Practice Essentials
Infection, though an uncommon complication of arthroplasty, may be among the most devastating complications for the patient, as well as for the surgeon. The economic consequences associated with treating periprosthetic infections are substantial. [1, 2, 3]
Revision procedures for infection are associated with a longer operating time, greater blood loss, and more frequent complications, along with increases in the total number of hospitalizations, duration of hospitalization, total number of operations, total hospital costs, and total outpatient visits and charges. When compared with revisions for aseptic loosening or primary total hip arthroplasties (THAs), revisions for sepsis are associated with significantly greater use of hospital and physician resources. [3]
Currently, the reported infection rate after arthroplasty is about 1%. [4] Kurtz et al quantified the current and historical incidence of periprosthetic infection associated with hip and knee arthroplasty in the United States using the Nationwide Inpatient Sample, as well as corresponding hospitalization charges and length of stay, and found that the rate of infected knee arthroplasties was 0.92%, significantly greater than the rate of infected hip arthroplasties (0.88%). [5]
The number of primary and revision procedures has been projected to expand dramatically over the next decade and beyond [6, 7] ; accordingly, the infection burden on patients, clinicians, and society as a whole will also increase. The estimated cost of infected revisions was projected to be as high as $1.85 billion in the United States by 2030. [7] Methods of preventing, diagnosing, and treating infection must be continually improved in order to reduce the cost and complications of total joint arthroplasty.
There is a need for both improved diagnostic methods and more efficient treatment protocols. Molecular diagnostic methods, such as polymerase chain reaction (PCR) testing, have been associated with high false-positive rates and are still not recommended for routine clinical use. Addressing bone defects during reimplantation is an area that also requires further research.
The problems of conducting randomized studies in the setting of a septic prosthetic failure are a major deterrent to the evolution of treatment protocols. Foolproof intraoperative diagnostic techniques, improved implant designs, and better local antibiotic delivery systems must be developed to face the menace of infection associated with joint replacement surgery.
Gains may be achieved not only by developing newer approaches but also by using currently available approaches more effectively. For example, in one study, culture of samples obtained via sonication of prostheses was more sensitive than conventional periprosthetic-tissue culture for microbiologic diagnosis of prosthetic hip and knee infection, especially in patients who had received antimicrobial therapy within the 14 days preceding surgery. [8]
In a meta-analysis, antigranulocyte scintigraphy with monoclonal antibodies had a reasonably high discriminating ability with respect to identification of prosthesis infection in patients who underwent total joint arthroplasty. [9]
The use of cefuroxime-impregnated cement was shown to be effective in the prevention of early-to-intermediate deep infection after primary total knee arthroplasty (TKA) performed with perioperative systemic antibiotic prophylaxis but without any so-called clean-air measures. [10] This measure may be particularly helpful in developing nations, where more and more arthroplasties are now being performed.
Additional pathogens are being found to cause prosthetic joint infections. A Swiss study drew attention toward infection by Propionibacterium acnes; a median of 10 biopsies, a 14-day incubation period, and histopathologic examination were needed to establish the association. [11]
Thus, the future of management of arthroplasty-associated infections lies in devising ways to prevent infections, developing investigations that allow early detection, and minimizing both the emergence of new pathogens and the spread of antibiotic resistance among existing pathogens.
Etiology
Factors influencing the occurrence of arthroplasty-associated infections include the following [12] :
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Host factors (ie, those related to the patient)
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Operating room (OR) environment
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Techniques and materials employed in the surgical procedure (including operating time)
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Characteristics of the infecting organism
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Use of preoperative antibiotics
Debreuve-Theresette et al described the development of a score to asses the endogenous risk of surgical-site infection (SSI) after THA and TKA. [13] They found the score useful for identifying SSIs but noted that further validation in larger studies would be required.
Host factors
Immunocompromised status, rheumatoid arthritis, and diabetes mellitus are some of the most important comorbid conditions associated with an increased risk of infection in a patient undergoing arthroplasty.
Malnutrition has been defined by many authors as a total white blood cell (WBC) count lower than 1500/µL and an albumin level lower than 3.5 mg/dL. [14] Malnourished patients have an increased chance of wound complications. [15] Hence, it is imperative to build up the patient’s nutritional status before the operation.
Obesity is another important factor to be considered. [16] One study found obesity to be an independent risk factor for the development of deep sepsis after hip arthroplasty. [17]
Chronic urinary tract infection (UTI) and ongoing sepsis in any other part of the body also increase the risk.
Smoking may increase the risk of SSI after total joint arthroplasty. [18]
Steroid use for an associated condition (eg, inflammatory arthritis or psoriasis) has been associated with increased susceptibility to infection.
A previous surgical procedure on the same joint is an independent risk factor that doubles the risk of deep infection in the knee and triples the risk in the hip. [19, 20] Prior knee arthroscopy has been found to increase the incidence of prosthetic joint infection after TKA. [21]
Elderly patients and patients with comorbid conditions that require a long time for optimization before surgery are more susceptible to infection as well. [22]
Patients who are receiving hemodialysis or have a history of renal transplantation, although they generally have a good functional outcome after THA, have been found to have a higher revision rate and a higher deep infection rate than would be expected in patients receiving THA for primary osteoarthritis. [23]
Operating room environment
The number of personnel and the amount of traffic in the OR exert an influence on the incidence of infection. Accordingly, changes in the OR environment have the potential to reduce infection. For example, some people shed a large number of bacteria; they can help decrease the risk of infection by using helmet aspirator suits.
Although various commercial preparations are available for preparing the surgical site, most surgeons prefer the iodophor compounds. Shaving the area is best avoided, but if it is considered essential, it should be done immediately before the procedure. The use of an iodophor-incorporated drape has been proved to decrease infection in arthroplasty patients and is now routine in this setting.
In one study, the use of an iodophor-incorporated drape during 649 TKAs was associated with an infection rate of only 0.5%. [24] In another study, the use of an iodophor-incorporated drape proved to be significantly better at preventing recolonization of the skin by bacteria than other methods of skin-site preparation were. [25]
Ultraviolet (UV) light has been employed to decrease the bacterial load in the OR. This measure adds to the cost of the procedure but has not been conclusively shown to produce a decrease in infection risk. [26]
Use of vertical laminar airflow has been found to yield a significant decrease in the bacterial load in the OR air and thereby decrease the infection rates with THAs. In an important study from the early 1980s, Lidwell et al concluded that laminar airflow systems and body exhaust suits independently reduced surgical infection risk by 50%. [27]
However, Miner et al, in a 2007 population survey designed to assess the efficacy of laminar flow and body exhaust suits, found no conclusive evidence to support this result. [28] The cost of laminar airflow systems and body exhaust suits is substantial, adding hundreds of dollars to the expense of each operation and complicating the environment in which the operating team works. The authors concluded that it would be worthwhile to obtain additional evidence about whether these widely used clean-air practices have a meaningful clinical benefit in today's OR.
Surgical techniques and materials
A prolonged operating time increases the risk of infection. [29] In one population-based survey, a prolonged operating time was in fact the only statistically significant risk factor for infection. [28]
The type of implant used also influences the infection risk. For example, a large hinged knee implant increases the risk of infection. Materials such as polymethylmethacrylate (PMMA), steel, cobalt-chromium (CoCr), and polyethylene (PE) are susceptible to the formation of a biofilm by the infecting organism around the implant, which protects the pathogen from the action of antibiotics. [30]
Characteristics of infecting organisms
The virulence of the infecting organisms is an important factor to consider in planning management. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated organisms. Gram-negative infections are resistant to treatment and are a frequent cause of recurrence after an exchange arthroplasty. [31] Organisms that can form glycocalyx, methicillin-resistant S aureus (MRSA), group D streptococci, and enterococci are considered highly virulent. Polymicrobial infections are likely to be harder to treat. [32]
A frequent cause of inability to isolate the organism is empirical antibiotic therapy. Other causes are infections caused by anaerobic organisms and fungi. Trampuz et al reported the frequencies with which different pathogens cause prosthetic joint infections (see Table 1 below). [33]
Table 1. Microorganisms Causing Prosthetic Joint Infections (Open Table in a new window)
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 |
Prosthetic joint infections are caused by pathogens living clustered together in biofilm, a highly hydrated extracellular matrix attached to the implant surface. Within the biofilm, the organisms grow either slowly or not at all; consequently, they are resistant to all growth-dependent antibiotics. The bacterial cells of the biofilm organize among themselves, communicate with each other, and behave like a multicellular organism. The biofilm helps the pathogens combat external and internal forces, whether from the host immune system or from antibiotics. [33]
There is some evidence to indicate that intracellular internalization of staphylococci may be a mechanism in the pathogenesis of infection and resistance to treatment. [34, 35]
Preoperative antibiotic prophylaxis
The Surgical Infection Prevention Project and its Surgical Infection Prevention Guideline Writers Workgroup promoted the following three major interventions to prevent SSIs [36] :
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Proper timing of prophylactic antibiotics, so that preoperative administration occurs within 1 hour of the surgical incision
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Correct selection of antibiotics
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Correct duration of postoperative antibiotic administration
With increasing frequency, patients are admitted to the hospital on the day of the operation and present to the OR just before their procedure. It is therefore essential to ensure that the institution of safeguards regarding the correct surgical site and the administration of prophylactic antibiotics no more than 1 hour before surgery are implemented as components of an institutional process. [37]
The cephalosporins cefazolin and cefuroxime are considered to have equal prophylactic efficacy. [38] Local guidelines that recommend beta-lactam agents as first-line prophylaxis should also recommend alternative drugs for those allergic to penicillin. Available evidence suggests that administering the first dose as near to the incision time as possible will reduce the likelihood of infection, whether superficial or deep.
There remains some controversy regarding the optimal duration of prophylaxis in connection with THA. The US advisory statement recommended that antimicrobial prophylaxis be administered no more than 1 hour before the incision and discontinued within 24 hours after the end of the operation. [36] However, European guidelines from 2000 recommended administering a single dose no more than 30 minutes before the incision and advise considering prophylaxis for as long as 24 hours after the operation. [39]
In a Dutch study, superficial and deep SSIs occurred in 2.6% of 1922 THA patients, and the highest odds ratios for infection were found in those who received prophylaxis after incision, those with an American Society of Anesthesiologists (ASA) score of 12, and those in whom the operating time was above the 75th percentile. [40] Prolonged prophylaxis after the end of the procedure and the use of antibiotic-impregnated cement did not contribute to fewer infections in this study.
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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 |
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Staphylococcus aureus or coagulase-negative staphylococci |
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Methicillin-susceptible |
Rifampin plus (flu)eloxacillin2 |
450 mg q12hr 2 g q6hr |
PO/IV IV |
||
For 2 wk, followed by |
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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 |
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Clindamycin |
300 mg q6hr |
PO |
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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 |
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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). |
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