Soft tissue skin infection
Elderly, UTI, skin breakdown
Gram-negative rods including enteric organisms
Sternoclavicular, sacroiliac, pubic symphysis
Pseudomonas, S. aureus
Oral flora including anaerobes, Pasteurella multocida
Southwestern USA, Central and South America
Staphylococcus is the most common cause of septic arthritis, seen in about 50% of cases. Septic arthritis caused by Staphylococcus is due to a transient bacteremia from a skin or mucous membrane source . About half of these are MRSA joint infections, which are associated with worse outcomes. This is also due to the fact that MRSA tends to affect older persons. It also reportedly commonly affects the shoulder – which is a difficult site to access .
Though the majority of streptococcal infections are monoarticular, polyarticular involvement has been reported in up to 36%. The incidence of S. pneumoniae has declined due to pneumococcal vaccinations. Beta-hemolytic strep seems most common in the elderly, those with diabetes, cirrhosis, and neurologic disease. Group B streptococcus has a high frequency of bacteremia with polyarticular involvement as a result. The mortality from septic arthritis caused by pneumococcus is high .
Gram-Negative Enteric Organisms
Gram-negative enteric organisms are seen most often in intravenous injection drug users, neonates, older adults, and the immunosuppressed population. They account for up to 10% of cases of septic arthritis [19, 20]. Outcomes are found to be favorable for these patients .
Usually present in sexually active individuals. Seventy-five percent of cases occur in women; menses and pregnancy increase the risk of disseminated infection. There are two classic presentations of a disseminated gonococcal infection, the arthritis-dermatitis syndrome and a purulent arthritis. Patients with a disseminated gonococcal infection usually present with fevers, skin lesions, polyarthralgias, and tenosynovitis. Within a few weeks, these can evolve into a persistent monoarticular or oligoarticular arthritis. This purulent arthritis is characterized by abrupt onset, usually involving distal joints with knees, wrists, and ankles, with the knee being the most common. Axial involvement is rare. Routine cultures wont usually establish the diagnosis . In order to isolate the organism, synovial fluid nucleic acid amplification testing or a culture on a chocolate agar or Thayer-Martin medium is usually required [22, 23]. That said, gonococci are recovered from joint fluid in fewer than 50% of cases. Current rising rates of gonorrhea resistant to fluoroquinolones and azithromycin suggest that epidemic gonorrhea may be recurring .
Mycobacterium tuberculosis should be suspected in cases of an indolent presentation of persistent culture-negative monoarticular or oligoarticular arthritis in the setting of relevant epidemiologic exposure. The most common sites are the hip or knee and this is most often monoarticular – multifocal lesions are seen in 10–15% of cases . Symptoms can be present for an average of a year before diagnosis. If patients present late in the course of they disease they may have evidence of joint destruction with deformity or reduced range of motion or chronic draining sinuses. The affected joint is generally cold, and obvious cardinal signs of infection, such as erythema and warmth, are usually absent. Constitutional symptoms such as fever and weight loss are seen in about 30% . In order to isolate mycobacteria, a Ziehl-Neelsen stain is used, but it is important to note that this has low sensitivity for detecting acid-fast bacilli. The diagnosis is most accurately established via synovial membrane biopsy with histopathology and culture .
Septic arthritis caused by fungal species usually has an indolent presentation. Similar to TB, this will be noted to have a persistent culture-negative oligo- or monoarthritis in the setting of relevant epidemiologic exposure. It is most commonly seen in those who are immunosuppressed. Fungal causes include sporotrichosis, coccidioidomycosis, and candidiasis. Diagnosis is established by a fungal stain and culture of synovial fluid or via synovial membrane histopathology and culture .
Usually present with polyarthritis and joints are sterile. Patients usually present with systemic symptoms including fevers, myalgia, and rashes. Examples include dengue, chikungunya, Zika, parvovirus, and rubella.
The spectrum of clinical disorders associated with B19 ranges from benign to life-threatening depending on age, hematologic status, and immunologic status of the host. Erythema infectiosum “fifth disease” is most common in children with fever, malaise, slapped cheek rash, and a maculopapular rash involving the trunk and limbs. Arthralgias may be seen in erythema infectiosum, but arthropathy usually only presents in adults and is more prevalent in women. The arthritis can mimic rheumatoid arthritis and is typically a sudden onset symmetric polyarthritis primarily affecting the wrists, knees, ankles, and MCPs. The articular symptoms are usually brief in duration, but some do have prolonged symptoms that last weeks to years. The pathogenesis of arthritis in parvovirus is thought to be due to deposition of immune complexes in the synovial tissue because the onset coincides with appearance of B19-specific antibodies in the serum. Diagnosis is made by the presence of parvovirus IgM in serum. Treatment is supportive, and arthritis responds well to NSAID therapy .
Chikungunya virus is a single-stranded RNA virus and is transmitted by the Aedes vector. Generally there are two phases of the virus; the initial acute phase of the disease is called chikungunya fever and presents with high fever, rash, headache, severe polyarthralgia, and myalgias. This is usually followed by episodic and debilitating joint pain with joint swelling, and these patients may also have associated fatigue, myalgia, depression, and cognitive disorders. The inflammatory arthritis will often present in the acute phase and is unremitting; however, there can also be a phase of temporary remission prior to the development of a persistent arthritis. The arthritis is usually a symmetric polyarthritis involving the PIPs, MCPs, wrists, ankles, and knees, but there have been additional reports of hip, shoulder, and temporomandibular joint involvement. The arthritis can mimic other forms of inflammatory arthritis, such as rheumatoid arthritis, and it has been suggested by the ACR that patients with rheumatic symptoms persistent for more than 3 months should be referred for evaluation and classification as rheumatoid arthritis, spondyloarthritis, or undifferentiated polyarthritis. These patients can be treated with DMARDS also .
Acute Lyme Arthritis
Caused by Borrelia burgdorferi. Acute monoarticular arthritis occurs in the setting of epidemiologic exposure in an endemic area. Erythema migrans, rash, fever, and migratory arthralgia may occur weeks or months prior. Diagnosis is usually established by serologic testing. The infection initially causes viral-like migratory arthralgia, followed by an intermittent oligoarticular arthritis that most commonly involves the knee but is also seen in other large joints. The diagnosis of Lyme arthritis can be made with a two-step serologic testing process involving enzyme-linked immunosorbent assay, followed by confirmation with a western blot or immunoblot test. B. burgdorferi cannot be cultured from synovial fluid, but PCR testing is positive in 85% of patients with Lyme arthritis, so this can also be used as a confirmatory test .
Less Common Pathogens
This usually develops several days into antibiotic therapy and the joint fluid is sterile. Patients present with an isolated septic joint or an arthritis dermatitis syndrome similar to that of gonococcal arthritis.
Whipples ( Tropheryma whippelii )
In the majority of cases, this causes a nondestructive peripheral arthritis preceding the onset of abdominal pain, diarrhea, malabsorption, and weight loss by a mean of 8 years. These patients are often HLAB27 positive. Accompanying symptoms also include fever, lymphadenopathy, cutaneous hyperpigmentation, and cardiac and neurologic involvement. In order to make a definitive diagnosis, a small bowel biopsy is needed to isolate the organism, but PCR of synovial fluid may also be used .
Prosthetic Joint Infections
Prosthetic joint infections occur in about 1% of knee and hip arthroplasties. These infections may lead to failure of the joint replacement . Prosthetic joint infections are usually caused by gram-positive cocci, including coagulase-negative staphylococci and S. aureus. Risk factors for the development of prosthetic joint infections include previous fracture, seropositive rheumatoid arthritis, obesity, revision arthroplasty, and surgical site infections . It is important to note that the intra-articular WBC cutoff values for a prosthetic joint infection may be as low as 1100. Another additional caveat making the diagnosis more difficult is the indolent clinical presentation. Antimicrobial treatment, debridement, exchange, or permanent removal of the prosthesis may be required. In some patients, long-term suppressive antimicrobial therapy may be warranted .
Empiric antibiotic therapy for suspected bacterial arthritis 
Ceftazidime, cefepime, piperacillin/tazobactam, carbapenems.
If penicillin allergic: aztreonam, fluoroquinolones
Negative gram stain
Vancomycin plus either ceftazidime or an aminoglycoside
Drainage should be performed in setting of septic arthritis. This can be in the form of a needle aspiration, arthroscopic drainage, or open surgical drainage. Surgical drainage is indicated for septic arthritis of the hip, failure to respond to antibiotics after 5–7 days of antibiotic therapy and arthrocentesis, and soft tissue extension of infection. Of note, there is no data to support the efficacy of surgical drainage over arthrocentesis [6, 39].
Prognosis and Complications
Predictors of mortality include age over 65, confusion at presentation, and polyarticular disease along with coexistent renal or cardiac disease and immunosuppression. Predictors of joint damage include age over 65, diabetes, and infection with beta-hemolytic strep . If untreated, septic arthritis of the sternoclavicular or sacroiliac joint can lead to osteomyelitis as these are cartilaginous joints .
A 37-year-old male presents with 2 days of pain and swelling in his L knee. He recently returned from a trip to Seattle with his friends, where he had two sexual partners and denies using any form of contraception. He denies any history of gout, or episodes of podagral. His vital signs are T 37.9, BP 122/78, HR 66, RR 18, POx 100% on room air. His CBC, CMP, and uric acid are unremarkable and his ESR is 42. On physical examination, you note no other systemic manifestations including absence of rashes and tenosynovitis. His knee is warm, with limited range of motion, and a palpable effusion. You decide to perform an arthrocentesis. In addition to routine cell count, gram stain, culture, and sensitivity, what else would you do at this time?