eMedicine Specialties > Rheumatology > Infectious Arthritis
Nongonococcal Infectious Arthritis
Updated: Oct 7, 2009
Introduction
Background
Nongonococcal infectious arthritis is an acute or subacute illness with potentially significant morbidity and mortality. Bacteria, mycobacteria, and fungi can cause the disease. Both healthy individuals and individuals with predisposing conditions can be infected. Nongonococcal infectious arthritis is typically a monoarticular disease, but, in approximately 10% of patients, it affects multiple joints.7 Without treatment, the condition results in joint destruction.
Pathophysiology
Infectious arthritis ensues when foreign organisms invade the synovium or joint space. These organisms invade the joint via (1) hematogenous dissemination from a distant site; (2) periarticular infection, such as osteomyelitis or adjacent soft-tissue infection; or (3) direct introduction through penetrating trauma or procedural intervention, such as arthrocentesis or surgical repair.
Frequency
United States
The yearly incidence of bacterial arthritis varies from 2-5 cases per 100,000 persons in the general population to 28-38 cases per 100,000 persons in patients with rheumatoid arthritis.7
Mortality/Morbidity
- Nongonococcal infectious arthritis carries a mortality rate of 11%.8
- Joint destruction occurs in 25%-50% of cases.5
Race
- No inherent racial predilections for infectious arthritis are recognized.
Sex
- Sex is not an independent risk factor for infectious arthritis.
Age
- Age older than 80 years has been shown in some studies to be an independent risk factor for susceptibility to bacterial arthritis.
Clinical
History
- The clinical course of bacterial arthritis is typically acute in onset.
- Patients with joint prostheses are the exception. These patients' symptoms may persist for weeks or months before a diagnosis is made.
- Individuals with mycobacterial or fungal arthritis also tend to have a much more indolent or subacute prodrome before the diagnosis is considered.
- The sternoclavicular and sacroiliac joints are preferentially involved in patients who use illicit parenteral drugs.
- Joint pain, swelling, erythema, and loss of motion are common presenting symptoms.
- The most commonly affected joint in persons with bacterial arthritis is the knee.
- The shoulder, hip, elbow, and wrist joints are infected less frequently.
- Approximately 10% of individuals with bacterial arthritis have infection in multiple joints, particularly in the presence of a preexisting destructive joint disease (eg, rheumatoid arthritis) or compromising medical conditions (eg, diabetes, those that require glucocorticoid therapy).6
Physical
- During the first 24 hours of hospitalization, 78% of patients with nongonococcal bacterial arthritis exhibit fever; however, the fever rarely exceeds 39°C (102.2°F).7
- The patient may have decreased range of motion in the joint.
- Swelling, tenderness to palpation, erythema, warmth to touch, and pain upon movement of the affected joint are common physical examination findings.
Causes
- Risk factors
- The presence of a preexisting, chronic, inflammatory, destructive arthritis, especially rheumatoid arthritis, is correlated with infectious arthritis. The recent introduction of anti–tumor necrosis factor (TNF) agents in the treatment of inflammatory arthritis may additionally predispose this population to infectious arthritis.
- A person undergoing immunosuppressive therapy, such as with corticosteroids or cytotoxic agents, is more likely to become infected.
- A person who has a prosthetic joint has greater risk of infection.
- Elderly individuals are particularly at risk for infectious arthritis.
- Comorbid nonarticular conditions, such as diabetes mellitus, immunodeficiency diseases, cancer, or intravenous drug abuse, also increase the risk of infectious arthritis.
- Bacteria
- Gram-positive cocci, especially Staphylococcus aureus, are the predominant etiologic agents. Streptococcal species are also common, especially group A streptococci.3
- If a prosthetic joint was implanted within the preceding 6 months, Staphylococcus epidermidis and S aureus are major pathogens.
- Gram-negative bacilli are more common in elderly patients with chronic medical conditions.
- Pseudomonas aeruginosa and methicillin-resistant S aureus are more prevalent in the infectious arthritis that affects individuals who abuse intravenous drugs.
- Salmonella species exhibit a predilection for individuals with systemic lupus erythematosus.
- Consider Pasteurella multocida subsequent to a cat bite or Eikenella corrodens after a human bite.
- Mycobacteria
- In addition to the common pathogen Mycobacterium tuberculosis, nontuberculous species, such as Mycobacterium kansasii, may spread from a pulmonary focus and infect a joint.
- Mycobacterium marinum should be considered in individuals exposed to aquatic or marine environments.
- Fungi
- Candida organisms, including Candida albicans and Candida parapsilosis, are causative in debilitated hospitalized patients or in patients on long-term antibacterial therapy.
- Sporothrix schenckii may infect the hand or wrist joints of a person frequently exposed to moist soil, rose thorns, or the outdoors.
Differential Diagnoses
Calcium Pyrophosphate Deposition Disease
Gonococcal Arthritis
Gout
Rheumatic Fever
Rheumatoid Arthritis
Viral Arthritis
Workup
Laboratory Studies
- Synovial fluid tests
- The synovial fluid cell count is generally higher than 50,000/µL, with a predominance of neutrophils greater than 90% in persons with acute bacterial arthritis.
- Results of a Gram stain of synovial fluid are positive in approximately 75% of patients with staphylococcal infections; however, results are positive in only 50% of patients with gram-negative infections.
- A microscopic examination of synovial fluid for monosodium urate crystals and calcium pyrophosphate crystals is performed to exclude crystal-induced arthritis (eg, gout, pseudogout); however, recognizing the possibility of infectious arthritis and crystal-induced arthritis coexisting in a single joint is also important, although this is reportedly very uncommon.
- A culture of synovial fluid should be performed for aerobic and anaerobic organisms. Inoculation of blood culture bottles is more sensitive than culture on solid medium, especially in patients pretreated with antibiotics.4
- A biopsy of synovial tissue for culture and histologic examination is important if mycobacterial or fungal infections are suggested. A culture of synovial fluid is an insensitive diagnostic test in this setting.
- Complete blood cell count
- Leukocytosis is common in patients with acute bacterial arthritis.
- Approximately 50% of persons with acute disease exhibit WBC counts greater than 10,000/µL.
- Blood culture: Results are positive in approximately 33%-50% of patients with nongonococcal bacterial arthritis.6
Imaging Studies
- Radiography
- Plain radiography findings are generally nonspecific and may reveal only a joint effusion in the early stages of infection.
- Cartilage destruction and joint space narrowing are late findings and may be difficult to interpret if the patient has a preexisting joint disease.
- CT scanning: This study may help to diagnose sternoclavicular or sacroiliac joint infections.
- MRI: MRI is most useful in assessing the presence of periarticular osteomyelitis as a causative mechanism.
- Radionuclide images
- Findings from radionuclide studies, such as bone scans, are positive for any inflammatory arthritis and are therefore very nonspecific.
- These may be useful for diagnosing sternoclavicular or sacroiliac joint infection.
Procedures
- Arthrocentesis with synovial biopsy
- If indicated, this is the single most important diagnostic procedure for evaluating infectious arthritis.
- It allows for culture and appropriate microscopic examination of the synovial fluid and tissue.
Treatment
Medical Care
- The most important consideration in the treatment of infectious arthritis is the rapid institution of appropriate antimicrobial therapy. Daily joint aspiration must be performed until inflammation subsides.
- Patients with bacterial arthritis must be hospitalized.
- Intravenous antibiotic therapy is initiated immediately upon admission. If the results of a Gram stain of synovial fluid identify no organism, initiate empiric therapy based on the clinical characteristics of the host.
- Healthy adults can be treated with antistaphylococcal penicillin or cephalosporin. Patients who reside in communities with a high prevalence of community-acquired methicillin-resistant S aureus should be initially treated with vancomycin pending culture results.1
- Elderly debilitated patients or patients with chronic medical conditions require expanded antimicrobial coverage to cover gram-negative bacteria. This usually requires the addition of a third-generation cephalosporin, an aminoglycoside, or a quinolone.
- Patients with nosocomial infections in whom pseudomonal species are considered may need an extended-spectrum penicillin such as piperacillin or carbenicillin.
- Cultural sensitivities, when available, may help identify appropriate modifications to subsequent therapy.
- Depending on the causative organism, most experts recommend 2-4 weeks of parenteral therapy.
- Institute daily arthrocentesis of the affected joint until synovial fluid culture results are negative or considerable clinical improvement in the joint is apparent.
- Fungal arthritis is appropriately treated with intravenous amphotericin B plus an oral azole. The recommended duration of therapy is 6-12 weeks, for a total dose of 1-3 g of amphotericin B.9
- Mycobacterial arthritis treatment varies depending on the infecting agent.
- Patients with M tuberculosis infection are treated initially with 4 drugs (rifampin, isoniazid, pyrazinamide, ethambutol [RIPE]) for 2 months; then, depending on the sensitivities, isoniazid and rifampin are continued for a total of 9-12 months.9
- An M marinum infection requires rifampin and ethambutol for 6-12 weeks.
Surgical Care
- Joints that do not respond to antimicrobial therapy and daily arthrocentesis require drainage and debridement, either with arthroscopy or with an open procedure.
- A joint with an infected prosthesis requires removal of the prosthesis and reimplantation after an appropriate course of antimicrobial therapy.
Consultations
- Rheumatologist
- Orthopedic surgeon
Activity
- Encourage either passive or active daily range-of-motion exercises.
- Avoid immobilizing the joint.
Medication
Antimicrobial therapy is dictated by the results of a Gram stain and the clinical characteristics of the host. If the Gram stain result is positive for gram-positive cocci, then S aureus and streptococci are the most likely infecting agents. If the patient is a healthy sexually active adult, gonococci and gram-positive cocci are the most likely infecting agents. If the Gram stain result is negative in an elderly or compromised host, gram-negative rods are likely. S epidermidis and gram-negative rods are more likely in a patient with a prosthetic joint or a patient who has undergone a recent operative procedure.
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Nafcillin (Unipen)
Initial therapy for possible penicillin G–resistant streptococcal or staphylococcal infections.
Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants.
Due to thrombophlebitis, particularly in elderly patients, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated.
Dosing
Adult
2 g IV q4h
Pediatric
50 mg/kg IV q6h
Interactions
Increases effects of warfarin; decreases levels of cyclosporin; associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
To optimize therapy, determine causative organisms and susceptibility; >10 d treatment to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm eradication of infection
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Dosing
Adult
1-2 g IV qd
Pediatric
Not established
Interactions
Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; caution in breastfeeding and penicillin allergy
Ciprofloxacin (Cipro)
Inhibits bacterial DNA synthesis and, consequently, growth. Active against gram-negative rods; administered with nafcillin
Dosing
Adult
400 mg IV q12h
Pediatric
Not recommended
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Vancomycin (Vancocin)
Active against S epidermidis. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Dose adjustment possible in renal impairment. Base adjustment on CrCl.
Dosing
Adult
500 mg IV q6h
Pediatric
Not established
Interactions
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal failure or neutropenia; red man syndrome is caused by IV infusion that is too rapid (dose given over a few min) but rarely occurs when dose given as 2-h administration or PO or IP; red man syndrome is not an allergic reaction
Antitubercular agents
These agents are used when therapy for tuberculous arthritis is indicated.
Isoniazid (NIH, Laniazid)
Best combination of effectiveness, low cost, and minor adverse effects. Coadministration of pyridoxine is recommended if peripheral neuropathies develop secondary to isoniazid therapy. Prophylactic doses of 6-50 mg/d of pyridoxine are recommended.
Dosing
Adult
300 mg PO qd
Pediatric
Not established
Interactions
Higher incidence of isoniazid-related hepatitis can occur with daily alcohol ingestion; aluminum salts may decrease serum levels (administer 1-2 h before taking aluminum salts); may increase effects of anticoagulants with coadministration; may inhibit metabolic clearance of benzodiazepines
Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function); coadministration with cycloserine may increase adverse CNS effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram
Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin
Contraindications
Documented hypersensitivity; previous isoniazid-associated hepatic injury or other severe adverse reactions
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Ingestion of alcohol increases risk of liver toxicity; monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations are recommended during therapy, even in the absence of visual symptoms
Rifampin (Rifadin, Rimactane)
For use in combination with at least one other antituberculous drug, such as isoniazid; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 mo or until 6 mo have elapsed since conversion to negative sputum culture result.
Dosing
Adult
600 mg PO qd
Pediatric
Not established
Interactions
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Obtain CBC counts and baseline clinical chemistry values prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
Antifungals
These agents are used when fungal arthritis, such as candidal arthritis, is documented.
Amphotericin B lipid complex (Abelcet)
Produced from a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.
Dosing
Adult
1.5 mg/kg IV qd
Pediatric
Not established
Interactions
Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC count, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Fluconazole (Diflucan)
Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation. Suggested for use with amphotericin administration
Dosing
Adult
200 mg PO/IV qd
Pediatric
Not established
Interactions
Levels may increase with hydrochlorothiazides; levels may decrease with long-term coadministration of rifampin; coadministration may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor closely if rashes develop and discontinue drug if lesions progress; caution in renal failure; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or a malignancy and while taking multiple concomitant medications; not recommended for nursing mothers
Follow-up
Further Inpatient Care
- Admit patients with infectious arthritis for parenteral antibacterial therapy and daily arthrocentesis.
- Perform surgical debridement if no response to medical therapy is observed.
Deterrence/Prevention
- Patients with prosthetic joints require antibacterial prophylaxis before surgical procedures. This prophylaxis is similar to the treatment indicated for endocarditis prophylaxis in patients with valvular heart disease.
Complications
- Irreversible loss of joint function may result if the condition is not treated immediately and for an appropriate duration.
Prognosis
- Morbidity and mortality rates are increased in elderly individuals and individuals with preexisting medical conditions.
Patient Education
- For excellent patient education resources, visit eMedicine's Arthritis Center and Bacterial and Viral Infections Center. Also, see eMedicine's patient education article Knee Pain.
Miscellaneous
Medicolegal Pitfalls
- Failure to consider an infectious etiology in monoarticular arthritic flares in the setting of chronic inflammatory polyarthritis
References
Chambers HF. Community-associated MRSA--resistance and virulence converge. N Engl J Med. Apr 7 2005;352(14):1485-7. [Medline].
[Best Evidence] Mathews CJ, Kingsley G, Field M, Jones A, Weston VC, Phillips M, et al. Management of septic arthritis: a systematic review. Ann Rheum Dis. Apr 2007;66(4):440-5. [Medline].
Shirtliff ME, Mader JT. Acute septic arthritis. Clin Microbiol Rev. Oct 2002;15(4):527-44. [Medline].
von Essen R. Culture of joint specimens in bacterial arthritis. Impact of blood culture bottle utilization. Scand J Rheumatol. 1997;26(4):293-300. [Medline].
Kaandorp CJ, Krijnen P, Moens HJ, Habbema JD, van Schaardenburg D. The outcome of bacterial arthritis: a prospective community-based study. Arthritis Rheum. May 1997;40(5):884-92. [Medline].
Goldenberg DL, Reed JI. Bacterial arthritis. N Engl J Med. Mar 21 1985;312(12):764-71. [Medline].
Smith JW, Chalupa P, Shabaz Hasan M. Infectious arthritis: clinical features, laboratory findings and treatment. Clin Microbiol Infect. Apr 2006;12(4):309-14. [Medline].
Gupta MN, Sturrock RD, Field M. A prospective 2-year study of 75 patients with adult-onset septic arthritis. Rheumatology (Oxford). Jan 2001;40(1):24-30. [Medline].
Harrington JT. Mycobacterial and fungal arthritis. Curr Opin Rheumatol. Jul 1998;10(4):335-8. [Medline].
Keywords
bacterial arthritis, fungal arthritis, candidal arthritis, mycobacterial arthritis, septic arthritis, infectious arthritis, non-gonococcal arthritis, nongonococcal infectious arthritis, non-gonococcal infectious arthritis, infected joint prosthesis, joint prosthesis infection, staphylococcal arthritis
Contributor Information and Disclosures
Author
Edward Dwyer, MD, Department of Medicine, Assistant Professor, Columbia University College of Physicians and Surgeons
Edward Dwyer, MD is a member of the following medical societies: Alpha Omega Alpha and American College of Rheumatology
Disclosure: Nothing to disclose.
Medical Editor
Robert E Wolf, MD, PhD, Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport
Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, and Society for Leukocyte Biology
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Managing Editor
Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.
CME Editor
Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.
Chief Editor
Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership
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