Prosthetic joint infection

Background

Microbiology

• Hip and knee
  • Early (<3 months): Staphylococcus aureus (38%), aerobic Gram-negative bacilli (24%), coagulase-negative staphylococci (22%), Enterococcus (10%), and Streptococcus (4%), anaerobes including Cutibacterium acnes (3%), culture-negative (10%); 31% are polymicrobial
  • Overall: Staphylococcus aureus (27%), coagulase-negative staphylococci (27%), aerobic Gram-negative bacilli (9%), Streptococcus (8%), anaerobes including Cutibacterium acnes (4%), Enterococcus (3%), culture-negative (14%); 15% are polymicrobial
• Shoulder: coagulase-negative staphylococci (42%), Cutibacterium acnes (24%), Staphylococcus aureus (18%), aerobic Gram-negative bacilli (10%), others, culture-negative (15%); polymicrobial in 16%
• Elbow: Staphylococcus aureus (42%), coagulase-negative staphylococci (41%), others, culture-negative (5%); polymicrobial in 3%

Epidemiology

• Complicates about 2% of arthroplasty
  • 2% of hip and knee arthroplasties
  • 1% of shoulder arthroplasties

Pathophysiology

• Bacteria grown on the prosthesis in a biofilm, making it resistant to medical management

Clinical Manifestations

• Most commonly occur within the 3 months after arthroplasty (early); 70% within the first two years
• Should be suspected when there is a sinus tract, persistent wound drainage, acute onset of pain, or chronic pain after a pain-free interval

Prognosis

• Recurrent rates after DAIR are 9% (with 12 weeks of antibiotics) to 18% (with 6 weeks)1
• In a large observational study, about 30-40% overall have recurrence
  • DAIR success was highest with early post-implant infection and lower with late acute and chronic infections
  • Knee joint and Staphylococcus aureus were associated with lower success2

Diagnosis

• Routine investigations should include ESR, CRP, plain film x-ray, diagnostic arthrocentesis, and blood cultures (if fever or other systemic symptom)
  • If clinically stable, try to obtain arthrocentesis samples before antibiotics
  • Other imaging should not be used routinely
• Diagnosis is made most definitively by histopathology of periprosthetic tissue biopsy, and supported by positive intraoperative tissue cultures
  • Should take 3 to 6 intraoperative samples
  • If clinically stable, try to obtain tissue cultures before starting antibiotics
• A definitive diagnosis of PJI requires any of the following:
  • Sinus tract that communicates with the prosthesis
  • Acute inflammation on histopathology of intraoperatic periprosthetic tissue sample
  • Periprosthetic purulence without other cause
  • Two or more intraoperative cultures with identical organism, though a single positive culture may be sufficient in some cases
• A diagnosis of PJI may still be possible if the above criteria are not met but clinical suspicion remains

Management

Surgical Therapy

• Ultimately the decision of whether and how to treat surgically rests with the orthopedic surgeon
• Options include:
  • Debridement and retention
  • One-stage replacement
  • Two-stage replacement
• Antibiotic-impregnated cement is often used for the spacer
  • Usually vancomycin 2 to 8 g per 40 g cement, or an aminoglycoside
    • No clear guidelines for dosing
  • No clear evidence of effectiveness, but recommended in all revisions for septic arthritis
  • Releases over a period of two to three days

Antimicrobial Therapy

Surgical Management	Species	Location	Duration IV	Total Duration	Adjunctive Rifampin	Chronic Suppressive Thearpy
debridement and retention	Staphylococcus	knee	2-6 weeks	6 months	yes; 4-6 weeks IV if not given	±
		hip		3 months		±
		elbow				±
		shoulder				±
		ankle				±
	species other than staphylococci	—	4-6 weeks			±
resection ± reimplantation	—	—	4-6 weeks
1-stage exchange	Staphylococcus	—	2-6 weeks	3 months	yes; 4-6 weeks IV if not given	±
	species other than staphylococci	—	4-6 weeks	3 months		±
amputation with source control	—	—	24-48 hours
amputation without source control	—	—	4-6 weeks

• IV therapy includes highly bioavailable oral therapy

Intravenous and Highly Bioavailable Oral Therapy

Choice of Antimicrobial

Species	Preferred Antimicrobials	Alternative Antimicrobials
Staphylococcus (oxacillin-susceptible)	nafcillin or cefazolin or ceftriaxone	vancomycin or daptomycin or linezolid
Staphylococcus (oxacillin-resistant)	vancomycin	daptomycin
Enterococcus (penicillin-susceptible)	penicillin G or ampicillin	vancomycin or daptomycin or linezolid
Pseudomonas aeruginosa	cefepime or meropenem	ciprofloxacin or ceftazidime
Enterobacter	cefepime	ciprofloxacin
Enterobacteriaceae	ampicillin or ceftriaxone or ciprofloxacin
β-hemolytic streptococci	penicillin G or ceftriaxone	vancomycin
Cutibacterium acnes	penicillin G or ceftriaxone	clindamycin or vancomycin

Dosing

Antimicrobial	Dose
ampicillin	12 g IV q24h continuously or split q4h
cefazolin	1-2 g IV q8h
cefepime	2 g IV q12h
ceftazidime	2 g IV q8h
ceftriaxone	2 g IV q24h
ciprofloxacin	750 mg PO bid
ciprofloxacin	400 mg IV q12h
clindamycin	300-450 mg PO qid
clindamycin	600-900 mg IV q8h
daptomycin	6 mg/kg IV q24h
ertapenem	1 g IV q24h
linezolid	600 mg PO/IV q12h
meropenem	1 g IV q8h
nafcillin	1.5-2 g IV q4-6h
penicillin G	20-24 MU IV q24h continuously or split q4h
vancomycin	15 mg/kg IV q12h

Adjunctive Rifamycins

• Adjunctive rifampin 300 to 450 mg twice daily is usually added for staphylococcal infection where strong contraindications do not exist3
• Alternatively , can potentially use rifabutin 300 mg PO daily4

Chronic Suppressive Therapy

• Duration unclear; 3-12 months or lifelong
• In people in whom there is recurrence, it tends to recur within 4 months of discontinuing suppressive therapy

Microorganism	Preferred treatment	Alternative treatment
Staphylococcus (oxacillin-susceptible)	Cephalexin 500 mg PO tid to qid; Cefadroxil 500 mg PO bid	Dicloxacillin 500 mg PO tid to qid; Clindamycin 300 mg PO qid; Amoxicillin-clavulanic acid 500mg PO tid
Staphylococcus (oxacillin-resistant)	TMP-SMX DS 1 tab PO bid; Doxycycline 100 mg PO bid
β-hemolytic streptococci	Penicillin V 500 mg PO bid to qid; Amoxicillin 500 mg PO tid	Cephalexin 500 mg PO tid to qid
Enterococcus (penicillin-susceptible)	Penicillin V 500 mg PO bid to qid; Amoxicillin 500 mg PO tid
Pseudomonas aeruginosa	Ciprofloxacin 250-500 mg PO bid
Enterobacteriaceae	TMP-SMX DS 1 tab PO bid	Beta-lactam, if susceptible
Cutibacterium	Penicillin V 500 mg PO bid to qid; Amoxicillin 500 mg PO tid	Cephalexin 500 mg PO tid to qid; Doxycycline 100 mg PO bid

Intra-Articular Infusion

• Used in veterinary practice for decades, but only used experimentally in humans
• Intraoperatively insert two Hickman catheters into the intraarticular space
  • Two catheters used to ensure that at least one will remain viable for the duration
• Vancomycin
  • May precipitate local inflammatory response necessitating holding it for several days

Further Reading

• Prosthetic Joint Infection. Clin Micro Rev. 2014;27(2):302-345. doi: 10.1128/CMR.00111-13
• Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the IDSA. Clin Infect Dis. 2013;56(1):e1-25. doi: 10.1093/cid/cis803