The reported incidence of septic arthritis varies from 2–10 per 100,000 per year in the general population, with substantially higher rates in patients with rheumatoid arthritis (RA) or joint prostheses (both ∼30–70 cases per 100,000 per year). The incidence of bacterial arthritis is significantly higher among children than adults.
Septic (bacterial) arthritis is a medical emergency, and delay in diagnosis and treatment can lead to irreversible joint destruction and an increase in mortality. Even with the advent of better antimicrobial agents and techniques of joint incision and drainage, the rate of permanent joint damage from septic arthritis is 25–50%. The case fatality rate for monoarticular bacterial arthritis also remains high at 11%, with increased mortality rates seen in the setting of polyarticular septic arthritis (as high as 50%), underlying RA, and in immunocompromised states. Risk factors for the development of bacterial arthritis include chronic arthritic syndromes, prosthetic joints, parenteral drug use, extremes of age, diabetes mellitus, and immunocompromised conditions (Table 47–1).
Table 47–1. Risk Factors and Mechanisms of Infection in Bacterial Arthritis. ||Download (.pdf)
Table 47–1. Risk Factors and Mechanisms of Infection in Bacterial Arthritis.
|Risk Factor||Mechanism of Infection||Comments|
|Rheumatoid arthritis (RA)|
- Local and systemic factors play a role
- Damaged joint serves as nidus for infection
- Immunosuppressive medications predispose to infection, especially previous use of oral or intra-articular glucocorticoids
- RA is complicated by septic arthritis in 0.3–3% of patients
- Polyarticular septic arthritis in RA has >50% mortality rate
- Staphylococcus aureus most likely organism
- Foreign body serves as nidus for infection, especially for pathogens that lay down biofilms or glycocalyx layer (eg, Staphylococcus epidermidis)
- No microvasculature in artificial joint
- Rates of infection have decreased over the past 30 years
- Higher incidence in revision arthroplasty (see text for details)
|Injection drug use; indwelling lines; chronic skin infections|
- Recurrent bacteremia with subsequent hematogenous seeding of joints
- Patients receiving long-term hemodialysis, with chronic indwelling lines, with repeated skin injections (eg, insulin), or with chronic skin infections are susceptible
- The knee is the most commonly infected joint in injection drug users, but also see axial joint infections, including sternoclavicular and sacroiliac joint involvement
- S aureus (often methicillin-resistant) most common cause in injection drug users
- Pseudomonas aeruginosa seen in ∼10% of cases
|Crystal-induced arthritis (gout, pseudogout)|
- Local factors
- Joint damage from crystals
- Synovial fluid acidosis in crystal-induced synovitis promotes cartilage damage
- Crystal-induced arthritis can cause high synovial WBC counts without infection
- Presence of crystals does not rule out infection
- Infection-mediated destruction of articular cartilage can rarely elicit crystals in synovial space
|Severe osteoarthritis, Charcot joint, hemarthroses|
- Joint disorganization, chronic synovitis, and blood within synovial space can provide a nidus for infection
- Always send a bloody synovial effusion for culture to exclude infection
|Chronic, systemic disease (eg, lupus, cancer, diabetes mellitus, other immunosuppressive conditions, including extremes of age [children <5 or adults >65])|
- Impaired host defenses from chronic illness, including phagocytic deficiencies
- Medications for chronic illnesses (eg, glucocorticoids in lupus) predispose to infection
- S aureus and gram-negative bacilli most common organisms
- In lupus, functional hyposplenism may occur, leading to susceptibility to encapsulated organisms (eg, Neisseria gonorrhoeae, Salmonella, Proteus)
|Intra-articular injection (or arthrocentesis)|
- Direct inoculation of the offending organism
- Most common agents are skin flora, including S epidermidis and S aureus
- Immunosuppression and an increased tendency to develop bacteremia with localized infections
- Even in asymptomatic HIV infection, underlying risk factors for acquiring HIV, such as injection drug use or hemophilia, can predispose
- Predisposes to localized gonococcal infection, which may disseminate to cause joint and skin disease
- DGI 2–3 times more common in women than men, especially after menses or in postpartum period
- Terminal complement deficiencies also predispose to DGI
Bacterial pathogens reach the joint spaces by hematogenous spread (>50% of cases), direct inoculation, or spread from adjacent bony or soft-tissue infections. The lack of a limiting basement membrane and high vascularity of the synovium allows for easy bacterial access. Although skin infections are the most common predisposing infections to joint infections, transient bacteremia from respiratory, gastrointestinal, or genitourinary infections can also lead to septic arthritis. Bacteria enter the closed joint space, and within hours the synovium becomes infected, leading to synovial membrane proliferation and infiltration by polymorphonuclear and other inflammatory cells. This inflammatory response in turn leads to enzymatic and cytokine-mediated degradation of the articular cartilage, neovascularization, and the eventual development of granulation tissue. Without appropriate treatment, irreversible subchondral bone loss and cartilage destruction occur within a few days of the initial infection.
The classic presentation of bacterial arthritis is the abrupt onset of a painful, warm, and swollen joint. More indolent presentations are seen in patients with preexisting rheumatic illnesses or immunocompromised states. An obvious joint effusion, moderate to severe joint tenderness to palpation, and marked restriction of both passive and active motion are common signs of septic arthritis.
A patient with an acute monoarticular arthritis should be considered to have septic arthritis until proven otherwise. Nongonococcal bacterial arthritis is monoarticular in 80–90% of cases, with polyarticular involvement (10–20%) carrying a poorer chance of survival. Polyarticular septic arthritis is more likely to occur in patients with RA or other systemic connective tissue diseases or in the syndrome of overwhelming sepsis. Infectious monoarthritis typically involves the knee (40–50%), hip (13–20%), shoulder (10–15%), wrist (5–8%), ankle (6–8%), elbow (3–7%), and the small joints of the hand or foot (5%). Bursitis, especially olecranon and prepatellar, may be the first manifestation of septic arthritis in patients with RA.
Septic arthritis manifests with fever in 60–80% of cases, although the temperature elevation is not usually pronounced. Twenty percent of patients with fever have shaking chills that usually correspond to waves of bacteremia. Cough, gastrointestinal symptoms, or dysuria may represent symptoms of the antecedent infection. Indeed, a preceding source of infection, such as pneumonia, otitis, bronchitis, pharyngitis, or cutaneous, gastrointestinal, or genitourinary infection, can be identified in up to 50% of septic arthritis cases.
The initial physical examination for septic arthritis should determine whether the source of inflammation and pain is articular or periarticular (specifically, localized to skin, bursae, or tendons). Septic arthritis produces warmth, swelling, and tenderness of the involved joint, and attempts at passive and active motion of the joint usually produce considerable discomfort. Similar findings occur in noninfectious forms of severe inflammatory arthritis, such as acute gout. In contrast, cellulitis and inflammation of bursae and tendons do not cause joint effusions, and passive motion of the adjacent joint usually does not elicit severe pain unless there is stretching of an inflamed tendon. Because septic arthritis can involve more than one joint, all joints should be examined for warmth, swelling, deformity, range of motion, pain on motion, and tenderness.
Septic arthritis of the sacroiliac (SI) joint is often difficult to distinguish from infection in the hip because both present with fever and pain upon ambulation and because examination of the SI joints is difficult (see Chapter 1). Moreover, findings of SI septic arthritis can be subtle and can be mistaken for the syndrome of a protruded disk or a paraspinous muscular strain. Similarly, infection of the shoulder joint is often difficult to identify given the usual lack of a visible effusion. Adults with shoulder infections tend to be elderly, with multiple risk factors for the development of septic arthritis. Infections of the sternoclavicular joint most often occur in injection drug users; an abscess of the chest wall or mediastinitis will develop in 20% of patients with septic arthritis of the sternoclavicular joint. Septic olecranon bursitis is distinguished from infection of the elbow joint by the presence of swelling and erythema overlying the olecranon process and the absence of joint pain with passive extension of the elbow. Infection of the olecranon bursa often follows minor trauma to the region, which leads to inoculation of organisms (usually S aureus) into the bursal space.
Peripheral Counts and Cultures
Peripheral white blood cell (WBC) counts are elevated in bacterial arthritis approximately two thirds of the time. The erythrocyte sedimentation rate and C-reactive protein are usually elevated and may be useful to monitor during treatment, however, they can also be elevated in other noninfectious arthropathies. Approximately 40–50% of patients with septic arthritis have associated bacteremia, so blood cultures should be obtained prior to the administration of antibiotics. Targeted cultures from extra-articular sites, such as respiratory, cutaneous, gastrointestinal, or genitourinary sites, should also be collected after a careful history and physical examination.
Synovial fluid analysis is critical for the definitive diagnosis of septic arthritis. Synovial fluid is usually obtained by emergent arthrocentesis, with fluoroscopic, computed tomographic (CT), or ultrasonographic guidance if necessary (see Chapter 2). An open surgical procedure may be required to obtain synovial fluid and biopsies of the synovial membrane for the diagnosis of bacterial arthritis, especially in suspected sternoclavicular, hip, or shoulder infections or in the presence of prosthetic joints. Of note, arthrocentesis is contraindicated if the needle must pass through an area of cellulitis, heavily colonized skin lesions (eg, psoriatic plaques), or infection of any kind because of the risk of introducing bacteria into the joint space. Bacteremia is also a relative contraindication for the performance of arthrocentesis.
Once synovial fluid has been collected, the following analyses should be performed (see Chapter 2):
- Appearance: Look for color and clarity of the fluid, since purulence or turbidity or both suggest a septic process.
- Cell count and differential: The joint fluid in nongonococcal septic arthritis has more than 50,000 WBC/mcL in 50–70% of cases. Low synovial fluid cell counts may be seen early in the process of infectious arthritis, in the setting of partially treated infections, or in immunosuppressed patients. The majority of WBCs in infected synovial fluid are neutrophils (usually >80% polymorphonuclear cells).
- Gram stain for organisms: A positive Gram stain is diagnostic for septic arthritis (highly specific), but a Gram stain that is negative for bacteria does not rule out an infected joint. The Gram stain is positive 50–75% of the time in nongonococcal bacterial arthritis, with gram-positive bacterial arthritis more likely to stain positive than gram-negative bacterial arthritis. The Gram stain should be used to guide presumptive therapy.
- Culture: Bacterial culture of the synovial fluid is positive in 70–90% of cases of nongonococcal arthritis, depending on the organism. Inoculating synovial fluid into blood culture bottles rather than solid media increases the yield of culture growth and decreases the contamination rate.
- Microbiology: Table 47–2 shows the typical pathogens of nongonococcal bacterial arthritis and risk factors for their acquisition. S aureus is the most common cause of septic monoarthritis in native joints (60–70%) (Figure 47–1). The remaining causes of septic arthritis include streptococcal species, gram-negative rods, and anaerobes in relatively constant proportions. Hematogenous infection can result from transient bacteremia secondary to a remote infection or a surgical procedure, including dental work or respiratory, gastrointestinal, or genitourinary manipulations. Group A streptococci are often isolated from the infected joint after procedures in the oral cavity, whereas gastrointestinal procedures can lead to bacteremia with non–group A streptococcal species, gram-negative bacilli, or anaerobes.
Table 47–2. Major Bacterial Organisms Implicated in Nongonococcal Septic Arthritis and the Percentage of Adult Infections Attributable to Each Pathogen. ||Download (.pdf)
Table 47–2. Major Bacterial Organisms Implicated in Nongonococcal Septic Arthritis and the Percentage of Adult Infections Attributable to Each Pathogen.
|Organism||% of Adult Infections||Comments|
- Most common pathogen in native joints and late prosthetic joint infections
- Rates of MRSA are increasing in injection drug users and in the community
- Group A streptococci most common streptococcal species implicated in septic arthritis
- Usually preceded by primary skin or soft-tissue infection
- Incidence is increasing of non–group A β-hemolytic streptococci (eg, groups B, C, and G streptococci), especially in immunocompromised persons or following gastrointestinal or genitourinary infections
- S pneumoniae infectious arthritis is rare
- Most common in neonates, infants younger than 2 months, the elderly, injection drug users, and the chronically ill (diabetes mellitus, cancer, sickle cell anemia, connective tissue disorders, and renal transplant recipients and other immunosuppressed conditions)
- Begin as urinary tract or skin infections, with subsequent hematogenous spread to a single joint
- Haemophilus influenzae arthritis has decreased markedly since routine H influenzae type b childhood vaccination
- Common species include Bacteroides, Propionibacterium acnes (skin flora), and various anaerobic gram-positive cocci
- 50% of anaerobic arthritis is polymicrobial
- Predisposing factors: diabetes mellitus, immunocompromise, or postoperative wound infections, especially following total joint replacement or joint arthroplasty
- Suspect if synovial fluid is foul smelling or air is present in the joint space radiologically
- Collect cultures under anaerobic conditions and incubate for at least 2 weeks
|Staphylococcus epidermidis||Rare in native joints|
- Common in postoperative prosthetic joint infections
- Forms glycocalyx layer over foreign surface
- Organism often difficult to eradicate without joint removal
- B melitensis most common Brucella species implicated
- Uncommon in the United States but more prevalent worldwide
- Risk factors: ingestion of unpasteurized milk or cheese or occupational exposures (eg, farmers and meat packers)
- Causes monoarthritis or an asymmetric peripheral oligoarthritis
- Sacroiliitis and spondylitis also common
- Diagnose with scintigraphy, CT scan, polymerase chain reaction, or positive blood or joint cultures
- Treatment courses lengthy and involve antimicrobial combinations
- More common in children than adults
- Seen in immunocompromised patients, particularly those with agammaglobulinemia
Gram stain of an inflammatory exudate showing the clustered gram-positive cocci of Staphylococcus aureus. (Courtesy of Dr. Thomas F. Sellers, Public Health Image Library, CDC.)
Plain radiographs are of little diagnostic usefulness in acute septic arthritis but are often obtained as a baseline and to exclude contiguous osteomyelitis. Radiographs usually reveal only soft-tissue swelling; in cases of infection with Escherichia coli or anaerobic organisms, however, radiographs may demonstrate gas formation within an untapped joint. In late septic arthritis (at least 8–10 days after infection), films may show subchondral bone destruction, periosteal new bone formation, joint-space narrowing, or osteoporosis.
Because the hip, shoulder, sternoclavicular, and SI joints are difficult to palpate and to aspirate, evaluation of these joints usually requires CT or MRI. CT is preferred for the sternoclavicular joint. CT scans may demonstrate early bone erosions; reveal soft-tissue extension and detect effusions; and facilitate arthrocentesis of the hip, shoulder, sternoclavicular, and SI joints.
Magnetic Resonance Imaging
MRI scans demonstrate adjacent soft-tissue edema or abscesses and may be especially helpful in detecting septic sacroiliitis. MRI can also detect the early bone erosions of incipient contiguous osteomyelitis.
Scintigraphy makes use of various agents, such as labeled WBCs, technetium colloid, or immunoglobulin, to highlight areas of infection. The drawback of this imaging technique in the diagnosis of septic arthritis is the rate of false-positives with contiguous soft-tissue infections; scintigraphy cannot reliably differentiate septic from aseptic joint inflammation. False-positive scans can also result from underlying fracture or a recent operation. Given this low specificity, scintigraphy is rarely used as the imaging study of choice for the diagnosis of septic arthritis.
Gallium accumulates where there is an extravasation of serum proteins and leukocytes and is better than scintigraphy in distinguishing infection from mechanical damage. Gallium scans have shown increasing usefulness in the diagnosis of septic arthritis and the identification of concurrent osteomyelitis.
Septic arthritis usually presents as acute monoarthritis, and occasionally as an acute oligoarthritis or a polyarthritis. The differential diagnoses of these syndromes are reviewed in Chapter 4, but several points warrant emphasis here. The cause of acute monoarthritis is presumed to be infection unless proved otherwise. Differentiating infection from crystal-induced arthritis can be particularly difficult, since acute flares of pseudogout or gout can also cause fever, peripheral leukocytosis, and markedly elevated synovial cell counts. Bacterial superinfection can complicate crystal-induced arthritis, although this is rare. A history of recurrent monoarthritis, typical podagra, or radiologic evidence of chondrocalcinosis are all suggestive of crystal-induced arthritis. However, only arthrocentesis with culture of the synovial fluid and analysis for crystals can definitively distinguish septic arthritis from crystal-induced arthritis.
Early diagnosis is the key to successful treatment of septic arthritis; delay in instituting appropriate antibiotic therapy and débridement measures almost invariably leads to poor outcomes. The two mainstays of treatment are drainage and intravenous antibiotic therapy. Progressive joint mobilization also helps prevent some of the long-term complications of septic arthritis.
The management of septic nongonococcal arthritis requires hospitalization for drainage of the infected joint. The joint must be thoroughly drained to decrease the number of inflammatory cells, which produce cytokines and proteolytic enzymes that cause permanent joint damage. Early arthroscopic lavage, débridement, and drain insertion have largely replaced the standard procedure of performing daily aspirations of the joint. Response to therapy can be gauged by monitoring the synovial fluid cell counts and culture results over the subsequent days of hospitalization.
Open surgical drainage and débridement (arthrotomy) may be required for the following indications:
- Failure to respond to more conservative therapy in 5–7 days.
- Coexistent osteomyelitis that needs surgical intervention.
- Involvement of joints that are difficult to drain using more conservative approaches, such as hips, shoulders, or SI joints.
- Involvement of a prosthetic joint (see section on prosthetic joint infections, below).
- Difficulty in performing adequate drainage of the joint with needle aspiration or arthroscopic manipulations.
- Refusal of the patient to accept repeated needle aspirations or catheter drainage (eg, young children).
- Open drainage is the initial procedure of choice in children with septic arthritis of the hip.
After the initial diagnostic joint aspiration, intravenous antibiotics should be immediately administered. Empiric antibiotic therapy is based on either the initial Gram stain results or the clinical situation (Table 47–3) in suspected bacterial arthritis. The duration of antibiotic therapy has not been studied in controlled trials, but most patients are treated for at least 4 weeks. Initial therapy is administered intravenously. Once there has been improvement, transition to oral therapy can be considered if the organism is sensitive to drugs with good oral bioavailability (eg, fluoroquinolones, trimethoprim-sulfamethoxazole) and the patient is likely to be compliant. For difficult to treat organisms (Pseudomonas) and for S aureus infections associated with bacteremia, the entire course of therapy is usually administered parenterally. Intra-articular antibiotic instillation has not been shown to be beneficial and may lead to a chemical synovitis.
Table 47–3. Initial Antibiotic Therapy for Septic Arthritis Based on Synovial Gram Stain or Clinical Situation. ||Download (.pdf)
Table 47–3. Initial Antibiotic Therapy for Septic Arthritis Based on Synovial Gram Stain or Clinical Situation.
|Synovial Fluid Gram Stain or Clinical Situation||Antibiotic Therapy|
- Use intravenous vancomycin initially due to increasing rates of MRSA in the community (dosing: 10–15 mg/kg per dose administered every 12 hours or every 8 hours; typical regimen is 1 g intravenously every 12 hours initially with doses subsequently adjusted to keep serum vancomycin troughs in the 15–20 mcg/mL range)
- Switch to nafcillin 2 g intravenously every 4 hours or cefazolin 2 g intravenously every 8 hours if MSSA; if penicillin-sensitive streptococcal species, can use penicillin 12–18 million units daily in divided doses or ampicillin 2 g intravenously every 4 hours; if penicillin-resistant streptococcal species, use ceftriaxone 1–2 g intravenously every 12 hours or vancomycin
- Oral options: ciprofloxacin (750 mg orally twice daily) plus rifampin (450 mg orally twice daily); combination provides bactericidal intra-articular concentrations, but these should be used only for prosthetic joint infections (see text); increasing data are available on linezolid (600 mg orally twice daily) in MRSA joint infections
- Initial therapy with high-dose third-generation cephalosporin specific for gram-negative organisms (eg, ceftazidime 2 g intravenously every 8 hours, cefepime 2 g intravenously every 8 hours). Also consider piperacillin/tazobactam 4.5 g intravenously every 6 hours if concern for hospital-associated infection
- If directed toward Pseudomonas, intravenous therapy with an aminoglycoside (eg, gentamicin 1 mg/kg intravenously every 8 hours or tobramycin 1.5 mg/kg intravenously every 8 hours) in synergistic combination with an antipseudomonal penicillin (eg, ticarcillin 4 g intravenously every 4 hours or piperacillin 4 g intravenously every 4 hours) or third-generation cephalosporin
- If sensitive enteric gram-negative bacteria, can use ceftriaxone or fluoroquinolone
|Injection drug use|
- Initial therapy with vancomycin for MRSA, as well as single or combination therapy for Pseudomonas as listed for gram-negative bacilli
- Tailor subsequent therapy based on culture results
- Initial therapy with intravenous vancomycin alone
- Tailor subsequent therapy based on culture
|Chronically ill or immunocompromised patient|
- Initial therapy with broad coverage for gram-positive organisms (eg, vancomycin), gram-negative organisms, and anaerobes if clinically suspected; anaerobic coverage can involve adding a β-lactamase inhibitor to the antipseudomonal penicillin (eg, ticarcillin/clavulanate 3.1 g intravenously every 4 hours or piperacillin/tazobactam 3.375 g intravenously every 6 hours) or adding metronidazole 500 mg intravenously every 8 hours
- Tailor subsequent therapy based on culture results
|Young adults with negative smear|
- Ceftriaxone 1 g intravenously every 24 hours for suspected gonococcal infection
|Neonates and children <2 months old|
- Broad-spectrum initial coverage for Haemophilus influenzae (assume ampicillin resistance, so use a third-generation cephalosporin with the doses given above), S aureus (vancomycin as above if MRSA; nafcillin if MSSA), group B streptococci (best covered by penicillin, although sensitive to vancomycin, ceftriaxone, and ceftizoxime) and gram-negative bacilli
- Combination of vancomycin, an extended-spectrum penicillin (eg, ticarcillin or piperacillin), and an aminoglycoside (eg, gentamicin or tobramycin) often used
- Tailor subsequent therapy based on culture results
Management of septic arthritis also includes passive motion exercises to prevent formation of adhesions and to enhance the clearance of purulent exudates after the acute inflammatory response has subsided. Passive mobilization is gradually followed by active strengthening of periarticular structures to help prevent joint contractures.
The major complications of septic arthritis include osteomyelitis, persistent or recurrent infection, a marked decrease in joint mobility, ankylosis, or persistent pain. Between 70% and 85% of patients with group A streptococcal infections recover without residual symptoms. Up to 50% of patients with septic arthritis secondary to S aureus or gram-negative rods, however, have residual joint damage. Patients with RA and polyarticular infection have a guarded prognosis, with a survival rate <50%.