Laboratory Studies
The erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level provide excellent diagnostic information for establishing the presence or absence of infection before surgical intervention in patients with pain at the site of a knee arthroplasty. ESR values higher than 35 mm/hr have been associated with deep infection. [46, 47] However, the ESR is not always elevated in a chronic deep infection. When the ESR is used alone, its reported specificity and sensitivity are 0.82 and 0.86, respectively.
The CRP level usually peaks on postoperative day 2 and falls back to normal levels within 2-3 weeks. It is usually normal in cases of aseptic loosening but is elevated by more than 10 mg/L in cases of infection. When used along with ESR, the CRP level has a specificity of 1.00 for diagnosing periprosthetic infections. [46, 47, 48] Repeated measures of the CRP level showing a rising or falling trend are more useful for deciding on management and planning follow-up.
The total white blood cell (WBC) count may be a helpful addition. In fulminant infections, leukocytosis with an increase in immature neutrophils may be noted. In indolent infections, the complete blood count (CBC) with differential may be normal. [4]
Serum D-dimer measurement appears promising for diagnosis of periprosthetic joint infection. [49]
Plain Radiography
Plain radiographs should always be obtained when infection in a prosthetic joint is suspected, even though they are rarely diagnostic in themselves. Serial radiographs often aid in diagnosing infection. A particular difficulty is distinguishing septic loosening from aseptic loosening. Periosteal new bone formation may help in differentiating these two conditions; this finding has been associated with the presence of deep sepsis in total hip arthroplasty (THA) and is considered by some to be pathognomonic for this condition. [50]
More severe and longstanding cases periprosthetic infection may show evidence of implant loosening, lysis, bone resorption adjacent to the implant, areas of new bone formation, and periosteal reaction (see the image below).
Progressive loosening is a worrying sign that suggests potential infection. Endosteal scalloping is highly suggestive of infective loosening. Loosening on the acetabular side is indicated by migration of the cement mantle or the socket (see the image below), protrusion, or fracture. Arthrography, sometimes done in conjunction with aspiration, can help diagnose loosening but cannot confirm infection.
Radiograph of 50-year-old patient for whom bipolar arthroplasty was done elsewhere for displaced fracture of neck of femur. Patient came with severe pain hip 1 year after procedure. Severe osteolysis and superior migration of prosthesis are seen.
Nuclear Scanning
Technetium-99m (99mTc) and indium-111 (111I) polyclonal antibody scans and monoclonal antibody scans have proved useful in diagnosing arthroplasty-associated infections; however, they cannot distinguish between septic and aseptic loosening. 99mTc scans are sensitive but not specific. Gallium scans are similar to 99mTc scans.
Sequential 99mTc- and 111I-labeled WBC scanning is highly sensitive and specific and can be used to make the diagnosis in equivocal situations. [51] The study is considered to be positive for periprosthetic infection when there is activity on the labeled leukocyte scan but no corresponding activity in the same area of distribution on the 99mTc scan. Love et al reported a sensitivity of 100%, a specificity of 91%, and an accuracy of 95% when both imaging modalities were used to detect periprosthetic infection at the site of total joint arthroplasty. [52]
Similarly, fluorodeoxyglucose positron emission tomography (FDG-PET) scanning has shown promising results in the majority of studies for the detection of periprosthetic infection. [53, 54]
Joint Aspiration
Aspiration of fluid from a suspected joint (arthrocentesis) is highly sensitive and specific for periprosthetic infection, and some recommend that it be done routinely in the setting of an abnormal ESR in a young implant. [42]
Aspiration is used to confirm a clinical suspicion of infection or to support or negate the findings of other preoperative investigations, such as the ESR and the CRP level, which may be falsely elevated because of connective-tissue disease. An additional benefit of aspiration in instances of suspected infection is the ability to identify the organism and its antibiotic-sensitivity profile, which may influence preoperative planning and the choice of an antimicrobial agent if use of an antibiotic depot is planned. [46]
Aspiration must be performed under aseptic conditions. Contamination of the sample by skin organisms of and inoculation of organisms into the joint are the main concerns. To increase the chances of culture positivity, antibiotics should be discontinued 2-3 weeks before aspiration. Glucose levels and cell counts are obtained, and cultures are done on three samples. If all three samples are positive, the diagnosis is established. If two are positive and blood parameters are elevated, the diagnosis of infection is made; otherwise, the aspiration is repeated.
Parvizi et al found that a calorimetric strip test for leukocyte esterase in the synovial fluid had high specificity and positive predictive value in the diagnosis of prosthetic joint infection. [55, 56] Synovial fluid interleukin (IL)-1 and IL-6 may become valuable indicators of infection. [57, 58] Alpha-defensin has shown promise as a biomarker for diagnosis of periprosthetic joint infection. [59, 56]
Tissue Analysis
Histopathologic examination of frozen tissue samples during surgery has a low sensitivity but a high specificity for diagnosing infection. [60] Tissue from the bone-cement or prosthesis-bone interface, as well as from abnormal-appearing areas of synovial tissue, should be examined. The presence of more than five polymorphonuclear leukocytes (PMNs) per high-power field is diagnostic of infection, but the presence of fewer than five does not suffice to rule out infection. [60]
A preoperative core biopsy provides the advantages of aspiration and tissue examination and is a useful investigation in suspected joints. [61]
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Final radiograph after stage II revision.
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Stage I revision with antibiotic spacer made from mold.
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Radiograph of 50-year-old patient for whom bipolar arthroplasty was done elsewhere for displaced fracture of neck of femur. Patient came with severe pain hip 1 year after procedure. Severe osteolysis and superior migration of prosthesis are seen.
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Infected total knee arthroplasty with sinus.
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Lateral radiograph showing lysis and loosening of prosthesis.
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Frankly infected tissue around prosthesis.
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Cement spacer application.
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Radiograph after stage I revision.
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Stage II revision. Bone loss at femoral side; allograft used.
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Astemmed femoral prosthesis and allograft used for bone loss.
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Final radiograph after stage II revision.
Tables
Microorganism |
Frequency (%) |
Coagulase-negative staphylococci |
30-43 |
Staphylococcus aureus |
12-23 |
Streptococci |
9-10 |
Enterococci |
3-7 |
Gram-negative bacilli |
3-6 |
Anaerobes |
2-4 |
Multiple pathogens (polymicrobial) |
10-12 |
Unknown |
10-11 |
Status of Prosthetic Joint Infection |
Treatment |
Duration of symptoms < 3 wk and stable implant and absence of sinus tract and susceptibility to antibiotics with activity against surface-adhering microorganisms |
Débridement with retention |
Intact or only slightly damaged soft tissue |
1-stage exchange |
Damaged soft tissue, abscess, or sinus tract |
2-stage exchange with short interval (2-4 wk), spacer |
Microorganism resistant or difficult to treat* |
2-stage exchange with long interval (6-8 wk), no spacer |
Inoperable, debilitated, or bedridden |
Long-term suppressive antimicrobial treatment |
No functional improvement by exchange of implant |
Implant removal without replacement |
Direct Exchange |
Delayed Exchange |
Advantages • Less morbidity • Reduced cost • Improved mechanical stability • Less complicated technique • Shorter duration of disability
Disadvantages • Inability to use sensitive antibiotic to mix with cement while fixation
Contraindications • Immunocompromise • Major soft tissue or skin defect • Gram-negative organisms • Actively discharging sinus or overt purulence |
Advantages • Ability to identify organisms, determine sensitivities, and give adequate antibiotics before reimplantation • Ability to repeat débridement if necessary • Ability to identify and correct other foci of infection and inciting factors
Disadvantages • Technical difficulty resulting from extensive scarring and contracture • Hardships of resection arthroplasty • Increased cost and hospital stay • Delayed rehabilitation |
Microorganism |
Antimicrobial Agent1 |
Dosage |
Route |
||
Staphylococcus aureus or coagulase-negative staphylococci |
|||||
Methicillin-susceptible |
Rifampin plus (flu)eloxacillin2 |
450 mg q12hr 2 g q6hr |
PO/IV IV |
||
For 2 wk, followed by |
|||||
Rifampin plus ciprofloxacin or levofloxacin |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr |
PO PO PO PO |
|||
Methicillin-resistant |
For 2 wk, followed by |
||||
|
Rifampin plus ciprofloxacin3 or levofloxacin3 or teicoplanin4 or fusidic acid or trimethoprim-sulfamethoxazole or minocycline |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr 400 mg q24hr 500 mg q8hr 1 forte tablet q8hr 100 mg q12hr |
PO PO PO IV/IM PO PO PO |
||
Streptococcus spp (except S agalactiae) |
Penicillin G3 or ceftriaxone |
5 million U q6hr 2 g q24hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterococcus spp (penicillin-susceptible) and S agalactiae |
Penicillin G or ampicillin or amoxicillin plus aminoglycoside5 |
5 million U q6hr 2 g q4-6hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterobacteriaceae (quinolone-susceptible) |
Ciprofloxacin |
750 g q12hr |
PO |
||
Nonfermenters (eg, Pseudomonas aeruginosa) |
Cefepime or ceftazidime plus aminoglycoside5 |
2 g q8hr |
IV |
||
For 2-4 wk, followed by |
|||||
Ciprofloxacin |
750 g q12hr |
PO |
|||
Anaerobes6 |
Clindamycin |
600 mg q6hr |
PO |
||
For 2-4 wk, followed by |
|||||
Clindamycin |
300 mg q6hr |
PO |
|||
Mixed infections (without methicillin-resistant staphylococci) |
Amoxicillin-clavulanate or piperacillin-tazobactam or imipenem or meropenem |
2.2 g q8hr 4.5 g q8hr 500 mg q6hr 1 g q8hr |
IV IV IV IV |
||
|
For 2-4 wk, followed by individual regimens according to antimicrobial susceptibility |
||||
PO= orally; IV= intravenously; IM= intramuscularly; forte tablet = trimethoprim 160 mg plus sulfamethoxazole 800 mg; MRSA = methicillin-resistant S aureus. 1. If implant retention or one-stage exchange is performed, the total duration of antimicrobial treatment is 3 months for hip prosthesis and 6 months for knee prosthesis. 2. In patients with delayed hypersensitivity, cefazolin (2 g IV q8hr) may be administered. In patients with immediate hypersensitivity, penicillin should be replaced with vancomycin (1 g q12hr). 3. MRSA should not be treated with quinolones, because antimicrobial resistance might emerge during treatment. 4. On the first day of treatment, the teicoplanin dose should be increased to 800 mg IV (loading dose). 5. Aminoglycosides can be administered in a single daily dose. 6. Alternatively, penicillin G (5 million U IV q6hr) or ceftriaxone (2 g IV q24hr) may be used for gram-positive anaerobes (eg, Propionibacterium acnes), and metronidazole (500 mg IV or PO q8hr) for gram-negative anaerobes (eg, Bacteroides spp). |
|||||
