Septic Arthritis 

Updated: Dec 06, 2018
Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD 

Overview

Background

Septic arthritis, also known as infectious arthritis, may represent a direct invasion of joint space by various microorganisms, most commonly caused by bacteria. However, viruses, mycobacteria, and fungi have been implicated. Reactive arthritis is a sterile inflammatory process that may result from an extra-articular infectious process. Bacteria are the most significant pathogens in septic arthritis because of their rapidly destructive nature. For this reason, the current discussion concentrates on the bacterial septic arthritides. Failure to recognize and to appropriately treat septic arthritis results in significant rates of morbidity and may even lead to death.

Approximately 20,000 cases of septic arthritis occur in the United States each year (7.8 cases per 100,000 person-years), with a similar incidence occurring in Europe.[1] The incidence of arthritis due to disseminated gonococcal infection is 2.8 cases per 100,000 person-years.

Because of the increasing use of prosthetic joints, infection associated with these devices has become the most common and challenging type of septic arthritis encountered by most clinicians.[2] The incidence of prosthetic joint infection (PJI) among all prosthesis recipients ranges from 2% to 10%. These figures may be falsely low because surveillance is limited to the operative hospital, which may lead to underestimation of the rate of PJIs.[3]

Septic arthritis is also becoming increasingly common among people who are immunosuppressed and elderly persons. Of people with septic arthritis, 45% are older than 65 years; these groups are more likely to have various comorbid disease states. Fifty-six percent of patients with septic arthritis are male.

Gonococcal and nongonococcal bacterial/suppurative arthritis

Septic arthritis due to bacterial infections is commonly classified as either gonococcal or nongonococcal.[1, 2, 4, 5, 6] Overall, although Neisseria gonorrhoeae remains the most common pathogen (75% of cases) among younger sexually active individuals,[7, 8] Staphylococcus aureus infection is the cause of the vast majority of cases of acute bacterial arthritis in adults and in children older than 2 years.[9] The increased incidence of this pathogen parallels the increase in presence of prosthetic joints and in the use of immunosuppressive agents. This pathogen is the cause in 80% of infected joints affected by rheumatoid arthritis.

Streptococcal species, such as Streptococcus viridans, S pneumoniae,[10, 11] and group B streptococci,[12] account for 20% of cases. Aerobic gram-negative rods are involved in 20-25% of cases. Most of these infections occur in people who are very young, who are very old,[13] who are diabetic, who are immunosuppressed, and who abuse intravenous drugs.[2]

Infection of the sternoclavicular and sacroiliac joints with Pseudomonas aeruginosa or Serratia species occurs almost exclusively in persons who abuse intravenous drugs. Persons with leukemia are predisposed to Aeromonas infections.[14]

Polymicrobial joint infections (5-10% of cases) and infection with anaerobic organisms (5% of cases) are usually a consequence of trauma or abdominal infection. The organism of Lyme disease (ie, Borrelia burgdorferi), a large variety of viruses (eg, human immunodeficiency virus [HIV], lymphocytic choriomeningitis virus, hepatitis B virus, rubella virus), mycobacteria, fungi (eg, Histoplasma species, Sporothrix schenckii, Coccidioides immitis, Blastomyces species), and other pathogens may produce nonsuppurative joint infection.[15]

Types of prosthetic joint infections

Three major types of prosthetic joint infections exist: (1) those that occur early, within 3 months of implantation; (2) those that are delayed, within 3-24 months of implantation; and (3) those that occur later than 24 months following the implantation. Most cases of early prosthetic joint infection are caused by S aureus, whereas delayed infections are due to coagulase-negative S aureus (CoNS) and gram-negative aerobes. Both of these types are acquired in the operating room. Late cases of prosthetic joint infection are secondary to hematogenous spread from various infectious foci.[16]

See also Pediatric Septic Arthritis, Pediatric Septic Arthritis Surgery, and Septic Arthritis Surgery.

Etiology and Pathophysiology

Organisms may invade the joint by direct inoculation, by contiguous spread from infected periarticular tissue, or via the bloodstream (the most common route).[14]

The normal joint has several protective components. Healthy synovial cells possess significant phagocytic activity, and synovial fluid normally has significant bactericidal activity. Rheumatoid arthritis and systemic lupus erythematosus hamper the defensive functions of synovial fluid and decrease chemotaxis and phagocytic function of polymorphonuclear leukocytes. Patients with deficiencies of the terminal components of complement are susceptible to neisserial bacteremia and joint infections.

Pathogenic invasion

Previously damaged joints, especially those damaged by rheumatoid arthritis, are the most susceptible to infection. The synovial membranes of these joints exhibit neovascularization and increased adhesion factors; both conditions increase the chance of bacteremia, resulting in a joint infection. Some microorganisms have properties that promote their tropism to the synovium. S aureus readily binds to articular sialoprotein, fibronectin collage, elastin, hyaluronic acid, and prosthetic material via specific tissue adhesion factors (microbial surface components recognizing adhesive matrix molecules [MSCRAMMs]). In adults, the arteriolar anastomosis between the epiphysis and the synovium permits the spread of osteomyelitis into the joint space.

The major consequence of bacterial invasion is damage to articular cartilage. This may be due to the particular organism's pathologic properties, such as the chondrocyte proteases of S aureus, as well as to the host's polymorphonuclear leukocytes response. The cells stimulate synthesis of cytokines and other inflammatory products, resulting in the hydrolysis of essential collagen and proteoglycans. Infection with N gonorrhoeae induces a relatively mild influx of white blood cells (WBCs) into the joint, explaining, in part, the minimal joint destruction observed with infection with this organism relative to destruction associated with S aureus infection.

As the destructive process continues, pannus formation begins, and cartilage erosion occurs at the lateral margins of the joint. Large effusions, which can occur in infections of the hip joint, impair the blood supply and result in aseptic necrosis of bone. These destructive processes are well advanced as early as 3 days into the course of untreated infection.

Viral infections may cause direct invasion (rubella) or production of antigen/antibody complexes. Such immunologic mechanisms occur in infections with hepatitis B, parvovirus B19, and lymphocytic choriomeningitis viruses.[15]

Reactive/postexposure process

Reactive, or postexposure, arthritis is observed more commonly in patients with human lymphocyte antigen B27 (HLA-B27) histocompatibility antigens. Although various infections can cause reactive arthritis, gastrointestinal processes are by far the most common. Gastrointestinal pathogens associated with reactive arthritis include the following:

  • Salmonella enteritidis

  • Salmonella typhimurium

  • Yersinia enterocolitica

  • Campylobacter jejuni

  • Clostridium difficile

  • Shigella sonnei

  • Entamoeba histolytica

  • Cryptosporidium

Genitourinary infections, especially those due to Chlamydia trachomatis, are the second most common cause of reactive arthritis. The arthritis of Lyme disease usually results from immunologic mechanisms, with a minority of cases due to direct invasion by an organism.

A reactive/postexposure process may occur months after the gastrointestinal or genitourinary process has resolved.

Local infection

Prosthetic joint infections (PJIs) may be a consequence of local infection, such as intraoperative contamination (60-80% of cases), or of bacteremias (20-40% of cases).[2] The bacteremias may be spontaneous (ie, gingival disease) or secondary to various manipulations. Delayed wound healing is a major factor behind early prosthetic joint infection. Until the fascia has healed, the usual tissue barriers to infection of the implant are not present. Eventually, the implanted hardware becomes less susceptible to infection by hematogenous spread, because the pseudocapsule develops around it.

The biofilm of coagulase-negative S aureus (CoNS) protects the pathogen from the host's defenses, as well as from various antibiotics. Polymethylmethacrylate cement inhibits WBC and complement function.

Overall, the most common organisms of prosthetic joint infections are CoNS (22% of cases) and S aureus (22% of cases). Enteric gram-negative organisms account for 25% of isolates.[17] Streptococci, including S viridans, enterococci, and the beta-hemolytic streptococci, cause 21% of cases. Anaerobes are isolated from 10% of patients.

Other distinctive host and/or situation-pathogen associations have been described, including Pasteurella multocida, Capnocytophaga species (dog and cat bites), Eikenella corrodens, anaerobes (especially Fusobacterium nucleatum and streptococcal species [human bites]), Aeromonas hydrophila (myelogenous leukemia), P aeruginosa, Serratia species, Candida species (particularly common in persons who abuse intravenous drugs), Mycobacterium marinum (water exposure), S schenckii (gardening), and S pneumoniae (sickle cell anemia).

Unlike osteomyelitis, Salmonella species are not associated with the septic arthritis of sickle cell anemia. Ten to 30% of patients with brucellosis have lumbosacral spine involvement.

Prognosis

The primary morbidity of septic arthritis is significant dysfunction of the joint, even if treated properly. Fifty percent of adults with septic arthritis have significant sequelae of decreased range of motion or chronic pain after infection.[1] Thirty percent of cases of reactive arthritis may become chronic. Complications include dysfunctional joints, osteomyelitis, and sepsis.

Predictors of poor outcome in suppurative arthritis include the following:

  • Age older than 60 years

  • Infection of the hip or shoulder joints

  • Underlying rheumatoid arthritis

  • Positive findings on synovial fluid cultures after 7 days of appropriate therapy

  • Delay of 7 days or longer in instituting therapy

The mortality rate depends primarily on the causative organism. N gonorrhoeae septic arthritis carries an extremely low mortality rate, whereas that of S aureus can approach 50%.[18] S aureus is the most common cause of septic arthritis in all age groups. Among those aged 15-50 years, N gonorrhea runs a close second, especially among those who are sexually active.

 

Presentation

History

Because joint infections are uncommon, be especially attentive to features of the patient's history that may indicate an infectious process instead of a primary rheumatologic or orthopedic process.[6]

Pay attention to the following symptoms:

  • Acuteness of onset of the joint pain

  • Whether the pain is superimposed on chronic pain

  • Previous history of joint disease or trauma, whether accidental or iatrogenic (eg, infection complicates 0.4% of arthrocenteses)

  • Whether the process is monoarticular or polyarticular and which joints are involved

  • The presence of extra-articular symptoms

  • Whether the patient has had vascular invasion due to catheterizations or intravenous drug abuse

Obtain a thorough history regarding the possible presence of sexually transmitted diseases (STDs) or exposure to ticks (Lyme disease). The increase of group B streptococcal joint infections is associated with the increased prevalence of diabetes and increasing life expectancy.

Numerous conditions that adversely affect the host's defenses (eg, liver disease, diabetes mellitus, lymphoma, solid tumors, complement deficiencies [C7, C8], immunosuppressive drugs, hypogammaglobulinemia) are increasingly observed in patients with septic arthritis. Determine the possible contribution of these diseases to the clinical presentation.

The most important historical feature is the existence of underlying joint disease, especially rheumatoid arthritis. In addition, the possibility of recent injury to the joint or penetrating or blunt trauma must be explored. Ask the patient about needle aspiration of the joint or injections of corticosteroids into the joint. Elicit a history of diarrheal disease.

Symptoms

Patients with an infected joint typically present with the triad of fever (40-60% of cases), pain (75% of cases), and impaired range of motion. These symptoms may evolve over a few days to a few weeks. Fever is usually low-grade (< 102°F), with rigors present in only 20% of cases. Spiking fevers and chills are much more common with crystalline arthritis.

Lyme disease

Months after infection onset, 60% of patients with untreated Lyme disease develop swelling and pain, chiefly affecting the large joints. Usually, Lyme disease affects 1-2 joints at a time, with the knee involved most commonly. The distinguishing pattern is attacks extending from a few weeks to months and separated by periods of complete remission. The rate of recurrence lessens by about 15% per year. A small percentage of individuals develop chronic arthritis (ie, inflammation of a joint lasting ≥ 1 y). This type of relapsing course almost always precedes the chronic stage of Lyme arthritis.

Prosthetic joint infection

Compared with patients with infections of native joints, most patients with prosthetic joint infection (PJI) exhibit a prolonged low-grade course with gradually increasing pain. However, with gram-negative infections, especially with enteric organisms, PJI may be far more acute in onset.

Usually, no significant fever or swelling occurs (delayed prosthetic joint infection). However, individuals with early prosthetic joint infection present with an acute illness characterized by high-grade fever, focal swelling, and redness. Cellulitis and draining sinus tracts often develop.

Because late prosthetic joint infection is usually secondary to bacteremia, the clinical picture is often dominated by the source of the bloodstream infection.

The nature of the invading organism, the type of tissue infected, and the route of infection determine presentation. Thus, a high index of suspicion is needed for identification of bacteremic and delayed prosthetic joint infection. Because of its many pathogenic mechanisms, S aureus is usually associated with a fulminant course, as opposed to the indolent course of coagulase-negative S aureus (CoNS) that dominates delayed prosthetic joint infection. Relatively devitalized tissues (eg, wound hematomas) are conducive to rapid bacterial replication and a more acute course. Bacteremic spread allows infection with fewer organisms and leads to a more muted course.

Reactive and tuberculous arthritides

Reactive arthritis usually begins several weeks after the underlying infection has resolved. Few concurrent systemic symptoms occur.

Symptoms of tuberculous arthritis are quite indolent; the diagnosis may be delayed for several years. Usually, the purified protein derivative (PPD) results are negative, and no signs, past or present, of pulmonary tuberculous exist.

Viral septic arthritis

Table 1, below, provides a summary of the clinical features of arthritis caused by various viral organisms.

Table 1. Clinical Features of Viral Disease–Associated Arthritis (Open Table in a new window)

Virus

Clinical Features of Viral Disease–Associated Arthritis

Parvovirus B19

Occurs in adult women with erythema infectiosum, often an itchy rash

Hepatitis A

Muscle aches and rash in 10% of cases

Hepatitis B

Onset in the preicteric phase; usually resolves as jaundice develops; chronic arthritis possible in patients with chronic hepatitis B infection

Hepatitis C

History similar to hepatitis B joint infection; usually associated with cryoglobulinemia

Rubella (natural infection and vaccine related)

Onset is possible before, during, or after the appearance of the rash; usually resolves in a few weeks; may recur and, more commonly, may persist

Human immunodeficiency virus [HIV] (2 types occur, both with noninflammatory, sterile joint fluid)

Develops over several days, and severe knee or ankle pain is characteristic; excellent response to nonsteroidal anti-inflammatory agents (NSAIDS)

Sudden onset of severe pain in the shoulders and elbows, closely resembling an acute gouty attack; Opiates often necessary to control pain

Mumps

Occurs in adult men 2 weeks after the presentation of parotitis

Physical Examination

The most commonly involved joint in septic arthritis is the knee (50% of cases), followed by the hip (20%), shoulder (8%), ankle (7%), and wrists (7%). The elbow, interphalangeal, sternoclavicular, and sacroiliac joints each make up 1-4% of cases.

A thorough inspection of all joints for signs of erythema, swelling (90% of cases), warmth, and tenderness is essential for diagnosing infection. Infected joints usually exhibit an obvious effusion, which is associated with marked limitation of both active and passive ranges of motion (ROMs). Frequently, these findings are apparent but may be diminished or poorly localized in cases of infection of the spine, hip, and shoulder joints.[15]

Signs and symptoms of infection may be muted in people who are elderly, who are immunocompromised (especially those with rheumatoid arthritis), and who abuse intravenous drugs.

Pattern of joint involvement

Nongonococcal bacterial/suppurative arthritis

The pattern of joint involvement is an extremely important diagnostic feature. Of cases of nongonococcal suppurative arthritis, 85-90% are monoarticular. If the disease affects more than one joint, S aureus is most commonly implicated. Polyarticular arthritis is usually observed in gonococcal disease, various viral infections, Lyme disease, reactive arthritis, and various noninfectious processes.

Group B streptococci most commonly infect the sacroiliac and sternoclavicular joints.

Gonococcal bacterial/suppurative arthritis

Gonococcal musculoskeletal involvement may present in 1 of 2 ways, as described below.

Fever, arthralgias of multiple joints, and multiple skin lesions (dermatitis-arthritis syndrome) characterize disease that develops soon after the gonococcus disseminates from the cervix, urethra, or pharynx. Usually, this disease exhibits no clinical direct joint findings, but the process is one of tenosynovitis of asymmetric distribution. Typically, hand joints are involved most often, as well as those of the knee, wrist, ankle, and elbow. Skin lesions are multiple but seldom number more than 12, whereas lesions associated with meningococcemia may number more than 100. The lesions evolve over a few days from papular to pustular or vesicular to necrotic. This course may recur for several months. Findings on cultures of blood and mucosal surfaces are often positive; findings on cultures of joint fluid are usually negative. Sixty percent of disseminated gonococcal infections are of this type.

Monoarticular arthritis without associated systemic symptoms, tenosynovitis, or skin lesions characterizes disease that begins later after gonococcal dissemination than does dermatitis arthritis syndrome.[8] Dermatitis-arthritis syndrome may or may not precede this phase. In a joint infected by the Lyme organism, swelling may be disproportionate to the level of pain. Baker cysts are a frequent feature of this type of infectious arthritis. Because the pain of an infected hip joint may not be localized directly and swelling of the joint is inconspicuous, perform specific maneuvers, such as the Fabere maneuver. Infection of the sacroiliac joint often presents as buttock, hip, or anterior thigh pain. Direct pressure usually elicits tenderness in the joint. Alternatively, hyperextension of the hip and leg while the patient is lying down (ie, Gaenslen maneuver) elicits pain in a suppurative sacroiliac joint.

Septic bursitis most commonly involves the olecranon and prepatellar bursae. Swelling and pain are present. However, an infected bursa does not limit the range of motion of the underlying joint the way an actual joint infection does.[19]

Prosthetic joint infections

Physical findings are usually minimal in an infection of the prosthetic joint, and swelling is usually slight. The most distinctive finding is a draining sinus presumed to originate in the underlying infected prosthetic joint.

Reactive, viral, and tuberculous arthritides

Most cases of reactive arthritis involve a few large joints in an asymmetric fashion, whereas viral arthritis usually exhibits symmetric involvement of the smaller joints, especially the hands, with a concurrent rash. The joints of tuberculous arthritis can appear to be boggy on palpation.

 

DDx

Diagnostic Considerations

When evaluating a patient with suspected septic arthritis, also consider conditions such as primary rheumatologic disorders (eg, vasculitis, crystalline arthritides), drug-induced arthritis, and reactive arthritis (eg, postinfectious diarrhea syndrome, postmeningococcal and postgonococcal arthritis, arthritis of intrinsic bowel disease[15] ).

In early disseminated gonococcal infection, an early tenosynovitis predominates without actual joint invasion such as occurs in the later variety of disseminated gonococcal infection. A viral syndrome usually produces polyarticular arthritis. Pustular lesions are consistent (as is almost any type of skin lesion) with staphylococcal bacteremia. Whenever vesicles are present, always consider staphylococcal infection.

Unlike salmonella osteomyelitis, the frequency of salmonella septic arthritis is not greatly increased in patients with sickle cell anemia. However, when septic arthritis does occur, Salmonella is more commonly identified.

Staphylococcus aureus remains the most common infectious agent in people who abuse intravenous drugs. However, a high rate of infections with gram-negative organisms, especially Pseudomonas aeruginosa and Serratia species, occurs in cases of septic arthritis. In addition, a higher rate of fungal and anaerobic infections occurs. Unusual locations, such as the sternoclavicular joint, are involved.

 

Workup

Approach Considerations

An approach to rapid evaluation of an acutely inflamed joint is to screen the synovial fluid for crystals via polarizing microscopy and for organisms via Gram stain (63-96% sensitive). If crystals are present and the Gram stain findings are negative, treatment for crystal-associated arthritis should be initiated. However, an exception to this would be the presence of significant risk factors for infection (eg, the focus of infection lies somewhere that could lead to bacteremia, such as pneumonia or pyelonephritis). Therapeutic decisions cannot be delayed until results of the synovial fluid culture are available.

If microscopy demonstrates no crystals, treat the patient for presumed infection even if the Gram stain findings are negative. The Gram stain has variable sensitivity for detection of bacteria in synovial fluid. Always send the fluid for culture, regardless of the result of the screening evaluation. A joint damaged by gout or pseudogout is prone to be infected. Culture of synovial tissue may be necessary to detect mycobacteria or fungi.

If the patient's condition does not improve significantly after 5 days, the joint must be reaspirated and examined. Most septic joints have a white blood cell (WBC) count that exceeds 50,000/μL, with more than 75% polymorphonuclear leukocytes. However, various sterile inflammatory processes may exhibit the same cellular profile.

Other considerations

The fluid of an infected bursa closely resembles that of a bacterial joint infection.[16]

An elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) is useful in following response to therapy, as well as in detecting an acute process in chronically affected joints.

Measurement of serum uric acid levels cannot be used to establish or negate the diagnosis of uric acid arthropathy. Values may range widely during an acute attack.

Appropriate serologic tests for the diagnosis of various vasculitides or rheumatologic disorders are often indicated.[20]

Obtaining a biopsy of the synovium may be necessary to diagnose one of the many causes (ie, mycobacterial, fungal) of granulomatous synovitis. Examining the synovium histologically often establishes a diagnosis of fungal or mycobacterial joint infections.

Joint Fluid Analysis and Culture

Always perform joint aspiration under the most sterile conditions possible to prevent the introduction of infection.

Normal joint fluid is clear and colorless and produces a stringlike structure when ejected from a syringe, indicating normal viscosity. Infected joint fluid is typically yellow-green due to elevated levels of nucleated cells, and the cell count is usually markedly elevated, demonstrating a predominance of polymorphonuclear leukocytes. An evaluation of the synovial fluid (ie, via leukocyte count, appearance on Gram stain, polarizing microscopy examination, culture) is the most rewarding approach in assessing a potentially infected joint. Additional stains and/or cultures should be obtained depending on the differential diagnosis considered.[9, 21] Alterations in the glucose and protein concentration of the synovial fluid are nonspecific; these should not be measured routinely.

Culture of the synovial fluid or of synovial tissue itself is the only definitive method of diagnosing septic arthritis. Culture results in patients with nongonococcal septic arthritis are almost always positive, unless the patient has received antibiotics before the joint aspiration. Cultures of the joint fluid in gonococcal infections yield positive results in only about 25% of cases. If this diagnosis is suspected, the organism can be cultured from other sites, such as the cervix, urethra, or throat. The effectiveness of standard culture techniques is much more limited in patients with prosthetic joint infection (PJI), probably because of the high rate of antibiotic preadministration prior to arthrocentesis or surgery. If the patient is clinically stable, stop the administration of antibiotics for 2 weeks prior to obtaining cultures and hold for 14 days.

A minimum of 3 and preferably 6 periprosthetic tissue samples should be obtained. Ultrasonication of removed prosthetic material increases the return of cultures, especially in patients who had recently received antibiotics. This technique also helps retrieve organisms that reside in the biofilms that coat the prosthetic material.[22]

If possible, stopping antibiotics for 4 days and holding cultures for 14 days may increase the yield.[23]

In addition, sonication of removed prosthetic material appears to increase the sensitivity of culture, especially in patients who have received antibiotics before surgery.

Lyme disease

Findings from examination of the synovial fluid in Lyme arthritis are similar to those found in infection caused by any other type of bacterium. Positive serology results (ie, antibody measurements, Western blot, polymerase chain reaction [PCR] for Lyme disease) do not establish the diagnosis of Lyme arthritis. A positive result on any of these tests simply indicates that the patient has encountered B burgdorferi; a positive result does not necessarily establish a connection between the patient's musculoskeletal symptoms and Lyme disease.

Silver stains can be used to detect organisms in 5% of cases of Lyme arthritis.

Prosthetic joint infection

Evaluation of a possibly infected prosthetic joint is similar to that of a natural joint.[2, 24] The presence of leukocytes in the aspirated fluid is variable. Because many of the potential pathogens are also classic contaminating organisms (eg, coagulase-negative S aureus [CONS], Propionibacterium species, Corynebacterium species), repeat aspirates are often required to confirm the diagnosis. The use of multiple types of media with prolonged incubation times may increase both the sensitivity and specificity of the culture in prosthetic joint infection. The sensitivity of periprosthetic-tissue culture ranges from 65% to 94%.[19] Material from fistulous tracts is associated with a high rate of contamination and is probably best avoided.

Reactive and tuberculous arthritides

The synovial fluid of reactive arthritis demonstrates few signs of inflammation. PCR may reveal the DNA of the purported causative organism.

The synovial fluid of a joint infected with Mycobacterium tuberculosis shows marked leukocytosis. Although findings on acid-fast stains are usually negative, culture results are positive in 80% of cases. Culture results of synovial biopsies are positive in 94% of specimens.

Blood and Other Cultures

Obtain at least 2 sets of blood cultures to rule out a bacteremic origin of the septic joint.

In the setting of possible gonococcal infection, obtaining cultures from the patient's rectum, cervix, urethra, and pharynx and from any skin lesions is most helpful. Immediate plating of the joint fluid directly onto appropriate media and/or rapid delivery of the specimen to the laboratory for appropriate plating and culturing are of benefit in improving the relatively low yield.[25]

Polymerase Chain Reaction

Polymerase chain reaction (PCR) holds promise for detection of bacterial DNA in joint fluid and synovial tissue. PCR has led to diagnosis of infective arthritis due to Yersinia species, B burgdorferi, Chlamydia species, N gonorrhoeae, and Ureaplasma species. However, caveats concerning this approach are raised, because it cannot be used to distinguish between live and dead organisms and it is susceptible to contamination.

PCR also techniques hold some promise in detecting pathogens in patients who have recently received antibiotics. Unfortunately, many patients receive empirically administered antibiotics before the collection of synovial fluid.

Radiologic Studies

At times, imaging studies may be required to determine the significance of a given culture.

Radiography and ultrasonography

Plain radiography is of limited value in evaluating a joint for infection[18] ; periarticular soft-tissue swelling is the most common finding. This imaging modality is most useful in ruling out underlying osteomyelitis or periarticular osteomyelitis caused by the joint infection itself.

In addition, plain radiography can reveal the linear deposition of calcium pyrophosphate. The radiographic findings of reactive arthritis are usually limited to those of soft-tissue swelling. Periarticular osteoporosis may be detected.

See the x-ray films below.

A 30-year-old man who was taking steroids presente A 30-year-old man who was taking steroids presented with a joint effusion and knee pain. Anteroposterior view of the knee demonstrates patchy demineralization of the tibia and femur and joint-space narrowing. This was caused by tuberculoid infection of the joint.
Septic arthritis. Anteroposterior view of the shou Septic arthritis. Anteroposterior view of the shoulder demonstrates subchondral erosions and sclerosis in the humeral head. These are relatively late findings of septic arthritis. Periosteal reaction due to coincident osteomyelitis is present adjacent to the surgical neck of the humerus.
During the progression of infectious arthritis of During the progression of infectious arthritis of the hip, this image was obtained early in the disease and shows only concentric joint-space loss.

Ultrasonography may be used to diagnose effusions in chronically distorted joints (secondary to trauma or rheumatoid arthritis).

CT scanning, MRI, and radionuclide scanning

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are more sensitive for distinguishing osteomyelitis, periarticular abscesses, and joint effusions. The information gained usually does not justify the increased cost; however, these tests are most helpful in patients with sacroiliac or sternoclavicular joint infection to rule out extension into the mediastinum or pelvis. MRI is preferred because of its greater ability to image soft tissue.

Radionuclide scans (ie, technetium-99m [99m Tc], gallium-67 [67 Ga], indium-111 [111 In] leukocyte scans) are used to nonspecifically localize areas of inflammation. They cannot be used to distinguish infectious from sterile processes. However, radionuclide scans may be of use in diagnosing septic arthritis in relatively sequestered areas, such as the hip and sacroiliac joints.

Imaging in prosthetic joint infection

In prosthetic joint infection [PJI], plain radiography can reveal new subperiosteal bone growth and transcortical sinus tracts.[2] These findings are specific for infection. Arthrography can demonstrate loosening of the prosthesis and abscesses. Nuclear scans of all types are of limited diagnostic use in patients with prosthetic joint infection, and MRIs are limited by the type of implanted material (this diagnostic modality can safely image only titanium or tantalum devices). Fludeoxyglucose-positron emission tomography (FDG-PET) scans may hold some promise in diagnosing lower-extremity prosthetic joint infections. However, this approach cannot differentiate aseptic loosening from infection. Sensitivity and specificity were 87% and 82%, respectively.[26] CT scans are useful in ascertaining the state of the surrounding soft tissue.

 

Treatment

Approach Considerations

Medical management of infective arthritis focuses on adequate and timely drainage of the infected synovial fluid, administration of appropriate antimicrobial therapy, and immobilization of the joint to control pain.

Acute prosthetic joint infection (PJI) (< 3 wk in duration) can be cured medically if it is of the early type or secondary to hematogenous spread without any evidence of periarticular soft-tissue involvement or joint instability.[7]

Overall, the mean length of hospitalization for septic arthritis is 11.5 days. However, outpatient antibiotic therapy in stable patients can significantly reduce hospital stays.[27]

Consultations

In general, obtain a consultation with an orthopedic surgeon or rheumatologist. If the initial treatment response is poor or the etiology of the synovitis remains unknown, consult with an infectious disease specialist.

Antibiotic Therapy

In native joint infections, antibiotics usually need to be administered parenterally for at least 2 weeks. However, each case must be evaluated independently. Infection with either methicillin-resistant S aureus (MRSA) or methicillin-susceptible S aureus (MSSA) requires at least 4 full weeks of intravenous antibiotic therapy. Orally administered antimicrobial agents are almost never indicated in the treatment of S aureus infections.

In MSSA, MRSA, and CoNS prosthetic joint infections in the setting of retained hardware, rifampin should always be used because of its unique ability to penetrate the biofilm in which these pathogens reside.

Gram-negative native joint infections with a pathogen that is sensitive to quinolones can be treated with oral ciprofloxacin for the final 1-2 weeks of treatment. As a rule, a 2-week course of intravenous antibiotics is sufficient to treat gonococcal arthritis.[25] Because of the high worldwide resistance rates to the quinolones (20%-100%), they should be used only when the particular isolate is sensitive to this class of antimicrobial.[28]

In addition, patients with gonococcal arthritis should receive concurrent therapy for chlamydia, such as one dose of 2 g of azithromycin or 7 days of doxycycline twice a week.

Antibiotic selection

Initial antibiotic choices must be empirical, based on the sensitivity pattern of the pathogens of the community. Consider the rise of resistance among potential bacteria when choosing an initial antibiotic regimen. If local incidence of MRSA is high (in particular, marked increase in the resistance of the pneumococcus), prescribe alternate antibiotics initially. Because many isolates of group B streptococci have become tolerant of penicillin, use a combination of penicillin and gentamicin or a later-generation cephalosporin. MRSA is becoming established outside of the hospital setting. Enterobacteriaceae and P aeruginosa are becoming more resistant to multiple antibiotics. Knowing the resistance patterns in the community, as well as in the hospital, is most important.

Preferably, the antibiotic should be bactericidal with some effect against the slow-growing organisms that are protected within a biofilm (eg, coagulase-negative S aureus [CONS]). Rifampin fulfills these requirements; however, this agent should never be used alone because of the rapid development of bacterial resistance to the drug.

If, after 5 days of therapy, the joint shows some degree of improvement, consider an empirical trial of an anti-inflammatory agent. If the joint fails to respond after 5 days of appropriate antibiotic therapy (eg, presence of clinically significant fever, continued synovial purulence, persistently positive findings on culture), reassess the therapeutic approach, as follows:

  • Reculture the fluid and reexamine for crystals

  • Perform appropriate serologies for diagnosis of Lyme disease; if these are positive, treat per current guidelines

  • If fungal or mycobacterial infection is possible, consider obtaining a synovial biopsy

  • Consider the possibility of reactive arthritis; nonsteroidal inflammatory agents (NSAIDs) are the primary therapeutic agents for reactive arthritis

  • Perform imaging studies, either radiographs or magnetic resonance imaging (MRI), to rule out periarticular osteomyelitis.

Antibiotics have a role in suppressing associated chronic osteomyelitis and chronically infected prosthetic material that cannot be removed for various reasons.

The use of fluoroquinolones for an extended period should be considered when the removal of an infected prosthesis is not possible. Cure rates as high as 62% have been documented in relatively small series. Generally, such prolonged therapy is seen as suppressive and not curative.[29]

Oral antibiotics are usually used in treating gonococcal joint infections.

Joint Immobilization and Physical Therapy

Usually, immobilization of the infected joint to control pain is not necessary after the first few days. If the patient's condition responds adequately after 5 days of treatment, begin gentle mobilization of the infected joint. Most patients require aggressive physical therapy to allow maximum postinfection functioning of the joint.

Initial physical therapy consists of maintaining the joint in its functional position and providing passive range-of-motion exercises. The joint should bear no weight until the clinical signs and symptoms of synovitis have resolved. Aggressive physical therapy is often required to achieve maximum therapy benefit.

Synovial Fluid Drainage

The choice of the type of drainage, whether percutaneous or surgical, has not been resolved completely.[20, 30] In general, use a needle aspirate initially, repeating joint taps frequently enough to prevent significant reaccumulation of fluid. Aspirating the joint 2-3 times a day may be necessary during the first few days. If frequent drainage is necessary, surgical drainage becomes more attractive.

Gonococcal-infected joints rarely require surgical drainage.

Surgical drainage is indicated when one or more of the following occur:

  • The appropriate choice of antibiotic and vigorous percutaneous drainage fails to clear the infection after 5-7 days

  • The infected joints are difficult to aspirate (eg, hip)

  • Adjacent soft tissue is infected

Routine arthroscopic lavage is rarely indicated. However, drainage through the arthroscope is replacing open surgical drainage. With arthroscopic drainage, the operator can visualize the interior of the joint and can drain pus, debride, and lyse adhesions.

Surgical Intervention in Prosthetic Joint Infection

Debridement and retention of the prosthesis should be considered in patients who develop prosthetic joint infection within 30 days of implantation or who present within 3 weeks of the development of symptoms if the prosthesis appears to be well fixed and is without a sinus tract.[22]

First, remove the prosthesis and follow with 6 weeks of antibiotic therapy. Then, place the new joint, impregnating the methylmethacrylate cement with an anti-infective agent (ie, gentamicin, tobramycin). Antibiotic diffusion into the surrounding tissues is the goal. The success rate for this approach is approximately 95% for both hip and knee joints.

An intermediate method is to exchange the new joint for the infected joint in a 1-stage surgical procedure with concomitant antibiotic therapy. This method, with concurrent use of antibiotic cement, succeeds in 70-90% of cases.

Infection Prevention

Strictly adhere to sterile procedures whenever the joint space is invaded (eg, in aspiration or arthroscopic procedures).

Antibiotic prophylaxis with an antistaphylococcal antibiotic has been demonstrated to reduce wound infections in joint replacement surgery. Polymethylmethacrylate cement impregnated with antibiotics may decrease perioperative infections.

Using antibiotic prophylaxis on the same theoretic basis as that for cardiac valvular disease has been advocated. Whenever a sustained bacteremia may be encountered, be aware of the possibility of joint involvement, especially for prosthetic joints. Consideration should be given to more prolonged treatment of the bacteremia to cover the possibility of very early joint infection (secondary prophylaxis). The implanted hardware most likely is at greatest risk of bacteremia infection within a few months of placement. The risk probably decreases as a pseudocapsule evolves. During this time, prophylaxis is probably most beneficial. A recent well-designed study refutes the recommendation that all joint replacement patients require antibiotic prophylaxis prior to dental procedures.[31]

Treat any infection promptly to lessen the chance of bloodstream invasion. In addition, decreasing the incidence of underlying infections best prevents reactive arthritis.

Patient education

Instruct patients with a prosthetic joint in place to recognize early signs of joint infection and, more importantly, to recognize bacterial infections in other parts of their bodies to prevent associated bacteremias.

For patient education information, see Arthritis Center as well as Knee Pain and Ticks.

 

Medication

Medication Summary

The empirical choice of antibiotic therapy is based on results of the Gram stain and the clinical picture and background of the patient. When the Gram stain fails to reveal any microorganisms (40-50% of cases), the individual's age and sexual activity become the major determinants to differentiate gonococcal from nongonococcal arthritis. When no evidence suggests infection elsewhere, antibiotics must cover S aureus, streptococcal species, and gonococci (in patients who are sexually active).

Evidence shows that earlier initiation of an appropriate antibiotic regimen produces better functional results. Generally, treatment is administered intravenously for 3-4 weeks. The major exception to this is in the case of joints with gonococcal infection, for which total therapy is approximately 2 weeks, with switch to oral therapy. No indication exists for direct installation of antibiotics into the joint cavity. Such practice may increase the degree of inflammation.

Antibiotics

Class Summary

Antibiotic therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. The use of linezolid with or without rifampin should be considered for staphylococcal prosthetic joint infection (PJI).

Note: After a period of unavailability, oral cefixime is again US Food and Drug Administration (FDA)–approved in tablet and suspension formulations.[32, 33] Wyeth Pharmaceuticals (Collegeville, Pa) discontinued manufacturing Suprax in the United States. In October 2002, the company ceased marketing cefixime tablets (200 mg and 400 mg) because of depletion of company inventory. Wyeth's patent for cefixime expired on November 10, 2002. However, cefixime 400-mg tablets became available again in the US in April 2008. Lupin Pharmaceuticals received FDA approval to manufacture and market oral cefixime (table and suspension formulations) in February 2004.

Ceftriaxone (Rocephin)

Ceftriaxone is the drug of choice (DOC) against N gonorrhoeae. This agent is effective against gram-negative enteric rods. Monitor sensitivity data.

Ciprofloxacin (Cipro)

Ciprofloxacin is an alternative antibiotic to ceftriaxone to treat N gonorrhoeae and gram-negative enteric rods.

Cefixime (Suprax)

Cefixime is a third-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, this agent arrests bacterial cell wall synthesis and inhibits bacterial growth.

Oral cefixime is used as a follow-up to intravenous (IV) ceftriaxone to treat N gonorrhoeae.

Note: After a period of unavailability, oral cefixime is again US Food and Drug Administration (FDA)–approved in tablet and suspension formulations. Wyeth Pharmaceuticals (Collegeville, Pa) discontinued manufacturing Suprax in the United States. In October 2002, the company ceased marketing cefixime tablets (200 mg and 400 mg) because of depletion of company inventory. Wyeth's patent for cefixime expired on November 10, 2002. However, cefixime 400-mg tablets became available again in the US in April 2008. Lupin Pharmaceuticals received FDA approval to manufacture and market oral cefixime (table and suspension formulations) in February 2004.

Oxacillin

Oxacillin is useful against methicillin-sensitive S aureus (MSSA).

Vancomycin (Vancocin)

Vancomycin is an anti-infective agent used against methicillin-sensitive S aureus (MSSA), methicillin-resistant coagulase-negative S aureus (CONS), and ampicillin-resistant enterococci in patients allergic to penicillin.

Linezolid (Zyvox)

Linezolid is an alternative antibiotic that is used in patients allergic to vancomycin and for the treatment of vancomycin-resistant enterococci.

 

Questions & Answers

Overview

What is septic arthritis?

What is the incidence of septic arthritis?

Which groups are at highest risk for septic arthritis?

What are the most common causes of septic arthritis?

What is the prevalence of septic arthritis caused by streptococcal species?

What is the role of polymicrobial joint infections (PJI) in the etiology of septic arthritis?

What are the types of prosthetic joint infection (PJI)?

What is the pathogenesis of septic arthritis?

Why are previously damaged joints more susceptible to septic arthritis?

What is the pathophysiology of joint destruction in septic arthritis?

What is the role of viral infections in the pathogenesis of septic arthritis?

Which GI pathogens associated with reactive arthritis?

Which infections cause of reactive arthritis?

How do prosthetic joint infections (PJIs) lead to septic arthritis?

What is the role of coagulase-negative S aureus (CoNS) in the etiology of septic arthritis?

Which prosthetic joint infections (PJIs) cause septic arthritis?

What are situation-pathogen associations for septic arthritis?

What are the morbidities of septic arthritis?

Which factors are predictors of poor outcome in septic arthritis?

What is the mortality rate for septic arthritis?

Presentation

What should be the focus of history in suspected septic arthritis?

What are the signs and symptoms of septic arthritis?

Which conditions in a patient’s history increase the likelihood of septic arthritis?

What are possible comorbidities of septic arthritis?

What is the most important historical feature in septic arthritis?

What is the typical presentation of septic arthritis?

What is the presentation of Lyme disease-caused septic arthritis?

What is the presentation of prosthetic joint infection (PJI) septic arthritis?

What are the signs and symptoms of reactive arthritis?

What are the symptoms of tuberculous septic arthritis?

What are the clinical features of viral septic arthritis?

What is the most commonly involved joint in septic arthritis?

What physical findings suggest septic arthritis?

In which patients can signs and symptoms of septic arthritis be muted?

What is the significance of the pattern of joint involvement in the diagnosis of septic arthritis?

Which joints are most commonly infected in GBS septic arthritis?

What is the presentation of gonococcal musculoskeletal involvement in patients with septic arthritis?

What are the physical findings of septic arthritis caused by prosthetic joint infections (PJIs)?

How are reactive, viral, and tuberculous arthritis differentiated?

DDX

Which conditions should be considered in the differential diagnoses of septic arthritis?

What is characteristic of early disseminated gonococcal infection?

What is the frequency of salmonella septic arthritis in patients with sickle cell anemia?

What is the most common cause of septic arthritis among IV drug users?

Workup

When is reaspiration indicated in the evaluation of septic arthritis?

What is the initial screening method for septic arthritis?

What is the role of microscopy in screening for septic arthritis?

Which lab tests may be useful in the evaluation of septic arthritis?

What is the role of joint aspiration in the diagnosis of septic arthritis?

What is the role of synovial fluid culture in the diagnosis of septic arthritis?

Which synovial fluid findings are characteristic of Lyme septic arthritis?

How are prosthetic joint infections (PJIs) evaluated for septic arthritis?

Which synovial fluid findings suggest reactive arthritis?

Which synovial fluid findings suggest tuberculous septic arthritis?

What is the role of blood cultures in the diagnosis of septic arthritis?

What is the role of PCR in the diagnosis of septic arthritis?

What imaging findings suggest prosthetic joint infection septic arthritis?

What is the role of imaging studies in the diagnosis of septic arthritis?

What is the role of radiography in the diagnosis of septic arthritis?

How is ultrasonography used to diagnose septic arthritis?

How are CT scanning and MRI used to diagnose septic arthritis?

What is the role of radionuclide scanning in the diagnosis of septic arthritis?

Treatment

What is the focus of medical management of septic arthritis?

When is a medical cure for acute prosthetic joint infection (PJI) septic arthritis most likely?

What is the typical length of inpatient treatment for septic arthritis?

What specialist consultations are indicated for the treatment of septic arthritis?

What are the treatment options for native joint infections of septic arthritis?

When is rifampin indicated in the treatment of septic arthritis?

What are the treatment options for gram-negative joint infections of septic arthritis?

How is gonococcal arthritis treated?

What is the basis for antibiotic selection in the treatment of septic arthritis?

What are the treatment options for septic arthritis if antibiotic therapy fails?

What is the role of antibiotics in the management of septic arthritis?

What is the role of fluoroquinolones in the treatment of septic arthritis?

When are oral antibiotics used to treat septic arthritis?

What is the role of joint immobilization in the treatment of septic arthritis?

What is included in physical therapy for septic arthritis?

How is synovial fluid drainage performed in the treatment of septic arthritis?

What is the role of surgical drainage for gonococcal-infected joints in patients with septic arthritis?

When is surgical drainage indicated for treatment of septic arthritis?

What is the role of arthroscopic lavage in the treatment of septic arthritis?

What is the role of debridement in treatment of septic arthritis?

How is debridement and retention of prosthesis performed in patients with septic arthritis?

What is the intermediate method for debridement and retention of prosthesis in septic arthritis?

How can infections of joint replacements be prevented?

What information about septic arthritis should patients receive?

Medications

How are medications selected for the treatment of septic arthritis?

Which medications in the drug class Antibiotics are used in the treatment of Septic Arthritis?