Orthopedics

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Review Article 

Evaluation and Management of the Infected Total Hip and Knee

Thomas F. Moyad, MD, MPH; Thomas Thornhill, MD; Daniel Estok, MD

Abstract

Infections following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) can be a devastating complication leading to significant morbidity. Multiple risk factors have been identified including: 1) revision surgery, 2) rheumatoid arthritis, 3) diabetes mellitus, 4) obesity, 5) poor nutrition, 6) immunosuppressive medications, and 7) presence of psoriatic skin lesions.1-3 Classification systems devised to help guide treatment algorithms are primarily based on the duration of signs and symptoms. Therefore, early recognition and proper management of these infections is important, not only from a medicolegal standpoint, but it also has significant public health implications. This review focuses on current diagnostic and management strategies, in particular with regards to single stage versus two staged resection arthroplasty for chronic hip and knee infections.

Deep infection occurs in approximately 1% to 2 % of all primary total hip and knee arthroplasties.4 While the infection rate has remained fairly low over the past several decades, given the increasing number of total joints performed throughout the United States, total hip and knee infections create a significant burden on our health care system. The institutional cost of treating an individual patient has been estimated to result in a net loss of $15,000 to $30,000. Furthermore, the cost of treating THA infections in the United States alone is approximately $200 million per year.5

Host factors such as diabetes, rheumatoid arthritis, and immune status are important considerations. However, revision surgery carries the highest risk of infection. Although the exact percent varies in the literature, revision surgery appears to carry two to three times the risk of infection versus primary THA and TKA.3

Prevention of infection is obviously an important consideration. A thorough history and physical examination to identify sources of potential infection, such as infected diabetic foot ulcers, is paramount prior to undergoing any arthroplasty surgery.

Furthermore, a recent advisory statement provided by the American Academy of Orthopaedic Surgeons discussed routine prophylaxis with keflex, amoxicillin, or clindamycin (if penicillin allergic) for 2 years following THA or TKA prior to various procedures, such as dental cleaning.3 Routine prophylaxis after 2 years following THA or TKA may be also considered in some patients who have immune suppression due to certain medical conditions or immunosuppressive medications.

Lastly, adding prophylactic antibiotics to cemented arthroplasties has been advocated, especially in revision surgery.6 However, currently no studies conclusively demonstrate whether this technique lowers infection during primary THA and TKA surgery.

Staphylococcus epidermidis and Staphylococcus aureus are the two most common isolates found in infected total hip and knee arthroplasties. Some series point to S aureus as the most prevalent organism.7-10 Other series show that S epidermidis is the most common.11-15 Some common but less frequent organisms include Streptococcus species and gram negatives such as Pseudomonas, Klebsiella, and Escherichia coli. Occasionally, mixed infections with anaerobes like Enterococcus and Peptococcus are present. Finally, fungal infections such as Mycobacterium tuberculosis and Candida albicans are infrequent, but may be present, especially in the immune compromised host.

An important consideration with regard to etiology is the virulence of the organism. Previous investigators have cited increased difficulty with eradication of certain bacteria. Some authors have proposed differing treatment recommendations depending on which microorganism(s) are present.16,17

In an early, often cited publication, Buchholz et al7 reported results with single staged resection and reimplantation hip arthroplasty, and found that gram negatives including Klebsiella, Proteus, and Pseudomonas groups were associated with a high rate of failure. In this study, it was found that approximately 50% of these gram negative infections failed treatment. However, these results must be viewed cautiously, since many patients in this study did not receive intravenous antibiotics postoperatively, which…

Infections following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) can be a devastating complication leading to significant morbidity. Multiple risk factors have been identified including: 1) revision surgery, 2) rheumatoid arthritis, 3) diabetes mellitus, 4) obesity, 5) poor nutrition, 6) immunosuppressive medications, and 7) presence of psoriatic skin lesions.1-3 Classification systems devised to help guide treatment algorithms are primarily based on the duration of signs and symptoms. Therefore, early recognition and proper management of these infections is important, not only from a medicolegal standpoint, but it also has significant public health implications. This review focuses on current diagnostic and management strategies, in particular with regards to single stage versus two staged resection arthroplasty for chronic hip and knee infections.

Epidemiology

Deep infection occurs in approximately 1% to 2 % of all primary total hip and knee arthroplasties.4 While the infection rate has remained fairly low over the past several decades, given the increasing number of total joints performed throughout the United States, total hip and knee infections create a significant burden on our health care system. The institutional cost of treating an individual patient has been estimated to result in a net loss of $15,000 to $30,000. Furthermore, the cost of treating THA infections in the United States alone is approximately $200 million per year.5

Host factors such as diabetes, rheumatoid arthritis, and immune status are important considerations. However, revision surgery carries the highest risk of infection. Although the exact percent varies in the literature, revision surgery appears to carry two to three times the risk of infection versus primary THA and TKA.3

Prevention of infection is obviously an important consideration. A thorough history and physical examination to identify sources of potential infection, such as infected diabetic foot ulcers, is paramount prior to undergoing any arthroplasty surgery.

Furthermore, a recent advisory statement provided by the American Academy of Orthopaedic Surgeons discussed routine prophylaxis with keflex, amoxicillin, or clindamycin (if penicillin allergic) for 2 years following THA or TKA prior to various procedures, such as dental cleaning.3 Routine prophylaxis after 2 years following THA or TKA may be also considered in some patients who have immune suppression due to certain medical conditions or immunosuppressive medications.

Lastly, adding prophylactic antibiotics to cemented arthroplasties has been advocated, especially in revision surgery.6 However, currently no studies conclusively demonstrate whether this technique lowers infection during primary THA and TKA surgery.

Etiology

Staphylococcus epidermidis and Staphylococcus aureus are the two most common isolates found in infected total hip and knee arthroplasties. Some series point to S aureus as the most prevalent organism.7-10 Other series show that S epidermidis is the most common.11-15 Some common but less frequent organisms include Streptococcus species and gram negatives such as Pseudomonas, Klebsiella, and Escherichia coli. Occasionally, mixed infections with anaerobes like Enterococcus and Peptococcus are present. Finally, fungal infections such as Mycobacterium tuberculosis and Candida albicans are infrequent, but may be present, especially in the immune compromised host.

An important consideration with regard to etiology is the virulence of the organism. Previous investigators have cited increased difficulty with eradication of certain bacteria. Some authors have proposed differing treatment recommendations depending on which microorganism(s) are present.16,17

In an early, often cited publication, Buchholz et al7 reported results with single staged resection and reimplantation hip arthroplasty, and found that gram negatives including Klebsiella, Proteus, and Pseudomonas groups were associated with a high rate of failure. In this study, it was found that approximately 50% of these gram negative infections failed treatment. However, these results must be viewed cautiously, since many patients in this study did not receive intravenous antibiotics postoperatively, which is the current standard of care.

A few small series in the literature have shown reduced efficacy in treating specific organisms such as coagulase positive Staphylococcus, and certain gram negatives.7,16-18 However, due to the lack of solid evidence based medicine, the decision to retain versus remove the implant should not be based primarily on the specific type of bacteria encountered, but rather on the duration of symptoms.

Classification

In general, classifying total hip and knee infections relies on establishing the temporal relationship between the index procedure and the onset of symptoms, as well as the route by which the infecting organism gains access to the joint space.

Acute or early infections are usually defined as infections presenting within approximately 1 month postoperatively or alternatively a symptom onset of <1 month="" duration="" irrespective="" of="" when="" the="" index="" arthroplasty="" was="" performed.="" chronic="" or="" late="" infections="" are="" those="" that="" present="" after="" approximately="" a="" one="" month="" duration.="" it="" is="" extremely="" important="" to="" ascertain="" when="" the="" symptoms="" first="" began,="" as="" treatment="" recommendations="" differ="" depending="" on="" the="" duration="" of="" symptoms.="" in="" general,="" irrigation="" and="" debridement="" with="" retention="" of="" components="" can="" be="" attempted="" if="" the="" infection="" is="" acute.="" chronic="" infections="" have="" no="" chance="" of="" eradication="" without="" some="" form="" of="" resection="">13,16,19

Another important consideration is the route of infection. Postoperative sources include contamination during the index procedure as well as wound colonization from prolonged drainage at the incision or drain site. Hematogenous sources may be early in the postoperative period or present late, years after the THA or TKA. Systemic seeding may occur from a variety of sources including: 1) urinary tract infections, 2) upper respiratory infections, 3) cellulitis, 4) chronic venous stasis ulcers, 5) dental abscesses, 6) bone and joint infections at other sites, and 7) virtually any procedure that disrupts local skin and mucosal barrier immunity such as cystoscopy, colonoscopy, broncoscopy, prophylactic teeth cleaning and intra-articular joint injections. Identifying the origin of infection helps to determine when the joint became infected, as well as aids in preventing subsequent infections by eradicating the source.

Diagnosis

The first step in evaluation of a total joint infection begins with a detailed history and physical examination. Specifically, the patient should be questioned about any wound complications following their previous surgery. In addition, prolonged drainage or extended use of antibiotics following the original surgery are possible indicators of a postoperative infection. Furthermore, the onset of symptoms such as fevers, night sweats, chills, swelling, stiffness, and pain with motion may help define whether the infection is acute or chronic. Lastly, one should inspect for signs of infections such as redness, induration, callor, effusions, regional lymphadenopathy, incisional drainage, sinus tracts and pain with range of motion.

Routine blood tests and radiographs should accompany every workup for total hip or knee infection. Radiographs should be inspected for progressive radiolucent regions around previous implants or areas of necrotic bone.

While a complete blood count alone has little diagnostic value, the combination of an erythrocyte sedimentation rate and C-reactive protein is invaluable. A study from Vancouver, British Columbia prospectively analyzed 202 revision hips. The sensitivity of the C-reactive protein and erythrocyte sedimentation rate for infection was .96 and .82 respectively. Most importantly, when both the C-reactive protein and erythrocyte sedimentation rate were negative, the probability of infection was zero.5 Although, false positive results can occur, this study demonstrated that negative laboratory values are helpful in ruling out infection. Most recently, Il-6 was also shown to be a sensitive as well as specific marker for infection.20 However, at the present time, routine clinical use of this test is limited.

An aspiration of the joint should be considered if either the C-reactive protein or erythrocyte sedimentation rate is positive or if there is enough clinical suspicion to warrant its use. Although, a knee aspiration is easy to perform, a hip arthrocentesis often requires the use of fluoroscopy and may lead to a delay in treatment unless it can be performed expediently. Furthermore, the sensitivity of aspiration varies in the literature. For example, some authors have found hip aspiration, cell count, and culture to have a sensitivity and specificity >90%, while others have had less success.21-23 This may be related, in part, to the use of antibiotics in some patients in the days or weeks prior to the aspiration. However, a hip or knee aspiration, cell count and culture should be viewed as an adjunctive test that may provide useful information when performed in combination with a thorough clinical examination and routine blood work.

The benefit of nuclear imaging has been debated and results vary in the literature.24-27 This seems to be, at least partly due to the various techniques used. In an early study that combined technetium and gallium, the sensitivity of diagnosing a joint infection was low at 38%.25 In a latter study that used sequential technetium and indium labeled leukocyte scans, the sensitivity was found to be 64%.27 Two further studies performed by Palestro et al26 using indium labeled leukocyte scans demonstrated sensitivities of 86% in one report, while the other study had 100% sensitivity for diagnosing joint infection. Therefore, it is important to ascertain which method of radioisotope imaging is being used to account for any institutional limitations that may decrease its accuracy. It is also important to realize that nuclear imaging often remains positive for >1 year following routine THA or TKA, which limits its use in this setting. Although it may be indicated as an adjunctive test in certain situations, in general the results should not be viewed as definitive.

Lastly, the accuracy of intraoperative tests such as frozen sections and gram stains also varies widely in the literature.4,23,28,29 Furthermore, the specificity and sensitivity of frozen sections may depend on the area and number of tissue samples that are obtained, as well as the number of white blood cells visualized per high power field. Lonner et al23 has recommended using 10 white blood cells/high power field for diagnosing periprosthetic infection to improve the specificity of the frozen section.

Despite their routine use, the surgeon should not rely solely on intraoperative frozen sections or gram staining to guide his or her intraoperative treatment. Rather, in the majority of situations, a complete preoperative workup including the history and physical examination, radiographs, and laboratory values should help determine the preoperative plan. Intraoperative tests are most useful as guides to postoperative management. Several tissues samples should be taken from the most inflamed areas of the joint, as well as the intramedullary canal (if component resection is performed). The excised tissue should then be sent for both anaerobic and aerobic cultures (as well as fungal cultures if clinical suspicion exists). This may be the only chance to isolate the offending microorganism and is paramount for targeting specific antibiotic therapy in the postoperative period. It is critical that the patient discontinue antibiotics for at least several weeks prior to obtaining cultures if possible, otherwise a false negative result may occur.

Treatment

Acute total hip and knee infections presenting within one month of symptom onset are often initially treated with irrigation and debridement with component retention, as well as polyethylene liner exchange in implants with modular components. The success rate of this approach varies in the literature from <10% to="">50%. A delay in treatment appears to be the most detrimental factor to a successful outcome.13,16,30,31

In a study performed by Crockarell et al 42 patients with an infected THA were treated with open debridement and component retention, followed by intravenous antibiotics.13 Success was demonstrated in the group treated at a mean of 6 days after symptom onset. However, patients with symptoms of infection averaging >3 weeks failed treatment. Although the success rate appeared to be high at 1-year postoperative, the re-infection rate steadily increased over time. Moreover, at 6 years mean follow up, approximately 33% of the cases were cured with ≥1 irrigation and debridement when performed within the first 2 weeks of symptom onset versus none in those with >2 weeks of symptoms.13

Tsukayama et al had somewhat better results with irrigation and debridement and component retention in 35 acutely infected total hips (<4 weeks="" from="" symptom="" onset).="" approximately="" 70%="" of="" postoperative="" infections="" and="" 50%="" of="" acute="" hematogenous="" infections="" were="" successfully="" treated="" in="" this="">19,32

There is also some evidence to suggest that certain microorganisms are more difficult to eradicate and may require more aggressive forms of treatment.7,16,17,18 Deirmengian et al published his series of 31 acute total knee infections treated with irrigation, debridement, and systemic antibiotic therapy with retention of components. In this small, retrospective review the author found that S aureus was more difficult to eradicate. Patients with Streptococcus species and S epidermidis had better than a 50% chance of cure versus <10% success="" in="" individuals="" with="" positive="" cultures="" to="">S aureus. The average duration of symptoms in all patients before debridement was 9 days.16

These results demonstrate that prompt surgical intervention is the key to a successful outcome. However, despite early, aggressive treatment, irrigation and debridement with retention of components frequently results in persistent infection over the long run.

It is well accepted that chronic total joint infections that present late are best managed with component revision and at least 6 weeks of intravenous antibiotics. Whether the best approach is a single staged revision or a two staged, delayed resection arthroplasty with interval placement of an antibiotic spacer has been a matter of debate in the literature. The trend in the United States is to perform a staged resection arthroplasty for chronically infected total hips and knees, as this has shown the highest rate of success.8-11,14,18,31-37 However, in certain circumstances, single staged revision has been used successfully in chronic infections as well.7,11,12,15,17,38

In a large study performed in the early 1980s, direct exchange hip arthroplasty for infection demonstrated an overall success rate of 77%, even without routine postoperative intravenous antibiotics, which is the current standard of care. The results of this study may have been further skewed due to the fact that the antibiotic dose used within the bone cement was variable.7

Amstutz et al15 published a small series of 20 patients with infected THA. Their success rate with a single staged revision was 100% at an average 10-year follow-up. However, 5 of 20 patients were lost to follow-up, which may have biased these results.

Callaghan et al12 reviewed their results in 24 infected total hips with single staged revision arthroplasty. No patients were lost to follow-up. Infection reoccurred in only 8% of patients, although the authors carefully selected their patients in this study. The majority of microorganisms were S epidermidis isolates. Furthermore, patients with a visible sinus tract, those with any immunosuppression or inadequate bone stock were viewed as contraindications and underwent resection arthroplasty instead.12

In a literature review of direct exchange arthroplasty for infected THAs, >1200 infected joints were pooled from >12 studies. Eighty-three percent of the cases were infection free with an average 5-year follow-up. Factors that were cited as positive prognostic indicators included patients with a good baseline health status and those with S epidermidis, methicillin-sensitive S aureus, and Streptococcal species. A significant weakness of this review was that nearly 50% of the patients came from a single study with inherent biases. For instance, many of the patients were treated without routine systemic intravenous antibiotics postoperatively, which may have led to an underestimation of the success rate.17

A recent series of 22 infected total knees treated with single stage revision arthroplasty were reviewed at an average 10-year follow-up. The authors of this study found a >90% success rate with direct exchange arthroplasty and the use of intravenous antibiotics postoperatively. Although the average follow-up was adequate to screen for the presence of infection, individual follow-up was variable (range, 1.4-19.6 years). Therefore, it is possible that a few of the patients with short term follow up may have presented with infection at a later date, which could have led to an overestimation of the success rate in this study.11

Staged resection typically involves resection of the implant with placement of antibiotic cement in the form of beads, blocks, or articulated spacers (Figures 1, 2). In general, specifically targeted intravenous antibiotics are used for 6 to 8 weeks followed by oral antibiotics if necessary. A complete blood count, C-reactive protein, and erythrocyte sedimentation rate are obtained at routine intervals, and these laboratory values as well as knee or hip aspirations are often performed to guide the timing of re-implantation. There are a number of proposed advantages and disadvantages to the different types of antibiotic spacers.

Antibiotic beads and blocks are relatively simple to implant and antibiotic beads have a large surface area for antibiotic elution due to the numerous spheres that are created.6 However, the main drawback for both the block and bead techniques are that joint motion is more restricted during the period between resection and re-implantation. Furthermore, the second stage surgery may be more difficult due to scarring, improper soft tissue tensioning and possibly bone loss.

More recently, articulated spacer blocks and the PROSTALAC (prosthesis of antibiotic loaded acrylic cement) have gained popularity (Figures 3-5). Although, these are somewhat more labor intensive and are associated with increased cost, proposed advantages included ease of second stage revision and better patient function during the interval treatment period.

In general, direct comparisons of antibiotic delivery systems for infected two stage revision hip and knee surgery have similar efficacy in terms of eradication of infection.18,37 The antibiotic dosage within the cement warrants special consideration. While antibiotics are frequently added to cement during the second stage re-implantation (ie, in revision TKA and hybrid THA), the dose is limited to approximately 1 g of antibiotic powder per one packet of cement (approximately 40 g). Higher doses have been found to substantially reduce the strength of the bone cement.3,6

Figure 1A: Static knee spacer block. Note the subluxation of the spacer leading to distal femoral bone loss Figure 1B: Static knee spacer block. Note the subluxation of the spacer leading to distal femoral bone loss
Figure 1: Static knee spacer block. Note the subluxation of the spacer leading to distal femoral bone loss (A, B).

However, antibiotic dosages placed in temporary spacers are usually higher, which has favorable elution characteristics including increasing the amount and duration of antibiotics within the local environment of the hip or knee joint.6 The total amount of antibiotics within the cement spacers vary considerably in the literature. In some series, as low as 2 g have been used, while other authors have placed close to 20 g of antibiotics per spacer without reported systemic side effects.39 Although antibiotic spacers are often felt to be clinically safe, it is prudent to monitor patients in the postoperative period. This includes evaluating renal function when using antibiotic loaded cement and intravenous medications such as gentamicin and vancomycin.

Figure 2A: AP radiograph showing spacer block with reinforcement wire Figure 2B: Lateral radiograph showing spacer block with reinforcement wire
Figure 2: AP (A) and lateral (B) radiographs showing spacer block with reinforcement wire. Note the wire acts as a checkrein against subluxation, decreasing the amount of bone loss that can occur during the interval placement of the antibiotic cement.

Numerous studies of delayed, two staged hip and knee arthroplasty have demonstrated high efficacy in terms of eradication of infection. In a study by Younger et al, 61 infected total hips were treated with staged revision using the PROSTALAC spacer.31 At final follow-up, 94% of infections were eradicated. Most importantly, the authors aspirated all hip prior to re-implantation and followed intraoperative cultures obtained at the time of re-implantation, which appeared to improve their overall success rate.31

Hoffman et al8 had similar success, with a 94% eradication rate, using a two staged articulated hip spacer technique. Unfortunately, approximately 1/3rd of patients in this review were lost to follow-up, which may have biased the results.

In another study comparing the use of antibiotic beads to molded articulated spacer for THA infections, success rates were similar between both groups with a 95% cure rate.37

Two recently published studies of infected TKA used a staged resection technique with articulated spacers fabricated from the original components. In both studies, the femoral component was removed, autoclaved and re-cemented with a new polyethylene insert coated with antibiotic loaded cement. The cure rate was ≥90% using this technique. 9,14

Meek et al10 used a PROSTALAC system for 58 total knee infections and found a 96% cure rate. They followed trends in the sedimentation rate and C-reactive protein in the interval period as well as aspirated all knees prior to final re-implantation. The protocol involved discontinuing all antibiotics 4 weeks prior to aspiration and culture to reduce the number of false negative results.10

Summary

Infection should be in the differential for any painful total hip or knee. A thorough history and physical, complete set of radiographs and appropriate labs including C-reactive protein and erythrocyte sedimentation rate are essential in the initial evaluation. Ancillary tests such as aspiration and nuclear imaging may be helpful in unclear cases or when labs are concerning for infection. It is essential that all antibiotics are discontinued several weeks prior to gram stain and culture, if possible, to reduce the number of false negative test results.

Classifying infection into acute versus late infection aids in the treatment plan. For acute infections presenting within 2 to 4 weeks of symptom onset, irrigation and debridement with polyethylene liner exchange and retention of components may be possible. When attempting component retention, thorough debridement and rapid treatment of the infection prior to the accumulation of any biofilm is paramount for a successful outcome. Other important prognostic factors to consider include the virulence of the microorganism as well as the immune status of the host.

Despite expeditious management, irrigation and debridement of acute total hip and knee infections frequently leads to recurrent infection. Thus, patients should be counseled accordingly. Further management may be needed following an initial attempt at component retention. These options include resection arthroplasty with or without re-implantation, long term antibiotic suppressive therapy, arthrodesis and even above the knee amputation in rare circumstances.

Figure 3: Articulated hip spacer
Figure 3: Articulated hip spacer.
Figure 4: A bulb from an irrigation syringe can be used to fashion an articulated femoral head cement spacer
Figure 4: A bulb from an irrigation syringe can be used to fashion an articulated femoral head cement spacer.

For chronic infections, a successful outcome depends on several factors including the baseline health status of the patient, implant removal with a thorough debridement followed by culture specific antibiotic treatment. Furthermore, methods of monitoring for persistent infection include following laboratory values such as the C-reactive protein, erythrocyte sedimentation rate, and cultures from joint aspirations.

Whether to perform a direct exchange versus a delayed revision arthroplasty for chronic total hip and knee infections can be debated. Several published series have reported successful outcomes with single stage procedures when patients are carefully selected. However, the majority of chronic infections in the United States are treated with two stage resection, since this method has consistently provided the highest cure rates, with many current studies demonstrating >90% success.

References

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Authors

Drs Moyad, Thornhill, and Estok are from the Department of Orthopedics, Brigham & Women’s Hospital, Boston, Massachusetts.

Drs Moyad, Thornhill, and Estok have no relevant financial relationships to disclose. Dr Morgan, CME Editor, has disclosed the following relevant financial relationships: Stryker, speakers bureau; Smith & Nephew, speakers bureau, research grant recipient; AO International, speakers bureau, research grant recipient; Synthes, institutional support. Dr D’Ambrosia, Editor-in-Chief, has no relevant financial relationships to disclose. The staff of Orthopedics have no relevant financial relationships to disclose.

The material presented at or in any Vindico Medical Education continuing education activity does not necessarily reflect the views and opinions of Vindico Medical Education or Orthopedics. Neither Vindico Medical Education or Orthopedics, nor the faculty endorse or recommend any techniques, commercial products, or manufacturers. The faculty/authors may discuss the use of materials and/or products that have not yet been approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or utilizing any product.

Correspondence should be addressed to: Thomas F. Moyad, MD, MPH, Department of Orthopedics, Brigham & Women’s Hospital, 45 Francis St, Boston, MA 02115.

10.3928/01477447-20080601-22

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