II. Epidemiology
- Incidence: 2-10 per 100,000 cases/year (16,000) of Monoarticular Arthritis in the Emergency Department (U.S., 2018)
- Age
- Bimodal distribution peaks <15 years old and over 55 years old
- Young children <18-24 months are more susceptible to Septic Arthritis
- Bridging veins between metaphysis and epiphysis allow spread of infection to joint
- Bridging veins close after age 18-24 months
III. Causes
- See Septic Joint Causes
- Most common causes of Septic Joint
- Streptococcus
- Staphylococcus (including MRSA or Methicillin Resistant Staphylococcus Aureus)
- MRSA is associated with more severe infection and subperiostal abscess
- Gonorrhea is the most common cause of Septic Arthritis in young adults
IV. Risk Factors
- No risk factor present in up to 22% of cases
- Systemic comorbidity
- Immunosuppression
- HIV Infection
- Diabetes Mellitus
- Intravenous drug use (unusual joints affected)
- Alcoholism
- Sickle Cell Anemia
- Elderly patients over age 80 years old
- Tobacco Abuse
- Joint disorders (47% of cases have previously deranged affected joint)
- Rheumatoid Arthritis (14% of cases)
- Higher mortality risk with Immunosuppressants (TNF agents, Systemic Corticosteroids)
- TNF agents predispose atypical and virulent infections (e.g. Salmonella, Actinobacillus, Listeria)
- Higher risk of Oligoarticular infection
- Osteoarthritis
- Inflammatory Bowel Disease
- Prosthetic joint (1-2% risk at 2 years, >2% at 10 years; nearly half occur in the first 3 months after surgery)
- Prosthetic Hip Joint
- Prosthetic Knee Joint
- Other Joint surgery
- Rheumatoid Arthritis (14% of cases)
- Overlying skin disruption
- Chronic dermatitis
- Skin Ulceration
- Skin Infection such as Cellulitis
- Large vein catheterization (unusual joints affected)
- Fungal Arthritis Risk Factors (esp. Candida, also Aspergillus, Coccidioides, Histoplasma, Blastomyces, Cryptococcus)
- Diabetes Mellitus
- HIV Infection
- Immunosuppression
- Organ Transplantation
- Parenteral Hyperalimentation
- Indwelling Catheter
- Substance Abuse
- Broad Spectrum Antibiotics
- Bariteau (2014) J Am Acad Orthop Surg 22(6): 390-401 [PubMed]
-
Periprosthetic Joint Infection Risk Factors
- Obesity (highest risk)
- Cardiac disease
- Immunocompromised
- Peripheral Vascular Disease
- Inflammatory Arthritis
- Prior joint infection
- Renal disease
- Liver disease
- Malnutrition
- Alcohol Abuse
- Tobacco Abuse
- Diabetes Mellitus
- Anemia
- Tubb (2020) J Am Acad Orthop Surg 28(8): e340-8 [PubMed]
V. Pathophysiology
- Hematologic seeding in most cases from Occult Bacteremia
- Once joint seeding occurs, infection progresses rapidly
- Joint is susceptable to hematogenous spread
- Synovial lining lacks a protective basement membrane
- Sources
- Pneumonia
- Skin or soft tissue infection
- Pyelonephritis
- Other, less causes of joint infection
- Trauma
- IV Drug Abuse
- Iatrogenic Infection (e.g. Joint Injection, arthroscopy)
VI. Precautions
- Septic Arthritis has a high inpatient mortality (approaches 15%)
- Delayed diagnosis significantly increases morbidity and mortality
- Examination is unreliable in ruling out Septic Arthritis
- Poor reliability in distinguishing from Gouty Arthritis
- Crystals in Synovial Fluid does not exclude Septic Joint (actually increases its risk)
- Lab testing (outside of Joint Aspiration) is unreliable
- No lab value (e.g. CRP, ESR, WBC) outside of Joint Fluid examination excludes Septic Joint
- Joint infection leads to rapid joint destruction
- Inflammatory reaction directly associated with infection
- Intra-articular pressure with secondary vascular compromise
- Risk of permanent joint injury increases when appropriate Antibiotics are delayed >24-48 from onset
-
Gout or Pseudogout exacerbation does NOT exclude Septic Arthritis
- Septic Arthritis occurs concurrent with gout or Pseudogout in 1.5 to 5% of cases
VII. Differential Diagnosis
- See Monoarticular Arthritis
- See Joint Pain Causes (Monoarticular)
- See Septic Joint Causes
VIII. History
- Fever (<60% of cases)
- Recent joint surgery
- Pain with joint range of motion
- Reduced ability to ambulate on affected joint (e.g. hip)
- Sexually Transmitted Disease exposures or history (especially Gonorrhea)
IX. Symptoms: Presentations in newborns
- Fever only present in 24-50% of cases
- Ill appearance
- Decreased use of the affected extremity
X. Findings: Signs and symptoms
- Rapid onset monoarticular joint inflammation
- Joint Pain with motion (Test Sensitivity 100%, but poor Specificity)
- Joint Swelling with effusion
- Joint warmth (unreliable)
- Joint erythema
- Significantly decreased joint range of motion (limited by pain)
- Significantly decreased weight bearing on infected joints
- Limb paralysis from inflammatory neuritis
- Joint with overlying Cellulitis (significantly increased risk of Septic Joint)
- Native Joints affected in Bacterial Infection
- Septic Arthritis is Polyarticular in 10-20% of cases (evaluate for endocarditis when multiple joints involved)
- Oligoarticular infection, often with fever, most commonly affects Shoulder, wrist and elbow
- Septic Knee (40-50% of cases)
- Septic Hip (15-20% of cases, especially in young children)
- Septic Shoulder (10-15% of cases, although some studies list 5%, more often associated with bacteremia)
- Septic Ankle (6-9% of cases)
- Septic Wrist (5-8% of cases)
- Septic Elbow (3-8% of cases)
- Septic Arthritis is Polyarticular in 10-20% of cases (evaluate for endocarditis when multiple joints involved)
- Joints affected with Intravenous Drug Abuse
- Sacroiliac joint
- Sternoclavicular joint
- Symphysis Pubis
- Vertebral disc spaces (e.g. Spinal Epidural Abscess, Diskitis)
- Risks for subtle presentations of Septic Joints
- Periprosthetic Joint Infections
- Small joint infections
- Atypical infections (fungal infection, Lyme Disease, Tuberculosis)
- Immunosuppression
XI. Labs: General
- Precaution
- Arthrocentesis is the only accurate method to exclude Septic Arthritis
- None of these labs (CBC, ESR nor CRP) absolutely excludes Septic Arthritis at any level
- These labs may all be normal or even low despite Septic Arthritis
- Lab markers are useful as baseline to follow response to therapy
-
Erythrocyte Sedimentation Rate (ESR)
- Children
- ESR typically > 25 mm/hour in pediatric Septic Arthritis
- Adults
- ESR >10 mm/hour (Test Sensitivity 98%) or ESR >15 mm/hour (Test Sensitivity 94%)
- Hariharan (2011) J Emerg Med 40(4): 428-31 [PubMed]
- Children
-
C-Reactive Protein (C-RP)
- C-RP typically >20 mg/L in pediatric Septic Arthritis
- Closely mirrors infectious, inflammatory process
- Test Sensitivity: 95% in children
- C-RP >2 mg/dl has Test Sensitivity >92% in adults
- C-RP typically >20 mg/L in pediatric Septic Arthritis
-
Complete Blood Count
- WBC Count typically >12,000 in pediatric Septic Arthritis
- Other tests in severe cases or as directed by history
- Blood Culture
- Bacteremia is present in up to one third of cases of Septic Arthritis
- Comprehensive Metabolic Panel
- Typically obtained in severe Septic Arthritis, to establish end-organ injury, Renal Dosing of Antibiotics
- May also evaluate Pseudogout
- Uric Acid
- Evaluate for gout in differential diagnosis
- STD Testing
- Gonorrhea (PCR from Urethra or Cervix, or Throat Culture)
- Syphilis
- Procalcitonin
- Procalcitonin >0.5 ng/ml has Positive Likelihood Ratio approaching 11
- Blood Culture
XII. Labs: Synovial Fluid Exam via Arthrocentesis
- Approach: Synovial Fluid Testing
- Synovial Fluid White Blood Cell Count
- Non-inflammatory Arthritis: 200-2000 White Blood Cells
- Inflammatory Arthritis: 2000 to 50,000 White Blood Cells
- Infectious Arthritis: >50,000 White Blood Cells (LR+ 3.6)
- Synovial FluidGram Stain
- Falsely negative in 20-40% of Septic Arthritis patients
- Synovial Fluid culture
- Imperative to obtain (Gram Stain alone is insufficient)
- Best inoculated into Blood Culture medium (less contamination, better yield than solid plating)
- Synovial Fluid Crystal Exam
- Evaluates for the alternative, inflammatory Arthritis (e.g. gout, Pseudogout)
- However, crystalline Arthritis (e.g. gout) does not exclude Septic Joint
- Patients with underlying crystalline Arthritis are at a higher risk for Septic Joint
- Avoid Joint FluidGlucose and Protein (not useful)
- Synovial Fluid Lactate
- Lactic Acid >10 mmol/L consistent with Septic Arthritis
- Lactic Acid 5-10 mmol/L is suspicious for Septic Arthritis
- Synovial Fluid White Blood Cell Count
- Bacterial Arthritis
- Opaque to turbid Synovial Fluid
- Synovial Fluid WBC
- Non-prosthetic joint: >50,000 White Blood Cells (or >90% PMNs)
- Likelihood Ratio: 4.7 for Septic Arthritis
- Prosthetic joint: >1700 White Blood Cells per mm3 (or >65% PMNs)
- Non-prosthetic joint: >50,000 White Blood Cells (or >90% PMNs)
- Gram Stain
- Test Sensitivity: 29-60%
- Bacterial Culture
- Test Sensitivity: 30-50% (75% if Polyarticular)
- Guides Antibiotic therapy when positive
- Synovial lactate
- Synovial lactate >10 mmol/L has a very high Likelihood Ratio for Septic Arthritis (rules in Septic Arthritis)
-
Gonococcal Arthritis
- Clear to opaque Synovial Fluid
- Synovial Fluid WBC: 30,000 to 100,000 (>80% PMNs)
- Gram Stain Positive in <25% of cases
- Culture positive in <50% of cases
- Also obtain other Gonorrhea testing (e.g. PCR from urine or Cervix, culture of Cervix, throat or Rectum
-
Tuberculous Arthritis
- Opaque Synovial Fluid
- Synovial Fluid WBC: 10,000 to 20,000 (>50% PMNs)
- Gram Stain Positive in <20% of cases
- Culture positive in 80% of cases
- Prosthetic Joint
- Synovasure Lateral Flow Test
- Detects human alpha defensins released by activated Neutrophils
- Positive test suggestive of Bacterial periprosthetic infection
- Synovasure Lateral Flow Test
XIII. Imaging
- Joint Xray
- Early changes
- Distention of joint capsule
- Joint Dislocation
- Late changes
- Joint space destruction
- Epiphyseal cartilage resorption
- Metaphysis erosion
- Early changes
- Joint Ultrasound
- Bedside Ultrasound using high frequency linear probe (9-15 MHz)
- Identifies effusion
- Have patient move joint to distinguish effusion (re-distributes) from synovial thickening (static)
- Guides aspiration
- Especially helpful in Hip Joint evaluation and needle aspiration
- See Hip Ultrasound (Anterior Hip in Long Axis or LAX)
- Advanced imaging
- CT or MRI joint for unclear diagnosis
- Perform MRI with and without contrast to evaluate for Osteomyelitis and soft tissue involvement
- CT-guided aspiration may also be considered if Ultrasound-guided aspiration results in dry tap
- CT or MRI joint for unclear diagnosis
XIV. Imaging: Possibly Infected Prosthetic Joint
- Nuclear scan
- Negative Nuclear scan excludes septic prosthetic joint
- Pet Scan
- Avoid CT Scan or MRI in infected prosthetic joint
- Does not distinguish infected prosthetic joint from other causes of pain
XV. Management: General
- Obtain early Consultation
- Septic Arthritis management requires two components
- Thorough Joint Fluid drainage of purulent fluid
- Antimicrobial management to cover the causative organisms
-
Antibiotics are started after obtaining joint culture and Blood Culture
- See Septic Arthritis Causes for Antibiotic considerations
- Gram Stain of fluid may assist Antibiotic selection
- Empirically Antibiotics based on age and risk factors (see below) until culture results available
- Initial Antibiotic coverage for Gram Positive Cocci (Staphylococcus and Streptococcus)
- Additional Gram Negative coverage indications (if not otherwise directed by Gram Stain)
- Older age
- Immunosuppression
- Suspected bacteremia from genitourinary source
- Consider other coverage based on risk factors and history
- See Septic Joint Causes
- See Gonococcal Arthritis
- See Lyme Disease (Late Disseminated Lyme Disease)
- See Tuberculous Arthritis
- Antibiotics do not need to be injected into joints
- Joint cultures are recommended before Antibiotics in most cases even if 24-48 hour Antibiotic start delay
- Antibiotics may be considered prior to Arthrocentesis ONLY if
- Septic Shock (hemodynamically unstable) OR
- Strong suspicion of Septic Arthritis AND
- Consultant agrees that Antibiotics should be started before the culture has been obtained AND
- Procedure is delayed >24-48 hours
- Difficult Arthrocentesis requiring Intervention Radiology or rheumatology
- Intraarticular Anesthetic injection
- Consider at time of Arthrocentesis, after aspiration of diagnostic studies
- Ropivacaine (up to 3 mg/kg)
- Adjunctive Corticosteroids (only if directed by speciality care)
- Do not inject intraarticular Corticosteroids in suspected Septic Arthritis
- Discuss with consultant (orthopod)
- Associated with decreased duration and Disability in studies of pediatric Septic Arthritis
- Odio (2003) Pediatr Infect Dis J 22(10): 833-8 [PubMed]
XVI. Management: Surgical
- Urgent orthopedic Consultation is indicated in all cases of suspected Septic Arthritis
- Serial Joint Aspiration
- Repeat for reaccumulation of fluid as needed up to once to twice daily
- Consider saline lavage
- Arthroscopy
- Preferred in Shoulder and Knee Joints (better visualization and irrigation, less post-op morbidity)
- Open Surgical drainage indications
- Difficult Joint Aspiration access (e.g. hip)
- Persistent fever and symptoms >24 hours
- Leukocytosis persists beyond 48 to 72 hours
- Repeat blood or joint cultures positive >48 hours
- Infected joint prosthesis
- Prosthesis may be salvaged if infection <1-2 weeks
- Many infected prostheses may still need to be removed
- Surgically debride the infection
- Treat with Parenteral combination Antibiotic therapy for 4 weeks (equivalent outcome to 6 week course)
- Use Rifampin as part of Antibiotic regimen
- Prosthesis may be salvaged if infection <1-2 weeks
- Failed single joint washout risk factors
XVII. Management: Antibiotics for Infants (age <3 months)
- See Septic Arthritis Causes
- Empiric Antibiotics (2 drug regimen)
- Drug 1: Vancomycin 40 mg/kg divided q6-8 hours IV
- Drug 2: Cefotaxime 50 mg/kg IV q8 hours
- Modify Antibiotic selection based on Blood Culture (positive in a majority of cases)
- Assume Osteomyelitis of adjacent bone (occurs in two thirds of cases)
XVIII. Management: Antibiotics for Children (3 months to 14 years)
- See Septic Arthritis Causes
- Primary regimen
- Two drug regimen (most cases)
- Drug 1: Vancomycin 40 mg/kg divided q6-8 hours IV
- Drug 2: Cefotaxime 50 mg/kg IV q8 hours
- One drug regimen (if Gram Stain only with Gram Negative organisms)
- Cefotaxime 50 mg/kg IV q8 hours
- Two drug regimen (most cases)
- Alternative regimen (2 drug regimen)
- Drug 1: Aztreonam 30 mg/kg IV q6 hours
- Drug 2: Choose one
- Clindamycin 7.5 mg/kg IV q6 hours or
- Linezolid 10 mg/kg IV q8 hours
- Modify Antibiotic selection based on Blood Culture
- Duration of therapy is typically 30 days
- Ten days may be adequate in quickly resolving symptom, signs and C-RP
- Peltola (2009) Clin Infect Dis 48:1201–10 [PubMed]
XIX. Management: Antibiotics for Adolescents and Adults (age over 14 years)
- Acute monoarticular with STD risk
- Gram Stain clear or with Gram Negative diplococci
- Ceftriaxone 1 gram IV q24 hours or
- Cefotaxime 1 gram IV q8 hours or
- Ceftizoxime 1 gram IV q8 hours
- Gram Stain with Gram Positive Cocci
- Vancomycin 15-20 mg/kg IV q8-12 hours
- Gram Stain with Gram Negative Bacilli
- Gram Stain clear or with Gram Negative diplococci
- Acute monoarticular without STD risk
- Gram Stain Negative (2 drug regimen)
- Drug 1: Vancomycin 15-20 mg/kg IV q8-12 hours
- Drug 2: Choose one
- Ceftriaxone 1 gram IV q24 hours or
- Cefepime 2 grams IV q8 hours
- Alternative: Ciprofloxacin 400 mg q12 hours or Levofloxacin 750 mg IV q24 hours
- Gram Stain with Gram Positive Cocci
- Vancomycin 15-20 mg/kg IV q8-12 hours
- Gram Stain with Gram Negative Bacilli
- Pseudomonas suspected
- Cefepime OR
- Piperacillin-Tazobactam
- Gram Stain Negative (2 drug regimen)
-
Polyarticular Arthritis
- Ceftriaxone 1 gram IV q24 hours
XX. Management: Iatrogenic Infection (Joint Injection or prosthesis)
- Empiric therapy before culture results
- Option 1 (2 drug regimen)
- Drug 1: Vancomycin
- Drug 2: Ciprofloxacin, Aztreonam, or Gentamycin
- Option 2 (2 drug regimen)
- Drug 1
- Ciprofloxacin 750 PO bid or
- Ofloxacin 200 mg PO tid
- Drug 2: Rifampin 900 mg PO qd
- Drug 1
- Option 1 (2 drug regimen)
-
Ciprofloxacin and Rifampin sensitive by culture
- Option 1 (2 drug regimen)
- Drug 1: Ciprofloxacin or Ofloxacin
- Drug 2: Rifampin 900 mg PO qd
- Option 2 (2 drug regimen)
- Option 1 (2 drug regimen)
-
Ciprofloxacin or Rifampin resistance by culture
- Vancomycin and
- Rifampin (if sensitive)
XXI. Management: Antibiotic Course
- Nongonococcal Bacterial Infection (total course of 6 weeks is typical)
- ParenteralAntibiotics for 2 to 4 weeks
- Oral Antibiotics for 2 to 4 weeks
- See Gonococcal Arthritis
- See Tuberculous Arthritis
XXII. Prognosis
- Early joint drainage and Antibiotics
- Good prognosis
- Risk Factors for Poor functional outcome (e.g. amputation, arthrodesis, osteonecrosis, prosthetic surgery, occurs in 24-33% of cases)
- Delayed management >24 hours
- Large joint involvement (e.g. knee, hip, Shoulder)
- Older age
- Preexisting joint disease
- Synthetic intraarticular material
- Mortality
- Mortality at 90 days is 7%
- Mortality may be as high as 20% in elderly
- Other risk factors for increased mortality
- Immunocompromised
- Disseminated infection (e.g. bacteremia)
- Diabetes Mellitus
- Rheumatoid Arthritis
- Decreased Creatinine Clearance
- Oligoarticular Septic Arthritis (compared with monoarticular involvement)
- Ferrand (2016) BMC Infect Dis 16:239 [PubMed]
XXIII. References
- Buddendorff (2021) Crit Dec Emerg Med 35(12): 18-9
- Gilbert (2012) Sanford Guide to Antimicrobials
- Klippel (1997) Primer Rheumatic Diseases, p. 196-200
- Merenstein (1994) Handbook Pediatrics, Lange, p.710-2
- Mann and Papp (2022) Crit Dec Emerg Med 36(17): 22-8
- Papp and Mann (2016) Crit Dec Emerg Med 30(8): 17-23
- Shahideh (2013) Crit Dec Emerg Med 27(9):10-18
- Shoenberger and Swaminathan in Swadron (2021) EM:Rap 21(11): 1-2
- Earwood (2021) Am Fam Physician 104(6): 589-97 [PubMed]
- Carpenter (2011) Acad Emerg Med 18(8):781-96 [PubMed]
- Stimmler (1996) Postgrad Med 99(4):127-39 [PubMed]
- Kallio (1997) Pediatr Infect Dis 16:411-2 [PubMed]
- Kaandorp (1995) Arthritis Rheum 38:1819-25 [PubMed]