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Diagnosis of
Infected total knee arthroplasty
Warakorn Jingjit, MD
Orthopaedic Department, Faculty of Medicine
Chiang Mai University
One of the most devastating & challenging complication
Immense financial & psychological burden
Cost of treatment 15,000 - 60,000 $ / TKA
Hebert CK, CORR, 1996
Sculco TP, Orthopedics, 1995
Incidence
• 0.39% in primary TKA
• 0.97% in revision TKA
Projection of the TKA & THA number

Kurtz S, JBJS, 2008
Projection of the TKA & THA infection

Kurtz S, JBJS, 2007
Risk factors
1.
2.
3.
4.

Patient / host
Surgical environment
Surgical technique
Postoperative management
Risk factors
Patient / host
• Immunocompromise

•

– RA (4.4%)
– Steroid therapy
– DM (7%)
– Poor nutrition
• Albumin <3.5g/dl: 7-fold
• Lymphocyte <1,500 cells/mm3: 5-fold
•
– HIV
– Organ transplant
•

•
•
•

Hypokalemia
Tobacco use
Obesity

•
•
•

Debilitation
–
–
–
–
–

Advanced age
Alcoholism
Renal failure
Cirrhosis
Prolonged pre-op
hospitalization

Hypothyroidism
Previous surgery
Psoriasis
Previous infection
Concurrent infection
Risk factors
Surgical environment
• Personnel
• Clean air
Laminar air flow, UV light
• Surgical attire
• Operative site preparation
Ritter MA, CORR,1988
Ritter MA, Orthop Clin North Am,1989
Berg M, JBJS (Br), 1991
Ritter MA, CORR, 1999
Peersman G, CORR, 2001
Risk factors
Surgical technique

•

Surgical time

Operative time > 2.5 hrs
Peersman, CORR, 2001
Risk factors
Surgical technique
Prophylactic antibiotic
Single most effective method of ↓ infection
1st gen. cephalosporin
Allergy  vancomycin / clindamycin
30-60 min before incision
(peak serum bone conc. within 20 min)
 Repeat every 4 hrs & bleed >1,000 ml
 Discontinue 24 hrs after surgery




Risk factors
Surgical technique
Prophylactic antibiotic bone cement

•

High risk 1o TKA, revision TKA
Risk factors
Surgical technique
Implant

• Hinged prosthesis
• Infection rate at 10 yrs ~ 15%

• Bengtson S, Acta Orthop Scand, 1991
• Hanssen AD, CORR, 1995
• Schoifet SD, JBJS, 1990
Risk factors
Post operative management
• Bacteremia: oral > GI > GU procedure
• Avoid in first 3-6 mo (high incidence)
AAOS & ADA 1997
• First 2 yrs, specific risk factor for all pts  ATB prophylaxis
• After 2 yrs  consider in high risk pts
Recommended regimens (before procedure 1 hr)
• Cephalexin, cephradine, amoxicillin 2 g. oral
• Cephalosporin 1 g / ampicillin 2 gm IV / IM
• Clindamycin 600 mg oral (allergy to penicillin)
• Clindamycin 600 mg IV / IM (allergy to penicillin)
Advisory statement. J Am Dent Assoc, 1997
Potential risks of hematojenous
total joint infection
• All patients for the first 2 years after joint replacement
• lmmunocompromised / immunosuppressed patients
- Inflammatory arthropathies
- Drug-induced immunosuppression
- Rheumatoid arthritis
- Radiation-induced immunosuppression
- Systemic lupus erythematosus

• Patients with comorbidity conditions
- Previous prosthetic joint infections - HIV infection
- Poor nutrition
- Insulin-dependent diabetes
- Hemophilia
- Malignancy
Advisory statement. J Am Dent Assoc, 1997
Microbiology
Predominant organisms

Goldman RT, CORR, 1996
Microbiology
• Fungal infection = rare
 Candida = predominant

• Mycobacterium tuberculosis = rare
Microbiology

• Mucopolysaccharide biofilm
• Protect from antibodies, phagocytes, ATB.,
• ↑ virulence
Microbiology
• Methicillin-resistant organism  vancomycin
Ries MD, J Arthroplasty, 2001

• Rifampicin = good biofilm & tissue penetration
 improve success when use ĉ other synergistic agent
Zimmerli W, JAMA, 1998
Differential diagnosis
A painful knee is infected until proved otherwise
Insall, 1981

•
•
•
•

Periprosthetic fx
PF problem
Aseptic loosening
Soft tissue disruption

•
•
•
•

Instability
RSD
HO
Arthrofibrosis
Diagnosis
Fundamental of diagnosis
* * * High index of suspicion * * *

Clinical history Physical examination Radiography Aspiration Hematologic
studies

Radionuclide studies

Pathology
Diagnosis
History
• Pain = most common presenting symptom
• Typical = rest / night / persistent / progressive pain
• Progressive stiffness
• Hx of prolong postop drainage, ATB treatment
Physical examination
• Swelling, effusion, warmth, erythema, tenderness
• Painful range of motion
• Persistent wound drainage
 strongly suggestion  early aggressive Rx
Diagnosis
• Swab wound  not recommend
• Empirical ABO for wound drainage  mask symptoms,
affect subsequent C/S, predispose for drug resistant
• Diagnosis in early postop period
– ESR, CRP  limit value
– Typically by arthrocentesis
Aspiration
• Leucocyte count & differentiation
• Gram strain (sens 97%, spec 26%) (
• Culture for aerobic & anarobic bacteria

>1,700/ml3, PMN > 65% (sens 94-97%, spec 88-98%)
Trampuz A, Am J Med, 2004

• Ongoing ATB  stop for several wks before aspiration
Mark Coventry Award Paper
Diagnosis of early post-operative infection following TKA:
The utility of synovial fluid cell count and differential
“Synovial WBC count is an excellent test for diagnosing
infection within 6 wks after 1oTKA
with an optimal cut-off 27,800 cells/mm3 and 89% PMN”
Sens 84%, spec 99%, PPV 94%, NPV 98%
Craig J. Della Valle
Presented at the Knee Society Specialty Day Meeting
March 13, 2010, New Orleans
Hematologic studies
For chronic infection

ESR
– Positive > 30 mm/hr (sens 80%, spec 62.5% )
– False positive: infection elsewhere, inflammation,
CNT dis, neoplasm, recent operation (< 3 mo)
– False negative: prior antibiotics
CRP
– Positive > 10 mg/L (sens & spec 85%)
– Return to normal within 3 wks after operation
ESR + CRP: PPV 83%, NPV 100%
Barrack RL, CORR, 1997
Swanson KC, The adult knee, 2003
Guideline for ESR & CRP
1. Normal ESR & CRP reliable for the absence of infection
2. CRP more useful than ESR for monitoring
3. Use with other tests for the diagnosis of infection

Spangehl MJ, JBJS, 1999
PCR
•
•
•
•
•

Molecular genetic diagnosis
Identify 16S RNA gene
Expensive
Time-dependent
False positive
Remain experimental modality !!!
Mariani BD, CORR, 1996
X-ray
Sequential plain radiographs
• Progressive radiolucencies
• Focal osteopenia / osteolysis of subchondral bone
• Periosteal new bone formation
Morrey BF, CORR, 1989

• Bone destruction – infection present > 10-21 days
• Lytic lesion – destroy 30-50% of bony matrix
Early infection – no abnormal finding !!!
Radioisotope scan
Occasionally helpful in chronic infection
• Tc-99m MDP
• In-111 leukocyte scan
• Tc-99m sulfur colloid
Radioisotope scan
Occasionally helpful in chronic infection
Isotope

Sensitivity Specificity Accuracy

Tc 99m

95%

20%

54%

Indium 111

77%

75%

90%

Tc 99m + In111

100%

97%

97%

Palestro CJ, Radiology, 1991
Intraoperative tissue frozen section
• Widely use
• Result depend on
 Adequate & representative tissue obtaining
 Accurate interpretation by skilled pathologist
> 5 PMN/HPF at least 5 fields  Sens 100%, spec 96%
>10 PMN/HPF at least 5 fields  Sens 25%, spec 98%
Feldman DS, JBJS, 1995
Della Valle CJ, JBJS 1999
Intraoperative tissue frozen section
Reliable predictor for infection

• >10 PMN/HPF: sens 84%, spec 99%, PPV 89%, NPV 98%
• 5-10 PMN/HPF: need other test to differentiate
• <5 PMN/HPF: infection was highly unlikely
Lonner Jh et al, JBJS,1996
Intraoperative gram strain

• Unreliable
• Low sensitivity = 0-14.7%
Atkins BL, J Clin Microbiol, 1998
Della Valle CJ, J Arthroplasty, 1999
Intraoperative culture
Gold standard
Sample: fluid & tissue
 Joint capsule
 Synovial lining
 IM tissue
 Granulation tissue
 Bone fragments
• False +ve: contamination
• False -ve: prior ATB, transport system, lab
- Duff GP, CORR, 1996
- Bauer TW, JBJS, 2006
Definite diagnosis
At least one of the following
1. Same organism from c/s ≥ 2 specimens by aspiration /
deep tissue from surgery
2. Intraarticular tissue histopathology = acute inflammation
3. Gross purulence at the time of surgery
4. Actively discharging sinus tract

Hansen, CORR, 1994
Definite diagnosis
At least one of the following
1. Open wound / sinus tract communicate ĉ joint
2. Systemic signs / symptoms ĉ pain & purulent fluid
3. At least 3 of 5
 ESR > 30 mm/hr
 CRP >10 mg/L
 Frozen section > 5 PMN/HPF
 Preoperative aspiration c/s ≥ 1 +ve
 Intraoperative c/s ≥ 1 +ve
Spangehl MJ, JBJS, 1999
Segawa &Tsukayama classification
“Classify on the basis of clinical presentation”
Type1
Timing

Definition

Type2

Type3

Type4

Positive
intraop C/S

Early
postoperative
infection

Acute
hematogenous
infection

Late (chronic)
infection

Same
Occurring within
organism
first month after
≥2 from C/S
surgery

Hematogenous
Chronic
seeding of
indolent
previously
clinical course;
well-functioning
present >1
prosthesis
month

* * * Guide to treatment * * *
Treatment
Basic treatment options
1.
2.
3.
4.
5.
6.

Antibiotic suppression
Debridement ĉ prosthesis retention
Resection arthroplasty
Arthrodesis
Amputation
Reimplantation - one / two stage
Diagnosing Infected Total Knee Arthroplasty
Diagnosing Infected Total Knee Arthroplasty

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Diagnosing Infected Total Knee Arthroplasty

  • 1. Diagnosis of Infected total knee arthroplasty Warakorn Jingjit, MD Orthopaedic Department, Faculty of Medicine Chiang Mai University
  • 2. One of the most devastating & challenging complication Immense financial & psychological burden Cost of treatment 15,000 - 60,000 $ / TKA Hebert CK, CORR, 1996 Sculco TP, Orthopedics, 1995
  • 3. Incidence • 0.39% in primary TKA • 0.97% in revision TKA
  • 4. Projection of the TKA & THA number Kurtz S, JBJS, 2008
  • 5. Projection of the TKA & THA infection Kurtz S, JBJS, 2007
  • 6. Risk factors 1. 2. 3. 4. Patient / host Surgical environment Surgical technique Postoperative management
  • 7. Risk factors Patient / host • Immunocompromise • – RA (4.4%) – Steroid therapy – DM (7%) – Poor nutrition • Albumin <3.5g/dl: 7-fold • Lymphocyte <1,500 cells/mm3: 5-fold • – HIV – Organ transplant • • • • Hypokalemia Tobacco use Obesity • • • Debilitation – – – – – Advanced age Alcoholism Renal failure Cirrhosis Prolonged pre-op hospitalization Hypothyroidism Previous surgery Psoriasis Previous infection Concurrent infection
  • 8. Risk factors Surgical environment • Personnel • Clean air Laminar air flow, UV light • Surgical attire • Operative site preparation Ritter MA, CORR,1988 Ritter MA, Orthop Clin North Am,1989 Berg M, JBJS (Br), 1991 Ritter MA, CORR, 1999 Peersman G, CORR, 2001
  • 9. Risk factors Surgical technique • Surgical time Operative time > 2.5 hrs Peersman, CORR, 2001
  • 10. Risk factors Surgical technique Prophylactic antibiotic Single most effective method of ↓ infection 1st gen. cephalosporin Allergy  vancomycin / clindamycin 30-60 min before incision (peak serum bone conc. within 20 min)  Repeat every 4 hrs & bleed >1,000 ml  Discontinue 24 hrs after surgery    
  • 11. Risk factors Surgical technique Prophylactic antibiotic bone cement • High risk 1o TKA, revision TKA
  • 12. Risk factors Surgical technique Implant • Hinged prosthesis • Infection rate at 10 yrs ~ 15% • Bengtson S, Acta Orthop Scand, 1991 • Hanssen AD, CORR, 1995 • Schoifet SD, JBJS, 1990
  • 13. Risk factors Post operative management • Bacteremia: oral > GI > GU procedure • Avoid in first 3-6 mo (high incidence) AAOS & ADA 1997 • First 2 yrs, specific risk factor for all pts  ATB prophylaxis • After 2 yrs  consider in high risk pts Recommended regimens (before procedure 1 hr) • Cephalexin, cephradine, amoxicillin 2 g. oral • Cephalosporin 1 g / ampicillin 2 gm IV / IM • Clindamycin 600 mg oral (allergy to penicillin) • Clindamycin 600 mg IV / IM (allergy to penicillin) Advisory statement. J Am Dent Assoc, 1997
  • 14. Potential risks of hematojenous total joint infection • All patients for the first 2 years after joint replacement • lmmunocompromised / immunosuppressed patients - Inflammatory arthropathies - Drug-induced immunosuppression - Rheumatoid arthritis - Radiation-induced immunosuppression - Systemic lupus erythematosus • Patients with comorbidity conditions - Previous prosthetic joint infections - HIV infection - Poor nutrition - Insulin-dependent diabetes - Hemophilia - Malignancy Advisory statement. J Am Dent Assoc, 1997
  • 16. Microbiology • Fungal infection = rare  Candida = predominant • Mycobacterium tuberculosis = rare
  • 17. Microbiology • Mucopolysaccharide biofilm • Protect from antibodies, phagocytes, ATB., • ↑ virulence
  • 18. Microbiology • Methicillin-resistant organism  vancomycin Ries MD, J Arthroplasty, 2001 • Rifampicin = good biofilm & tissue penetration  improve success when use ĉ other synergistic agent Zimmerli W, JAMA, 1998
  • 19. Differential diagnosis A painful knee is infected until proved otherwise Insall, 1981 • • • • Periprosthetic fx PF problem Aseptic loosening Soft tissue disruption • • • • Instability RSD HO Arthrofibrosis
  • 20. Diagnosis Fundamental of diagnosis * * * High index of suspicion * * * Clinical history Physical examination Radiography Aspiration Hematologic studies Radionuclide studies Pathology
  • 21. Diagnosis History • Pain = most common presenting symptom • Typical = rest / night / persistent / progressive pain • Progressive stiffness • Hx of prolong postop drainage, ATB treatment Physical examination • Swelling, effusion, warmth, erythema, tenderness • Painful range of motion • Persistent wound drainage  strongly suggestion  early aggressive Rx
  • 22. Diagnosis • Swab wound  not recommend • Empirical ABO for wound drainage  mask symptoms, affect subsequent C/S, predispose for drug resistant • Diagnosis in early postop period – ESR, CRP  limit value – Typically by arthrocentesis
  • 23. Aspiration • Leucocyte count & differentiation • Gram strain (sens 97%, spec 26%) ( • Culture for aerobic & anarobic bacteria >1,700/ml3, PMN > 65% (sens 94-97%, spec 88-98%) Trampuz A, Am J Med, 2004 • Ongoing ATB  stop for several wks before aspiration
  • 24. Mark Coventry Award Paper Diagnosis of early post-operative infection following TKA: The utility of synovial fluid cell count and differential “Synovial WBC count is an excellent test for diagnosing infection within 6 wks after 1oTKA with an optimal cut-off 27,800 cells/mm3 and 89% PMN” Sens 84%, spec 99%, PPV 94%, NPV 98% Craig J. Della Valle Presented at the Knee Society Specialty Day Meeting March 13, 2010, New Orleans
  • 25. Hematologic studies For chronic infection ESR – Positive > 30 mm/hr (sens 80%, spec 62.5% ) – False positive: infection elsewhere, inflammation, CNT dis, neoplasm, recent operation (< 3 mo) – False negative: prior antibiotics CRP – Positive > 10 mg/L (sens & spec 85%) – Return to normal within 3 wks after operation ESR + CRP: PPV 83%, NPV 100% Barrack RL, CORR, 1997 Swanson KC, The adult knee, 2003
  • 26. Guideline for ESR & CRP 1. Normal ESR & CRP reliable for the absence of infection 2. CRP more useful than ESR for monitoring 3. Use with other tests for the diagnosis of infection Spangehl MJ, JBJS, 1999
  • 27. PCR • • • • • Molecular genetic diagnosis Identify 16S RNA gene Expensive Time-dependent False positive Remain experimental modality !!! Mariani BD, CORR, 1996
  • 28. X-ray Sequential plain radiographs • Progressive radiolucencies • Focal osteopenia / osteolysis of subchondral bone • Periosteal new bone formation Morrey BF, CORR, 1989 • Bone destruction – infection present > 10-21 days • Lytic lesion – destroy 30-50% of bony matrix Early infection – no abnormal finding !!!
  • 29. Radioisotope scan Occasionally helpful in chronic infection • Tc-99m MDP • In-111 leukocyte scan • Tc-99m sulfur colloid
  • 30. Radioisotope scan Occasionally helpful in chronic infection Isotope Sensitivity Specificity Accuracy Tc 99m 95% 20% 54% Indium 111 77% 75% 90% Tc 99m + In111 100% 97% 97% Palestro CJ, Radiology, 1991
  • 31. Intraoperative tissue frozen section • Widely use • Result depend on  Adequate & representative tissue obtaining  Accurate interpretation by skilled pathologist > 5 PMN/HPF at least 5 fields  Sens 100%, spec 96% >10 PMN/HPF at least 5 fields  Sens 25%, spec 98% Feldman DS, JBJS, 1995 Della Valle CJ, JBJS 1999
  • 32. Intraoperative tissue frozen section Reliable predictor for infection • >10 PMN/HPF: sens 84%, spec 99%, PPV 89%, NPV 98% • 5-10 PMN/HPF: need other test to differentiate • <5 PMN/HPF: infection was highly unlikely Lonner Jh et al, JBJS,1996
  • 33. Intraoperative gram strain • Unreliable • Low sensitivity = 0-14.7% Atkins BL, J Clin Microbiol, 1998 Della Valle CJ, J Arthroplasty, 1999
  • 34. Intraoperative culture Gold standard Sample: fluid & tissue  Joint capsule  Synovial lining  IM tissue  Granulation tissue  Bone fragments • False +ve: contamination • False -ve: prior ATB, transport system, lab - Duff GP, CORR, 1996 - Bauer TW, JBJS, 2006
  • 35. Definite diagnosis At least one of the following 1. Same organism from c/s ≥ 2 specimens by aspiration / deep tissue from surgery 2. Intraarticular tissue histopathology = acute inflammation 3. Gross purulence at the time of surgery 4. Actively discharging sinus tract Hansen, CORR, 1994
  • 36. Definite diagnosis At least one of the following 1. Open wound / sinus tract communicate ĉ joint 2. Systemic signs / symptoms ĉ pain & purulent fluid 3. At least 3 of 5  ESR > 30 mm/hr  CRP >10 mg/L  Frozen section > 5 PMN/HPF  Preoperative aspiration c/s ≥ 1 +ve  Intraoperative c/s ≥ 1 +ve Spangehl MJ, JBJS, 1999
  • 37.
  • 38. Segawa &Tsukayama classification “Classify on the basis of clinical presentation” Type1 Timing Definition Type2 Type3 Type4 Positive intraop C/S Early postoperative infection Acute hematogenous infection Late (chronic) infection Same Occurring within organism first month after ≥2 from C/S surgery Hematogenous Chronic seeding of indolent previously clinical course; well-functioning present >1 prosthesis month * * * Guide to treatment * * *
  • 39. Treatment Basic treatment options 1. 2. 3. 4. 5. 6. Antibiotic suppression Debridement ĉ prosthesis retention Resection arthroplasty Arthrodesis Amputation Reimplantation - one / two stage