Prosthetic joint infection is a devastating complication of joint replacement surgery and occur in1–3% of patients. Prosthetic joint infection can occur due to direct inoculation at the time of surgery or hematogenous spread of organisms to the prosthesis at a later time.
One of the peculiarity of these infections is that the organism on attachment to prosthesis, it causes a change in its form or phenotype to become the sessile bacteriae which secrete an extracellular matrix. Together bacteriae and matrix form what is called biofilm.
Surgical site infection is most common risk factor for prosthetic joint infection. Other factors are older age, poor nutritional status, underlying joint disease like rheumatoid arthritis, obesity, diabetes mellitus, malignancy, remote infection, prior joint infection, presence of bacteremia, advanced HIV infection, a revision surgery, or preoperative use of low-molecular-weight heparin.
Etiopathogenesis of Prosthetic Joint Infection
Gram-positive cocci with coagulase-negative staphylococci, S. aureus and enterococci account for 65% of cases. Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, and other Aerobic Gram-negative bacilli, including are present in about six percent. Anaerobes, including Propionibacterium acnes, account for 4% of infections. About 7% of patients with prosthetic joint infection do not exhibit any growth.
Biofilms are hallmark and the essential factors in the persistence of prosthetic joint infection. Biofilms enable bacteriae to persist despite body’s defense cells and/or antimicrobial drugs.
Early and delayed infections are thought to be due to organisms introduced at the time of surgery, whereas late infections are more likely to be hematogenously acquired.
The infection persists because there is
- Decreased biofilm penetration
- Antimicrobial enzymes
- Quorum-sensing [intercellular signaling]
- Altered growth rate
- Stress response
- Gene over-expression
Criteria for Prosthetic Joint Infection
According to the musculoskeletal infection Society, prosthetic joint infectiion is said to exist when
There is a sinus tract communicating with the prosthesis
A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic
Four of the following six criteria exist.
- Raised ESR and CRP
- Raised WBC count
- Increased synovial neutrophil percentage
- Presence of purulence in the affected joint
- Isolation of a microorganism in one culture of periprosthetic tissue or fluid
- >5 neutrophils per high power field in five high-power fields at x400 magnification.
Clinical Presentation of Prosthetic Joint Infection
Prosthetic joint infections are classified as
- Early – (occurring within 3 months of implantation)
- Delayed – (occurring 3–12 months after implantation)
- Late – (Occurring more than 12 months after implantation)
Early infections may present with a persistent wound discharge, fever, pain, swelling, effusion and redness at the implant site. Untreated infections may form chronic sinuses. Bacteremia and a systemic sepsis syndrome may occur in some cases.
Late infections generally present with joint pain that gradually becomes worse. Joint effusion and restriction of movement may be present. Sinuses may also occur. There may be radiological evidence of loosening. Late infections occasionally present with an acutely inflamed joint with systemic symptoms.
Late chronic infection is characterized by subtle signs and symptoms i.e. persistent pain and accompanied by loosening of the prosthesis at the bone–cement interface, and sometimes by sinus tract formation with chronic discharge. This type of infection is caused by less virulent microorganisms, such as coagulase-negative staphylococci and P. acnes.
Diagnosis of Prosthetic Joint Infection
The diagnosis of prosthetic joint infection should be considered in patients with any of the following
- Intraoperatively pus is encountered
- Isolation of microorganisms on at least two specimens taken intraoperatively
- Presence of a sinus tract in communication with the prosthetic joint
- Histopathological features of acute infections
Aseptic failure or aseptic loosening is usually defined as failure of prosthesis in the absence of any of these criteria.
The combination of blood investigation and joint aspiration is sufficient for diagnosis of prosthetic joint infection in the majority of cases. Where prosthetic joint infection is suspected but cannot be confirmed, additional tests such as nuclear imaging may be done.
Normal erythrocyte sedimentation rate along with a normal C-reactive protein level is suggestive of a very low probability of infection but raised levels are not specific. Serial postoperative measurements are more informative than a single value.
But abnormal levels of either tests should prompt further investigation such as joint aspiration.
ESR and CRP are standard screening tests for these infections.
Joint Fluid Aspirate Analysis
Hip and/or knee aspiration is suggested in patients with abnormal levels of either ESR or CRP.
A synovial fluid WBC count >1700 cells/ul or a neutrophil percentage >65% is highly suggestive of chornic infection.
Culture of aspirated joint fluid taken from three to five locations around the prosthesis is used to aid the diagnosis. However, negative cultures have been reported in 7%.
Positive cultures are detected in 65–94% of the cases. The sensitivity of tissue culture increases as the number of specimens collected increases. However cultures may be negative in
- Prior antibiotics exposure
- Low number of organisms
- Lab factors like prolonged transport time or inappropriate culture media
- Fastidous organism
In case of joint revisions, at the time of surgery, multiple sample, about five using separate instruments should be taken and cultured for at least 5 days but culture as prolonged as 14 days may be required for better yields.
Special culture techniques to look for fungi and, mycobacteriae may be required when routine cultures are negative.
It is recommended to stop antibiotics at least 2 weeks before to tissue sampling for culture.
Sonication of a removed implant may increase the culture yield by disrupting adherent bacterial biofilm, especially in patients who have recently received antibiotics.
PCR is a rapid, sensitive diagnostic test in the diagnosis of prosthetic joint infection but lacks clinical correlation.
Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) uses mass spectrometry to differentiate bacterial and fungal organisms and has the potential to improve the yield and rapidity of diagnosis. MALDI-TOF has the potential ability to subtype bacterial species.
Intraoperative frozen sections of periprosthetic tissues have excellent accuracy in predicting a diagnosis of prosthetic joint infection but is not a very useful too to rule out the infection.
Leukocyte esterase strips, measure of inflammatory biomarkers in the synovial fluid, and lbis T5000 universal biosensor are some advances that are being validated.
Serial plain radiographs help to detect infection. They many show radiolucency, osteolysis and implant migration are observed in both infection and aseptic loosening.
CT provides better contrast between normal and abnormal tissue and detects joint effusion, sinus tracts, soft tissue abscesses, bone erosion and periprosthetic lucency.
MRI can only be performed in patients with implants that are safe for MRI and provides greater resolution for soft-tissue abnormalities.
Combined leukocyte-marrow scintigraphy is currently regarded as the imaging modality of choice for diagnosing prosthetic joint infection.
F-fluoro-2-deoxyglucose positron emission tomography [FDG-PET] scan is relatively newer technique enables that helps to visualize leukocytes, macrophages and other immunologically active cells.
Antigranulocyte scintigraphy with monoclonal antibodies or antibody fragments may be another attractive approach to detect prosthetic joint infection but needs further studies.
Treatment of Prosthetic Joint Infection
The main objectives of prosthetic joint infection to end pain, to restore the function and to eradicate/control the infection.
Acute Infections may be managed without removal of the implant whereas chronic late infections almost always require implant removal.
A loose implant is always removed.
Patients with multiple medical conditions and other problems, patients who reject surgery may be best managed conservatively. This may be achieved by long-term antibiotic suppression, accepting chronically discharging sinus, or creating a sinus.
However in such cases, the success rate decreases with time and second, stopping the therapy is associated with a more rapid treatment failure. Long-term toxicity to antimicrobials is another problem that should be taken into consideration.
Joint removal or fusion
When an individual is immobile, for example due to neurological illness, in spite of functional prosthesis, prosthesis removal may be sought. or when repeated revision and salvage may fail to eradicate infection, an excision arthroplasty may be appropriate.
For prosthetic knee infections, an instrumental arthrodesis is the most commonly performed procedure when the patient is not a candidate for a new prosthetic joint.
Antibiotics are administered for a period of 4-6 weeks after surgery.
Debridement, antibiotics and implant retention (DAIR)
This involves debridement of a joint with exchange of modular components and/or liners but retaining the prosthesis itself, combined with prolonged antibiotic therapy. Open debridement is said to yield better results than arthroscopic debridement.
Patients with a short duration of symptoms, a well fixed and functional implant and well identified susceptible organism are good candidates for DAIR.
Antibiotics are administered for 3-6 months.
Rifampin, ciprofloxacin, levofloxacin, and linezolid are the antibiotic drugs used for treating prosthetic joint infections in DAIR. Rifampin has excellent oral bioavailability, achieves high concentrations in biofilm, is active against nongrowing bacteria and decreases the risk of development of resistance to ciprofloxacin and perhaps other antistaphylococcal agents. But rifampicin should never be used alone as resistance to it develops quickly when used alone.
Daptomycin has been shown to be effective against multidrug-resistant Gram-positive bacteria and against nongrowing bacteriae.
Cotrimoxazole combination with rifampin, has shown efficacy in treating bone and joint infections after debridement. Fusidic acid, also seems promising.
The combination of ceftazidime and ciprofloxacin has been successful in the treatment of Gram-negative organism.
This is the most frequently chosen therapy. Joint revision may be performed as either a one or two stage procedure.
Infected joint and all cement is removed and sampled, and after thorough cleaning and new prosthesis is inserted. It may be appropriate for those too frail to withstand two procedures. It may not be advisable in those with resistant or difficult-to-treat organisms.
This procedure involves sampling, joint removal, thorough debridement and closure in one stage followed by new implant after a weeks or months. An antibiotic impregnated [gentamycin, tobramycin] cement spacer may be used. Debridement includes removal of all necrotic tissue, sinucement, cements restrictors and prosthetic material and is followed by good antibiotic therapy. Whenever required s tract, tissue coverage procedures are also undertaken.
Intra-operative samples for culture and histology are taken with separate instruments and placed into separate containers.
Infected prosthesis and reimplantation is spaced by 2–4 weeks for uncomplicated infections and 8 weeks for difficult-to-treat microorganisms.
Exchange procedures are the standard strategy for delayed and late prosthetic joint infections or if there is evidence of loosening of the prosthesis.
For uncomplicated infections, antibiotic therapy is continued for a total duration of 6-12 weeks in both one stage and two stage exchange procedures.
In two-stage exchange with difficult to treat microorganisms, 6 weeks of antibiotic therapy should be given, reimplantation delayed for a further 2 weeks, at which time multiple intraoperative specimens are obtained for microbiological culture. Antibiotic therapy is continued for a further 3 months.
In one-stage procedures, 6 weeks of antibiotic therapy after the surgical procedure is the most commonly used duration of therapy. Recent studies have suggested that systemic antibiotics may not be necessary when antibiotic-loaded cement spacers are used however further studies are desirable.
Rifampin has not been usually included in the antimicrobial regimen.
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