Nongonococcal Infectious Arthritis

Updated: Mar 09, 2021
Author: Edward Dwyer, MD; Chief Editor: Herbert S Diamond, MD 


Practice Essentials

Nongonococcal infectious arthritis is an acute or subacute illness with potentially significant morbidity and mortality. It can be caused by bacteria, mycobacteria, or fungi. Both healthy individuals and individuals with predisposing conditions can be infected.[1] Nongonococcal infectious arthritis is typically a monoarticular disease, but in approximately 10% of patients, it affects multiple joints.[2, 3] Septic arthritis is an emergency; without treatment, it can progress rapidly and result in irreversible damage to the joint.[4, 5]

For patient education information, see Septic Arthritis.

Pathophysiology and Etiology

Infectious arthritis ensues when foreign organisms invade the synovium or joint space. These organisms invade the joint via the following 3 pathways:

  • Hematogenous dissemination from a distant site
  • Periarticular infection, such as osteomyelitis or adjacent soft-tissue infection
  • Direct introduction through penetrating trauma or procedural intervention, such as arthrocentesis or surgical repair



Gram-positive cocci, especially Staphylococcus aureus, are the predominant etiologic agents. Streptococcal species are also common, especially group A streptococci.[6] If a prosthetic joint was implanted within the preceding 6 months, S epidermidis and S aureus are major pathogens. S  pneumoniae septic arthritis may also occur, and may involve serotypes not covered by pneumococcal vaccines.[7]

The Gram-negative coccobacillus Kingella kingae has emerged as a prime etiology of septic arthritis and osteomyelitis in children aged 6-48 months.[8, 9]  Kingella kingae is unlikely to be a novel human pathogen; rather, its increased recognition appears to be the result of improved methods of detection.[8]

Gram-negative bacilli are also more common in elderly patients with chronic medical conditions. Pseudomonas aeruginosa and methicillin-resistant S aureus (MRSA) are more prevalent in the infectious arthritis that affects individuals who abuse intravenous (IV) drugs. Salmonella species exhibit a predilection for individuals with systemic lupus erythematosus and those with sickle cell disease.[10]

Septic arthritis from Mycoplasma should be considered in immunocompromised patients with repeated negative cultures and poor response to empiric antibiotic treatment.[11]

Pasteurella multocida should be considered after a cat bite, Eikenella corrodens after a human bite. In endemic areas, Brucella species can be a cause of monoarticular arthritis.[12]

Dubost and colleagues examined changes in the distribution and antibiotic susceptibility profiles of organisms responsible for septic arthritis in a single-center retrospective study of 374 patients treated between 1979 and 2008 at a French hospital. Over the three decades studied, no significant time trends in the proportions of staphylococci (67%, 65%, and 64%), streptococci (14%, 21%, and 17%), or Gram-negative rods (7%, 10%, and 14%) were detected. Tuberculosis was significantly more common between 1979 and 1988 (10%, 4%, and 2% over the three decades studied). There were no significant changes in the proportions of methicillin-resistant staphylococci over time (13%, 11%, 15%).[13]


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.[14]


Candida organisms, including Candida albicans and Candida parapsilosis, may cause infectious arthritis 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.[14]

Risk factors

The presence of a preexisting, chronic, inflammatory, destructive arthritis, especially rheumatoid arthritis, is correlated with infectious arthritis. The introduction of anti–tumor necrosis factor (TNF) agents into the treatment of inflammatory arthritis may further 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 at particular risk for infectious arthritis. Comorbid nonarticular conditions, such as diabetes mellitus, immunodeficiency diseases, cancer, or IV drug abuse, also increase the risk of infectious arthritis.

Epidemiology and Prognosis

The yearly incidence of bacterial arthritis ranges 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 (RA).[2]

Age older than 80 years has been shown in some studies to be an independent risk factor for susceptibility to bacterial arthritis. Sex is not an independent risk factor for infectious arthritis. No inherent racial predilections for infectious arthritis are recognized.

Nongonococcal infectious arthritis carries a mortality of 11%.[15] Irreversible loss of joint function may result if the condition is not treated immediately and for an appropriate duration. Joint destruction occurs in 25%-50% of cases.[16] Morbidity and mortality are higher in elderly individuals and individuals with preexisting medical conditions.




The clinical course of bacterial arthritis is typically acute in onset. Patients with joint prostheses are the exception to this general rule: Their 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. Onset of Kingella kingae septic arthritis in pediatric patients likewise is typically insidious, and clinical manifestations tend to be milder than those of septic arthritis from other bacteria.[8]

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. The sternoclavicular and sacroiliac joints are preferentially involved in patients who use illicit parenteral drugs.

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 and conditions necessitating glucocorticoid therapy).[17]

Physical Examination

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).[2]

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.





Approach Considerations

Leukocytosis is common in patients with acute bacterial arthritis. Approximately 50% of persons with acute disease exhibit white blood cell (WBC) counts higher than 10,000/µL. Blood culture results are positive in approximately 33%-50% of patients with nongonococcal bacterial arthritis.[17]

If indicated, arthrocentesis for synovial fluid analysis is the single most important diagnostic procedure for evaluating infectious arthritis. It allows culture and appropriate microscopic examination of the synovial fluid and tissue.

Diagnostic imaging modalities may be helpful but are often nonspecific.[5]

Arthrocentesis and Synovial Fluid Analysis

The synovial fluid cell count is generally higher than 50,000/µL, with neutrophils predominating (>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 but 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 or pseudogout). It is important, however, to be mindful of the possibility that infectious arthritis and crystal-induced arthritis may be coexisting in a single joint, though such coexistence is reportedly very uncommon.

Culture of synovial fluid should be performed for aerobic and anaerobic organisms. Inoculation of blood culture bottles is more sensitive than culture on solid media, especially in patients pretreated with antibiotics.[18]

In infants and young children (especially those 6 to 48 months of age), consideration should be given to infection with Kingella kingae, which is notoriously fastidious and often fails to be detected by traditional culture methods. Polymerase chain reaction (PCR) testing of synovial fluid for the16S rRNA gene can markedly improve identification of K kingae.[8, 9]

Biopsy of synovial tissue for culture and histologic examination is important if mycobacterial or fungal infections are suggested. Culture of synovial fluid is an insensitive diagnostic test in this setting.

Radiography, CT, MRI, and Radionuclide Imaging

Plain radiography is 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 there is a preexisting joint disease.

Computed tomography (CT) may help diagnose sternoclavicular or sacroiliac joint infections. Magnetic resonance imaging (MRI) is most useful in assessing the presence of periarticular osteomyelitis as a causative mechanism.

Radionuclide studies (eg, bone scans) yield positive results for any inflammatory arthritis and thus have poor specificity. They may be useful for diagnosing sternoclavicular or sacroiliac joint infection.



Approach Considerations

The most important consideration in the treatment of infectious arthritis is the rapid institution of appropriate antimicrobial therapy. Patients with bacterial arthritis must be hospitalized for parenteral antibacterial therapy and daily arthrocentesis. Daily joint aspiration must be performed until inflammation subsides. Mycobacterial and fungal infections are treated with appropriate agents. Perform surgical debridement if no response to medical therapy is observed.

Consultations that may be obtained include the following:

  • Rheumatologist
  • Orthopedic surgeon

Encourage either passive or active daily range-of-motion exercises. Avoid immobilizing the joint.

Pharmacologic Therapy

Intravenous (IV) antibiotic therapy is initiated immediately upon admission, as 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 Staphylococcus 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. Staphylococcus 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. 

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 (MRSA) should be initially treated with vancomycin until culture results are available.[19]

Kingella kingae infections in pediatric patients are typically susceptible to aminoglycosides, macrolides, trimethoprim-sulfamethoxazole  fluoroquinolones, and chloramphenicol. Many strains are clindamycin nonsusceptible, and all are highly resistant to vancomycin and other glycopeptide antibiotics.[8]

Elderly debilitated patients or patients with chronic medical conditions require expanded antimicrobial coverage to address 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.

Fungal arthritis is appropriately treated with IV 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.[14]

Mycobacterial arthritis treatment varies, depending on the infecting agent. Patients with M tuberculosis infection are initially treated with 4 drugs (rifampin, isoniazid, pyrazinamide, and ethambutol [RIPE]) for 2 months; after this period, depending on the sensitivities, isoniazid and rifampin are continued for a total of 9-12 months.[14] Treatment of an M marinum infection requires administration of rifampin and ethambutol for 6-12 weeks.

Arthrocentesis, Arthroscopy, and Surgical Drainage

Daily arthrocentesis of the affected joint should be performed until synovial fluid culture results are negative or considerable clinical improvement in the joint is apparent. 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. The antibacterial prophylactic regimen indicated for patients with prosthetic joints undergoing surgical procedures is similar to that indicated for endocarditis prophylaxis in patients with valvular heart disease.



Medication Summary

Antimicrobial therapy is dictated by the results of a Gram stain and the clinical characteristics of the host. If the results of a Gram stain of synovial fluid identify no organism, empiric therapy is initiated on the basis of the clinical characteristics of the host. Mycobacterial and fungal infections are treated with agents appropriate to the causative pathogen.


Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.


Nafcillin is used as initial therapy for possible penicillin G–resistant streptococcal or staphylococcal infections. In a patient with severe infections, it should be given parenterally at first, then orally as the patient's condition warrants. Because of the risk thrombophlebitis, particularly in elderly patients, parenteral administration should be continued for a short period (1-2 days) only.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins (PBPs).

Ciprofloxacin (Cipro, Cipro XR)

Ciprofloxacin inhibits bacterial DNA synthesis and thus growth. It is active against gram-negative rods and may be administered with nafcillin.


Vancomycin is active against Staphylococcus epidermidis. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose in a sample drawn 0.5 hours before the next dose. Dose adjustment is possible in patients with renal impairment; the adjustment should be based on creatinine clearance.

Antitubercular agents

Class Summary

Antitubercular agents are used when therapy for tuberculous arthritis is indicated.


Isoniazid offers the best combination of effectiveness, low cost, and minor adverse effects. Coadministration of pyridoxine is recommended if peripheral neuropathies develop secondary to isoniazid therapy. Prophylactic pyridoxine 6-50 mg/day is recommended.

Rifampin (Rifadin)

Rifampin is given in combination with at least 1 other antituberculous drug (eg, isoniazid); it inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 months or until 6 months have elapsed since conversion to a negative sputum culture result.

Antifungals, Systemic

Class Summary

These agents are used when fungal arthritis, such as candidal arthritis, is documented.

Amphotericin B lipid complex (Abelcet)

Amphotericin B is produced from a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. This agent binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.

Fluconazole (Diflucan)

Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation. It is suggested for use in combination with amphotericin.


Questions & Answers


What is nongonococcal infectious arthritis?

What is the pathophysiology of nongonococcal infectious arthritis?

What is the role of bacteria in the etiology of nongonococcal infectious arthritis?

What is the role of mycobacteria in the etiology of nongonococcal infectious arthritis?

What is the role of fungi in the etiology of nongonococcal infectious arthritis?

What are the risk factors for nongonococcal infectious arthritis?

What is the prevalence of nongonococcal infectious arthritis?

What is the prognosis of nongonococcal infectious arthritis?


Which clinical history findings are characteristic in nongonococcal infectious arthritis?

Which physical findings are characteristic of nongonococcal infectious arthritis?


What are the differential diagnoses for Nongonococcal Infectious Arthritis?


How is nongonococcal infectious arthritis diagnosed?

What is the role of arthrocentesis and synovial fluid analysis in the workup of nongonococcal infectious arthritis?

What is the role of imaging studies in the workup of nongonococcal infectious arthritis?


How is nongonococcal infectious arthritis treated?

Which specialist consultations are beneficial to patients with nongonococcal infectious arthritis?

What is the role of medications in the treatment of nongonococcal infectious arthritis?

What is the role of surgery in the treatment of nongonococcal infectious arthritis?


Which medications are used in the treatment of nongonococcal infectious arthritis?

Which medications in the drug class Antifungals, Systemic are used in the treatment of Nongonococcal Infectious Arthritis?

Which medications in the drug class Antitubercular agents are used in the treatment of Nongonococcal Infectious Arthritis?

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