Prosthetic joint infection

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Background

Microbiology

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
    • 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 ±
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
  • 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 exist4
  • Alternatively , can potentially use rifabutin 300 mg PO daily5

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
  • 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

References

  1. a b c  Louis Bernard, Cédric Arvieux, Benoit Brunschweiler, Sophie Touchais, Séverine Ansart, Jean-Pierre Bru, Eric Oziol, Cyril Boeri, Guillaume Gras, Jérôme Druon, Philippe Rosset, Eric Senneville, Houcine Bentayeb, Damien Bouhour, Gwenaël Le Moal, Jocelyn Michon, Hugues Aumaître, Emmanuel Forestier, Jean-Michel Laffosse, Thierry Begué, Catherine Chirouze, Fréderic-Antoine Dauchy, Edouard Devaud, Benoît Martha, Denis Burgot, David Boutoille, Eric Stindel, Aurélien Dinh, Pascale Bemer, Bruno Giraudeau, Bertrand Issartel, Agnès Caille. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. New England Journal of Medicine. 2021;384(21):1991-2001. doi:10.1056/nejmoa2020198.
  2. ^  Joshua S Davis, Sarah Metcalf, Benjamin Clark, J Owen Robinson, Paul Huggan, Chris Luey, Stephen McBride, Craig Aboltins, Renjy Nelson, David Campbell, L Bogdan Solomon, Kellie Schneider, Mark R Loewenthal, Piers Yates, Eugene Athan, Darcie Cooper, Babak Rad, Tony Allworth, Alistair Reid, Kerry Read, Peter Leung, Archana Sud, Vana Nagendra, Roy Chean, Chris Lemoh, Nora Mutalima, Ton Tran, Kate Grimwade, Marjoree Sehu, Davis Looke, Adrienne Torda, Thi Aung, Steven Graves, David L Paterson, Laurens Manning. Predictors of treatment success following peri-prosthetic joint infection: 24-month follow up from a multi-center prospective observational cohort study of 653 patients. Open Forum Infectious Diseases. 2022. doi:10.1093/ofid/ofac048.
  3. ^  Javad Parvizi, Timothy L. Tan, Karan Goswami, Carlos Higuera, Craig Della Valle, Antonia F. Chen, Noam Shohat. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. The Journal of Arthroplasty. 2018;33(5):1309-1314.e2. doi:10.1016/j.arth.2018.02.078.
  4. ^  Werner Zimmerli, Parham Sendi. Role of Rifampin against Staphylococcal Biofilm InfectionsIn Vitro, in Animal Models, and in Orthopedic-Device-Related Infections. Antimicrobial Agents and Chemotherapy. 2018;63(2):e01746-18. doi:10.1128/aac.01746-18.
  5. ^  James B. Doub, Emily L. Heil, Afua Ntem-Mensah, Renaldo Neeley, Patrick R. Ching. Rifabutin Use in Staphylococcus Biofilm Infections: A Case Series. Antibiotics. 2020;9(6):326. doi:10.3390/antibiotics9060326.