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, as well as special considerations.[2, 3, 4, 5, 6, 7, 8, 9]

Orally administered antibiotics should not be part of either the empiric or organism specific regimens for SA. In general, a switch over to PO agents should be considered when there is documentation that the infection is responding to treatment(see below).

A study involving native and prosthetic joint infections found that orally administered antibiotics started within 7 days of instituting IV therapy were noninferior to antibiotics administered intravenously through the entire therapeutic course (13% and 15%, respectively). The primary pathogens included S aureus (38%), coagulase-negative staphylococci (27%), and Streptococcus species (15%). Sixty-one percent had prosthetic-related infections. Rifampin was given to 41% of the IV group and 56% of the PO group.

For initial oral treatment, the pathogen must be sensitive to antibiotics and 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. This study may be useful in justifying switchover to PO antibiotics earlier than has been done in the past.[10]

It is important to emphasize that the duration of antibiotic therapy for a given patient is dependent on that individual's clinical response to the provided medical and surgical care. This needs to be regularly assessed by the results of serial focused physical examinations; appropriate imaging studies; and pertinent cultures of tissue, blood, and joint fluid. Experience has shown that the studies are relatively insensitive indicators. Many, such as sedimentation rate or WBC, may improve or 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.[11, 12, 13, 14, 15, 16]

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.

*Rifampin must always 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)*{ref 11]

The following medications are 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

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
• Levofloxacin750 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 theraputic levels of antibiotic in necrotic bone and tissue, adding an aminoglycoside should be considered. 

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[17] 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%. ^{[18, 19]}
• Blood cultures should be obtained in all patients with suspected PJI. ^[20]
• 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. ^[18]
• 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. ^[18]
• 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 may also 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.  ^{[17, 21, 22]}

• Specific antibiotic choices should always be made with consideration of the  antibiotic stewardship plan of the facility.