Septic Arthritis
Authors: Nalini Rao, M.D., FACP, FSHEA, Bruce H. Ziran, M.D.
Septic arthritis is a medical and surgical emergency that can lead to rapid destruction of the joint and irreversible loss of function. It is caused by invasion of the microorganisms into the synovial space. Bacteria are the most common cause of joint of infection although other pathogens such as viruses, fungi and mycobacteria may also be responsible.
Bacteria enter the joint through several mechanisms including direct inoculation, penetrating trauma, surgical incision including arthroscopy, spread from a contiguous focus of soft tissue infection or hematogenous seeding from a distant focus. Hematogenous seeding is the most common route. Negative prognostic factors include older age, delay in onset of treatment, pre-existing arthritis, immunosuppressive therapy, resistant organisms and multiple joint involvements. Septic arthritis results in loss of function in 25% to 50% of patients despite appropriate therapy. Table 1 lists the microbiology of bacterial arthritis in relationship to patient’s age.
RISK FACTORS
Degenerative joint disease, rheumatoid arthritis, and corticosteroid therapy are the most common predisposing conditions. Total joint arthroplasties are susceptible to intraoperative or hematogenous seeding which can result in subsequent prosthetic infection. While patients infected with HIV demonstrate a higher prevalence of septic arthritis or osteomyelitis than does the general population this may be due to intravenous drug abuse and multiple transfusions in this patient population (25).
NON GONOCOCCAL BACTERIAL SEPTIC ARTHRITIS
In adults non gonococcal acute septic arthritis occurs with an incidence of 0.034% to 0.13%. One to two percent of patients with total joint arthroplasty may develop septic complications. 90% of cases are mono-articular with knee being involved in 50% of these cases. Staphylococcus aureus and streptococci remain the predominant organism although certain other unusual organisms may be seen in specific clinical settings (Table 2). In addition, certain microorganisms may be associated with reactive arthritis (Table 3). Several unusual organisms such as Kingella spp., A. actinomycetemcomitans, M. catarrhalis and P. multocida have been implicated in osteoarticular infections.
PATHOPHYSIOLOGY
Bacterial invasion of the highly vascular synovium results in bacterial trapping and multiplication in the subsynovium. The host responds with acute inflammatory reaction and phagocytosis by the polymorphonuclear leucocytes. Toxins and enzymes are released by bacterial and stimulated T-cells leading to destruction of the articular cartilage. Revascularization, synovial proliferation and granulation tissue develop. Synovial fluid white blood cell count can exceed over 50,000/mm3 and increased intracavitary of pressure from accumulation of the purulent fluid resulting in necrosis of the synovium and cartilage. Pro-inflammatory cytokines such as interluken-1 and tumor necrosis factor α also contribute to joint injury.
CLINICAL PRESENTATION
Clinical signs and symptoms may be variable and imprecise. The key to diagnosis is thorough clinical history, physical examination along with laboratory studies of the synovial joint fluid from the affected joint. Pain and limited motion of the involved joint is present in more than 80% of the patients. Fever is seen in 60% to 80% of the patients unless masked by the use of anti-inflammatory agents and steroids.
Joint Distribution
Knee is the most commonly involved joint. 45% to 50% of the septic arthritis in adults involves the knee. Other large joints include hip 15%, ankle 9%, elbow 8%, wrist 6% and shoulder 5%. Polyarticular disease is seen in 10% to 20% of cases. It is usually asymmetric and involves an average of four joints. Major risk factors are steroid therapy, rheumatoid arthritis, lupus and diabetes mellitus.
LABORATORY DIAGNOSIS
The laboratory abnormalities suggestive septic arthritis includes peripheral leucocytosis, elevated sedimentation rate and C-reactive protein. The synovial fluid cell count greater than 50,000/mm3 with more than 75% polymorphonuclear leucocytes is a commonly used threshold for empiric therapy. Blood cultures are likely to be positive in non gonococcal bacterial arthritis. A presumptive diagnosis of septic arthritis may be made with positive blood culture and a negative synovial fluid culture in an appropriate clinical setting.
The definitive diagnosis of bacterial arthritis requires identification of bacteria from synovial fluid obtained through athrocentesis. This procedure should be performed in all patients with inflammatory arthritis in whom septic arthritis is suspected. Synovial WBC count >25000/μL, percentage of polymorphonuclear cells ≥ 90% and LDH> 250 U/L provide the high sensitivity in diagnosing septic arthritis (sensitivity: 88%, 92% and 100%, respectively) (17, Table 7).
Microscopic examination of the synovial fluid may eliminate crystal-induced inflammatory arthritis. Gram stain of the fluid is highly specific but not sensitive and may vary based upon the pathogen (Table 7). Culture of the synovial fluid is essential and the yield for positive culture may be maximized with inoculation into blood culture medium rather than plating on solid media. Direct inoculation of synovial fluid into blood culture medium bottles may improve the recovery of pathogens (12, 31).
Polymerase chain reaction (PCR) can be used in microbiological confirmation of septic arthritis. The problem of false-positive results needs to be addressed by more refined techniques which may replace the current methods of diagnosis.
MANAGEMENT
Treatment comprises of three facets: appropriate antibiotic therapy to eradicate the infection, decompression of the joint with evacuation of infected and inflammatory exudate and restoration of stability and function of the joint.
Antimicrobial Agent Therapy
Septic arthritis is frequently a medical and surgical emergency. It is important to withhold antibiotics until operative cultures are obtained, especially if the clinical course is atypical or subacute. After obtaining appropriate cultures of blood and synovial fluid, empiric antibiotic therapy should be started immediately.
Gram stains are important to review. If positive, antibiotic therapy can be more readily targeted toward a specific pathogen. If negative, empiric therapy should almost always include therapy against S. aureus (Table 4). Age is an important consideration for coverage against H. influenza and N. gonorrhoeae (Table 1). The three variables of antimicrobial therapy are selection, route and duration of treatment (Tables 4-5).
Adjunctive Therapy
Joint decompression may be accomplished by several methods and often debated between medical and surgical specialists. However, there are no randomized controlled studies comparing different forms of drainage. In the order of invasiveness, cost and effectiveness in the drainage procedure, the methods include needle aspiration, tidal irrigation, arthroscopy and arthrotomy as outlined in Table 6. If the joint is easily accessible and if the infected material be easily removed, patients may be treated at the bed side with repeated aspirations. Tidal irrigation can also be performed at the bed side and is reported as effective as arthroscopy. Arthroscopic lavage is being used increasingly in the management of septic arthritis including hips. Surgeons tend to prefer open drainage which allows rapid decompression, complete removal of accumulated debris including polymorphonuclear byproducts and bacterial toxins. In addition, this procedure allows for lysis of adhesions, removal of thick exudate, clot and fibrin. Arthrotomy is often recommended in cases where joint needs to be decompressed urgently. The role of synovectomy in acute septic arthritis is unclear. It is an essential part of persistent or chronic infection.
Rehabilitation of the joint begins at the time of diagnosis. Initially the joint should be immobilized in a position of function. Active and passive range of motion should begin as soon as the acute symptoms subside or soon after the drains are removed and the drain-sites are sealed.
READING LIST
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Tables
Table 1. Microbiology of Bacterial Septic Arthritis Related to Age of Patient.
| Organism | Children (6 mo. to 5 yrs.) | Young adult | Adult | Elderly |
|---|---|---|---|---|
| Staphylococcus aureus | 10% - 20% | 15% - 20% | 60% - 70% | 45% - 65% |
| Streptococci | 5% - 10% | 1% - 5% | 15% - 20% | 10% - 15% |
| Gram-negative bacteria | 1% - 5% | Rare | 10% - 15% | 15% - 35% |
| Haemophilus influenzae | 30% - 50% | 1% - 5% | 1% - 5% | Rare |
| Neisseria gonorrhoeae | 1% - 5% | 60% - 80% | 1% - 5% | Rare |
Adapted from Gorbach SL et al (Eds), Infectious Diseases, 2nd Edition, 1998
Table 2. Septic Arthritis Complicating a Clinical Setting
Clinical Setting |
Risk Factors |
Pathogen |
Frequency of Pathogen |
Special Points |
|---|---|---|---|---|
Rheumatoid Arthritis
|
Disabling arthritis Skin lesions Infected rheumatoid nodule TNF suppression therapy |
Listeria –with TNF suppression Therapy) |
40-60% 10-20% |
Patient education Early diagnosis Surgical debridement and antibiotics Special caution with TNF suppression therapy |
Advanced Age |
Diabetes mellitus, Urinary tract infection Biliary tract infection, Diverticulitis |
Staphylococcus aureus Gram negatives bacilli |
30-40% 10-20% |
Poor outcome if treatment started after 7 days of symptoms
|
Bacterial Endocarditis |
Septic immobilization Reactive immune arthritis Intravenous drug use
|
10-30% 40-60% 5-10% |
Adverse affects of antibiotics Duration 4- 6 weeks |
|
Prosthetic Joints |
Dental procedures SLE Immunosuppression DM, hemophilia, UTI, Skin Infection, Previous Joint infection Joint replacement < 2 yrs |
Staphylococcus species Streptococcus species Gram negative bacilli |
40-60% 10-30% 10-15% |
Antibiotic prophylaxis indicated |
Immunosuppression, AIDS and Stem cell transplantation |
Immunosuppression Decreased humoral and cell mediated immunity |
Salmonella Agrobacterium Fungi Atypical mycobacteria |
Rare |
Nonpathgenic and unusual organisms |
Whipple’s Disease |
|
Rare |
|
|
Hypogammaglobinemia |
Decreased humoral immunity |
Ureaplasma |
Rare |
|
Hemoglobinopathy |
Microinfracts in intestinal wall. |
Salmonella Staphylococcus aureus |
Rare |
Osteomyelitis more common than septic arthritis |
Human and Animal Bites |
Inoculation of indigenous mouth flora |
Rare |
Septic arthritis in proximity to site of injury. Knuckle osteo with clenched fist injury. |
|
Intravenous drug use |
Endocarditis Discitis |
Staphylococcus aureus Pseudomonas aeruginosa Candida species |
60-80% Rare Rare |
Seen in sacroiliac, strenocostal and strenclavicular clavicular joints |
Plant Thorns |
Puncture wound Foreign body |
Pantoea agglomerans,Sporotrichosis, Atypical mycobacteria,Nocardia, |
Rare |
Image joint for foreign body |
Resident in endemic area with known or suspected tick exposure |
|
|
|
|
Exposure to aquatic environment |
|
|
Small joints of hand |
|
Positive Tuberculin skin test. Resident in endemic area |
|
|
|
Axial skeleton and large joint |
Table 3. Microorganisms Associated with Reactive Arthritis
Salmonella typhimurium |
Adapted from Hughes and Keat (11)
Table 4. Empiric Antibiotic Therapy of Suspected Septic Arthritis
Gram stain of synovial fluid |
Antibiotic therapy |
|---|---|
Gram-positive cocci |
|
No risk factors for MRSA |
Cefazolin 2 g IV q 8 h |
MRSA risk factors or β-lactam allergy |
Vancomycin 1 g IV q 12 h |
Gram negative cocci (presumptive Neisseria sp) |
Ceftriaxone 1 g IV q 24 h |
Gram-negative rods |
Cefepime 2 g IV q 8 h, or 4.5 g IV q 6 h |
No organisms on gram stain |
|
Previously healthy, low MRSA risk |
Cefazolin 2 g IV q 8 h |
MRSA risks present |
Vancomycin 1 g IV q 12 h plus cefepime, 2 g IV q 8 h, or Piperacillin/tazobactam 4.5 g IV q 6 h |
MRSA = methicillin-resistant Staphylococcus aureus
Table 5. Antibiotic Therapy for Specific Pathogens
Microorganism |
Antimicrobial agent |
Alternative |
Duration |
|---|---|---|---|
Streptococcus species |
Clindamycin or first-generation cephalosporin Vancomycin |
3 – 4 weeks |
|
Nafcillin or first-generation cephalosporin |
Vancomycin,Quinupristin/Dalfopristin,Linezolid |
3 – 4 weeks or longer |
|
Vancomycin |
Daptomycin Quinupristin/Dalfopristin Linezolid |
3 – 4 weeks or longer |
|
Fluoroquinolone IV |
2 – 3 weeks |
||
Gram-negative bacilli other than Pseudomonas aeruginosa |
Third-generation cephalosporins |
Extended spectrum penicillin, Fluoroquinolone, TMP/Sulfa |
3 – 4 weeks |
Pipercillin plus aminoglycosides |
Cefepime plus aminoglycosides Ciprofloxacin,Levofloxacin |
3 – 4 weeks or longer |
TMP/Sulfa=Trimethrorim/Sulfamethoxazol
Table 6. Comparison of Drainage Procedures in Septic Arthritis
| Factors | Aspiration | Tidal irrigation | Arthroscopy | Arthrotomy |
|---|---|---|---|---|
Location |
Bedside |
Bedside |
Operating room |
Operating room |
Anesthesia |
Local |
Local |
Regional/general |
Regional/general |
Joint accessibility |
All joints (rpt aspirations limited to large, superficial joints |
Limited to large, superficial joints |
Limited to Large joints |
All joints |
Drainage accessibility |
Modest |
Modest |
Excellent |
Excellent |
Adhesion lysis |
No |
No |
Yes |
Yes |
Synovectomy |
No |
No |
Yes |
Yes |
Morbidity |
Minimal |
Minimal |
Moderate |
Significant |
Recovery time |
Short |
Short |
Short |
Prolonged |
| Cost | Inexpensive | Inexpensive | Expensive | Expensive |
Table 7. Test Characteristics of Synovial Fluid Studies
| Septic arthritis | Acute inflammatory | Non-inflammatory | Normal | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Appearance | Turbid yellow |
Turbid yellow |
Clear, straw |
Clear, colorless |
|||||
Fibrin clot |
Positive |
Positive |
Negative |
Negative |
|||||
| WBCs count (/μL) | Septic Arthritisa | Gonococal Arthritis | TB Arthritis |
Acute Gouty Arthritis | Rheumatic Fever | Rheumatoid Arthritis | <5000 | <200 | |
| Range | 15600- 21,300 | 1500-10,800 | 2500-10,500 | 750-45,000 | 300-98,000 | 300-75,000 | |||
| Average | 65400 | 14000 | 23500 | 13500 | 17800 | 15500 | |||
| PMN (%) | Range | ≥90 b | 2-96 | 29-96 | 48-94 | 8-98 | 5-96 | <25 | <25 |
| Average | 95 | 64 | 67 | 83 | 46 | 65 | |||
Blood- synovial glucose difference (mg/dL)c Low glucosed |
Range | 40-122 | 0-97 | 0-108 | 0-41 | 0-88 | <10 |
<10 |
|
| Average | 71 | 25 | 57 | 12 | 6 | 31 | |||
| LDH (U/L) | >250e | >100 | <250 | <250 | |||||
| Gram stein/ Culture | Positivef | Negative | Negative | Negative | |||||
| Crystals | Negative | Monosodium urate (gout), Calcium pyrophosphate (pseudogout), Hydroxyappatite | Negative | Negative | |||||
a) Sensitivity/Specificity (%) for septic arthritis (Data taken from 32)
>10,000 40/99
> 50,000 70/92
> 25,000 88/71
b) Highly sensitive (Sensitivity/Specificity 92/78 (%)) for septic arthritis
c) Glucose concentration may give spurious results unless obtained after prolonged fasting, and differences between joint and blood samples may not be significant unless >50 mg/dL. Joint tap should be performed, preferably after the patient has been fasting for >4 hrs, and a blood glucose determination should be performed simultaneously.
d) Serum/synovial fluid glucose ratio of less than 0.5 or 0.75, synovial fluid glucose level of less than 1.5mmol/mL, or both Sen/Spe 64/85(%) for septic arthritis
e) Highly sensitive (Sensitivity/Specificity 100/51 (%)) for septic arthritis.
Gas liquid chromatography assay is superior to enzymatic analysis of LDH
f) Gram stain: highly specific, low sensitive (Sensitivity/Specificity 50-70/100(%)).
Gram-negative diplococci for gonococcal arthritis are demonstrated in only 10-25%
Culture Sensitivity Specificity
Non-gonococcal 75-95 >90
Gonococcal 10-50 >90
What's New
Eberst-Ledoux J, et al. Septic arthritis with negative bacteriological findings in adult native joints: a retrospective study of 74 cases. Joint Bone Spine 2012;79:156-159.
Zeller V, et al. Continuous Clindamycin Infusion, an Innovative Approach to Treating Bone and Joint Infections. Antimicrobial Agents and Chemotherapy. 2010;54(1):88-92.