Bacterial arthritis is a serious infectious disease with significant morbidity and mortality¹. If not recognized early, it can produce a crippling condition, particularly in the elderly or in patients with preexisting joint disease (i.e. rheumatoid arthritis)² . Of the acute inflammatory arthritides, bacterial arthritis is the most serious; its incidence has not decreased during the past few decades, despite improvements in antibiotic therapy. Severe joint destruction from bacterial arthritis is seen in patients with infections from virulent bacterial species, as well as in those who receive insufficient treatment or delayed diagnosis³ . Therefore, early diagnoses and rapid initiation of therapy is crucial to avoid unnecessary joint damage or even death⁴.

Acute septic arthritis is uncommon and despite frequent hematogenous dissemination, the majority of cases of bacterial arthritis involve only one joint^1,5. In nongonococcal bacterial arthritis only 10-20% of adults have polyarticular involvement^2,4,5,6. The average age at diagnosis of nongonococcal septic arthritis is 55 with 40% of patients over 60 years of age⁷ . Significantly, the occurrence of acute infectious arthritis is relatively unchanged over the last several decades^3,8.

The majority of cases of bacterial arthritis occur via hematogenous spread of bacteria to the joint from a distant site. Bacteria may also infect a joint via a deep penetrating wound, arthrocentesis, arthroscopy, prosthetic joint surgery, or via the extension of adjacent osteomyelitis, cellulitis and abscesses^9,10. Development of joint infection is a complex interaction of factors including the integrity of the joint, the host’s resistance to infection, the duration of bacteremia, and the virulence of the microorganism¹¹.

Synovial tissue is highly vascularized and lacks a basement membrane, thus allowing easy access of blood contents into the synovial space¹² . The inflammatory process of acute septic arthritis starts within the synovium. Intracapsular inflammation with synovial proliferation and an exudate or transudate of fluid may distend the joint capsule, causing laxity, subluxation, or dislocation⁵. This build-up of joint fluid results in increased intraarticular pressure. The increased pressure and the presence of proteolytic enzymes released by the accumulation of polymorphonuclear leukocytes in the joint space causes destruction of the articular cartilage, then the surrounding bone⁵ .

Causes of cartilage destruction.

Invasion of microorganisms

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Intracapsular inflammation

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Build-up of joint fluid

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Increased intraarticular pressure

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Proteolytic enzyme release

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Destruction of articular cartilage

Gonococcal disease is the most common cause of septic arthritis in the 15-40 year old age group (accounting for approximately 94% of the cases of septic arthritis). In those younger than 15 or older than 40, gonococci accounts for 13% of the cases of septic arthritis, while 87% are attributed to other organisms⁴. Excluding gonococcal arthritis, infections due to gram positive microorganisms, especially those caused by Staph aureus, are the most frequently encountered articular infections^8,9. According to one source, approximately 75% of nongonococcal cases of arthritis are due to gram positive cocci, and 20% of cases are due to gram negative bacilli¹³. Infections due to gram negative bacilli occur primarily in patients with malignancies, medical immunosuppression, underlying chronic debilitating diseases, prior noninfectious joint disease or a history of intravenous drug and/or narcotic abuse⁹. For example, Serratia and Pseudomonas species have been found with increasing frequency in heroin addicts with septic arthritis. Anaerobic joint infections appear to be uncommon but have been reported in patients with predisposing factors such as prosthetic devices, diabetes mellitus and rheumatoid arthritis. Prosthetic joint infections can be caused by a wide variety of bacteria, with Staph aureus and Staph epidermidis involved in more than half of the cases⁴.

In reviewing the literature, it appears that the distribution of causative organisms is relatively the same for both monoarticular and polyarticular septic arthritis (MASA and PASA, respectively) - with Staph aureus being the most frequently isolated microorganism in both. Pneumococcus, group G streptococcus and Haemophilus influenzae, however, appear to have an increased association with polyarticular infection¹. Infections caused by anaerobic or gram negative microorganisms appear to be less frequently associated with polyarticular infection¹. In comparing cases of PASA caused by S. aureus, Strep and gram negative bacilli, no difference was noted in the frequency of fever, leukocytosis or positive blood cultures. It was found that rheumatoid arthritis was more common in patients with PASA caused by S. aureus than in the other two groups, and that S. aureus PASA required surgery more often and had a higher death rate. An association was also observed between patients with lupus and an increased occurrence of gram negative PASA⁷ .

To begin, a careful history is important in identifying a primary site of infection elsewhere. Concurrent extraarticular infections (i.e. skin and soft tissue infections, UTI and infective endocarditis) place patients (especially older patients) at increased risk¹¹. A history of trauma or skin infection is a significant risk factor for joint infections caused by Staph¹⁴. This is likely due to the propensity of this bacteria to colonize the broken skin. Skin lesions have become less prominent as a source in recent years, likely due to earlier use of antibiotics and improved wound care. The duration of symptoms may also give some clue to the etiology. Symptoms of bacterial infections are usually recent (within days of presentation) while patients with mycobacterial or fungal infections often report symptoms that have been present for months or even years¹. The presence of risk factors (i.e. IV drug and narcotic use, immunosuppressive disease or therapy, rheumatoid arthritis, or the presence of a prosthetic joint) are also key in determining possible microbial etiology and in initiating appropriate therapy and treatment modalities⁴.

Important factors to consider when taking a history⁴.

• Extraarticular infections
• Duration of symptoms
• Joint trauma
• Intravenous drug/narcotic abuse
• Impaired host defense mechanism
• Immunosuppressive dz or therapy
• Arthritis
• Surgical manipulation

Host-bacteria interactions are important in understanding why septic arthritis develops in certain people, whereas most bacteremias do not result in a septic joint¹⁰. Specific host factors can predispose a patient to recurrent bacteremia and further development of septic arthritis, or may interfere with the body’s ability to eradicate a deep-seated infection. Common conditions in which an impaired host defense mechanism is present include hypogammaglobulinemia, cancer, chronic liver disease, immunosuppresive drugs, rheumatoid arthritis, and serious or chronic underlying illnesses such as diabetes mellitus, chronic renal failure, and alcoholism¹⁰. Rare conditions include chronic granulomatous disease and Chediak-Higashi syndrome, which impair phagocytic function^5,10.

Age is important to consider due to the increased prevalence of both preexisting comorbidities and impaired immunological response often found in the elderly⁴. In addition to an aging population, several other factors have led to an increase in the number of immunosuppressed patients being cared for in recent years⁹. These factors include the AIDS epidemic, an increase in the number of individuals receiving organ transplants and the increase in use of immunosuppressants for the treatment of nonmalignant disorders (i.e. lupus, rheumatoid arthritis, etc.).

Arthritis is also an important risk factor for developing bacterial arthritis¹⁰. Any form of chronic arthritis may predispose the joint to bacterial infection, but rheumatoid arthritis has received the most attention. This is due to a number of factors which may predispose patients with rheumatoid arthritis to bacterial arthritis¹⁵. These include the therapeutic use of corticosteroids and/or cytotoxic drugs. Other defects, such as decreased chemotaxis and phagocytosis of synovial fluid neutraphils, depressed hemolytic complement levels, and decreased bacteriolytic activity of synovial fluid also lead to an impairment of normal host defenses. Rheumatoid joints are also more prone to hematogenous infection, which is probably secondary to increased vascularity in the setting of synovial tissue hypertrophy and pannus formation¹⁵. A joint characterized by chronic rheumatoid inflammation and granulation tissue serves as an excellent site for bacterial infection¹⁶.

The etiology of the septic process can also include surgical manipulation¹⁷. This includes arthroscopy, arthrocentesis and prosthetic joint placement, replacement or repair. The frequency of early prosthetic infections has decreased, however, as a result of better surgical techniques, improved air flow in the operating room, and perioperative use of cephalosporins. It has been proposed to prophylax these patients during procedures in which bacteremia is likely to occur (i.e. dental, urological procedures) - as is done in patients with prosthetic valves - to prevent late infections (those occurring more than one year after placed)⁹ . This idea has not been universally accepted, however. Infection occurs in 1-4% of the prostheses followed for 10 years and more frequently after revision of a previous total joint replacement¹³. Arthroscopy, an alternative to open surgery, may also serve as a point of entry for joint infections. The frequency of postarthroscopic bacterial arthritis has not been clearly established, but it has been estimated to be approximately 1% or even less with the small needle arthroscope⁹.

• Joint inflammation
• Decreased ROM and or pain in joint(s)
• Specific joints involved
• Fever
• Tenosynovitis
• Skin rashes
• Heart murmur

The majority of patients with bacterial arthritis will present with limitation of and pain on motion, usually severe and incapacitating, in a single joint^2,9. The knee is the most frequently affected joint, followed by the hip, shoulder, wrist, and ankle^7,14,18 . The frequency and severity of systemic or constitutional complaints varies¹¹. Not all patients present with the classic syndrome. Bacterial arthritis often occurs in severely ill elderly patients who may not be able to mount a systemic inflammatory response⁹. Furthermore, many of the usual focal signs of inflammation (erythema, swelling and tenderness) may not be present in patients who are immunosuppressed by disease or chemotherapy⁴ . Fever is present in the majority of patients with septic arthritis, but mostly only low-grade⁴ . In fact, the largest series of PASA to date found that 20% of the 25 patients studied had no fever at all⁷. Specific joint involvement may also help in determining likely pathogens. For example, infections of the interphalangeal joints of the hands are rare except after animal bites or when Neisseria gonorrhoeae or Mycobacterium tuberculosis are the underlying pathogens. Infections involving the sacroiliac and sternoclavicular joints occur primarily in IV drug abusers, who are at increased risk for developing gram negative bacterial arthritis². Polyarticular joint involvement can occur in any bacteremia, but is particularly prevalent in Staph and gonococcal infections⁴. Tenosynovitis may be seen as a common manifestation of gonococcal disease. Skin rashes are also important to note, especially if disseminated gonococcal disease is being considered as a possible diagnosis. The presence of a heart murmur or other peripheral manifestations (i.e. splinter hemorrhages, Osler nodes, or Janeway lesions) is also significant, given that septic arthritis can originate from infective endocarditis.

Once the suspicion of septic arthritis has been raised from the history and physical examination, the key to diagnosis is immediate aspiration and proper analysis of the synovial fluid¹⁰. Examination of the synovial fluid (SF) is the most important test and it, along with bacterial cultures, has the greatest diagnostic value^6,19.

Diagnostic and treatment algorithm for nongonococcal bacterial arthritis.

The table below outlines the specific characteristics of synovial fluid in pyogenic and inflammatory arthritis⁴. In septic arthritis, the synovial fluid leukocyte count is usually greater than 50,000 with greater than 75% of polymorphonuclear leukocytes present. This finding is not specific for bacterial arthritis. The synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis, and crystalline joint disease may also appear similar². The absence of fluid leukocytosis and polymorphonuclear cell predominance does not exclude septic arthritis. This can occur in an immunocompromised host or if the joint is aspirated early in the course of the infection^20,21. Given the wide variability of leukocyte counts which can occur, it is imperative to obtain a gram stain and culture of the synovial fluid for diagnostic purposes⁴ . In reviewing the literature, studies revealed that gram stains were positive in approximately 75% of patients with staphylococcal infections and 50% of those with gram negative bacilli, but in less than 25% of patients with gonococcal arthritis². In contrast, synovial fluid cultures were noted to be positive in most patients (approximately 90%) with nongonococcal bacterial arthritis, unless the patient had recently taken antibiotics^2,10,13,22. Of note, in patients with polyarticular involvement, all joints should be tapped⁹. Other tests, such as bacterial antigen detection, have been proposed as a rapid diagnostic tests for certain etiologic agents. The above mentioned test successfully detects antigens of Haemophilus influenzae Type B, Strep pneumonia, group B strep, and Neisseria meningitidis.^4,13 . Although controversial, measurements of D-lactic acid level have also been used experimentally as a diagnostic indicator for bacterial arthritis, but this test is not used clinically.

Other studies have been performed to evaluate the utility of polymerase chain reaction(PCR) amplification in the molecular diagnosis of venereal-associated arthritis (this includes arthritis caused by N. gonorrhoeae, Chlamydia, and Ureaplasma). While additional studies are needed to further evaluate the clinical applicability of PCR in these diseases, this technique may allow earlier diagnosis and provide an objective measure as to the efficacy of antibiotic therapy in patients with venereal-associated arthritidies²³.

Measure Normal Inflammatory Septic

Clarity Transparent Translucent-opaque Opaque

Color Clear Yellow-opalescent Yellow-Green

WBC/mm³ <200 2,000->50,000 >50,000

Polymorphonuclear <25% ³ 50% ³ 75%

leukocytes

Culture Negative Negative Often positive

Peripheral blood leukocytosis is relatively common (ranging from 45-75% of cases depending upon the study) in patients who present with bacterial arthritis^9,19,21. The majority of elderly patients with infected joints had a leukocytosis, although normal leukocyte counts and leukopenia can occur¹¹. Leukocytosis may also be absent in immunosuppressed patients or in patients with a prosthetic joint²⁰ .

If medical attention is sought early in the illness, a source of bacteremia is usually identified and the causative microorganism can be isolated from the blood in approximately 50% of the cases^5,9,13. It also appears that blood cultures are more often positive in patients with PASA than in those with MASA. Any potential source of bacteremia must be cultured and may provide the only positive microbial identification, especially in disseminated gonococcal infections. Common sites of positive cultures include urine in arthritis caused by gram negative bacilli, sputum in pneumococcal arthritis, and skin in staphylococcal arthritis.

Duration of the infection is very important in accurately diagnosing bone and joint infections radiographically¹⁹. Radiographs have limited diagnostic value early in the infectious process⁴ . The only findings that are expected on initial evaluation are distention of the joint capsule and periarticular soft tissue swelling. Early films are useful for establishing a baseline for subsequent evaluation¹³. Destructive changes and/or changes in contiguous bony structures are rarely observed before the second to third week of untreated infection^4,13 . By this time in the course of the infection, juxtaarticular osteoporosis, bony erosions of the articular surface, and joint space narrowing due to cartilage destruction may be apparent¹³. CT and MRI are also used and can reveal extensive bony involvement and parasynovial abscesses when conventional x-rays are negative¹³. A CT scan is helpful if infection is suspected in the sacroiliac or sternoclavicular joints. According to one study, an MRI is the method of choice in patients with acute sudden onset of hip pain in which a deep seated infectious process is suspected⁹. Radioisotope scans can also provide evidence of septic arthritis when the plain radiograph may appear normal or show only soft tissue swelling¹³.

A synovial tissue biopsy may be indicated in patients with chronic, undetermined processes in which synovial fluid analysis and routine studies and cultures have not been helpful in determining the diagnosis. A biopsy is particularly helpful in cases of mycobacterial infections⁴.

Diagnosis of Bacterial Arthritis

• Immediate joint-fluid aspirations

• Blood culture positive
• Positive cultures from other possible sites of infection

• Peripheral blood leukocytes
• Antigen determination (fatty acid or cell-wall antigen)
• Radionuclide scans
• X-ray films (loosening of prosthetic joint)
• Synovial fluid leukocyte count markedly elevated

The main principles of treatment in septic arthritis include antimicrobial therapy, drainage of the joint fluid, and early immobilization. Intraarticular antibiotic injections are not required since parenteral antibiotics easily reach bactericidal concentrations in the synovial fluid. If the gram stain does not reveal the causative organism, the antimicrobial regimen should be tailored to cover the most likely pathogens. Treatment regimens to cover both gram positive and gram negative organisms are indicated in the very sick patient while awaiting specific identification of the causative organism⁹ . Therapy with vancomycin should be reserved for patients who have a very high likelihood of MRSA infection. Otherwise, a penicillinase-resistant penicillin is the drug of choice. Gram negative organisms are usually well-covered with a first or third generation cephalosporin or an aminoglycoside.

The duration of therapy varies depending on the age of the patient, their underlying clinical condition, the causative organism, and the patient's response to the therapy. Most older patients require a minimum of at least two weeks of IV therapy and often are treated for as long as six weeks¹¹. For arthritis due to Haemophilus influenzae, Strep or gram negative cocci, two weeks of IV therapy is recommended. In contrast, infections caused by Staph or gram negative bacilli require three to six weeks of IV therapy^2,5,11,24. Serial synovial fluid counts are important in monitoring the patient's response to therapy. Repeated aspirations of the joint are the preferred method of joint drainage⁸. Open drainage is required, however, if repeated needle aspirations fail to improve the patient's symptoms, the fluid is too thick and loculated, the debridement or removal of necrotic synovial tissue or bone is necessary, or if the joint is not accessible to repeated needle drainage (i.e. deep sites such as the shoulder, hip, and sacroiliac joint)¹¹. Drainage not only permits relief of pressure within the joint space, but also removes enzymes and toxins. This reduces the risk of further joint damage secondary to ischemic changes or chondrolysis¹¹. Drainage of acidic, purulent fluid also improves the bactericidal activity of neutraphils. During the acute phase of infection, the joint should be immobilized in a position that minimizes capsular tension¹³. Prolonged immobilization, however, has been proven to be detrimental. It is important to begin passive range of motion to the affected joint early to preserve joint function. When clinical symptoms permit and inflammation has almost cleared, active motion and weight-bearing should be initiated.

Although some patients with bacterial arthritis recover and experience no long term effects, certain clinical findings are associated with a poor outcome². Prognosis depends on multiple variables, including: the affected individuals (taking into consideration age, comorbidities, medications), the number of joints involved, the organism and its virulence, the length of time to diagnosis, and the presence of bacteremia^9,25.

• Age >60 years
• Preexisting (rheumatoid) arthritis and/or presence of other comorbidities
• Involvement of multiple joints
• Patients with Staph aureus as a causative organism
• Duration of symptoms before treatment ( ³ 1 week)
• Bacteremia

The death rate of septic arthritis in the general adult population has remained stable over the last several decades, with mortality averaging 10%. In contrast, the mortality rate for elderly patients with joint infection increases to as much as 33% in one study¹¹. Older patients also experience a worse prognosis in terms of the number of complications present (i.e. loss of joint function and increased duration of immobility)¹¹.

Patients on immunosuppressive medications or with underlying chronic illnesses (i.e. diabetes mellitus, neoplasm, or chronic liver disease) have an increased mortality (noted to be greater than 20% in some studies)²⁴. As noted earlier, recent studies which have focused largely on rheumatoid arthritis have shown that damaged joints are more susceptible to infection. Thus, any form of chronic arthritis may predispose the joint to bacterial infection¹⁰.

One of the most important prognostic indicators is the number of joints involved. Case fatality rates are much higher in individuals with polyarticular involvement (25-30%) than those with monoarticular infections (4-9%)^1,2,7,25. An even higher death rate (up to 56%) has been shown when patients have polyarticular infection superimposed on rheumatoid arthritis^1,7 .

Staph aureus as causative organism

Patients with Staph aureus as the causative organism also had a more unfavorable outcome⁷. Staph aureus produces a large number of virulence factors which enable the organism to establish infection and enhance its potential to cause disease^24,26. This organism is capable of producing infection through either tissue invasion and destruction or the production of toxins that mediate disease²⁷.

The collagen binding protein is an important virulence factor that acts as an adhesin that mediates the attachment of Staph aureus to cartilage^28,29,30. Once it is attached, chondrocyte proteases are produced that hydrolyze the synovial tissue⁴. Other factors, such as capsular polysaccharide and protein A, may assist in avoidance of phagocytosis following adherence, but this remains unclear. After infection of the synovial membrane, there is an influx of polymorphonuclear leukocytes that result in the release of enzymes that are destructive to the articular surface. In the absence of appropriate treatment, the cartilage erodes and the joint space narrows^4,26.

The duration of symptoms prior to diagnosis correlates positively with the length of time serial cultures of synovial fluid remained positive after the initiation of treatment¹⁹. Therefore, delay in diagnosis leads to a slower response to treatment and increases the likelihood of a poor outcome²⁵. The sooner the diagnosis is established and appropriate treatment initiated, the better the likelihood of survival and joint preservation⁹.

In patients with septic arthritis, a positive blood culture has been found to be related to a higher mortality. This was believed to be due to the association of a positive blood culture with the increased likelihood of the presence of a generalized infection and the increased possibility of other focuses of infection.

The incidence of bacterial arthritis has remained relatively unchanged over the last several years, and should be suspected in any patient who presents with a swollen joint. This is particularly true in the elderly and those with associated risk factors. Any delay in diagnosis and the initiation of treatment can lead to unnecessary joint destruction and even death.

Nongonococcal Bacterial Arthritis in Adults Treated at Boston University Medical Center, 1965 to 1982*

*Patients with Osteomyelitis or prosthetic joints are not included.