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

2018 Definition of Periprosthetic Hip and Knee Infection3

Criterion	Points	Interpretation
Major Criteria
Two positive cultures of the same organism	N/A	Infected
Sinus tract with evidence of communication to the joint or visualization of the prosthesis	N/A
Minor Preoperative Criteria
Elevated serum CRP or D-dimer	2	≥6: infected 2-5: possibly infected ≤1: not infected
Elevated serum ESR	1
Elevated synovial WBC count or LE	3
Positive synovial alpha-defensin	3
Elevated synovial PMN %	2
Elevated synovial CRP	1
Intraoperative Criteria for Inconclusive Preoperative Scores
Preoperative score	-	≥6: infected 4-5: inconclusive ≤3: not infected
Positive histology	3
Positive purulence	3
Single positive culture	2

Marker	Cutoff
	Chronic >90 days	Acute <90 days
Serum CRP (mg/dL)	1	10
Serum D-dimer (ng/mL)	860	860
Serum ESR (mm/h)	30	-
Synovial WBC (cells/μL)	3000	10 000
Synovial PMN (%)	80	90
Synovial CRP (mg/L)	6.9	6.9
Synovial alpha-defensin	1	1

• The above criteria may be inaccurate in patients with adverse local tissue reaction (ALTR), crystalline deposition arthropathy, inflammatory arthopathy flare, or infection with slow-growing organisms such as Cutibacterium acnes and coagulase-negative staphylococci

Management

Surgical Management

• Ultimately the decision of whether and how to treat surgically rests with the orthopedic surgeon
• Options include:
  • Debridement and implant retention (DAIR), preferred if well-fixed prosthesis, no sinus tract, susceptible to oral antibiotics, joint age <30 days, and symptoms <3 weeks
    • Need for further revision is 20-30% and is lowest is done within 4 weeks from index arthroplasty4
  • One-stage replacement
  • Two-stage replacement, where the prosthesis is removed and replaced with a cement spacer, the infection is treated, and then a new prosthesis is placed
• 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 Therapy
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	12 weeks†	no	±
resection ± reimplantation (2-stage exchange)	—	—	4-6 weeks	—		no
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	no	±
amputation with source control	—	—	24-48 hours	—	no	no
amputation without source control	—	—	4-6 weeks	—	no	no

• ^* IV therapy includes highly bioavailable oral therapy
• ^† per DAPITO trial1

Intravenous and Highly Bioavailable Oral Therapy

Choice of Antimicrobial

• Increasing evidence suggests that regimens of fluoroquinolone plus rifampin has the lowest risk of recurrence, and should likely be the preferred regimen in staphylococcal infections with susceptible organisms

IDSA guideline-based antimicrobial recommendations

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 exist5
• Alternatively , can potentially use rifabutin 300 mg PO daily6

Management after DAIR

• Mostly 12 weeks of antibiotics (24 weeks for staphylococcal knee infections), as in above table
• DAPITO trial showed inferiority of 6 weeks compared to 12 weeks after DAIR1

Chronic Suppressive Therapy

• Sometimes considered after debridement and implant retention
• Duration unclear; 3-12 months or indefinite
• In people in whom there is recurrence, it tends to recur within 4 months of discontinuing suppressive therapy
• Chronic suppression is recommended where there is a high risk of recurrence or where the consequences of recurrence would be devastating
  • High-risk bacteria like Staphylococcus aureus or Multidrug-resistant Gram-negative bacteria
  • Limited life expectancy
  • Prior treatment failure
  • Poor candidate for future surgeries
• Reassess the suppressive therapy every 6 to 12 months

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

Management With One-Stage Replacement

• Duration 6 to 12 weeks of antibiotics

Management With Two-Stage Replacement

• Initially 6 to 12 weeks of antibiotics, followed by a 2+ week antibiotic holiday, then reimplantation

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
• Microbiology of polymicrobial prosthetic joint infection. Diagnostic Microbio Infect Dis. 2019;94(3):255-259. doi: 10.1016/j.diagmicrobio.2019.01.006
• 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