Septic Arthritis of Prosthetic Joints Organism-Specific Therapy

Organism-specific therapeutic regimens for septic arthritis (SA) of prosthetic joints, or periprosthetic joint infection (PJI), are provided below, including those for methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), coagulase-negative staphylococci (CoNS), penicillin-sensitive and penicillin-resistant Streptococcus pneumoniae,[1]  gram-negative rods, and Pseudomonas aeruginosa.[2, 3, 4, 5, 6, 7, 8, 9]

A fungus identified in 2009, Candida auris, is distinctive in its ability to disseminate and persist on all types of healthcare surfaces as well as the skin of patients and providers. It thrives in water containing equipment and is resistant to most antfungals. The COVID-19 pandemic has promoted its nosocomial spread.[10]

Besides in vitro sensitivity, the initial oral treatment should have superior GI absorption, and the patient should be without any major suppurative complications that would require surgery. These results need to be confirmed by follow-up studies.[11]  It is important to emphasize that the duration of both parenteral and oral antibiotic therapy for a given patient is dependent on that individual's clinical response to the provided medical and surgical care. In addition to in vitro efficacy, this needs to be regularly assessed by the results of serial physical examinations; appropriate imaging studies; and pertinent cultures of tissue, blood, and joint fluid. Experience has shown that these studies are relatively insensitive indicators. While on therapy, many studies, such as erythrocyte sedimentation rate or WBC, may significantly improve or even normalize in chronically infected bone or periprosthetic tissue. This leads to delays in necessary surgery. Support is growing for following inflammatory markers such as CRP or procalcitonin as more reliable indicators of active infection.[12, 13, 14, 15, 16, 17, 18, 19]

Please see Septic Arthritis of Prosthetic Joints Empiric Therapy.

Vancomycin has been the traditional drug to administer to those with severe beta-lactam allergies and as treatment of CoNS and MRSA. Because of challenges in maintaining therapeutic levels (trough levels of 5-12 mcg/ml) in the severely ill and an evolving pattern of resistance, vancomycin is no longer the author's "go to" choice.

In the author's opinion rifampin should be part of the antibiotic regime for treating staphylococcal PJI.{11}

Methicillin sensitive staphylococcus aureus (MSSA)*

The following medications are given for MSSA

• Nafcillin 2 g IV q4h or
• Ceftriaxone 1-2 g IV q12h
• Rifampin 300 mg PO/IV q12h
• In patients with severe penicillin allergy, the author recommends linezolid 600 mg PO/IV q12h rather than vancomycin

Methicillin-resistant S aureus (MRSA)*

The following medications may given for MRSA:

• Linezolid 600 mg IV q12h or
• Daptomycin 6-12 mg/kg IV q24h or
• Minocycline loading dose 200 mg (IV/PO ) then 100 mg (ID/PO) q12h
• Rifampin 300 mg PO/IV q 12h

Coagulase-negative staphylococci (CoNS)*

The following medications are given for CoNS:

• Linezolid 600 mg IV q12h or
• Daptomycin 6 -12 mg/kg IV q24h

Streptococcus pneumoniae (penicillin sensitive) (minimal inhibitory concentration [MIC] < 4 mcg/ml)

The following medications are given for penicillin-sensitive Streptococcus pneumoniae:

• Ampicillin 2 g IV q4h or
• Ceftriaxone 1-2 g IV q12-24h 

S pneumoniae (penicillin resistant) (MIC ≥4 mcg/mL)

The following medications are given for penicillin-resistant S pneumoniae:

• Ceftriaxone 1-2 g IV q12h or
• Levofloxacin 750 mg IV or PO q24h

Gram-negative rods (other than Pseudomonas)

The following medications are given for gram-negative rods other than Pseudomonas:

• Ceftriaxone 1-2 g IV q12h or
• Ciprofloxacin 400 mg IV or 500 mg PO q12h or
• Levofloxacin 500 mg IV or PO q24h for 3 weeks

Pseudomonas aeruginosa

The following medications are given for Pseudomonas aeruginosa:

• Cefepime 2 g IV q8h plus * gentamicin or tobramycin 5 mg/kg IV q24h  or
• Piperacillin-tazobactam 3.375-4.5 g IV q6h plus* gentamcin or tobramycin 5 mg/kg IV q24h
• Because of significant challenges to acheive therapeutic levels of antibiotic in necrotic bone and tissue, adding an aminoglycoside should be considered.

Candida auris

Casofungin 70 mg IV daily

Alternative Antibiotics

Because the length of therapy is so prolonged, there is a real possibility that significant side effects of the initial choices will lead to significant side effects or resistance patterns.

Certain cases of PJI cannot be cured but need to be suppressed. The pharmacokinetics of dalbavancin (see below) make its use attractive in such cases.

Aztreonam 2 gm IV q12h is useful in patients with severe beta-lactam allergy who have sensitive Gram-negatives

Ceftazidime/avibactam 2.5 gm IV q8h is useful in highly resistant Gram-negative, especially Pseudomonas

Dalbavancin[20] Loading dose 1500 mg IV times x1, then 500 mg IV every 7 days

Special considerations

Special considerations include the following:

• The sensitivity of synovial fluid culture ranges from 45% to 100%.
• Culture results of periprosthetic tissues have a sensitivity ranging from 65% to 94%. ^{[21, 22]}
• Blood cultures should be obtained in all patients with suspected PJI. ^[23]
• In PJI, plain radiography can detect new subperiosteal bone growth and transcortical sinus tracts—both are signs of active infection.
• The 2-stage joint-replacement procedure is the preferred surgical procedure; the prosthesis is removed, and an antibiotic-impregnated spacer is placed after thorough debridement of the infected tissue. IV antibiotics are delivered for 6 to 8 weeks before the new joint is implanted. ^[21]
• The 1-stage joint-replacement procedure consists of simultaneous removal and replacement of the joint, and it is usually employed in patients with highly sensitive organisms; however, the success rate is lower than the 2-stage procedure. ^[21]
• Early stages of PJI may respond to simple debridement, followed by 2-6 weeks of IV antibiotics and orally administrated antibiotics for up to 6 months; this approach also may be taken in patients with very high operative risk.
• Indefinite suppressive antibiotic therapy is an option if the prosthesis cannot be removed (high operative risk) and there is an appropriate orally administrated antibiotic.
• For prolonged antibiotic treatment of infections with all non-enterococcal streptococci, MSSA, MRSA, CoNS, and vancomycin-sensitive enterococci, dalbavancin should be considered owing to its weekly administration regimen: 1500 mg IV as loading dose, followed by 500 mg IV weekly.  ^{[20, 24, 25]}
• Specific antibiotic choices should always be made with consideration of the antibiotic stewardship plan of the facility.