Arthritis is the most common cause of disability in adults.1 While the substantial pain and disability caused by this disease are major factors in limiting quality of life, arthritis is often undiagnosed and undertreated.2 Infectious arthritis (IA), also referred to as septic arthritis, is a condition in which one or more offending organisms directly invade the synovial or periarticular tissues.3,4 IA is considered a potentially serious condition since the infection may have the ability to cause rapid destruction of the joint and result in permanent deformities.3 While this microorganism invasion of the joint space is most commonly caused by a variety of bacteria, other organisms that have been implicated include viruses, mycobacteria, and fungi.4
IA usually affects a joint that has already been compromised by disease, typically osteoarthritis or rheumatoid arthritis (RA).5 Additionally, because of the increase in prosthetic-joint surgery, infection secondary to these device implantations has become the most common and challenging type of IA encountered by most clinicians.6 In the acute form of IA, there is rapid onset of joint pain, heat, redness, swelling, and effusion (fluid accumulation), and joint restriction of both active and passive motion occurs, with these symptoms usually affecting a single joint, a pattern referred to as monoarticular.7-9 Prompt recognition and immediate and effective therapeutic management, including IV antibiotics, prevent rapid joint destruction.3,5
Seniors at Risk
The risk of developing IA increases with advancing age, and this condition is becoming more common among the elderly and individuals who are immunosuppressed.5 Among people with IA, 45% are older than 65 years of age and 56% are male.4 Among all prosthesis recipients, the incidence of prosthetic joint infection ranges from 2% to 10%.4 The elderly and immunosuppressed are more likely to have a variety of serious comorbidities that predispose an individual to IA, including diabetes mellitus, RA, systemic lupus erythematosis (SLE), malignancy, and hemodialysis.5 Patients with chronic lung or liver disease, anemia, sickle cell disease, and hemophilia are also at increased risk for IA. Additional IA risk factors include alcoholism, IV drug abuse, and immunodeficiency, including HIV infection.
Other etiologic factors for the development of acute IA include direct joint penetration secondary to trauma, surgery, and arthrocentesis (puncture of a joint cavity with aspiration of fluid); bite wounds from humans, dogs or cats, and rats, which are often polymicrobial and usually affect the small joints of the hands.8,9 IA may also occur via extension from adjacent infection such as osteomyelitis, a soft-tissue abscess, or an infected wound, such as a pressure ulcer.8,9 Of note, dissemination of bacteria through the bloodstream, termed hematogenous spread, may also occur from a remote infection and is the mechanism by which IA is usually acquired.7-10
In the elderly, gram-negative bacteria (e.g., Enterobacter species, Pseudomonas aeruginosa, Serratia marcescens) commonly cause acute IA, typically originating from the skin and urinary tract.8 These organisms are the causative factor in patients who have severe joint trauma and serious disease, such as diabetes mellitus, RA, SLE, and malignancy, are immunosuppressed, or are receiving hemodialysis.8 In adults and adolescents, organisms such as Neisseria gonorrhoeae are especially likely to infect a joint during bacteremia.9 For a table of organisms that commonly cause acute IA, see Reference 8.
Signs, Symptoms and Types of IA
As previously mentioned, the onset of joint pain is usually rapid and monoarticular, although it may also occur in more than one joint, particularly with movement. There is also heat, redness, swelling, and restricted range of motion of the joint. Systemic findings include sudden onset of fever, shaking chills, a general feeling of illness, leukocytosis, and elevated erythrocyte sedimentation rate (ESR).5,8 The large joints are primarily affected, most commonly the knee, hip, shoulder, wrist, ankle, and elbow.3,5 Gonococcal arthritis causes a distinct dermatitis-polyarthritis-tenosynovitis syndrome.8 Nongonococcal bacterial arthritis is monoarticular in 80% of adults.8 Of note, however, in some cases patients may present with no noted changes in how they normally look or feel, except for a slight fever.5
Acute IA: In some cases, acute IA can evolve over hours or days with rapid onset of symptoms, limitation in range of motion, and, as previously mentioned, the potential to destroy joint structures; inflammatory synovitis—fluctuating swelling due to effusion accompanied by pain, particularly on motion—may occasionally persist even after the infection has been eradicated by antibiotics.7,8
Chronic IA: Accounts for 5% of IA and develops over weeks; it is usually caused by mycobacteria, fungi, or bacteria with low pathogenicity and is most likely to develop in patients with RA, HIV infection, immunosuppression, or prostethetic joints.8 The arthritis of Lyme disease, while typically acute, may be chronic.8 Prolonged treatment with multiple antibiotics is usually required for mycobacterial and fungal joint infections.8
Prosthetic Joint IA: In approximately two-thirds of cases, prosthetic joint IA develops within 1 year of surgery.8 In approximately 25% of cases, there is a history of a fall within 2 weeks of the onset of symptoms, and in about 20% of patients there is history of prior surgical revision.8 About half of the cases are caused by Staphylococcus aureus in the first few months following surgery.8 Prolonged treatment is required and includes long-term antibiotic therapy and a variety of surgical procedures (e.g., prosthesis removal, cement debridement, abscess removal).
Laboratory InvestigationsWhen IA is suspected, a white blood cell count is ordered to check for the abnormality of leukocytosis.2 Immediate joint aspiration and analysis (i.e., culture and sensitivity) of synovial fluid is of the utmost importance (see also Joint drainage, below).9 Additionally, the blood is cultured to evaluate for bacteria.2 A recommended monitoring protocol, including other laboratory parameters, is discussed below.
ManagementThe most important therapeutic interventions in the management of IA are appropriate antibiotics, joint drainage, and joint rest.11
Antibiotic therapy: Early recognition and intervention in an infection is of the utmost importance, since delaying the initiation of antibiotic therapy will significantly increase the likelihood for long-term complications.9 Selection of a specific antibiotic is dependent on the most likely infecting organism.
Key pointers in the selection of IV antibiotic therapy are: 1) all likely pathogens should be covered in the context of the clinical setting; 2) laboratory analysis of the synovial fluid may be useful in selecting appropriate antibiotic therapy initially; and 3) organisms that are resistant or atypical may require modification of antibiotic therapy.4,6,9 The recommendations in TABLE 1 may be used as a guide to the use of antibiotic therapy in IA.4,12
Joint drainage: Aspiration of synovial fluid is undertaken to avoid permanent damage to the affected joint and articular cartilage and bone, which can occur secondary to leukocyte (proteolytic) enzyme activity.5,10 This procedure is repeated daily, usually for 5 to 7 days, until effusions cease accumulating and a desired white blood cell count in the synovial fluid is achieved.5,9 Surgical debridement may be required if clinical signs and symptoms of inflammation (e.g., fever and joint pain) are not substantially reduced within 48 to 72 hours or resolved after appropriate empirical antibiotic therapy. 5,9
Joint rest: Weight-bearing exercise, such as walking, during the initial phase of the infection should be avoided; to maintain joint mobility, however, passive range-of-motion exercises should commence when the pain begins to subside.13
Considering pharmacoeconomic issues is especially important in the treatment and monitoring of patients with IA. Alternatives to extended hospitalization for the administration of 4 to 6 weeks of parenteral antibiotics should be evaluated, such as home care or oral antibiotic therapy, if appropriate; cost of therapy and quality-of-life factors should be incorporated into the evaluating equation.14 Of note, complications of comorbidities, such as diabetic retinopathy, intention tremor, coagulopathies, and various neurologic disorders, can preclude patients from receiving antibiotics via home care.9 Further, a history of alcoholism or intravenous drug abuse is also considered an important exclusion criterion.9 Ongoing monitoring of antimicrobial therapy is essential once a patient is receiving home-care antibiotic therapy; monitoring for adherence to the antimicrobial medication regimen is also vital.
Monitoring Protocol to Evaluate Therapeutic Outcomes
Poor joint outcome (e.g., severe functional deterioration), associated with older patients, those with preexisting joint disease, and patients with an infected joint containing synthetic composition, occurs in approximately one-third of patients with bacterial arthritis.9,15 Armstrong and Friedman discuss the importance of pharmaceutical-care monitoring and recommend a monitoring protocol involving specific parameters and their recommended frequency.9 The monitoring protocol includes culture and sensitivity of synovial fluid and blood at initiation of treatment; white blood cell count once weekly until within normal range; C-reactive protein or erythrocyte sedimentation rate weekly; evaluation for clinical signs of inflammation (pain, tenderness, redness, swelling, fever) daily during initiation of therapy; and reinforcement of compliance with outpatient therapy prior to initiation of oral therapy and at each health care visit.9
Infectious arthritis requires early recognition and therapeutic intervention to prevent the increased likelihood for long-term complications associated with delaying the initiation of antibiotic therapy. The elderly and immunosuppressed with serious comorbidities, as well as postprosthetic joint–surgery patients, are particularly at risk. Pharmacists have an important and integral role in the monitoring protocol for this serious inflammatory and potentially joint-destructive condition.
1. 47.5 Million adults in U.S. report a disability; arthritis remains most common cause. May 2009. www.cdc.gov/Features/dsAdult Disability Causes/. Updated June 21, 2011. Accessed July 30, 2012.
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7. Dorland’s Pocket Medical Dictionary. 28th ed. Philadelphia, PA: Elsevier Saunders; 2009.
8. Acute infectious arthritis, chronic infectious arthritis, prosthetic joint infectious arthritis.
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15. Shirtliff ME, Mader JT. Acute septic arthritis. Clin Microbiol Rev. 2002;15:527-544.
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