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
- 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
- Usually vancomycin 2 to 8 g per 40 g cement, or an aminoglycoside
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
| 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
- 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
References
- 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
