Orthopaedic fracture fixation and joint implants are responsible for improving the quality of life for millions of patients worldwide, and the number of arthroplasty and nonarthroplasty procedures is steadily rising. In 2010, just over 1 million total hip and knee arthroplasties (THA and TKA, respectively) were performed in the United States; this number is projected to rise to >4 million by 2030.1,2 Unfortunately, the risk of musculoskeletal infection associated with primary or revision prosthetic implantation procedures remains a formidable challenge. Such infections have significant clinical and socioeconomic consequences; they are associated with increased patient morbidity and sometimes, mortality, as well as increased length of stay, resulting in increased healthcare costs. Reported infection rates vary between 1% to 5% for primary and revision hip and knee arthroplasties and could be as high as 30% for orthopaedic trauma procedures in which open wounds and contamination increase the risk for infection.3,4 The problem is compounded by the growing presence of antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), which lack reliable treatment regimens.
Infections After Hip and Knee Arthroplasty
THA and TKA are the most common joint arthroplasty procedures, and their numbers continue to rise steadily. Although the success of these procedures and their benefits to patients are well documented in the literature, failures related to periprosthetic joint infection (PJI) continue to be a concern. PJI accounts for the most common cause of early failures in TKA and is the third most common cause of failure in THA.5-7
Common treatment options for infection include irrigation and débridement with retention of components, direct or single-stage exchange, or staged reconstruction with interim placement of an antibiotic spacer. However, variable successes have been reported. For example, irrigation and débridement with polyethylene exchange, a common strategy used in the treatment of acute postoperative or late acute hematogenous infection, is associated with a lower morbidity and cost, but concern remains regarding the limited and inconsistent success of this procedure in the literature. Published studies describe a range of 20% to 85% for successful outcomes with this approach.8-11 Various reports have shown improved outcomes with appropriate patient selection (ie, host factors), the type of infecting organisms, and the use of antibiotic beads with repeat irrigation and débridement.8,12-14 Biofilm-related PJIs are the most challenging and are associated with the highest failure rates. Both mechanical and chemical biofilm disruption agents may prove highly useful in treating these challenging infections.
Outcome measures in the treatment of PJI have focused on eradication of infection, with little insight into the functional outcomes of patients. Recent data suggest that two-stage exchange arthroplasty in which all infected, necrotic, and prosthetic material is removed in the initial stage, long considered the benchmark in the United States, has a treatment success rate of 80% to 90%, but functionally, patients do poorly.15-20 The use of articulating spacers has been shown to improve patient-related outcome measures both in the interim stage and following reimplantation;5,6,21-23 however, a prolonged period of immobility and the necessity for a second surgery create significant hurdles for patients to overcome. In addition to the added morbidity of a two-stage exchange, patients with a chronic PJI have a higher mortality rate compared with patients undergoing aseptic revision.24 These data highlight the significant treatment challenges clinicians face when current modalities may ultimately be harmful to patients.
Future directions should focus on novel methods of infection prevention and improving eradication rates while maintaining patient mobility and satisfaction. Increased interest has been expressed in the role of single-stage exchange arthroplasty for the treatment of PJI. Although this method is not universally accepted in the United States as a treatment option, the literature suggests eradication rates similar to that of two-stage exchange.25,26 In addition, the economic benefits of a single-stage exchange have been shown to be superior to those of a two-stage exchange. Before becoming widely accepted, however, strict criteria and standardization of treatment principle for a single-stage exchange should be better elucidated.
The development of PJI is an interaction of the host and the environment, but much attention is currently focused on host factors only. New technology may allow us to focus on minimizing bacterial colonization from an environmental standpoint. Most of the infecting strains of bacteria that cause PJI are biofilm-producing organisms. Once formed, the biofilm creates an environment in which bacterial susceptibility to antibiotics is limited and disruption of the biofilm is difficult.27 Prevention of biofilm formation on implants and the ability of implants to repel biofilm formation have received much attention. The introduction of nanotechnology has the potential to allow for the application of biofilm-resistant material to implants.28 In addition, the introduction of antibiotic-coated implants may aid in the initial prevention and early treatment of PJI.29
Infections After Shoulder Arthroplasty
More than 45,000 total shoulder arthroplasty procedures are performed annually in the United States, and, similar to that of THA and TKA procedures, the trend is a sustained, rapid increase.30,31 Meanwhile, the incidence of total elbow arthroplasty in some countries is steady or even declining because improved medical antirheumatic therapy is being used to treat rheumatoid arthritis, the most common indication.32 Given this disparity, most research has been dedicated to the larger public health issue of periprosthetic shoulder infection (PSI).
The traditional definition of PJI33-35 shows a very low rate of PSI, with prevalence for primary shoulder arthroplasty as low as 0.7%36 and as high as 15.4% for revision surgery.33 Unfortunately, the traditional definition of PJI does not take into account our current understanding of nonsuppurative microorganisms, such as Propionibacterium acnes and coagulase-negative Staphylococcus. Although the pathogenic implications of these bacteria are a current area of discussion, P acnes is now recognized as the most common cause of PSI.37-41 The discrepancy between traditional musculoskeletal pathogens and P acnes leads to significant diagnostic challenges.42 This difficulty in diagnosis leads to treatment uncertainty, which is considered the biggest challenge in the management of potential shoulder infections. Unlike more familiar infection agents, P acnes does not reliably cause erythema, purulence, wound drainage, or an elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, white blood cell (WBC) differential, or interleukin 6 (IL-6) level.34,37,43,44 Aspiration of synovial fluid and intraoperative pathologic analysis of frozen sections for acute inflammation have been shown to be ineffective for diagnosis.38,39,43 Currently, no commercially available preoperative or intraoperative test reliably predicts P acnes culture growth.38 The only standard for P acnes diagnosis is long-hold cultures of tissue obtained with arthroscopic biopsy,45 via open biopsy, or at the time of revision surgery.38 The mean time to growth of the organism ranges from 7 to 13 days but can take up to 3 weeks; this factor only adds to the diagnostic challenge.43,46 Practically, physicians evaluating a painful and/or loose shoulder arthroplasty should still follow the same algorithm as that used for diagnosis of a PJI of the hip or knee. Although the tests mentioned earlier are not helpful for diagnosis of P acnes, the most common cause of PSI, approximately one third to one half of PSIs are caused by suppurative pathogens, and these tests will have utility in those cases.39,47
Treatment options for PSI include antibiotic suppression, irrigation and débridement with prosthesis retention, resection arthroplasty, one-stage exchange, staged reimplantation, arthrodesis, and amputation. Antibiotic suppression alone has shown poor outcomes, with persistent, symptomatic infection in most patients.48 This treatment strategy should be considered an option for patients only when the surgical risks are overwhelming secondary to medical comorbidities. Both Coste et al48 and Sperling et al49 reported their experience with débridement and implant retention with recurrence rates of 12% and 50%, respectively. Although Coste et al48 reported a low recurrence rate, 63% of their patients required revision surgery, and functional outcomes remained poor. This approach may be helpful for acute infections, but it is rarely indicated because most PSIs present in a subacute or chronic manner.48,49
One-stage exchange arthroplasty has shown promising results.50 The advantages include less destruction/dissection, immediate reconstruction, avoidance of secondary adhesions, less patient angst, and lower hospitalization costs.51 Ince et al50 reported encouraging results using this method in treating predominantly subacute and late infections. Advocates of this method report that when cultures are unexpectedly positive for P acnes at the time of revision surgery, only 6% to 10% of patients exhibit any signs of persistent infection.35,52
Modeled after what has been demonstrated in the hip and knee arthroplasty literature, two-stage reimplantation is currently the most common treatment of choice.53,54 Articulating antibiotic cement spacers allow for the preservation of a soft-tissue envelope and can often act as the definitive implant in a patient with minimal functional demands.55-57 Failure rates for infection clearance have been reported between zero and 36%.48,49,57-59 Nonetheless, both the surgeon and the patients should be aware that the subjective outcomes of revision for infection are the least favorable compared with revisions for any other indication.59 In the patient with low functional demands and a higher surgical risk, resection arthroplasty is an option to consider because it can provide pain relief in addition to low infection recurrence rates, frequently at the expense of function.60 Recurrence rates have been reported between zero and 30%.48,61-63
As a general protocol, any painful, loose shoulder arthroplasty should be evaluated with a thorough history to elicit for wound drainage issues and constitutional symptoms; serology should include an ESR and a CRP level. If these studies are positive, suspicion should be directed toward a traditional prosthetic joint infection that is caused by common pathogens such as S aureus, coagulase-negative Staphylococci, or gram-negative bacteria. However, if the traditional signs and symptoms are negative, there is still a concern for infection, in this case due to P acnes. In this scenario, we generally proceed to surgery with long-hold cultures taken at the time of the procedure. Frozen sections are also obtained. If there is an obvious mechanical cause for implant loosening (ie, subscapularis failure with glenoid loosening), we consider single-stage surgery in select patients. Otherwise, two-stage exchange arthroplasty with postoperative parenteral antibiotics is considered from an infection perspective because P acnes cannot be reliably ruled out before the long-hold culture results are finalized 2 weeks after surgery.
If the cultures are negative, antibiotics are stopped, and we proceed with reimplantation. If more than one fifth of the cultures are positive, we continue a full 6-week course of antibiotics before proceeding with reimplantation. Because bony and soft-tissue deficits frequently accompany these cases, reverse total shoulder arthroplasty may be helpful during the reimplantation/reconstructive phase for patients without significant upper extremity strength demands. Finally, we acknowledge that in the case of P acnes, there is still uncertainty whether two-stage revision arthroplasties are superior to single-stage procedures in terms of overall durable shoulder function and comfort. These factors apply provided that patients are able to tolerate prolonged oral antibiotic treatment following a single-stage procedure with aggressive débridement, humeral head exchange, and glenoid removal. Thus, the choice between single-stage and two-stage reconstruction remains at the discretion of the treating surgeon until further long-term clinical outcomes provide guidance.
Infections After Musculoskeletal Trauma Surgery
The incidence of traumatic injuries, especially those caused by motorized vehicles, has increased significantly throughout the world. In Africa, trauma is now designated as an epidemic.64 The late effects of long bone fractures, especially open injuries, are chronic osteomyelitis and infected nonunion. The Centers for Disease Control and Prevention has estimated the incidence of osteomyelitis in the United States to be 2 per 10,000 persons. This number is most likely underestimated and is certainly much higher in Third World countries.
Orthopaedic surgeons face many challenges in the treatment of posttraumatic osteomyelitis, not the least of which is proper training in this subspecialty during residency. Few orthopaedic surgeons specialize in the treatment of osteomyelitis, and no fellowships for this subspecialty exist in the United States at this time. Along these same lines, the average orthopaedic surgeon encounters possibly one case of trauma-related osteomyelitis every 3 years. With this rate of infrequency, these cases do not allow the practitioner to expand his or her clinical knowledge.
Goodacre65 best stated the role of pathogens in musculoskeletal infections when he wrote that “…many pathogens did not initially evolve as pathogens, but simply take on this role as a result of a lack of ability of the host to maintain homeostasis.” Nowhere is this truer than in posttraumatic infections and, in particular, osteomyelitis. These pathogens create a symbiotic state in their new-found host environment and have found the perfect mechanism to accomplish this with the biofilm state. It is important to understand that these microbes do not behave as a single organism but rather act as a true multicellular entity once the mature biofilm biosphere is formed. They are then 103 times less sensitive to antibiotics because of their sessile growth phase state. The biofilm also provides a selective barrier to penetration by antibiotics, and the sessile phase bacteria are protected by the semi-hydrophobic biofilm matrix. Classification of the area of osteomyelitis using the Cierny-Mader classification is extremely useful because it helps tailor treatment (Table 1).
Treatment and eradication of an infection of bone requires a four-stage treatment algorithm.66 The first stage involves the removal of all necrotic and compromised bone and surrounding soft tissue, creating a void. Antibiotic beads or vacuum-assisted devices are then needed to manage the dead space, along with provisional bony stabilization. The surgical team should select fixation that allows for later reconstruction. Once a healthy and viable wound bed is established, the third stage addresses soft-tissue reconstruction. This may require flaps, muscle transfers, or other procedures. Bony reconstruction is the fourth and final stage. In confined defects, this may be accomplished with simple bone grafting, but in segmental defects, more complex alternatives are required, including that of bone transport.
Infections After Foot and Ankle Surgery
The rate of foot and ankle infections after elective surgery has been reported to range between zero and 6.5% in the normal adult nonimmunocompromised population.67,68 This rate is higher than that in other parts of the body and is attributed to the unique environment of the foot and the native organisms.69 Several patient-related factors alter the risk of infection. Careful preoperative evaluation and counseling, as well as risk stratification and optimization, are essential to prevent postoperative infections in this patient population. Patients with systemic conditions, such as poorly controlled diabetes, peripheral vascular disease, thyroxine-supplemented patients, and patients who are steroid dependent, are at a much higher risk for infection.68,70-72 Diabetics with neuropathy are at a tenfold greater risk of infection than is the normal population and at a sixfold greater risk compared with patients with uncomplicated diabetes.72 In contrast to common perception, however, perioperative use of disease-modifying agents in patients with rheumatoid arthritis does not increase the risk of infection.73 Smoking and malnourishment are among the highest preventable causes of periprosthetic foot infections; therefore, smoking cessation and nutritional optimization are crucial to reduce risk.68
Proper surgical technique, including skin preparation, draping, surgical scrub, and meticulous soft-tissue management, is critical to the prevention of infections. Ostrander et al74 reported continued contamination even after prepping in the foot. Skin preparation with chlorhexidine and alcohol prep has been shown to be the most effective combination for reducing preoperative bacterial loads, although many other combinations have been proposed.75-79 However, no studies show their effect on infection rates. Additionally, the length of the surgical procedure is directly related to the risk of infection.68 Preoperative antibiotics, when given within 60 minutes before the time of incision, have been shown to reduce the risk of periprosthetic infections dramatically, regardless of their timing relative to tourniquet inflation.80,81 However, postoperative outpatient oral antibiotic treatment remains controversial.
Little consensus exists in the literature regarding optimal methods of prevention or detection of periprosthetic foot and ankle infections. Preoperative and postoperative foot baths have been highly debated and understudied.82,83 Additionally, most foot and ankle surgeries lead to increased foot swelling and pain; therefore, early recognition of periprosthetic infections is difficult. This situation is further complicated by the fact that most patients retain their postoperative dressings for 1 to 2 weeks. Finally, wound complications are not uncommon after certain procedures; these can lead to the risk of infection and deteriorated outcomes. Infection markers and novel infection proteins have not been studied in foot and ankle surgery. However, periprosthetic infections are rarely missed because of the paucity of soft-tissue coverage and the obvious symptoms of infections in foot and ankle patients.
A high index of suspicion and early and aggressive treatment of suspected infection are essential for optimizing patient outcomes. Postoperative superficial cellulitis typically presents with warmth of the skin, tenderness, and erythema without fluctuance or joint involvement. S aureus and β-hemolytic streptococci are the most common causative organisms. Treatment should consist of 7 to 10 days of oral antibiotics and frequent evaluations. Surgical intervention may be necessary. Deep infections and abscess formation are also serious complications. Aggressive treatment is always warranted to salvage the lower extremity. Presentation usually involves increased pain, skin warmth, possible fluctuance, leukocytosis, and fevers. Plain radiographs, MRI, and needle aspiration may be helpful in making the diagnosis. Early surgical débridement and targeted, culture-based antibiotic treatment are necessary. Multiple irrigations and débridements also may be necessary.
Current and future research in periprosthetic foot and ankle infections should be directed at identifying the optimal skin preparation as it relates to infection rates, diagnostic criteria and markers of infection, postoperative management protocols to reduce infections, wound management optimization, and appropriate antibiotic regimens.
Infections After Spine Surgery
The best estimate of the incidence of infection after spinal surgery is high at 4%.84 Timely diagnosis is often delayed because most spine infections are deep seated, and a surgeon’s reliance on the status of the wound often delays the diagnosis. One third of patients with postoperative spinal infections do not have wound drainage. Because many patients tend to have significant postoperative pain that may not be related to infection, a patient’s report of pain is often not taken into consideration as a sign of infection. Radiographic tests, such as MRI, may show fluid collection, but fluid is often present in noninfected spines for weeks following the surgery. Lack of a fever and a normal WBC count are often misleading clues, as well. The combination of these factors may account for a rather lengthy interval between the surgery and diagnosis.85
The CRP level appears to be the most accurate modality for identification of infection, although it remains elevated for 2 to 3 weeks after surgery, even in the absence of infection.86,87 Obtaining a CRP level at discharge may provide a baseline for comparison because the levels should steadily decline over time. However, obtaining the levels as a routine procedure is controversial given the low rate of infection. Obtaining CRP levels at two separate times, along with the presence of higher levels at the second time point, may be indicative of infection, but this has not yet been proven.
Obtaining fluid or tissue samples for identification of organisms is often not standardized and is considered inadequate. Wound swabbing should be avoided because this does not allow differentiation between skin flora contamination and skin flora infection. What constitutes adequate tissue sampling has not been well established. However, cultures at multiple separate sites may be needed to adequately differentiate certain nonvirulent organism (eg, S epidermidis, P acnes) infection versus a contamination. Infection with these organisms is becoming more prevalent.88 Identification of these organisms may also require a prolonged incubation period.89 Unfortunately, a cost-benefit analysis associated with multiple and prolonged cultures has not been assessed and cannot be routinely recommended for all cases, especially when the suspicion is low. A promising report describes looking for more than five white blood cells per high-field magnification on pathologic specimens to diagnose infection in spine wounds.90 However, the process cannot be used to identify the offending organism, and it may not improve diagnosis compared with what is possible with multiple and prolonged cultures.
There is no debate as to the need for good surgical débridement. However, whether instrumentation is helpful or detrimental to the eradication of infection is not known. Some reports suggest that well-fixed implants do not interfere with the eradication of postoperative infection.87,91 An investigation by Mohamed et al92 suggests that internal stabilization may actually assist in treating spinal infection. However, maintenance of a less than well-fixed implant is controversial. MRI or CT may be helpful in tracking infection from posterior tissue to the anterior vertebral body,93 but whether this information can be used in the choice of implant retention versus removal is yet to be resolved. Although the use of a suction drain after surgical débridement is well accepted, the recent use of vacuum-assisted devices is much more controversial. Successful eradication of infection and maintenance of instrumentation is reported,94 but there is also a reported risk of excessive bleeding leading to death.95 Furthermore, there is a danger of uncontrolled drainage of cerebrospinal fluid and neurologic injury from either recognized or unrecognized dural tears.
With early diagnosis, identification of the organism, surgical treatment, and antibiotics, good results and retention of implants are possible after postoperative spine infection. However, an optimal and cost-effective diagnostic and treatment algorithm still needs to be refined.
Clinical Perspective on Antibiotic Prophylaxis
Antibiotics play an important role in the prevention of periprosthetic infections; antibiotic prophylaxis has become part of the standard of care for arthroplasty and nonarthroplasty procedures. Based on older placebo-controlled data, approximately 50 patients need to receive perioperative prophylaxis to prevent one infection.96 The number needed to harm is even more elusive, but the risk of major events, such as anaphylaxis or Clostridium difficile infection, is greatly outweighed by the benefit of this practice. Evidence-based guidelines for perioperative antimicrobial prophylaxis are clear. The proper drug or drugs should be prescribed, dosed at the right time, and stopped on time.97 However, questions still arise frequently in clinical practice.
One dilemma that arises is when cefazolin is the prophylactic drug of choice, but the patient says that he or she is allergic to penicillin. Approximately 10% of Americans believe they are allergic to penicillin, but only about 10% of these persons actually have a true, immunologically mediated reaction to penicillin. Most patients are inaccurately labeled as penicillin allergic and can safely receive β-lactam antibiotics.98,99 This is important to note because cefazolin has a strong track record of providing a favorable balance of coverage and tolerability.100 Most patients considered to be allergic can be assessed by history alone; those who remain of concern can safely undergo pre-pen skin testing in an allergist’s office. To help orthopaedic surgeons decide whether a patient labeled as penicillin allergic should receive cefazolin or a second-line agent, a suggested algorithm is given in Figure 1.
When determining the optimum antibiotic dose for obese patients undergoing elective arthroplasty, it is important to note that obese patients may benefit from higher doses of antibiotics, assuming their renal function is normal. Although proper skin preparation technique should result in a small organism burden in the field, the risk of surgical site infection falls when antibiotic concentration rises in the wound. Unfortunately, modest clinical evidence suggests that drug distribution through the larger soft-tissue mass of obese patients may result in unacceptably low antibiotic delivery to the surgical field.101 These patients are at higher risk of infection than are lean patients, presumably for a variety of reasons, including insulin resistance, hyperglycemia, and tension on the skin closure. Antibiotic dosing is an easily modifiable factor, and current Infectious Diseases Society of America guidelines address this concern (Table 2).
A higher dose of cefazolin may still be infused quickly, but the challenge with higher doses of vancomycin relate to the increased amount of time required to administer it fully. Because of concern for histamine-mediated red man syndrome, the suggestion is to give larger doses over 90 or 120 minutes. This protocol may pose challenges for workflow in the operating room because, ideally, the full dose should be administered before tourniquet inflation and incision. However, at some centers, the infusion may be started in preoperative holding. If this is not feasible, then anesthesiology can prioritize starting the infusion as soon as possible after the patient arrives in the operating room so that much of the dose is administered before the surgery begins. Cefazolin remains the dependable prophylactic choice, and it should always be given fully before making the incision. Furthermore, there is no national regulatory requirement that the full vancomycin dose be administered before incision, only that the infusion begin before incision.
Other questions regarding antibiotic prophylaxis remain unresolved and are open for further clinical investigation, such as tailoring prophylaxis for special populations. For example, should anti-MRSA coverage be included in all elective arthroplasties, or should it be used only for procedures deemed to be at high risk (eg, history of infection or colonization)? Should prophylaxis for shoulder arthroplasties include more aggressive coverage of P acnes (eg, replace cefazolin with ceftriaxone)? Orthopaedic surgeons and infectious disease specialists should be encouraged to examine their own local clinical experience and respond in a rational fashion. For example, if an orthopaedic surgeon experiences a considerable number of MRSA periprosthetic infections, then coverage of that organism is reasonable to consider. However, there is no standardized definition of what constitutes a considerable number. Furthermore, this finding should trigger a thoughtful, open investigation of whether other remediable factors might contribute to the increased infection rate. Finally, specific centers or individual providers should be encouraged to track and share their experience so that the efficacy of various regimens can be measured.
Another area of discussion is the use of an efficacious regimen of cefazolin and vancomycin for MRSA coverage for arthroplasty prophylaxis, compared with the use of ceftaroline alone. Ceftaroline is a new cephalosporin antibiotic with the unique characteristic of covering both MRSA and methicillin-sensitive S aureus aggressively, as well as many common gastrointestinal gram-negative rods. It can be administered quickly, it has predictable pharmacology, and single doses are generally very well tolerated. This valuable drug is not currently indicated for surgical prophylaxis, and concerns for resistance with widespread use are warranted. However, if careful studies are performed, it may prove to be an attractive option for this role in patients who require MRSA coverage in their prophylactic regimen.
The issue of patients receiving oral antibiotic prophylaxis before major or minor dental care is a topic of discussion. Patients may become bacteremic as a result of dental procedures, and the use of antibiotics immediately before dental work can reduce the bacteremia. Although organisms typically associated with the oral microbiome are not commonly cultivated from infected prosthetics,102 many senior surgeons have personal experience with this scenario. Furthermore, many patients with periprosthetic infection report undergoing elective dental care in the weeks or months before infection diagnosis, raising that as a possible source. Unfortunately, confounding is difficult to exclude because routine dental care is so common. The situation is analogous to whether dental antibiotic prophylaxis should be offered to prevent infective endocarditis. Indications recommending dental prophylaxis for infective endocarditis have been significantly reduced based on concerns for the risk of adverse effects and toxicity and a paucity of convincing data.103 However, the physiology of bacterial clearance from prosthetics differs from that of the bloodstream. The current Infectious Diseases Society of America guidelines on prosthetic joint infections leave this as an open question.104 Conversely, the International Consensus on Periprosthetic Joint Infection achieved strong consensus (81% agreement) that the use of dental antibiotic prophylaxis in patients who have undergone total joint arthroplasty should be individualized based on patient risk factors and the complexity of the dental procedure to be performed.105 In summary, data to settle this important question are lacking, and it is difficult to envision the implementation of a prospective randomized trial that would provide adequate answers. Judicious use of antibiotics in select cases, especially within the first 2 years post implantation, may be warranted.
Orthopaedic fracture fixation and joint implants are responsible for improving the quality of life of millions of patients worldwide, and the number of arthroplasty and nonarthroplasty procedures is steadily rising. Unfortunately, the risk of musculoskeletal infection associated with primary or revision prosthetic implantation procedures continues to be a problem because such infections have significant clinical and economic consequences. Orthopaedic surgeons need to have a working understanding of the current perioperative prophylaxis and treatment strategies for infections associated with the most common arthroplasty procedures (ie, hip, knee, shoulder) and nonarthroplasty procedures (ie, trauma, foot, ankle, spine). Future directions should focus on novel methods of infection prevention and improving eradication rates while maintaining patient mobility and satisfaction.
Each author has equally participated in preparation of this paper, including literature review, manuscript writing, and revisions.
The authors acknowledge the contributions of the 2014 AAOS-ORS Musculoskeletal Infection Symposium Chairs and participants during the ideation and conception of this manuscript.
References printed in bold type are those published within the past 5 years.
2. Kurtz S, Ong K, Lau E, Mowat F, Halpern M: Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007;89(4):780–785.
3. Uçkay I, Hoffmeyer P, Lew D, Pittet D: Prevention of surgical site infections in orthopaedic surgery and bone trauma: State-of-the-art update. J Hosp Infect 2013;84(1):5–12.
4. Trampuz A, Widmer AF: Infections associated with orthopedic implants. Curr Opin Infect Dis 2006;19(4):349–356.
5. Fehring TK, Odum S, Griffin WL, Mason JB, Nadaud M: Early failures in total knee arthroplasty. Clin Orthop Relat Res 2001;392:315–318.
6. Furnes O, Espehaug B, Lie SA, Vollset SE, Engesaeter LB, Havelin LI: Early failures among 7,174 primary total knee replacements: A follow-up study from the Norwegian Arthroplasty Register 1994-2000. Acta Orthop Scand 2002;73(2):117–129.
7. Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ: The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am 2009;91(1):128–133.
8. Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill JJ, Parvizi J: Irrigation and debridement in the management of prosthetic joint infection: Traditional indications revisited. J Arthroplasty 2010;25(7):1022–1027.
9. Bradbury T, Fehring TK, Taunton M, et al.: The fate of acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. J Arthroplasty 2009;24(suppl 6):101–104.
10. Marculescu CE, Berbari EF, Hanssen AD, et al.: Outcome of prosthetic joint infections treated with debridement and retention of components. Clin Infect Dis 2006;42(4):471–478.
11. Silva M, Tharani R, Schmalzried TP: Results of direct exchange or debridement of the infected total knee arthroplasty. Clin Orthop Relat Res 2002;404:125–131.
12. Meehan AM, Osmon DR, Duffy MC, Hanssen AD, Keating MR: Outcome of penicillin-susceptible streptococcal prosthetic joint infection treated with debridement and retention of the prosthesis. Clin Infect Dis 2003;36(7):845–849.
13. Estes CS, Beauchamp CP, Clarke HD, Spangehl MJ: A two-stage retention débridement protocol for acute periprosthetic joint infections. Clin Orthop Relat Res 2010;468(8):2029–2038.
14. Mont MA, Waldman B, Banerjee C, Pacheco IH, Hungerford DS: Multiple irrigation, debridement, and retention of components in infected total knee arthroplasty. J Arthroplasty 1997;12(4):426–433.
15. Mortazavi SM, Vegari D, Ho A, Zmistowski B, Parvizi J: Two-stage exchange arthroplasty for infected total knee arthroplasty: Predictors of failure. Clin Orthop Relat Res 2011;469(11):3049–3054.
16. Diwanji SR, Kong IK, Park YH, Cho SG, Song EK, Yoon TR: Two-stage reconstruction of infected hip joints. J Arthroplasty 2008;23(5):656–661.
17. Masri BA, Panagiotopoulos KP, Greidanus NV, Garbuz DS, Duncan CP: Cementless two-stage exchange arthroplasty for infection after total hip arthroplasty. J Arthroplasty 2007;22(1):72–78.
18. Wang CJ, Hsieh MC, Huang TW, Wang JW, Chen HS, Liu CY: Clinical outcome and patient satisfaction in aseptic and septic revision total knee arthroplasty. Knee 2004;11(1):45–49.
19. Azzam K, McHale K, Austin M, Purtill JJ, Parvizi J: Outcome of a second two-stage reimplantation for periprosthetic knee infection. Clin Orthop Relat Res 2009;467(7):1706–1714.
20. De Man FH, Sendi P, Zimmerli W, Maurer TB, Ochsner PE, Ilchmann T: Infectiological, functional, and radiographic outcome after revision for prosthetic hip infection according to a strict algorithm. Acta Orthop 2011;82(1):27–34.
21. Emerson RH Jr, Muncie M, Tarbox TR, Higgins LL: Comparison of a static with a mobile spacer in total knee infection. Clin Orthop Relat Res 2002;404:132–138.
22. Fehring TK, Odum S, Calton TF, Mason JB: Articulating versus static spacers in revision total knee arthroplasty for sepsis: The Ranawat Award. Clin Orthop Relat Res 2000;380:9–16.
23. Park SJ, Song EK, Seon JK, Yoon TR, Park GH: Comparison of static and mobile antibiotic-impregnated cement spacers for the treatment of infected total knee arthroplasty. Int Orthop 2010;34(8):1181–1186.
24. Berend KR, Lombardi AV Jr, Morris MJ, Bergeson AG, Adams JB, Sneller MA: Two-stage treatment of hip periprosthetic joint infection is associated with a high rate of infection control but high mortality. Clin Orthop Relat Res 2013;471(2):510–518.
25. Zeller V, Lhotellier L, Marmor S, et al.: One-stage exchange arthroplasty for chronic periprosthetic hip infection: Results of a large prospective cohort study. J Bone Joint Surg Am 2014;96(1):e1–e9.
26. Hansen E, Tetreault M, Zmistowski B, et al.: Outcome of one-stage cementless exchange for acute postoperative periprosthetic hip infection. Clin Orthop Relat Res 2013;471(10):3214–3222.
27. Costerton JW: Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Relat Res 2005;437:7–11.
28. Nablo BJ, Rothrock AR, Schoenfisch MH: Nitric oxide-releasing sol-gels as antibacterial coatings for orthopedic implants. Biomaterials 2005;26(8):917–924.
29. Schmidmaier G, Lucke M, Wildemann B, Haas NP, Raschke M: Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: A review. Injury 2006;37(suppl 2):S105–S112.
30. Kim SH, Wise BL, Zhang Y, Szabo RM: Increasing incidence of shoulder arthroplasty in the United States. J Bone Joint Surg Am 2011;93(24):2249–2254.
31. Day JS, Lau E, Ong KL, Williams GR, Ramsey ML, Kurtz SM: Prevalence and projections of total shoulder and elbow arthroplasty in the United States to 2015. J Shoulder Elbow Surg 2010;19(8):1115–1120.
32. Jämsen E, Virta LJ, Hakala M, Kauppi MJ, Malmivaara A, Lehto MU: The decline in joint replacement surgery in rheumatoid arthritis is associated with a concomitant increase in the intensity of anti-rheumatic therapy: A nationwide register-based study from 1995 through 2010. Acta Orthop 2013;84(4):331–337.
33. Cofield RH, Edgerton BC: Total shoulder arthroplasty: Complications and revision surgery. Instr Course Lect 1990;39:449–462.
34. Dodson CC, Craig EV, Cordasco FA, et al.: Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge. J Shoulder Elbow Surg 2010;19(2):303–307.
35. Foruria AM, Fox TJ, Sperling JW, Cofield RH: Clinical meaning of unexpected positive cultures (UPC) in revision shoulder arthroplasty. J Shoulder Elbow Surg 2013;22(5):620–627.
36. Bohsali KI, Wirth MA, Rockwood CA Jr: Complications of total shoulder arthroplasty. J Bone Joint Surg Am 2006;88(10):2279–2292.
37. Pottinger P, Butler-Wu S, Neradilek MB, et al.: Prognostic factors for bacterial cultures positive for Propionibacterium acnes and other organisms in a large series of revision shoulder arthroplasties performed for stiffness, pain, or loosening. J Bone Joint Surg Am 2012;94(22):2075–2083.
38. Kelly JD II, Hobgood ER: Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res 2009;467(9):2343–2348.
39. Topolski MS, Chin PY, Sperling JW, Cofield RH: Revision shoulder arthroplasty with positive intraoperative cultures: The value of preoperative studies and intraoperative histology. J Shoulder Elbow Surg 2006;15(4):402–406.
40. Zeller V, Ghorbani A, Strady C, Leonard P, Mamoudy P, Desplaces N: Propionibacterium acnes: An agent of prosthetic joint infection and colonization. J Infect 2007;55(2):119–124.
41. Levy PY, Fenollar F, Stein A, et al.: Propionibacterium acnes postoperative shoulder arthritis: An emerging clinical entity. Clin Infect Dis 2008;46(12):1884–1886.
42. Mook WR, Garrigues GE: Diagnosis and management of periprosthetic shoulder infections. J Bone Joint Surg Am 2014;96(11):956–965.
43. Millett PJ, Yen YM, Price CS, Horan MP, van der Meijden OA, Elser F: Propionibacterium acnes infection as an occult cause of postoperative shoulder pain: A case series. Clin Orthop Relat Res 2011;469(10):2824–2830.
44. Grosso MJ, Frangiamore SJ, Saleh A, et al.: Poor utility of serum interleukin-6 levels to predict indolent periprosthetic shoulder infections. J Shoulder Elbow Surg 2014;23(9):1277–1281.
45. Morman M, Fowler RL, Sanofsky B, Higgins LD: Arthroscopic tissue biopsy for evaluation of infection before revision arthroplasty. J Shoulder Elbow Surg 2011;20(3):e15–e22.
46. Lutz MF, Berthelot P, Fresard A, et al.: Arthroplastic and osteosynthetic infections due to Propionibacterium acnes: A retrospective study of 52 cases, 1995-2002. Eur J Clin Microbiol Infect Dis 2005;24(11):739–744.
47. Piper KE, Jacobson MJ, Cofield RH, et al.: Microbiologic diagnosis of prosthetic shoulder infection by use of implant sonication. J Clin Microbiol 2009;47(6):1878–1884.
48. Coste JS, Reig S, Trojani C, Berg M, Walch G, Boileau P: The management of infection in arthroplasty of the shoulder. J Bone Joint Surg Br 2004;86(1):65–69.
49. Sperling JW, Kozak TK, Hanssen AD, Cofield RH: Infection after shoulder arthroplasty. Clin Orthop Relat Res 2001;382:206–216.
50. Ince A, Seemann K, Frommelt L, Katzer A, Loehr JF: One-stage exchange shoulder arthroplasty for peri-prosthetic infection. J Bone Joint Surg Br 2005;87(6):814–818.
51. Joachim L: Surgical Management of the Infected Shoulder Arthoplasty, in Cofield RH, Sperling JW, eds: Revision and Complex Shoulder Arthroplasty. Philadelphia, PA, Lippincott Williams &Wilkins, 2010, pp 214–223.
52. Grosso MJ, Sabesan VJ, Ho JC, Ricchetti ET, Iannotti JP: Reinfection rates after 1-stage revision shoulder arthroplasty for patients with unexpected positive intraoperative cultures. J Shoulder Elbow Surg 2012;21(6):754–758.
53. Garvin KL, Hanssen AD: Infection after total hip arthroplasty. Past, present, and future. J Bone Joint Surg Am 1995;77(10):1576–1588.
54. Jämsen E, Stogiannidis I, Malmivaara A, Pajamäki J, Puolakka T, Konttinen YT: Outcome of prosthesis exchange for infected knee arthroplasty: The effect of treatment approach. Acta Orthop 2009;80(1):67–77.
55. Gorman MT, Crosby LA: Treatment of deep infection after total shoulder arthroplasty with an antibiotic-impregnated cement spacer. Tech Shoulder Elbow Surg 2006;7(2):82–85.
56. Themistocleous G, Zalavras C, Stine I, Zachos V, Itamura J: Prolonged implantation of an antibiotic cement spacer for management of shoulder sepsis in compromised patients. J Shoulder Elbow Surg 2007;16(6):701–705.
57. Coffey MJ, Ely EE, Crosby LA: Treatment of glenohumeral sepsis with a commercially produced antibiotic-impregnated cement spacer. J Shoulder Elbow Surg 2010;19(6):868–873.
58. Strickland JP, Sperling JW, Cofield RH: The results of two-stage re-implantation for infected shoulder replacement. J Bone Joint Surg Br 2008;90(4):460–465.
59. Dines JS, Fealy S, Strauss EJ, et al.: Outcomes analysis of revision total shoulder replacement. J Bone Joint Surg Am 2006;88(7):1494–1500.
60. Mileti J, Sperling JW, Cofield RH: Reimplantation of a shoulder arthroplasty after a previous infected arthroplasty. J Shoulder Elbow Surg 2004;13(5):528–531.
61. Braman JP, Sprague M, Bishop J, Lo IK, Lee EW, Flatow EL: The outcome of resection shoulder arthroplasty for recalcitrant shoulder infections. J Shoulder Elbow Surg 2006;15(5):549–553.
62. Rispoli DM, Sperling JW, Athwal GS, Schleck CD, Cofield RH: Pain relief and functional results after resection arthroplasty of the shoulder. J Bone Joint Surg Br 2007;89(9):1184–1187.
63. Muh SJ, Streit JJ, Lenarz CJ, et al.: Resection arthroplasty for failed shoulder arthroplasty. J Shoulder Elbow Surg 2013;22(2):247–252.
65. Goodacre R: Metabolomics of a superorganism. J Nutr 2007;137(suppl 1):259S–266S.
66. Lowenberg DW: Nonunions, malunions, and osteomyelitis, in Boyer MI, ed: AAOS Comprehensive Orthopaedic Review, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2014, pp 275–284.
67. Butterworth P, Gilheany MF, Tinley P: Postoperative infection rates in foot and ankle surgery: A clinical audit of Australian podiatric surgeons, January to December 2007. Aust Health Rev 2010;34(2):180–185.
68. Donley BG, Philbin T, Tomford JW, Sferra JJ: Foot and ankle infections after surgery. Clin Orthop Relat Res 2001;391:162–170.
69. Marshall J, Leeming JP, Holland KT: The cutaneous microbiology of normal human feet. J Appl Bacteriol 1987;62(2):139–146.
70. Grunfeld R, Kunselman A, Bustillo J, Juliano PJ: Wound complications in thyroxine-supplemented patients following foot and ankle surgery. Foot Ankle Int 2011;32(1):38–46.
71. Reeves CL, Peaden AJ, Shane AM: The complications encountered with the rheumatoid surgical foot and ankle. Clin Podiatr Med Surg 2010;27(2):313–325.
72. Wukich DK, Lowery NJ, McMillen RL, Frykberg RG: Postoperative infection rates in foot and ankle surgery: A comparison of patients with and without diabetes mellitus. J Bone Joint Surg Am 2010;92(2):287–295.
73. Bibbo C, Goldberg JW: Infectious and healing complications after elective orthopaedic foot and ankle surgery during tumor necrosis factor-alpha inhibition therapy. Foot Ankle Int 2004;25(5):331–335.
74. Ostrander RV, Brage ME, Botte MJ: Bacterial skin contamination after surgical preparation in foot and ankle surgery. Clin Orthop Relat Res 2003;406:246–252.
75. Bibbo C, Patel DV, Gehrmann RM, Lin SS: Chlorhexidine provides superior skin decontamination in foot and ankle surgery: A prospective randomized study. Clin Orthop Relat Res 2005;438:204–208.
76. Cheng K, Robertson H, St Mart JP, Leanord A, McLeod I: Quantitative analysis of bacteria in forefoot surgery: A comparison of skin preparation techniques. Foot Ankle Int 2009;30(10):992–997.
77. Keblish DJ, Zurakowski D, Wilson MG, Chiodo CP: Preoperative skin preparation of the foot and ankle: Bristles and alcohol are better. J Bone Joint Surg Am 2005;87(5):986–992.
78. Ostrander RV, Botte MJ, Brage ME: Efficacy of surgical preparation solutions in foot and ankle surgery. J Bone Joint Surg Am 2005;87(5):980–985.
79. Becerro de Bengoa Vallejo R, Losa Iglesias ME, Alou Cervera L, Sevillano Fernández D, Prieto Prieto J: Preoperative skin and nail preparation of the foot: Comparison of the efficacy of 4 different methods in reducing bacterial load. J Am Acad Dermatol 2009;61(6):986–992.
80. Akinyoola AL, Adegbehingbe OO, Odunsi A: Timing of antibiotic prophylaxis in tourniquet surgery. J Foot Ankle Surg 2011;50(4):374–376.
81. Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP: The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992;326(5):281–286.
82. Feilmeier M, Dayton P, Sedberry S, Reimer RA: Incidence of surgical site infection in the foot and ankle with early exposure and showering of surgical sites: A prospective observation. J Foot Ankle Surg 2014;53(2):173–175.
83. Ng AB, Adeyemo FO, Samarji R: Preoperative footbaths reduce bacterial colonization of the foot. Foot Ankle Int 2009;30(9):860–864.
84. Nandyala SV, Marquez-Lara A, Fineberg SJ, Hassanzadeh H, Singh K: Complications after lumbar spine surgery between teaching and nonteaching hospitals. Spine (Phila Pa 1976) 2014;39(5):417–423.
85. Nacke E, Ramos N, Stein S, Hutzler L, Bosco JA III: When do readmissions for infection occur after spine and total joint procedures? Clin Orthop Relat Res 2013;471(2):569–573.
86. Kraft CN, Krüger T, Westhoff J, et al.: CRP and leukocyte-count after lumbar spine surgery: Fusion vs. nucleotomy. Acta Orthop 2011;82(4):489–493.
87. Pull ter Gunne AF, Mohamed AS, Skolasky RL, van Laarhoven CJ, Cohen DB: The presentation, incidence, etiology, and treatment of surgical site infections after spinal surgery. Spine (Phila Pa 1976) 2010;35(13):1323–1328.
88. Maruo K, Berven SH: Outcome and treatment of postoperative spine surgical site infections: Predictors of treatment success and failure. J Orthop Sci 2014;19(3):398–404.
89. DeHaan A, Huff T, Schabel K, Doung YC, Hayden J, Barnes P: Multiple cultures and extended incubation for hip and knee arthroplasty revision: Impact on clinical care. J Arthroplasty 2013;28(suppl 8):59–65.
90. Ko JW, Ching AC, Yoo JU, Barnes P: The value of surgical pathology in revision posterior instrumented spine surgery. Annual meeting of American Academy of Orthopaedic Surgeons, New Orleans, LA, March 11-15, 2014.
91. Mok JM, Guillaume TJ, Talu U, et al.: Clinical outcome of deep wound infection after instrumented posterior spinal fusion: A matched cohort analysis. Spine (Phila Pa 1976) 2009;34(6):578–583.
92. Mohamed AS, Yoo J, Hart R, et al.: Posterior fixation without debridement for vertebral body osteomyelitis and discitis. Neurosurg Focus 2014;37(2):E6.
93. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Iwata A, Tanaka M: MRI-based decision-making of implant removal in deep wound infection after instrumented lumbar fusion. J Spinal Disord Tech 2014.
94. Mehbod AA, Ogilvie JW, Pinto MR, et al.: Postoperative deep wound infections in adults after spinal fusion: Management with vacuum-assisted wound closure. J Spinal Disord Tech 2005;18(1):14–17.
95. Jones GA, Butler J, Lieberman I, Schlenk R: Negative-pressure wound therapy in the treatment of complex postoperative spinal wound infections: Complications and lessons learned using vacuum-assisted closure. J Neurosurg Spine 2007;6(5):407–411.
96. Hill C, Flamant R, Mazas F, Evrard J: Prophylactic cefazolin versus placebo in total hip replacement: Report of a multicentre double-blind randomised trial. Lancet 1981;317(8224):795–797.
97. Bratzler DW, Dellinger EP, Olsen KM, et al.; American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013;70(3):195–283.
98. Pichichero ME: Use of selected cephalosporins in penicillin-allergic patients: A paradigm shift. Diagn Microbiol Infect Dis 2007;57(suppl 3):S13–S18.
99. Frumin J, Gallagher JC: Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: What are the chances? Ann Pharmacother 2009;43(2):304–315.
100. Ponce B, Raines BT, Reed RD, Vick C, Richman J, Hawn M: Surgical site infection after arthroplasty: Comparative effectiveness of prophylactic antibiotics: Do surgical care improvement project guidelines need to be updated? J Bone Joint Surg Am 2014;96(12):970–977.
101. Edmiston CE, Krepel C, Kelly H, et al.: Perioperative antibiotic prophylaxis in the gastric bypass patient: Do we achieve therapeutic levels? Surgery 2004;136(4):738–747.
102. Sandhu SS, Lowry JC, Morton ME, Reuben SF: Antibiotic prophylaxis, dental treatment and arthroplasty: Time to explode a myth. J Bone Joint Surg Br 1997;79(4):521–522.
103. Baddour LM, Wilson WR, Bayer AS, et al.; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America: Infective endocarditis: Diagnosis, antimicrobial therapy, and management of complications: A statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005;111(23):e394–e434.
104. Osmon DR, Berbari EF, Berendt AR, et al.; Infectious Diseases Society of America: Diagnosis and management of prosthetic joint infection: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013;56(1):e1–e25.
105. Chen A, Haddad F, Lachiewicz P, et al.: Prevention of late PJI. J Arthroplasty 2014;29(suppl 2):119–128.