Septic Arthritis Treatment & Management

Medical management of infectious arthritis should be focused on adequate and timely drainage of the infected synovial fluid; administration of appropriate antibiotic(s); and debridement of any associated osteomyelitis or soft tissue infection with immobilization of the joint to control pain. The major challenges are duration of oral and intravenous antibiotic administration, especially in the setting of PJI.

Acute PJI (< 3 wks in duration) can be cured medically if it is of the early type or secondary to hematogenous spread without any evidence of periarticular soft-tissue involvement or joint instability. ^[10]  However, it is imperative to monitor therapy by repeat ultrasounds or other imaging studies of the joint, as well as inflammatory markers such as CRP.

Overall, the mean length of hospitalization for septic arthritis is 11.5 days. However, outpatient antibiotic therapy in stable patients can significantly reduce hospital stays. ^[41]

Consultations

Typically, care providers have consulted orthopedic and /or infectious disease consultants in their management of septic arthritis. However, the ever-increasing amount of prosthetic joint surgery infections along with the lack of clearly defined approaches to their infectious complications have led to recommendations of interdisciplinary boards to oversee the care of these patients. ^{[42, 43]}  

In native joint infections, antibiotics usually are administered parenterally for at least 2 weeks. As a rule, the SA of disseminated gonorrhea responds to 2 weeks of intravenous antibiotic. ^[37]  However, each case must be evaluated independently. The medical dogma that infection with either methicillin-resistant S aureus (MRSA) or methicillin-susceptible S aureus (MSSA) requires at least 4 full weeks of intravenous treatment has recently been challenged.

In a randomized controlled study of 1054 patients(OVIVA trial), 61% had hardware-associated infections, 38% were infected with S aureus, and 27% were infected with CoNS. In the OVIVA trial, standard intravenous antibiotic therapy was begun within 7 days of surgery and administered for at least 6 weeks. In the other arm of the study, patients received oral antibiotic therapy. Both groups of patients could receive follow-up oral antibiotics. At the end of 1 year, there did not seem to be a significant difference in the rate of failure between both groups. Standard treatment failed in 14.6 % of the IV group and 13.2% of the oral group. ^[41] The oral agents were generally quinolones or penicillins. Intravenous agents usually were the glycopeptides and cephalosporins. In both groups, therapy was “tweaked" to meet the therapeutic challenges of each subject. More data are emerging to support shortened antibiotic courses for septic arthritis of native joints. ^[44]  

The DATIPO study compared the efficacy of 6 weeks versus 12 weeks of antibiotic therapy in patients with PJI who had undergone appropriate surgical procedures to eradicate associated osteomyelitis and soft issue infection or joint replacement by 1 or 2 stage procedure. The medium duration of IV antibiotic administration was 9 days for both groups. The failure rate to eradicate joint infection was 18.1% for the 6-week group and 9.4% for the 12-week group. ^[45]  The biggest risk for failure was among those who underwent one simple debridement without removal of the prosthetic material.

Remaining therapeutic challenges include types of antibiotics; total duration of their administration, including both IV and PO routes; and treatment of late PJI. From a functional perspective, antibiotic therapy along with debridement of infected periprosthetic tissue while retaining the infected prosthesis has the potential for providing optimum results. ^[46]

In summary, the study emphasized the importance of implant removal. Optimal duration of therapy needs to balance the increased risk for side effects related to prolonged exposure to these agents against treatment failure.

Caveats to this shortened course of IV antibiotic therapy include the presence of extensive periarticular osteomyelitis, leukopenia, or other immunosuppressive states. In patients with blood cultures that are positive for S aureus, it is imperative to exclude underlying valvular infection. More and more, it appears that prolonged antibiotic administration(>1 year) in periprosthetic PJI serves to suppress and not cure the periprosthetic PJI. Measuring the response of various inflammatory markers must be strongly considered to augment the clinical response to antibiotic treatment.

See Surgical Intervention in Prosthetic Joint Infection, below.

Antibiotic selection

Initial antibiotic choices must be empirical, based on the sensitivity pattern of the pathogens of the community. Consider the rise of resistance among potential bacteria when choosing an initial antibiotic regimen. If local incidence of MRSA is high (in particular, marked increase in the resistance of the pneumococcus), prescribe alternate antibiotics initially. Because many isolates of group B streptococci have become tolerant of penicillin, use a combination of penicillin and gentamicin or a later-generation cephalosporin. MRSA is becoming established outside of the hospital setting. Enterobacteriaceae and P aeruginosa are becoming more resistant to multiple antibiotics. Knowing the resistance patterns in the community, as well as in the hospital, is most important.

Preferably, the antibiotic should be bactericidal with some effect against the slow-growing organisms that are protected within a biofilm (eg, coagulase-negative S aureus [CoNS]) and S aureus. Rifampin fulfills these requirements. This agent should never be used alone because of the rapid development of bacterial resistance to the drug.

If, after 5 days of therapy, the joint shows some degree of improvement, consider an empirical trial of an anti-inflammatory agent for increased symptomatic relief. If the joint fails to respond after 5 days of appropriate antibiotic therapy (eg, presence of clinically significant fever, continued synovial purulence, persistently positive findings on culture), reassess the therapeutic approach, as follows:

• Follow up on the response of the inflammatory markers (CRP, procalcitonin) with the caveat that normalization of these may represent suppression and not eradication of the infection
• Reculture the fluid and reexamine for crystals
• Perform appropriate serologies for diagnosis of Lyme disease; if these are positive, treat per guidelines
• If fungal or mycobacterial infection is possible, consider obtaining a synovial biopsy
• Consider the possibility of reactive arthritis; nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary therapeutic agents for reactive arthritis
• Perform imaging studies, either radiographs or magnetic resonance imaging (MRI), to rule out periarticular osteomyelitis.
• Candida auris is a very recently isolated fungus that contaminates surfaces and sources of water ithroughout a healthcare facility. It  tenaciously colonizes the skin of those suffering from COVID-19 ^[47]

Antibiotics have a role in suppressing associated chronic osteomyelitis and chronically infected prosthetic material that cannot be removed for various reasons.

The use of fluoroquinolones for an extended period should be considered when the removal of an infected prosthesis is not possible. Cure rates as high as 62% have been documented in relatively small series. Generally, such prolonged therapy is seen as suppressive and not curative. ^[25]

Usually, immobilization of the infected joint to control pain is not necessary after the first few days. If the patient's condition responds adequately after 5 days of treatment, begin gentle mobilization of the infected joint. Most patients require aggressive physical therapy to allow maximum post-infection functioning of the joint.

Initial physical therapy consists of maintaining the joint in its functional position and providing passive range-of-motion exercises. The joint should bear no weight until the clinical signs and symptoms of synovitis have resolved. Aggressive physical therapy often is required to achieve maximum therapeutic benefit.

The choice of the type of drainage, whether percutaneous or surgical, has not been resolved completely. ^{[10, 33, 48]} In general, use a needle aspirate initially, repeating joint taps frequently enough to prevent significant reaccumulation of fluid. Aspirating the joint two to three times a day may be necessary during the first few days. If such drainage is required past this point, surgical drainage should be initiated.

Purulent gonococcal arthritis requires frequent joint drainage. However, the joints of patients with disseminated gonococcemia characterized by the triad of tenosynovitis, dermatitis, and polyarthralgia rarely require surgical drainage. ^[49]

Surgical drainage is indicated when one or more of the following occur:

• The appropriate choice of antibiotic and vigorous percutaneous drainage fails to clear the infection after 5 to 7 days
• The infected joints are difficult to aspirate (eg, hip)
• Adjacent soft tissue is infected

Routine arthroscopic lavage rarely is indicated. However, drainage through the arthroscope is replacing open surgical drainage. With arthroscopic drainage, the operator can visualize the interior of the joint and can drain pus, debride, and lyse adhesions.

Debridement and retention of the prosthesis can be considered in patients who develop periprosthetic joint infection (PJI) within 30 days of implantation or in those whose PJI presented within 3 weeks of the development of symptoms, if the prosthesis appears to be well fixed and is without a sinus tract. ^[24] The DAIR technique is to leave the prosthesis in place, perform aggressive wound debridement, and treat with appropriate antibiotics (See below). 

The PIANO Study reviewed the success rate of the DAIR approach. It was curative in 74% of early PJIs; 49% in LA-PJI; and 44% in chronic PJIs. This progressive loss of efficacy of the DAIR approach may be due to a number of factors:

1. Persistence of the periarticular soft tissue and/ or bony infection that escape detection by current imaging techniques (radionuclide scans, ultrasonograhy, MRIs). There often are periarticular areas of necrotic soft tissue and bone. These "safe havens" may promote resistance to the initially administered antibiotics (See Antibiotic Therapy, below). Intermittent short repeat courses of antibiotic promote development of bacterial resistance by decreasing the permeability of the bacteria's cellular membrane or by increasing the efflux of the antibiotic from the cellular interior. ^[38]
2. Because of the above, the choice of antibiotic and its dosing regimen should not be based solely on the initial data set. Essentially, the pathogen may have become resistant. A new regimen, often members of the tetracycline family, should be started. Even if not, a change in renal function or liver function may necessitate an overhaul of the therapeutic plan. 

Otherwise, removal of all the prosthetic material is mandatory. First, remove the prosthesis and follow with an appropriate antibiotic. Then, place the new joint, impregnating the methylmethacrylate cement with an anti-infective agent (ie, gentamicin, tobramycin). Antibiotic diffusion into the surrounding tissues is the goal. The success rate for this approach is approximately 95% for both hip and knee joints.

An intermediate method is to exchange the new joint for the infected joint in a 1-stage surgical procedure with concomitant antibiotic therapy. This method, with concurrent use of antibiotic cement, may be successful in 70-90% of cases. What is unclear is the total duration of post procedural antibiotic therapy. A recent study compared the effectiveness of 6 weeks versus 12 weeks of total antibiotic therapy. ^[41]  Forty-one percent underwent debridement alone; 37% underwent a one-stage exchange; and 22% received a two-stage exchange of the implants.

Thirty-eight percent of S aureus infections received 6 weeks of antibiotic therapy, whereas 30% received 12 weeks of antibiotics. Thirty percent of CoNS received 6 weeks and 35% received 12 weeks of antimicrobials. Both received 9 days of parenteral antimicrobials. The fluoroquinolones and rifampin were the most frequently employed.

The design of this study is problematic in that there was a wide variety of surgical interventions employed as well as specific antibiotic regimens. Even the 12-week course generally is shorter than that usually followed in the United States. It is consistent with recent studies. ^[44]  The response to antibiotic therapy needs to be monitored by follow-up exams and appropriate imaging studies and measurement of inflammatory markers.

Strictly adhere to sterile procedures whenever the joint space is invaded (eg, in aspiration or arthroscopic procedures).

Antibiotic prophylaxis with an anti-staphylococcal antibiotic has been demonstrated to reduce wound infections in joint replacement surgery. Polymethylmethacrylate cement impregnated with antibiotics may decrease perioperative infections.

Using antibiotic prophylaxis on the same theoretic basis as that for cardiac valvular disease has been advocated. Whenever a sustained bacteremia may be encountered, be aware of the possibility of joint involvement, especially for prosthetic joints. Consideration should be given to more prolonged treatment of the bacteremia to cover the possibility of very early joint infection (secondary prophylaxis). The implanted hardware most likely is at greatest risk for bacteremia infection within a few months of placement. The risk probably decreases as a pseudocapsule evolves. During this time, prophylaxis is probably most beneficial. The results of a recent well-designed study support the recommendation that all joint replacement patients require antibiotic prophylaxis prior to dental procedures. ^[50]  The author will continue to provide such prophylaxis.

Treat any infection promptly to lessen the chance of bloodstream invasion. In addition, decreasing the incidence of underlying infections best prevents reactive arthritis.

Patient education

Instruct patients with a prosthetic joint in place to recognize early signs of joint infection and, more importantly, to recognize bacterial infections in other parts of their bodies to prevent associated bacteremias.

For patient education information, see Arthritis Center as well as Knee Pain and Ticks.

The risk for repeat arthroplasty performed for septic arthritis is six times that of repeat arthroplasty for other indications. Patients with septic arthritis who underwent arthroplasty also exhibited a significantly increased mortality rate over the 15 years after the procedure. ^{[51, 52]}

For various reasons, joint infection may fail to respond to combined surgical and antibiotic therapy. ^[51] In such cases, an orally administered suppressive antibiotic therapy usually is administered. The increasing prevalence of resistant organisms among these individuals is eliminating this option; subcutaneous injection of beta-lactam drugs provides another option. ^[52]