses may still need to be removed
      2. Surgically debride the infection
      3. Treat with Parenteral combination antibiotic therapy for 4 weeks (equivalent outcome to 6 week course)
        1. Use Rifampin as part of antibiotic regimen
  5. Failed single joint washout risk factors
    1. Diabetes Mellitus
    2. Staphylococcus aureus
    3. Synovial White Blood Cell Count >85,000
    4. Hunter (2015) J Bone and Joint Surg 97(7): 558-64 [PubMed]

XVII. Management: Antibiotics for Infants (age <3 months)

  1. See Septic Arthritis Causes
  2. Empiric antibiotics (2 drug regimen)
    1. Drug 1: Vancomycin 40 mg/kg divided q6-8 hours IV
    2. Drug 2: Cefotaxime 50 mg/kg IV q8 hours
  3. Modify antibiotic selection based on Blood Culture (positive in a majority of cases)
  4. Assume Osteomyelitis of adjacent bone (occurs in two thirds of cases)

XVIII. Management: Antibiotics for Children (3 months to 14 years)

  1. See Septic Arthritis Causes
  2. Primary regimen
    1. Two drug regimen (most cases)
      1. Drug 1: Vancomycin 40 mg/kg divided q6-8 hours IV
      2. Drug 2: Cefotaxime 50 mg/kg IV q8 hours
    2. One drug regimen (if Gram Stain only with Gram Negative organisms)
      1. Cefotaxime 50 mg/kg IV q8 hours
  3. Alternative regimen (2 drug regimen)
    1. Drug 1: Aztreonam 30 mg/kg IV q6 hours
    2. Drug 2: Choose one
      1. Clindamycin 7.5 mg/kg IV q6 hours or
      2. Linezolid 10 mg/kg IV q8 hours
  4. Modify antibiotic selection based on Blood Culture
  5. Duration of therapy is typically 30 days
    1. Ten days may be adequate in quickly resolving symptom, signs and C-RP
    2. Peltola (2009) Clin Infect Dis 48:1201–10 [PubMed]

XIX. Management: Antibiotics for Adolescents and Adults (age over 14 years)

  1. Acute monoarticular with STD risk
    1. Gram Stain clear or with Gram Negative diplococci
      1. Ceftriaxone 1 gram IV q24 hours or
      2. Cefotaxime 1 gram IV q8 hours or
      3. Ceftizoxime 1 gram IV q8 hours
    2. Gram Stain with Gram Positive Cocci
      1. Vancomycin 15-20 mg/kg IV q8-12 hours
    3. Gram Stain with Gram Negative Bacilli
      1. Cefepime 2 grams q8 hours IV or
      2. Meropenem 1 gram q8 hours IV
  2. Acute monoarticular without STD risk
    1. Gram Stain Negative (2 drug regimen)
      1. Drug 1: Vancomycin 15-20 mg/kg IV q8-12 hours
      2. Drug 2: Choose one
        1. Ceftriaxone 1 gram IV q24 hours or
        2. Cefepime 2 grams IV q8 hours
        3. Alternative: Ciprofloxacin 400 mg q12 hours or Levofloxacin 750 mg IV q24 hours
    2. Gram Stain with Gram Positive Cocci
      1. Vancomycin 15-20 mg/kg IV q8-12 hours
    3. Gram Stain with Gram Negative Bacilli
      1. Cefepime 2 grams q8 hours IV or
      2. Meropenem 1 gram q8 hours iv
    4. Pseudomonas suspected
      1. Cefepime OR
      2. Piperacillin-Tazobactam
  3. Polyarticular Arthritis
    1. Ceftriaxone 1 gram IV q24 hours

XX. Management: Iatrogenic Infection (Joint Injection or prosthesis)

  1. Empiric therapy before culture results
    1. Option 1 (2 drug regimen)
      1. Drug 1: Vancomycin
      2. Drug 2: Ciprofloxacin, Aztreonam, or Gentamycin
    2. Option 2 (2 drug regimen)
      1. Drug 1
        1. Ciprofloxacin 750 PO bid or
        2. Ofloxacin 200 mg PO tid
      2. Drug 2: Rifampin 900 mg PO qd
  2. Ciprofloxacin and Rifampin sensitive by culture
    1. Option 1 (2 drug regimen)
      1. Drug 1: Ciprofloxacin or Ofloxacin
      2. Drug 2: Rifampin 900 mg PO qd
    2. Option 2 (2 drug regimen)
      1. Drug 1: Oxacillin 2 grams IV every 4 hours
      2. Drug 2: Rifampin 900 mg PO qd
  3. Ciprofloxacin or Rifampin resistance by culture
    1. Vancomycin and
    2. Rifampin (if sensitive)

XXI. Management: Antibiotic Course

  1. Nongonococcal Bacterial Infection (total course of 6 weeks is typical)
    1. Parenteral antibiotics for 2 to 4 weeks
    2. Oral antibiotics for 2 to 4 weeks
  2. See Gonococcal Arthritis
  3. See Tuberculous Arthritis

XXII. Prognosis

  1. Early joint drainage and antibiotics
    1. Good prognosis
  2. Risk Factors for Poor functional outcome (e.g. amputation, arthrodesis, osteonecrosis, prosthetic surgery, occurs in 24-33% of cases)
    1. Delayed management >24 hours
    2. Large joint involvement (e.g. knee, hip, Shoulder)
    3. Older age
    4. Preexisting joint disease
    5. Synthetic intraarticular material
  3. Mortality
    1. Mortality at 90 days is 7%
    2. Mortality may be as high as 20% in elderly
      1. Abram (2020) Lancet Infect Dis 20(3): 341-9 [PubMed]
    3. Other risk factors for increased mortality
      1. Immunocompromised
      2. Disseminated infection (e.g. bacteremia)
      3. Diabetes Mellitus
      4. Rheumatoid Arthritis
      5. Decreased Creatinine Clearance
      6. Oligoarticular Septic Arthritis (compared with monoarticular involvement)
      7. Ferrand (2016) BMC Infect Dis 16:239 [PubMed]

XXIII. References

  1. Buddendorff (2021) Crit Dec Emerg Med 35(12): 18-9
  2. Gilbert (2012) Sanford Guide to Antimicrobials
  3. Klippel (1997) Primer Rheumatic Diseases, p. 196-200
  4. Merenstein (1994) Handbook Pediatrics, Lange, p.710-2
  5. Mann and Papp (2022) Crit Dec Emerg Med 36(17): 22-8
  6. Papp and Mann (2016) Crit Dec Emerg Med 30(8): 17-23
  7. Shahideh (2013) Crit Dec Emerg Med 27(9):10-18
  8. Shoenberger and Swaminathan in Swadron (2021) EM:Rap 21(11): 1-2
  9. Earwood (2021) Am Fam Physician 104(6): 589-97 [PubMed]
  10. Carpenter (2011) Acad Emerg Med 18(8):781-96 [PubMed]
  11. Stimmler (1996) Postgrad Med 99(4):127-39 [PubMed]
  12. Kallio (1997) Pediatr Infect Dis 16:411-2 [PubMed]
  13. Kaandorp (1995) Arthritis Rheum 38:1819-25 [PubMed]

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