Septic arthritis is infection, usually bacterial, in the joint cavity. It is the most dangerous form of acute arthritis. The joint cavity is usually a sterile space, with synovial fluid and cellular matter including a few white blood cells.

The incidence of septic arthritis has been estimated at 2 to 10 cases per 100,000 in the general population and as high as 30 to 70 cases per 100,000 in patients with rheumatoid arthritis.^1,2 The most common mode of spread is hematogenous, with predisposing factors including intravenous drug use, presence of in-dwelling catheters, and underlying immunocompromised states. The other predisposing condition is a preexisting arthritis such as rheumatoid arthritis, gout, or osteoarthritis. The knee is the most commonly involved joint accounting for about 50% of the cases.³

The most common route of spread is hematogenous; other routes include trauma or inoculation as during steroid injections. On entering the joint space, the bacteria initially deposit in the synovial membrane and produce an inflammatory reaction, usually with polymorphonuclear and synovial cells, which readily spill into the synovial fluid. Synovial membrane hyperplasia develops in 5 to 7 days, and the release of cytokines leads to hydrolysis of proteoglycans and collagen, cartilage destruction, and eventually bone loss.⁴ Direct pressure necrosis due to large synovial effusion results in further cartilage damage. Both antigen-specific and polyclonal B-cell activation are seen in Staphylococcal aureus experimental arthritis.

The presence of the cna gene in S. aureus causes a higher incidence of septic arthritis in mice experiments. This suggests that the cna gene product, a collagen adhesion factor, may play an important role in the development of septic arthritis.⁵

Microbiology
Most septic arthritides are monomicrobial infections, but polymicrobial infections may be seen in patients with direct inoculation of the joint space. The most common bacterial isolates in native joints include gram-positive cocci, with S. aureus found in 40% to 50% of the cases. Other isolates include Neisseria gonorrhoeae, streptococci, and gram-negative cocci, each in about 10% to 20% of cases. Other organisms less commonly isolated include mycobacteria and fungi.^3,6 Gram-negative bacilli are often present in neonates, the elderly, and patients with immune deficiency disorders. N. gonorrhoeae is seen in sexually active young adults, usually with associated dermatitis and tenosynovitis. Mycobacterial infections should be suspected in patients from endemic areas, and fungal arthritides are seen in immunocompromised patients. Haemophilus influenzae was a common cause of bacterial arthritis in young children, but the incidence has decreased almost 70% to 80% since the widespread use of H. influenzae b vaccine.⁷

Patients with septic arthritis usually present with a single swollen joint with pain on active or passive movement. The knee is involved in about 50% of the cases, but wrists, ankles, and hips are also commonly affected. Septic arthritis may present as polyarticular arthritis in about 10% to 19% of patients and is more common in patients with prior joint damage as in rheumatoid arthritis, gout, and systemic connective tissue disorders.⁸

Pertinent history in any patient with suspected septic arthritis may include joint disease, immunosuppressive states, intravenous drug use, recent steroid injection, history of sexually transmitted disease, and any constitutional symptoms. Physical examination should include a careful assessment of the pattern of joint involvement and inflammation of the eyes, skin, or mucosa and other sites of potential infection. Please see Figure 1 for a suggested algorithm for work up of single, inflamed joint.

A classic presentation for septic arthritis would be a febrile patient having rigors, increased leukocyte count, and elevated sedimentation rate. However, none of these are highly sensitive or specific for septic arthritis. In different series, only 40% to 60% of patients with septic arthritis were febrile, only 25% to 60% had an elevated leukocyte count, and only 60% to 80% had a sedimentation rate greater than 50 mm/hr.^4,9

Synovial fluid analysis is of paramount importance in the diagnosis and management of septic arthritis. It should include gram stain, culture, leukocyte count with differential, and crystal examination under polarized microscope. Controversy exists as to whether synovial fluid culture yield is increased by the inoculation of blood culture bottles at the bedside as compared with using conventional agar plate culture in the laboratory. A study has shown no difference in the rate of isolation of bacteria by either of these methods.¹⁰

A synovial fluid leukocyte count of greater than 50,000 with a polymorphonuclear leukocyte predominance is usually seen in septic arthritis. This can, however, also be seen in crystal arthropathies, which can complicate the clinical picture. A history of gout in the same joint or the presence of crystals in the synovial fluid may indicate an episode of gout or pseudogout rather than septic arthritis.

Gram stain is positive in 11% to 80% of cases, but an occasional false positive may be seen due to precipitated mucin in the synovial fluid. Synovial fluid culture is positive in a majority (up to 90%) of nongonococcal bacterial arthritides.⁴

Synovial fluid glucose, protein, and lactic acid concentration are not well standardized and, hence, not useful in the diagnosis of septic arthritis. Synovial polymerase chain reaction (PCR) has been used to diagnose Yersinia spp, Chlamydia spp, Ureaplasma urealyticum, N. gonorrhoeae, and Borrelia burgdorferi.⁴ It may be useful in the diagnosis of a fastidious organism and assist in diagnosis of partially treated cases. Counterimmunoelectrophoresis has not been well studied in diagnosing synovial fluid infection and is not used for diagnosis of septic arthritis.

Other Rheumatic Diseases
In patients with chronic joint disease who present with one or more inflamed joints, septic arthritis should always be considered. These patients are inherently at a higher risk of infection due to their damaged joints. Septic arthritis in rheumatoid arthritis is associated with a higher mortality of 25% to 30% due to delay in diagnosis and initiation of treatment, as it may mimic an acute flare-up of the disease.¹¹

Gout and pseudogout usually present similarly to septic arthritis, with pain, inflammation, and occasional constitutional symptoms as well. The presence of crystals on synovial fluid analysis is imperative to making the diagnosis of crystal arthropathy. In all patients with acute effusion of unknown etiology, synovial fluid should be sent for gram stain and culture.

Viral Arthritis
Acute polyarthritis with a fever and rash can be the initial presentation of many viral infections including rubella, hepatitis B and C, and parvovirus. Human immunodeficiency virus (HIV) infection has also been associated with a subacute monoarthritis or oligoarthritis.

Lyme Disease
Lyme disease should be suspected in patients with a history of tick exposure or travel to endemic areas who present with typical erythema chronicum migrans, transient polyarthalgias, and other systemic symptoms. Chronic monoarthritis, especially of the knee, can be seen, and chronic persistent synovitis develops in 20% of the patients with untreated Lyme disease.³ Serological tests can be confirmatory in certain patients, and treatment with oral or intravenous antibiotics can be curative in most cases.

Reactive Arthritis
Seronegative spondyloarthropathies associated with HLA B27 antigens, including Reiter's syndrome, psoriatic arthritis, ankylosing spondylitis, and arthritis associated with inflammatory bowel disease, can present as an acute inflamed joint. These patients usually have other manifestations of the disease including gastrointestinal or genitourinary symptoms, skin lesions, or uveitis, which can suggest the diagnosis. These joint inflammations are sterile in nature and reactive to the presence of infection or inflammation elsewhere in the body. Post-streptococcal infection can also mimic septic arthritis. Persistent microbial antigens have recently been demonstrated with PCR studies in the synovial fluid of patients with reactive arthritis.³

Infective Endocarditis
About 15% of patients with infective endocarditis have septic arthritis or bone infection. These patients may also present with sterile synovitis or arthralgias mimicking septic arthritis.

One of the most important predictors of a good outcome in septic arthritis is the rapidity with which treatment is instituted. Patients treated within 7 days of onset of symptoms tend to do well, and those treated after 1 month of the onset of symptoms usually do poorly.¹³

Antibiotic Treatment
Initial antibiotic therapy should be started empirically without awaiting the final results of culture. Choice of antibiotic is based on the patient's age, presumed source of infection, patient's own infection profile, presence of immunosuppression including history of diabetes, and the suspected pathogenic organism. Parenteral antibiotics should always be used, at least in the initial part of the treatment regimen. Initial therapy should include a cephalosporin or a semi-synthetic penicillin to cover gram-positive cocci including staphylococci. In patients allergic to penicillins, clindamycin or vancomycin may be used empirically. Third-generation cephalosporins should be used for suspected gram-negative bacterial infection. The direct instillation of the antibiotic into the joint is not necessary and has not been shown to be more effective than parenteral antibiotics.

Duration of antibiotic treatment is more controversial and depends on the organism isolated at final culture and its response to the given antibiotic. In uncomplicated cases, 2 weeks' therapy for H. influenzae, streptococci, or gram-negative cocci and 3 weeks' therapy for staphylococci and gram-negative bacilli should be adequate.¹⁴ With the advent of home intravenous antibiotic therapy, these patients can be treated with parenteral antibiotics on an outpatient basis.

A decrease in the white blood cell count in serial synovial fluid samples between 5 and 7 days of therapy reflects a control of infection.⁹

Drainage of Infected Joints
Most uncomplicated cases can be drained with needle aspiration. Some infected joints, including the hip, shoulder, or the sacroiliac joints, may not be easily aspirated. In these cases, an open arthrotomy may be considered as an initial approach. Any joint with limited accessibility, including the sternoclavicular or the sternomanubrial joints, should also be managed surgically.^13,15 Any joint that does not respond quickly to antibiotic therapy must also be treated surgically. Patients with underlying disease, including diabetes, rheumatoid arthritis, immunosuppression, or other systemic symptoms, should be treated more aggressively with earlier surgical intervention. The goal of surgery is to remove all purulent material and nonviable tissue and to determine the need for synovectomy. Culture and synovial biopsies can be obtained after débridement to ensure sterility of the joint.^15,16

The knee, shoulder, and ankle joints are especially amenable to arthroscopic débridement in both adult and pediatric patients.

After arthrotomy, joints — especially hips — should be closed. Drainage of the joints with closed suction systems is recommended; there are no standards for how long drains should remain in place.

Repeated irrigation and distention of a joint at the bedside under local anesthetic has been described to be effective in certain cases. This approach, called 'tidal irrigation', may be a useful adjunct to medical therapy in certain patients.^13,15

Any infected limb should be splinted in the position of function, with knees splinted in extension, hips placed in balanced suspension in neutral rotation, elbow splinted at 90 degrees, and the wrists splinted in neutral to slight extension. Once an infection is under control, immediate joint mobilization should be started slowly. This will prevent contractures and promote healing of the articular cartilage.¹⁷

Prosthetic Joint Infection
Knee and hip prosthetic joints have a 0.5% to 2% risk of becoming infected. Elbow, shoulder, and ankle joints have a higher infection rate of up to 6% to 9%.¹⁸ Early infections (less than 12 weeks after implantation) are usually from a skin pathogen, most likely a coagulase-negative staphylococcus. By contrast, late-onset infections (>1 year after implantation) are usually caused by hematogenous spread of the common organisms, including gram negatives like Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and gram-positive organisms, with Staphylococcus epidermidis being more common than S. aureus.¹⁹ The prosthesis and binding cement provide an avascular region for bacteria to flourish away from the immunologic defenses of the body. Adherent bacteria multiply and elaborate glycocalyx, eventually forming thick biofilms that further impair host defenses. Also, bacteria in the biofilm older than 7 days have been shown to have higher resistance to antibiotics.²⁰

Patients with rheumatoid arthritis, prior joint infection, prolonged surgical time, postoperative bleeding, urinary tract infection, and advanced age have a higher risk of infection. Pain, wound drainage, erythema, and induration at the site of the incision in early-onset infection, and fever and increased C-reactive protein in late-onset infection, are the usual signs of prosthetic joint infection. The sensitivity and specificity of scintigraphy including technetium-colloid scan, gallium-67 scan, or indium-labeled autologous white blood cell scan are low.¹³ Joint space fluid or tissue is required for definite diagnosis. Surgical biopsy or arthroscopy may sometimes be required, especially in late-onset infection with minimal symptoms.

Removal of the prosthetic joint is necessary in an overwhelming majority of cases. This may be done by excision arthroplasty or by reimplantation of the joint, which may be a one-stage procedure or a two-stage procedure, with 4 to 6 weeks of antibiotic therapy between the removal and reimplantation of a new prosthesis. The success rates for reimplantation range from 39% to 91% for a one-stage procedure and 73% to 100% for a two-stage procedure.²¹ Long-term suppressive antibiotics without removal of the prosthetic joint may be considered in patients where surgical removal is not possible, with an avirulent pathogen sensitive to oral antibiotics, and if the prosthesis is not loose. Dental prophylaxis is not routinely recommended in patients with a prosthetic joint, but may be considered in patients with diabetes, immunosuppressive therapy, or rheumatoid arthritis.²²

N. Gonorrhoeae Septic Arthritis
Disseminated gonococcal infection is the most common cause of infection in young adults, particularly pregnant and peri-menstrual females. It accounts for 3% to 7.5% of all culture-positive septic arthritis reported. Women are four times more likely to be affected and usually have associated asymptomatic genital, anal, or pharyngeal gonococcal infections. These may present as monoarticular or disseminated infection.

Gram stain is positive in 25% and culture only in 50% of the cases.²³ Thus, the diagnosis is often made from signs and symptoms, such as the presence of a rash with positive N. gonorrhoeae culture from a genitourinary source. Synovial PCR may be useful in detecting gonococcal DNA from the joints. Third-generation cephalosporins like ceftriaxone are the agents of choice because of increasing penicillin resistance.

Polyarticular Septic Arthritis
Polyarticular septic arthritis is seen in 10% to 19% of nongonococcal infections, usually due to staphylococcal infection of large joints in patients with underlying rheumatoid arthritis.^8,11 The mean number of joints infected is four, and extra-articular signs of infection are frequently seen. The prognosis is poor, with up to 32% mortality noted in certain series. Poor prognosis is conferred by older age (> 50 years), rheumatoid arthritis, and staphylococcal infection, but the overall mortality has remained unchanged in the last 20 years.^8,13

Septic Arthritis Following Arthrocentesis
The incidence of septic arthritis following arthrocentesis is low, ranging between 1:1000 to 1:16,000; this may be increased if corticosteroids are instilled.²⁴ Most cases of infection usually occur when transient bacteremia colonizes the needle track and causes seeding of the joint. Skin flora are rarely found to be the cause, but aseptic technique during the procedure is imperative. The presentation is similar to septic arthritis from other causes and one should have a high level of clinical suspicion.

Septic Arthritis with Crystal-Induced Arthritis
Crystal-induced arthritis can mimic septic arthritis, with fever, constitutional symptoms, and high synovial white cell count. The coexistence of gout and septic arthritis is rare, although well documented cases have been reported in the literature.²⁵ This should be suspected in patients with worsening synovitis despite treatment of gout, fever accompanying polyarthritis, acute arthritis after treatment of infection at a different site, and new joint involvement in a patient with gout. Synovial fluid analysis with gram stain and culture is critical in making the diagnosis in such patients. In a series from the Mayo Clinic, five of the 314 patients with pseudogout had concomitant septic arthritis.

Septic Arthritis with Rheumatoid Arthritis
Septic arthritis in patients with rheumatoid arthritis can present very similarly to an acute flare of the disease. Septic arthritis in these patients can also be insidious in presentation as some of these patients may be on corticosteroids. In a series, fever and constitutional symptoms were often absent, and only 56% of cases had peripheral leukocyte count elevation. Use of corticosteroids, cytotoxic drugs, and impaired host defenses including decreased chemotaxis and complement levels predispose patients with rheumatoid arthritis to infection.¹³ S. aureus is the main pathogen (76% of patients), with gram-negative bacilli responsible for the remaining cases. Polyarticular infection can occur in 25% of the cases.¹³ These patients should be managed aggressively, and early surgical exploration and drainage of the joints is indicated.¹⁵

Septic Arthritis in HIV Patients
Septic arthritis is not seen more frequently in patients with HIV infection. Its occurrence is usually associated with parenteral drug use or behavioral risk factors. N. gonorrhoeae is the most common organism reported in homosexual men. In advanced HIV infection, atypical mycobacterial species including Mycobacterium avium-intracellulare and Mycobacterium kansasii have been implicated in joint infections. At CD 4+ count less than 100, HIV-infected patients are also at risk for fungal infections, particularly Candida albicans and Sporothrix schenchii.²⁶

Septic Arthritis in Intravenous Drug Users
Knee and wrist are the most common joints involved in intravenous drug users. Staphylococcus species and gram-negative bacteria including P. aeruginosa, Enterobacter, and Serratia species are the common pathogens. These patients usually have a very favorable outcome despite infection with virulent organisms.²⁷

Specific Associations:

Certain pathogens have been associated with specific patient subgroups such as Salmonella species in patients with systemic lupus erythematosus or in sickle cell disease patients.⁴ U. urealyticum infection has been described in hypogammaglobulinemic patients; PCR may aid in diagnosis. Pasteurella multocida rarely causes septic arthritis following a penetrating bite, particularly from cats and dogs. Metacarpophalangeal and proximal interphalangeal joints can be involved with Mycobacterium marinum infection acquired through exposure to fresh water or marine life.⁴

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