1. Infected Total Hip Arthroplasty
Husam Darwish
Seyon Sathiaseelan
Dr. P. Kim
December 13th 2006

2. History
The modern era of arthroplasty is about 30 years old
Initial series showed infection rates around 9%
Improvements in air quality in the OR, prophylactic antibiotics, and patient selection have greatly decreased those rates

3. Economics
US figures indicate that average cost of revision is $ to $60 000
3500 – 4000 infected THA per year
Total cost $150 -$200 million per year

4. Incidence of Infection
Reports in the literature range from:
0.3% (British Medical research council trial)
2.2% (US Medicare data )
Some evidence that dedicated institutions with large numbers of THA yearly have lower infection rates ~ 1%

5. Incidence Mayo Clinic data – 1969-1996 THA % Infection rates Primary
1.3
Revision
3.2
Overall
1.7

6. Incidence
Patient factors
OR environment
Surgical factors and technique
Perioperative care

7. Patient Factors
Rheumatoid arthritis
Diabetes
Sickle cell anemia – increase rate by 23%
Psoriasis – superficial infection 9.1% deep infection 5.5%
Renal or liver transplantation – 19%
ESRD on dialysis – 13%
Poor nutrition has been implicated in delayed wound healing but has not been correlated with deep infection

8. Surgical Factors
Increased incidence after revision surgery
3.2% vs 1.3% in Mayo clinic study for THA
Any previous surgery
2.3% vs 0.9% for THA
Revision for aseptic loosening – 2.5%
Revision with previous infection – 4%
Revision with structural femoral allograft – 5%
Conversion of arthrodesis to THA – 10-13%

9. Surgical Factors
Operative time
Avoid dead space and hematoma formation
Minimize tissue trauma
exposes collagen and basement membrane proteins to the bloodstream which enhances bacterial binding to fibronectin (esp S. aureus)

10. Peri-operative Care Systemic antibiotics
Hill et al – double blind RCT on 2137 THA showed reduction in infection from 3.3% (placebo) vs 0.9% (5 days cefazolin)
Nelson et al – demonstrated equal efficacy for 1 day vs 7 days of antibiotics in a randomized trial of 358 patients
Many other similar studies but power is an issue
Classen et al – large prospective trial showed lowest rate of wound infections with antibiotics given 2 hrs before incision vs just after incision or more than 2 hrs before incision

11. Recommendations
ancef 1 g iv minutes preop followed by 2-3 postoperative doses
Further doses intraoperatively if blood loss >2L or >4hrs operative time
Vancomycin 1g iv for anaphylactic penicillin allergy only followed by one postoperative dose

12. To drain or not to drain?
Drains
Willett et al – prospective study of 120 THA
Drain removed at 24, 48 or 72 hours
90.9% of total blood loss in first 24 hours
Seven positive deep wound cultures all in pts with drain removed at 48 or 72 hrs
All deep cultures had growth of identical organisms on pts skin

13. Beer et al – prospective study of bilateral THA (24) and TKA (76)
No difference in swelling or persistent wound drainage
Kim et al – prospective study of 96 bilateral THA
Significant increase in wound drainage and erythema in the undrained hips
No difference in infection rates or functional outcomes at 1 year

14. Recommendations
If using a drain, remove at 24 hrs in most situations

15. Perioperative Care Persistant wound drainage
No evidence to support use of prolonged antibiotics with persistant serous drainage
Permits overgrowth of antibiotic resistant organisms
Recommendations
Avoid prolonged postoperative Abx
Compressive bandages and minimize activity to allow wound to seal
If drainage persists >5-7 days wound debridement and tissue samples for culture allow for possible prosthesis retention if due to infection

16. Perioperative Care Urinary Retention
Wroblewski et al reported 6.2% deep infection rate in 195 men with postoperative urinary retention vs overall rate of 0.5%
59% of those who required catheterization received antibiotic coverage
Foley removed hrs post op has been shown to decrease urinary retention while not increasing UTI
Recommendations
Pts with urologic symptoms should have them treated prior to THA
Antibiotic prophylaxis should be given for urinary tract manipulation in the postoperative period

17. Routes of Infection
Direct contamination during OR
Direct or contiguous spread
Hematogenous spread
Reactivation of previous infection

18. Routes of Infection
Operating Room Environment
Horizontal laminar air flow – 93% reduction in airborne bacteria
Clinically decreased infection rates in one series from 1.4% to 0.9% in THA but increased infection rates from 1.4% to 3.9% in TKA.
Body exhaust suits – no difference in bacterial counts when used with laminar air flow but 80% reduction vs regular scrubs

19. Routes of Infection Operating Room Environment
Face masks – wearing a surgical face mask in the sterile core and/or the OR had no effect on the bacterial counts in either the core or the OR
Head cover – no statistically significant difference between no head cover, caps or hoods
Contaminated gloves (29%), suction tips (33%), skin blades(9%), needles(10%), surgical gowns(17%), light handles(14%)
UV light – infection rate of 0.5% for 2389 hips but all OR personnel must be protected from burns

20. Routes of Infection Direct Spread
Organisms migrate to the hip joint from a more superficial infection
Schmalzried et al – series of 3051 hips with 47 deep infections – 2/47 by direct spread from superficial infection
Surin et al – series of 803 hips with 34 deep infections – increased risk (3.2X) if there was increased postoperative wound drainage
Gaine et al – series of 301 hips had no deep infections despite 56 superficial infections

21. Routes of Infection
Hematogenous spread
Skin infections – remote from incision
Dental infections
Dental manipulation
Urinary tract infections
Reactivation
Reactivation of infection in a previously infected hip or knee

22. Antibiotic Prophylaxis
Case reports of hematogenous seeding of THA following dental procedures
Current recommendations of the AAOS
Prophylactic Abx recommended 1 hour prior to dental procedures during the first two years after surgery
Immunocompromised pts, RA, SLE, diabetes, hx of infected THA, malnourishment, hemophilia are candidates for lifelong prophylaxis
Amoxicillin 2 g po or ancef 1 g iv (or clindamycin 600mg po/iv if penicillin allergic) 1 hour prior to dental procedure

23. Classification of Periprosthetic Hip Infections
Fitzgerald et al
Stage I – acute fulminant infection
Stage II – delayed sepsis
Stage III – late hematogenous

24. Stage I – acute fulminant infection
Within 3 months of surgery
Present with systemic symptoms – fever, chills, sepsis and unremitting pain even at rest
Wound drainage, erythema, swelling or abscess

25. Stage II – delayed sepsis
Indolent infection within 2 years of surgery
May originate at time of OR but presentation delayed due to small inoculum or low virulence of infecting organism
Most common and most difficult to treat

26. Stage III – late hematogenous
Metastatic infections caused by hematogenous spread
Symptoms of acute infection similar to stage I in a previously asymptomatic THA
Seeding can occur regardless of status of fixation of the components

27. Bacteria Infecting organisms can be divided into
Planktonic – individual free floating cells
Usually early after inoculation
Easier to eradicate
Sessile – biofilm of glycocalyx
Can adhere to and survive on synthetic surfaces and are protected from antibiotics, complement activation and ingestion by neutrophils
Most bacteria in the correct environment can form a biofilm
Requires time to form after inoculation
Stable prostheses covered with living tissue are less vulnerable to adherence and biofilm formation

28. Bacteria
Biofilm producers
S. aureus
S. epidermidis
pseudomonas
Poor Biofilm producers
Gram negatives (except pseudomonas)

29. Bacteria
S. aureus (27%) and S. epi (28%) are the most common infecting organisms
Wide range of gm +ve and –ve organisms have been identified including anaerobes and fungus
S. aureus predominant in early infections
Skin flora bacteria (s. epi, propionobacterium, peptostreptococci) more common in delayed infections

30. Virulence and Resistance
Gram negative bacilli and Group D strep (enterococci) are considered more virulent organisms
S. epi is generally considered low virulence but may be difficult to eradicate due to glycocalyx - also this species is demonstrating increased antibiotic resistance
MRSA , VRE, methicillin resistant S. epi infections are becoming increasingly common

31. Susceptibility to Infection
Foreign bodies produce an inflammatory and necrotic tissue response
Response is greater with articulated implants and increases with high levels of wear debris
Polymethylmethacrylate has been shown to reduce chemotaxis, phagocytosis and killing ability of PMNs

32. Diagnosis of Infection
History
Risk factors
Persistent drainage or delayed wound healing
Constant pain
Physical
Inflammation, swelling, warmth, erythema, tenderness
Drainage or persistent sinuses

33. Laboratory Investigations
ESR
Measurement of red blood cells that have been caused to agglutinate by acute phase proteins
ESR>30mm/h - sensitivity 82%, specificity 85% (PPV – 58%, NPV 95%) for the diagnosis of infection
Elevated by other factors including concomitant infection, inflammatory arthritis, collagen vascular disease, recent surgical intervention (up to 12 months), malignancy
ESR>30mm/hr 6 months after a two stage revision has a 62% chance of indicating persistent infection
May be useful as a monitoring tool

34. Laboratory Investigations
CRP
Acute phase protein which contributes to an elevated ESR
Returns to normal within 3 weeks of surgery with peak levels 2-3 days post op
CRP>10mg/L sensitivity 96% specificity 92% (PPV – 74% and NPV – 99%)
Normal ESR and CRP can reliably rule out infection
Abnormal ESR and CRP indicate 83% probability of infection

35. Laboratory Investigations
WBC
Rarely elevated in chronic infection
WBC > 11
Sensitivity 20%
Specificity 96%
PPV 50%
NPV 85%

36. Radiographic Investigations
Plain xrays
Often normal in the early stages of infection
Subtle findings may be present
Periostitis
Localized osteopenia
Endosteal scalloping
Ring osteolysis around wires and cables
Loosening may or may not be associated with infection

37. Periosteal new bone formation
Focal osteolysis at tip
Faint periosteal elevation

38. Radiographic Investigations
MRI
Presence of signal loss adjacent to the metal components
Titanium less ferromagnetic than Co-Chromium
Can show periprosthetic abscesses or intrapelvic extension US
Can also be used to detect abscesses and for US guided aspiration of hip/abscess for diagnosis
Thickened capsule may indicate infection

39. Radiographic Investigations
Radionuclide Scans
Tc 99m bone scan is sensitive but not specific
Normal scan should rule out infection or loosening
Abnormal in both infection, loosening, for up to 1 year post operatively, heterotopic ossification, inflammatory conditions, fractures and tumours
In labelled WBC scans are sensitive at diagnosing conditions with increased vascularity and WBC uptake but can be negative in chronic infection due to poor uptake
PPV – 54-63%, NPV – 95%

40. Invasive Diagnostic Tests
Aspiration
Can confirm the presence of infection and identify the organism(s) involved and antibiotic sensitivities
Should be done prior to administration of antibiotics or two weeks since last dose
Sensitivity 92%, specificity 97%, accuracy 96%
Gram stain, cell count, glucose, protein, lactic acid?
If cell count > leukocytes/ml and >25 % PMNS infection suspected
Allows arthrogram at the same time

41. Hip Arthrogram Deep delayed infection in 84 yo man
Acetabular migration
Long sinus tract extending posterior to femoral shaft

42. Emerging Molecular Biological Techniques
Interleukin-2 and gamma interferon
PCR of aspirate to detect remnants of bacterial DNA or RNA
Difficult to determine whether bacteria are live or dead
Serologic markers for specific infections

43. Intraoperative Tests
Grossly abnormal tissues at time of revision surgery despite a negative workup - sensitivity 70% and specificity 87%
Send immediate gram stain
Sensitivity 19%, specificity 98%, PPV 63%, NPV 89%
Culture of synovial fluid
Frozen section of inflamed tissue >5 PMNs per hpf
Sensitivity % specificity 94-96%
Intraoperative Cultures
Gold standard - sensitivity 94%, specificity 97%, PPV 77%, NPV 99%
At least 3 tissue samples
Swab cultures from the removed inplant are less sensitive

44. Algorithm for Infection
High index of suspicion
History and physical and xrays
ESR and CRP
If normal – no further tests
If abnormal – hip aspiration under flouroscopy
Aspirate
If normal but high index of suspicion
Repeat aspirate with arthrogram or US or biopsy
If all tests normal but high index
May resort to intraoperative methods
If frozen section negative – may proceed with revision

45. Treatment
Consists of one or more of the following
Incision and drainage
Antibiotic therapy
Excision arthroplasty
One or two stage revision

46. Treatment Incision and drainage
Often used as initial treatment in acute early or late acute hematogenous infections
Retention rates in early acute infection – 26-71%
Retention rates in late acute hematogenous infection – 26-50%
Duration of symptoms correlates with success rates
Brandt et al – 56% retention if treated within 2 days
13% retention if treated after 2 days of symptoms
All components must be well fixed, any loose components must be removed
Poly exchange
In chronic periprosthetic infection failure rate is %

47. Treatment Antibiotic suppression
Small series involving patients who were deemed to be unsuitable for reconstruction or who had refused reconstruction – 37% revision rate
May be an option for pts who refuse OR or are medically unsuitable
Infection should not produce systemic symptoms, prosthetic components should be well fixed, organism should be sensitive to po Abx

48. Treatment Excision Arthroplasty
Most predictable procedure to eradicate infection
Bourne et al – 1/33 reinfection rate
Functional outcome is very poor including decreased active range of motion and strength
Oxygen consumption higher than an above knee amputation for THA
May allow for some ROM at knee but severely limits walking ability
Salvage procedure to provide some pain relief in patients not suitable for reconstruction

49. Reimplantation
Two Stage Exchange Arthroplasty
Provides a better environment for eradication of infection
Organisms may be cultured from tissue samples which allows for further microbiological assessment and adjustment of antibiotics
Goal is to prevent a complex reconstruction in the presence of unresolved sepsis

50. Two Stage Revision First stage is essentially an excision arthroplasty
May use antibiotic loaded cement as a temporary spacer
Allows some function and reduces soft tissue contracture
Minimum 6 weeks of antibiotics
Response to treatment is assessed by ESR, CRP
Mont et al proposed use of aspiration biopsy to confirm eradication
May rarely require second debridement
Second procedure is the reimplantation
Again send tissue for C&S and frozen section (specificity – 98% sensitivity – 25%)

51. Revision
Use same operative approach
Dislocate hip joint to facilitate removal of all infected and necrotic tissue
Components examined for loosening
Components and all cement are removed
Check cement mantle carefully for any retained cement
May require intra-pelvic approach if cup and cement mantle have protruded into pelvis

52. Prostalac
Prosthesis of antibiotic loaded acrylic cement
Most recent version consists of a constrained cemented acetabular component and a modular femoral component that are covered intraoperatively with antibiotic loaded cement using a series of molds
Acetabular component is loosely cemented and femoral component is press fit for ease of removal

53. Antibiotic Impregnated Bone Cement
To preserve the biomechanical properties of bone cement the antibiotics are added in powder form
Up to 2 g of oxacillin, cefazolin, or gentamicin in a single batch of cement does not significantly alter the compressive or tensile strength of the cement
Aqueous gentamicin interferes with the early prepolymerizing process during mixing and significantly reduces the strength
Doses > 4.5 g of gentamicin powder per cement batch decreased the compressive strength below 70 MPa
Recommendations
not currently recommended for prophylaxis in primary THA
benefit in revision surgery

54. Antibiotic Impregnated Cement
Choice of Antibiotic
Tobramycin
Predictable elution from cement at bactericidal levels
Vancomycin
Erratic elution from cement
May be combined with tobramycin
Gentamicin
Predictable elution from cement
A combination of two antibiotics may improve the elution of both agents

55. Antibiotic Beads
Cement beads may be used between stages of 2 stage revision
8-9 g of antibiotic powder per cement package may be used
May be extremely difficult to remove

56. Antibiotic Impregnated Bone Cement
Josefsson et al – prospective study comparing systemic antibiotics vs gentamicin impregnated cement
At 10 yrs – 1.6% vs 1.1%
Scandinavian Hip Registry – gentamicin cement had lowest risk ratio for revision
Norwegian hip review – THA for OA – failure rate ratio for infection
Systemic Abx + Abx bone cement – 1.0
Systemic Abx alone – 4.3
Abx bone cement alone – 6.3
No prophylaxis – 11.5
Lynch et al – retrospective review of 1542 THAs showed 4% infection rate for revision arthroplasty with plain cement vs 1.8% with antibiotic cement

57. Two Stage Revision

58. Results of Two Stage Revision
Timing of second stage is controversial
Must be no further evidence of infection
Some evidence to suggest that earlier reimplantation may have better results
Coyler – 22%(2 of 9) reinfection with reimplantation at 22 weeks vs 14%(4 of 28) within 6 weeks
82% success without antibiotic cement vs 90% with (Hanssen and Rand)

59. Two Stage Revision of an Uncemented Prosthesis
uncemented fixation avoids the challenging reoperation of the long stem cemented prosthesis
Results are generally inferior to cemented
Average infection rates 12-18%
Forfeit the benefit of antibiotic impregnated cement

60. Two Stage Revision of Uncemented Prosthesis

61. Reimplantation Single Stage Exchange Arthroplasty
Indications based on a series by Salvati et al
Subacute sepsis caused by a sensitive bacteria in an immunocompetent patient who has good soft tissue and bone stock to assure a successful biomechanical reconstruction
5-10% recurrence rate
Meticulous debridement is critical
Antibiotic loaded cement (success rate of 83% with and 60% without)
iv antibiotics for a minimum of 6 weeks
May also be indicated for elderly pts who could not tolerate a two stage procedure

62. One vs Two Stage Advantages Disadvantages Less morbidity
Reduction in cost
Technically easier
Quicker rehabilitation
Disadvantages
Unable to direct antibiotic in cement to specific organism
Unable to observe pts response to therapy
Higher reinfection rate
Only one debridement
Able to eradicate distant sites of infection
Informed decision whether disability from resection justifies risks of revision

63. Bone Allograft
Chronic infection may produce significant femoral and or acetabular bone loss
Bone graft could act as a sequestrum
Increased infection rates in primary THA with bone grafting
Could be related to confounding factors such as complexity of OR, increased OR time, disease transmission by the graft
Reported reinfection rates range from %
May be able to use morcellized bone graft as a carrier of antibiotics

64. Treatment
Positive intraoperative cultures at the time of revision without any preceding evidence of infection
Tsukuyama et al reported on 31 pts treated with 6 weeks of iv antibiotics
5/31 (16%) had recurrence of infection at 2 years
Dupont 6/15 (40%) recurrence without additional antibiotics

65. Treatment of Reinfection after Reimplantation
Very poor prognosis
Series by Pagnano et al
38% reinfection rate for further reconstruction
Pts who underwent reconstruction and had reinfection had the worst functional outcomes
Excision arthroplasty is the preferred treatment

66. Prevention of Infection
Principles
Augment the host response
Optimize the wound environment
Decrease the bacterial load introduced into the surgical wound

67. Thank you