One or multiple joints can be affected at the same time.Laboratory studies such as blood cultures, white blood cell count with differential, ESR, and CRP should also be included. However, white cell count, ESR, and CRP are nonspecific and could be elevated due to infection elsewhere in the body. Serologic studies should be done if lyme disease is suspected. Blood cultures can be positive in 25 to 50% of those with septic arthritis due to spread of infection from the blood. CRP more than 20 mg/L and ESR greater than 20 mm/hour together with typical signs and symptoms of septic arthritis should prompt arthrocentesis from the affected joint for synovial fluid examination.The synovial fluid should be collected before the administration of antibiotics and should be sent for gram stain, culture, leukocyte count with differential, and crystal studies. This can include NAAT testing for N. gonorrhoeae if suspected in a sexually active person.In children, the Kocher criteria is used for diagnosis of septic arthritis. Differential diagnosis
The differential diagnosis of septic arthritis is broad and challenging. First, it has to be differentiated from acute hematogenous osteomyelitis. This is because the treatment lines of both conditions are not identical. Noteworthy, septic arthritis and acute hematogenous osteomyelitis can co-occur. Especially in the hip and shoulder joints their co-occurrence is likely and represents a diagnostic challenge. Therefore, physicians should have a high suspicion index in that regard.
General guidelines are as follows:

Gram positive cocci – vancomycin
Gram negative cocci – Ceftriaxone
Gram negative bacilli – Ceftriaxone, cefotaxime, or ceftazidime
Gram stain negative and immunocompetent – vancomycin
Gram stain negative and immunocompromised – vancomycin + third generation cephalosphorin
IV drug use (possible pseudomonas aeruginosa) – ceftazidime +/- an aminoglycosideOnce cultures are available, antibiotics can be changed to target the specific organism. After a good response to intravenous antibiotics, people can be switched to oral antibiotics. The duration of oral antibiotics varies, but is generally for 1–4 weeks depending on the offending organism. Repeated daily joint aspiration is useful in the treatment of septic arthritis. Every aspirate should be sent for culture, gram stain, white cell count to monitor the progress of the disease. Both open surgery and arthroscopy are helpful in the drainage of the infected joint. During surgery, lysis of the adhesions, drainage of pus, and debridement of the necrotic tissues are done. Close follow up with physical exam & labs must be done to make sure the person is no longer feverish, pain has resolved, has improved range of motion, and lab values are normalized.In infection of a prosthetic joint, a biofilm is often created on the surface of the prosthesis which is resistant to antibiotics. Surgical debridement  is usually indicated in these cases. A replacement prosthesis is usually not inserted at the time of removal to allow antibiotics to clear infection of the region. People that cannot have surgery may try long-term antibiotic therapy in order to suppress the infection.