66
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage Matthew G. Kaufman, MD1
Jesse D. Meaike, BS1
1 Division of Plastic and Reconstructive Surgery, Baylor College of
Medicine, Houston, Texas
Shayan A. Izaddoost, MD, PhD1 Address for correspondence Shayan A. Izaddoost, MD, PhD, Department of Surgery, Baylor College of Medicine, 1977 Butler Blvd., Suite E6.100, Houston, TX 77030 (e-mail: [email protected]).
Abstract
Keywords
► orthopedic prosthetic infections ► diagnosis ► management
Orthopedic hardware infections are much feared and costly complications that can occur when these devices are implemented both in traumatic cases as well as in joint replacement surgery. Because these infections can lead to great morbidity, it is important to understand their pathophysiology as well as the principles behind their diagnosis and initial treatment. Plastic surgeons are frequently consulted as part of a multidisciplinary team to provide stable soft tissue coverage of the associated defects that result from these infections. A review of the existing literature was performed to identify the potential causes of these infections, to provide established diagnostic criteria guidelines, and to explain how these prosthetic infections are managed from an orthopedic surgery perspective prior to consulting the plastic surgery team.
Orthopedic implantable hardware, employed in a variety of situations from joint replacement surgeries to treatment of traumatic injuries, has been used to improve the lives of millions. Centers for Disease Control and Prevention (CDC) data from 2010 show that 719,000 total knee replacements and 332,000 total hip replacements were performed; it is expected that these numbers will continue to rise.1,2 One of the most common complications with procedures involving orthopedic hardware is infection. Joint infections are foreign bodies, and all patients have an increased risk of developing surgical site infections. These infections can be devastating, leading to loss of the affected extremities, or in some cases, death.3–7 Estimations of infected prosthesis incidences range from < 1% of total hip and shoulder procedures to < 2% of total knee procedures, but these may be underreported. However, infections have been shown to be the cause of revision surgeries in 14.8% of total hip arthroplasties and 25.2% of total knee arthroplasties, with the total cost of care in revision being approximately $50,000.4,5 Mainstays of treatment have traditionally included intravenous (IV) antibiotics, irrigation, and debridement. Often, orthopedic surgeons perform the initial aspects of the diagnosis and management of these infections. More recently, multidisciplinary approaches have been described for difficult cases, with the departments of orthopedic surgery, plastic surgery, and infectious diseases
Issue Theme Medical Device Infections; Guest Editor, Shayan A. Izaddoost, MD, PhD
working collaboratively. Plastic surgeons, with their expertise in complex wound management, are typically consulted to address associated soft tissue defects and provide coverage of exposed hardware with well-vascularized tissue. This review aims to summarize the growing body of knowledge regarding orthopedic prosthetic infections, with a majority of this information derived through studying joint replacement infections. It will define diagnostic criteria for prosthetic joint infections and discuss management, specifically how they are treated prior to consultation of the plastic surgery team. A second review will discuss the role of the plastic surgeon.
Defining Prosthetic Joint Infection Prosthetic joint infection (PJI) is one of the most devastating complications of prosthetic joint implantation. Until recently, however, no consensus on clinical or laboratory findings defining PJI existed. To that end, multiple professional organizations sought to define PJI to improve diagnosis and subsequent management. The Infectious Diseases Society of America (IDSA) defines PJI as the presence of a sinus tract that communicates with the prosthesis, the presence of purulence surrounding the prosthesis without another known etiology, or two or more intraoperative cultures or a combination of
Copyright © 2016 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0036-1580730. ISSN 1535-2188.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Semin Plast Surg 2016;30:66–72.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
67
PJI hematogenous seeding from skin, soft tissue, urinary, respiratory, or gastrointestinal infections, and the common presentation is that of an acute septic arthritis syndrome with the sudden onset of pain in the setting of simultaneous or recent infection elsewhere.8,12 Similar to early infections, virulent bacteria (i.e., S. aureus, streptococci, gram-negative bacilli) predominate in late infections.9,12
Diagnosis of Prosthetic Joint Infection Prosthetic joint infection should be suspected in any patient presenting with a sinus tract or persistent wound drainage over a joint prosthesis, acute onset of a painful prosthesis, or any chronic painful prosthesis at any time after prosthesis implantation. This is particularly the case in the absence of a pain-free interval in the first few years following implantation or if there is a history of prior wound-healing problems or superficial or deep infection. In those with suspected PJI, a thorough history and physical examination should be obtained, specifically noting the type of prosthesis used, the date of implantation, comorbid conditions, and history of wound-healing complications. Further evaluation should include laboratory studies, such as serum levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), a plain radiograph of the area in question, and diagnostic arthrocentesis for synovial fluid analysis, unless the diagnosis is clear clinically and arthrocentesis would not alter management.8 Erythrocyte sedimentation rate and CRP are nonspecific tests with high false-positive rates and no validated cutoff
Fig. 1 Diagnostic algorithm for prosthetic joint infection developed by the Infectious Diseases Society of America. 8 ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
preoperative aspiration and intraoperative cultures that yield the same organism.8 Similarly, the Musculoskeletal Infection Society (MSIS) recently proposed diagnostic criteria based upon the presence of major and minor criteria (►Fig. 1).9 One major criterion or 4/6 minor criteria are required for definitive diagnosis.10 Prosthetic joint infections and their associated wounds are further characterized by timing and depth of infection, as these factors may affect future management. Deep infections involve the exposure of deep structures (i.e., joint capsule, prosthesis, bone) and mandate immediate and aggressive management. On the other hand, superficial infections are confined to the skin and subcutaneous tissues but can progress to compromise the deep structures if not managed properly.11 Zimmerli and Trampuz classify PJI based upon the timing of symptom onset after implantation with < 3 months, between 3 and 24 months, and > 24 months from index surgery representing early, delayed, and late infections, respectively.9 Early and delayed PJI are the most common biomaterial-related infections and are often the result of perioperative contamination.12 Early infections are often caused by highly virulent microorganisms (i.e., Staphylococcus aureus, gram-negative bacilli like Escherichia coli) and present with local signs of erythema, swelling, pain, and cellulitis, with or without systemic symptoms.8,9,12 Delayed infections frequently present with vague complaints (i.e., chronic pain, prosthesis loosening) without systemic symptoms, and intuitively are caused by less virulent microorganisms like coagulase-negative staphylococci or Propionibacterium acnes.8,9,12 The most common etiology of late
Kaufman et al.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage values to predict PJI.8 However, baseline values may be helpful, and the combination of both negative or both positive values for ESR and CRP together may provide the best positive and negative predictive values for PJI.8 Though plain radiographs lack sensitivity and specificity for diagnosing PJI, they do serve as a good baseline for following diagnostic or therapeutic procedures, especially when compared temporally.8 Radiographic findings suggestive of PJI include the presence of a transcortical sinus tract, prosthesis loosening, or bone resorption—the latter two especially in the case of a chronic infection.8,12 Synovial fluid analysis should include total cell count, differential leukocyte count, and anaerobic and aerobic cultures.8 An aspirate with white blood cell count > 25,000/mm3 or 75% polymorphonuclear leukocytes is diagnostic of infection.13 If the initial diagnostic workup is inconclusive for PJI, intraoperative diagnosis should be pursued.8 Three to six periprosthetic tissue samples or the explanted prosthesis itself should be submitted for aerobic and anaerobic cultures at the time of debridement or prosthesis removal.9 If the patient is medically stable, withholding antibiotics for 2 weeks prior to collecting the intraoperative culture specimens may improve yield (►Table 1).8
Risk Factors and Prevention Device-associated infections are wrought with serious complications and involve complex management; therefore, a strong effort to prevent infection should be undertaken. The International Consensus Meeting on Periprosthetic Joint Infection (ICMPJI) found that the probability of developing a surgical site infection is a direct function of the interaction between three groups: inherent characteristics of the offending bacteria (inoculation load, virulence factors), host immune defenses, and environmental determinants of exposure (size, timing, and location of the surgical wound).9 Preoperatively, patients should be evaluated for the presence of active infections, particularly intraoral infections, and physicians may consider screening for methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). Short-term nasal application of mupirocin for patients colonized with MSSA/MRSA is recommended, as high carriage rates in patients’ anterior nares have been shown to be the
Kaufman et al.
only significant independent risk factor for development of S. aureus surgical-site infections.9 Intraoperatively, efforts to decrease bacterial load include strict adherence to antiseptic principles, sterile intraoperative technique, and appropriate use of perioperative antibiotics. Perioperative IV antibiotic prophylaxis is recommended for all patients undergoing implant placement, with first- or second-generation cephalosporins and vancomycin among the most commonly used.14,15 Laminar flow rooms and body exhaust suits have not been shown to have a lower incidence of surgical-site infections.9,16,17 Various aspects of the prosthesis itself have been scrutinized. The ICMPJI determined that hydroxyapatite coating or the type of prosthesis (cemented vs. uncemented) does not influence the incidence of infection.9 The use of antibiotic-impregnated cement in primary arthroplasty has been shown to result in the lowest rates of revision surgery, and the ICMPJI recommends the use of antibiotic-impregnated polymethylmethacrylate cement in all patients undergoing cemented or hybrid fixation in elective revision arthroplasty and in patients at high risk for PJI (i.e., patients with diabetes mellitus, immunocompromised patients) undergoing elective primary arthroplasty.14 However, this is not recommended in all patients due to cost.9 Postoperative care often includes a short duration of IV antibiotics followed by a prolonged course of oral suppressive antibiotics. Specific recommendations have been detailed previously. Surgeons routinely insert closed suction drains postoperatively, but there is no evidence that these drains improve infection-related outcomes in total knee arthroplasty and total hip arthroplasty.18 The American Academy of Orthopedic Surgeons recommends antimicrobial prophylaxis for patients with prosthetic joints undergoing dental, gastrointestinal, genitourinary, and other invasive procedures.19 Host risk factors play an important role in the development of infections and can be divided into two large subgroups: local and systemic factors. Local factors that increase the risk of PJI include peripheral vascular disease, history of previous surgery, history of irradiation, obesity, local trauma or infection, and presence of excessive foreign bodies. Systemic factors include, but are not limited to, poorly controlled diabetes mellitus (with fasting glucose > 200 mg/dL or hemoglobin A1c > 7%), active liver disease, chronic kidney disease, tobacco use, corticosteroid use, IV drug abuse, advanced age, bleeding diathesis, malnutrition, and severe
Table 1 Prosthetic joint infection diagnostic criteria10 Major criteria
Minor criteria
1. The presence of a sinus tract communicating with the prosthesis 2. A pathogen isolated by culture from at least 2 separate tissue or fluid samples obtained from the affected prosthetic joint.
1. Elevated serum erythrocyte sedimentation rate (> 33 mm/h) and serum C-reactive protein (>10 mg/L) concentration 2. Elevated synovial leukocyte count 3. Elevated synovial neutrophil percentage 4. Presence of purulence in the affected joint 5. Isolation of a microorganism in one culture of periprosthetic tissue or fluid 6. Greater than 5 neutrophils per high-power field in 5 high-power fields observed from histologic analysis of periprosthetic tissue at 400 magnification.
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
68
immunodeficiency. Systemic disease has been demonstrated to compromise the immune system and predispose to bacteremia.11 Although these risk factors impair wound healing and predispose the patient to complicated wound healing, no universally adopted algorithm has been described that delineates a threshold for when an elective procedure should be avoided given the presence of the above risk factors. Ultimately, surgeon discretion dictates when to proceed with surgery; however, effort should be directed to optimize patients medically prior to surgery.
Microbial Biofilms A microbial biofilm is a structured aggregation of microbial cells encased in a self-produced, polymeric matrix that adheres to surfaces.12 The formation of biofilms is intrinsic to the pathogenesis of PJI as the surfaces of many commonly used orthopedic devices (such as titanium, hydroxyapatite, and polymethylmethacrylate cement) are susceptible to colonization by biofilm-forming bacteria, and there is evidence that “aseptic” loosening can be attributed to an underlying biofilm-related infection.12,14 As the biofilm accumulates on an orthopedic implant, it eventually reaches a critical point at which it induces a host inflammatory response with cytokine release that may lead to implant failure.14 It is difficult to diagnose and thus treat biofilm-related infections as it is difficult access the bacteria harbored within the biofilm structure. Few bacteria are present at the surface of the biofilm, and their release from the biofilm is hindered by the extracellular slime. Additionally, the biofilm’s slow metabolic rate renders the bacteria difficult to culture.14 Biofilm-related PJIs are also difficult to treat because these properties make them less susceptible to antibiotics, host defenses, and antiseptics.14 Thus, a high clinical suspicion is necessary to identify a biofilm-related PJI (►Table 2).20 Standard culture methods are insensitive in detecting these infections due to their inability to detect the bacteria growing in the biofilm.12 Techniques that utilize polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) may be used to identify pathogens in chronic/persistent prosthetic joint infections and other biofilm-related infections.12 However, the high cost, heavy reliance on expertise, and lack of primers relevant to diagnosing PJI currently limits routine clinical use of these methods.12 Ultrasound sonification is another technique used to augment the yield of standard microbial culture. In this tech-
Kaufman et al.
nique, ultrasound is directed toward a liquid medium containing the explanted orthopedic implant. In a process called cavitation, ultrasonic waves transmitted through the liquid medium create microscopic air bubbles. The energy released when the microbubbles implode disrupts the biofilm architecture and liberates the trapped bacteria.12 The freed bacteria can subsequently be cultured as discussed in multiple studies demonstrating increased culture sensitivities and detection rates when sonification techniques are utilized.12 Ultrasound sonication remains the standard for the diagnosis of biofilm-related PJI.14 The sensitivity of detecting biofilmrelated PJI is further improved when sonication and PCR techniques are combined.12 Lastly, biofilms can be visualized directly with scanning electron microscopy. Stoodley et al were able to visualize viable bacteria in biofilm in joint fluid, wound tissue, and bone cement collected from an infected joint with consistently negative culture results.21 However, this method is subject to sampling error as a result of its small visual window.14 Additional diagnostic methods, such as serum antibodies to staphylococcal slime polysaccharide antigens and infection-specific radiotracers, are currently being studied as approaches to further increase the sensitivity of biofilm-related PJI detection.14
Orthopedic Management Once a prosthesis-associated infection has been diagnosed, proper management is paramount to eradicate the infection and maximize residual function of the joint. Orthopedic implants perform a multitude of functions from prostheses in joint replacement to plates that stabilize fracture segments. The type of implant guides management. Comprehensive management includes both medical therapy, namely antimicrobial agents, and surgical intervention. Surgical treatment is the gold standard for prosthetic joint infections.22 The extent of surgical intervention exists along a spectrum and can include debridement with retention of the prosthesis, one- or two-stage exchange, resection arthroplasty, joint arthrodesis, and limb amputation.8 Multiple factors are considered when choosing the proper approach including the duration of symptoms; the size, depth, and location of the associated wound, if present; prosthesis stability; the infecting pathogen and its antimicrobial susceptibility pattern; patient medical comorbidities; quality of periprosthetic soft tissues; and patient/surgeon preference.8,11 Regardless of the final decision, successful
Table 2 Possible indicators of a biofilm-related infection20 History of persistent or recurrent joint infection Infection localized to a particular implant site Recalcitrance of infection despite adequate use of appropriate antibiotic therapy (based on antibiotic sensitivity testing of bacterial cultures) Microscopic identification of persistent cell clusters and host inflammatory cells at the same site of infection Culture negative results despite a high degree of clinical suspicion of infection Direct microscopic visualization of a cellular aggregation of matrix-encased bacteria associated with a surface
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
69
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage management of PJI necessitates the early identification of the infection and prompt intervention thereafter.11 The duration of the infection is a common starting point of many PJI treatment algorithms. Acute PJIs, those presenting at < 4 weeks removed from index surgery or an acute hematogenous event, in the setting of a well-fixed prosthesis are routinely managed with debridement and prosthesis retention, as removal of the implant can result in bone loss, blood loss, and increased pain.8,22 Absence of a sinus tract and the susceptibility of the offending organism to oral antibiotics may also drive the decision toward debridement while retaining the prosthesis.22 The joint space is accessed, followed by meticulous debridement of the affected soft tissues (synovium, periarticular muscle), copious irrigation, and exchange of the modular components of the prosthesis.22 Optimal irrigation consists of a minimum of 9 L of an antibioticcontaining solution delivered via pulse lavage, though dilute betadine and sodium hypochlorite solutions have been shown to be as effective as antimicrobial solutions.22 An arthroscopic approach is associated with poorer outcomes.8 A review of 28 studies revealed an average success rate of 51%,22 but greater success has been achieved by adding prolonged oral antibiotics to postoperative care.22 Thus, for staphylococcal infections of total hip, total elbow, total shoulder, and total ankle joint replacements the IDSA recommends 2 to 6 weeks of pathogen-specific IV antibiotics plus rifampin followed by rifampin plus an oral companion antibiotic (ciprofloxacin, levofloxacin) for 3 months. For total knee replacement, 6 months of therapy are recommended.8 Higher failure rates have been observed with MRSA infections, debridement occurring > 2 weeks after presentation, infections with gram-negative organisms, and in wounds with sinus tracts.22 As opposed to acute PJI, chronic PJIs (those presenting at > 4 weeks following index surgery or an inciting hematogenous event) demand implant removal.22 Exchange arthroplasty, the removal and replacement of the prosthesis and all its components, is the gold standard for managing chronic PJI.22,23 It is thought that the pathogenesis of chronic infections involves biofilm-forming bacteria, which are difficult to eradicate with mechanical and chemical debridement alone.22 Exchange arthroplasty can be accomplished via a one- or two-stage approach. Multiple studies have shown no difference in functional outcomes between the two,22 but there are certain indications for each procedure. In direct-exchange arthroplasty, all prosthetic components are removed and replaced in a single operation. The hardware and cement are excised; the devitalized soft tissue and bone are debrided; the joint space is irrigated as described above; and the revision prosthesis is inserted using new instruments.8,22 Antibiotic-loaded cement is commonly used to anchor the revision implant in place, with vancomycin and tobramycin the antibiotics of choice.8,22 These antibiotics may also be tailored based on the susceptibilities of the infecting organism.22 Antibiotic-impregnated bone allograft can be utilized to provide prolonged, local release of antibiotics while also serving as a scaffold for new bone growth.22 A one-stage exchange is offered to relatively healthy patients Seminars in Plastic Surgery
Vol. 30
No. 2/2016
Kaufman et al.
with adequate bone stock and soft tissues and easily treatable infecting pathogens.8 This approach is contraindicated when two previous single-stage exchanges have failed; infection involves the neurovascular bundle; the infecting organism is unknown, highly resistant, or lacks specific antimicrobial therapy; and a draining sinus tract is present.8,22 Directexchange is more cost effective,22 and associated with lower patient morbidity, specifically earlier postoperative mobilization and decreased hospital length-of-stay, when compared with the two-stage technique.8,22 A 2011 decision analysis favored the direct-exchange over the two-stage approach, citing more favorable patient- and surgeon-derived utilities.8 A recent review found the success for direct-exchange arthroplasty ranges from 55% to 100%, with an average of 85%.22 The IDSA also recommends an antibiotic course following the exchange (2–6 weeks of postoperative IV antibiotics plus rifampin followed by 3 months of rifampin plus a companion antibiotic of either ciprofloxacin or levofloxacin).8 A two-stage prosthesis exchange involves removal of the prosthesis and all its components, debridement of devitalized soft tissue, and profuse irrigation, but provides for a “prosthesis holiday” with a temporary antibiotic delivery device inserted instead of another prosthesis.22 This delivery device is often polymethylmethacrylate cement mixed with antibiotics. The antibiotic delivery device serves to locally eradicate infection, and once the device is secured, IV antibiotics are administered for 2 to 6 weeks to provide systemic coverage.22 Common practice in the United States is to observe a 2to 8-week antibiotic holiday after IV antibiotics and before reimplantation.8,22 The ESR and CRP are surrogate markers to evaluate the effectiveness of antibiotic therapy; therefore, prerevision measurements are recommended to establish a baseline.8 Reimplantation is performed when infection is believed to be eliminated based upon clinical judgment. However, this should not be delayed indefinitely as studies have shown that reimplantation occurring > 6 months after the initial surgery results in poorer patient function and may not eradicate infection more effectively than those who undergo reimplantation < 6 months after initial surgery.22 There is no consensus on the need for oral suppressive antibiotics after reimplantation. The two-stage exchange is most often used in the United States in the treatment of chronic PJI associated with prosthesis loosening.8 The ideal patient for the two-stage exchange is a patient with chronic PJI and adequate bone stock who is both medically stable and willing to undergo two procedures8,22; it is the treatment of choice for PJI with sinus tract, difficult-to-treat or resistant organisms, unidentified organisms, and septic PJI.8,22 The two-stage exchange is successful in approximately 90% of patients.22 Resection arthroplasty and amputation are more radical operations. Resection arthroplasty, in which the prosthesis is removed but not replaced,22 has limited indications including patients with massive bone loss, wounds with poor soft tissue coverage, infections caused by highly resistant organisms with no or limited medical therapy, medical conditions precluding major therapy, multiple failed prior reconstructions, and patients who prefer a single definitive
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
70
operation.8,22 It is frequently performed in an effort to avoid amputation in ambulatory patients.8 With regards to the knee, arthrodesis with either intramedullary nail or external fixator placement may follow resection to allow weight bearing.8 Postoperative antimicrobial therapy involves 4 to 6 weeks of IV or highly bioavailable oral antibiotics.8 Success rates are typically lower than staged exchange procedures, possibly attributable to selection bias.8 Amputation should be considered in those with wound-healing problems (prosthetic joint infections), severe bone loss, failure to achieve soft tissue coverage, and failure to control infection via other measures.8 Pathogen-specific antibiotics should be continued for 24 to 48 hours after the amputation, given all infected tissue has been successfully debrided.8 There has been less description of the management of infected internal fixation devices used to stabilize fractures reported in the literature as compared with the management of prosthetic joint infections. Superficial infections without hardware exposure, such as pin-site infections associated with external fixator hardware, can consistently be treated without removal of the hardware.24 Current practice is to debride and irrigate the wound and administer antibiotics to eliminate the infection.25 Recent retrospective studies have demonstrated unexceptional success rates, defined as the achievement of osseous union with the original hardware in place, of 68% and 71% using this approach.25,26 Rightmire et al proposed an approach similar to the two-staged exchange of PJI with implant removal and reimplantation after the infection has been cleared.25 The decision of when to remove this type of hardware is dependent upon many factors, including the duration of infection, duration of hardware exposure (if present), presence of hardware loosening, and location of the hardware.24 Specific values regarding duration of infection and hardware exposure have not been generated, but shorter durations of infection and hardware exposure, typically < 2 weeks, are associated with higher salvage rates.24 Infection with prosthesis loosening is an indication for removal,24 but radiographic evidence of loosening is inconsistent and should not be the sole determinant of management.24 Clinical evidence of loosening, on the other hand, traditionally demands hardware removal in the extremities. Conversely, hardware salvage is generally the preferred management for spinal hardware due to the lack of alternatives to maintain stability and fusion after removal.24 Infection of spinal hardware represents a unique challenge, as instrument removal may lead to progressive deformity. Standard initial management includes early surgical debridement and washout.27 Multiple studies support instrument retention in early postoperative infections.28–32 Though it may be associated with higher rates of recurrent infections, retention may provide enough time for stable fusion to occur, after which the implant can be removed.27 In patients with delayed infection, especially in the setting of stable bony fusion, instrument removal at the time of the initial debridement is indicated. A study by Hedequist et al showed 100% recurrence of infection after implant retention in the setting of a delayed infection,33 whereas six other studies demon-
Kaufman et al.
strated near 100% success rates after debridement and instrument removal.27 However, one should be aware of a significant loss of deformity correction after implant removal, even if stable bony fusion is noted prior to removal.27 When spinal instrumentation is retained, postoperative treatment includes 4 to 6 weeks of IV antibiotics followed by 6 months of oral suppressive therapy, as this has demonstrated superior treatment-failure-free survival than IV therapy alone.29 A shorter treatment course is sufficient when the hardware is removed, as demonstrated by a 100% rate of infection eradication with 2 to 3 days of IV antibiotics and 1 week of cultureguided oral therapy.34 When a biofilm-associated infection is recognized and the implant is retained, the biofilm needs to be addressed to salvage the implant. Rifampin has proven the most effective at reducing the bacterial load of certain biofilms,35 but resistance develops rapidly with rifampin monotherapy.12,35 Combining two or more antibiotics can minimize the emergence of antibiotic resistance and provide synergy to more efficiently treat biofilms.12 In studies of a PJI model in guinea pigs, MRSA biofilms were more effectively treated with combinations of rifampin and either daptomycin or levofloxacin versus rifampin plus vancomycin.36,37 There is no consensus treatment course, but Trampuz and Zimmerli suggest 3 to 6 months of IV antibiotics followed by 2 to 6 weeks of oral antibiotics.38
Conclusion Infections of orthopedic implantable hardware can have devastating consequences. As the number of joint replacement procedures is expected to increase, these complications will continue to be an important public health issue. The focus has turned to prevention, accurate diagnosis, and timely management of these infections. A thorough understanding of the pathophysiology of orthopedic hardware infections is critical to identifying patients who are at risk for these infections and may help prevent them from occurring. In the context of modern multidisciplinary care, it is critical for the plastic surgeon to have a fundamental knowledge of these infections and their medical and surgical management by the orthopedic surgery team prior to their initial encounter to appropriately determine the best reconstructive approach.
References 1 Centers for Disease Control and Prevention. National Hospital
Discharge Survey: 2010 table, procedures by selected patient characteristics - number by procedure category and age. Available at: http://www.cdc.gov/nchs/data/nhds/4procedures/2010pro4_numberprocedureage.pdf. Accessed February 27, 2016 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 Hernández-Vaquero D, Fernández-Fairen M, Torres A, et al. Treatment of periprosthetic infections: an economic analysis. ScientificWorldJournal 2013;2013:821650 4 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 Seminars in Plastic Surgery
Vol. 30
No. 2/2016
71
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage 5 Bozic KJ, Kurtz SM, Lau E, et al. The epidemiology of revision total
6
7
8
9
10
11
12 13
14
15 16
17
18
19
20
21
knee arthroplasty in the United States. Clin Orthop Relat Res 2010; 468(1):45–51 Bohm ER, Dunbar MJ, Frood JJ, Johnson TM, Morris KA. Rehospitalizations, early revisions, infections, and hospital resource use in the first year after hip and knee arthroplasties. J Arthroplasty 2012;27(2):232–237.e1 Kurtz SM, Ong KL, Schmier J, et al. Future clinical and economic impact of revision total hip and knee arthroplasty. J Bone Joint Surg Am 2007;89(Suppl 3):144–151 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 Parvizi J, Gehrke T, Eds. Proceedings of the International Consensus Meeting on Periprosthetic Joint Infection. 2013. Available at: http://www.msis-na.org/wp-content/themes/msis-temp/pdf/ ism-periprosthetic-joint-information.pdf. Accessed February 27, 2016 Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 2011;469(11): 2992–2994 Gusenoff JA, Hungerford DS, Orlando JC, Nahabedian MY. Outcome and management of infected wounds after total hip arthroplasty. Ann Plast Surg 2002;49(6):587–592 Gbejuade HO, Lovering AM, Webb JC. The role of microbial biofilms in prosthetic joint infections. Acta Orthop 2015;86(2):147–158 Panni AS, Vasso M, Cerciello S, Salgarello M. Wound complications in total knee arthroplasty. Which flap is to be used? With or without retention of prosthesis?. Knee Surg Sports Traumatol Arthrosc 2011;19(7):1060–1068 Deva AK, Adams WP Jr, Vickery K. The role of bacterial biofilms in device-associated infection. Plast Reconstr Surg 2013;132(5): 1319–1328 Rezapoor M, Parvizi J. Prevention of Periprosthetic Joint Infection. J Arthroplasty 2015;30(6):902–907 Der Tavitian J, Ong SM, Taub NA, Taylor GJ. Body-exhaust suit versus occlusive clothing. A randomised, prospective trial using air and wound bacterial counts. J Bone Joint Surg Br 2003;85(4): 490–494 Hooper GJ, Rothwell AG, Frampton C, Wyatt MC. Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry J Bone Joint Surg Br 2011;93(1):85–90 Kosins AM, Scholz T, Cetinkaya M, Evans GRD. Evidence-based value of subcutaneous surgical wound drainage: the largest systematic review and meta-analysis. Plast Reconstr Surg 2013; 132(2):443–450 American Academy of Orthopedic Surgeons. Antibiotic prophylaxis for patients after total joint replacement. Available at: http:// orthodoc.aaos.org/davidgrimmmd/Antibiotic%20Prophylaxis% 20for%20Patients%20after%20Total%20Joint%20Replacement.pdf. Accessed April 5, 2016 Hall-Stoodley L, Stoodley P, Kathju S, et al. Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol Med Microbiol 2012;65(2):127–145 Stoodley P, Nistico L, Johnson S, et al. Direct demonstration of viable Staphylococcus aureus biofilms in an infected total joint
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
22 23
24
25
26
27
28
29
30
31
32
33
34 35
36
37
38
Kaufman et al.
arthroplasty. A case report. J Bone Joint Surg Am 2008;90(8): 1751–1758 Chen AF, Heller S, Parvizi J. Prosthetic joint infections. Surg Clin North Am 2014;94(6):1265–1281 Suda AJ, Cieslik A, Grützner PA, Münzberg M, Heppert V. Flaps for closure of soft tissue defects in infected revision knee arthroplasty. Int Orthop 2014;38(7):1387–1392 Viol A, Pradka SP, Baumeister SP, et al. Soft-tissue defects and exposed hardware: a review of indications for soft-tissue reconstruction and hardware preservation. Plast Reconstr Surg 2009; 123(4):1256–1263 Rightmire E, Zurakowski D, Vrahas M. Acute infections after fracture repair: management with hardware in place. Clin Orthop Relat Res 2008;466(2):466–472 Berkes M, Obremskey WT, Scannell B, Ellington JK, Hymes RA, Bosse M; Southeast Fracture Consortium. Maintenance of hardware after early postoperative infection following fracture internal fixation. J Bone Joint Surg Am 2010;92(4):823–828 Lall RR, Wong AP, Lall RR, Lawton CD, Smith ZA, Dahdaleh NS. Evidence-based management of deep wound infection after spinal instrumentation. J Clin Neurosci 2015;22(2):238–242 Cahill PJ, Warnick DE, Lee MJ, et al. Infection after spinal fusion for pediatric spinal deformity: thirty years of experience at a single institution. Spine 2010;35(12):1211–1217 Kowalski TJ, Berbari EF, Huddleston PM, Steckelberg JM, Mandrekar JN, Osmon DR. The management and outcome of spinal implant infections: contemporary retrospective cohort study. Clin Infect Dis 2007;44(7):913–920 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 Picada R, Winter RB, Lonstein JE, et al. Postoperative deep wound infection in adults after posterior lumbosacral spine fusion with instrumentation: incidence and management. J Spinal Disord 2000;13(1):42–45 Szöke G, Lipton G, Miller F, Dabney K. Wound infection after spinal fusion in children with cerebral palsy. J Pediatr Orthop 1998;18(6): 727–733 Hedequist D, Haugen A, Hresko T, Emans J. Failure of attempted implant retention in spinal deformity delayed surgical site infections. Spine 2009;34(1):60–64 Clark CE, Shufflebarger HL. Late-developing infection in instrumented idiopathic scoliosis. Spine 1999;24(18):1909–1912 Raad I, Hanna H, Jiang Y, et al. Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillinresistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 2007;51(5):1656–1660 John AK, Baldoni D, Haschke M, et al. Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin. Antimicrob Agents Chemother 2009;53(7):2719–2724 Trampuz A, Murphy CK, Rothstein DM, Widmer AF, Landmann R, Zimmerli W. Efficacy of a novel rifamycin derivative, ABI-0043, against Staphylococcus aureus in an experimental model of foreign-body infection. Antimicrob Agents Chemother 2007;51(7): 2540–2545 Trampuz A, Zimmerli W. Antimicrobial agents in orthopaedic surgery: Prophylaxis and treatment. Drugs 2006;66(8): 1089–1105
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
72
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage Matthew G. Kaufman, MD1
Jesse D. Meaike, BS1
1 Division of Plastic and Reconstructive Surgery, Baylor College of
Medicine, Houston, Texas
Shayan A. Izaddoost, MD, PhD1 Address for correspondence Shayan A. Izaddoost, MD, PhD, Department of Surgery, Baylor College of Medicine, 1977 Butler Blvd., Suite E6.100, Houston, TX 77030 (e-mail: [email protected]).
Abstract
Keywords
► orthopedic prosthetic infections ► diagnosis ► management
Orthopedic hardware infections are much feared and costly complications that can occur when these devices are implemented both in traumatic cases as well as in joint replacement surgery. Because these infections can lead to great morbidity, it is important to understand their pathophysiology as well as the principles behind their diagnosis and initial treatment. Plastic surgeons are frequently consulted as part of a multidisciplinary team to provide stable soft tissue coverage of the associated defects that result from these infections. A review of the existing literature was performed to identify the potential causes of these infections, to provide established diagnostic criteria guidelines, and to explain how these prosthetic infections are managed from an orthopedic surgery perspective prior to consulting the plastic surgery team.
Orthopedic implantable hardware, employed in a variety of situations from joint replacement surgeries to treatment of traumatic injuries, has been used to improve the lives of millions. Centers for Disease Control and Prevention (CDC) data from 2010 show that 719,000 total knee replacements and 332,000 total hip replacements were performed; it is expected that these numbers will continue to rise.1,2 One of the most common complications with procedures involving orthopedic hardware is infection. Joint infections are foreign bodies, and all patients have an increased risk of developing surgical site infections. These infections can be devastating, leading to loss of the affected extremities, or in some cases, death.3–7 Estimations of infected prosthesis incidences range from < 1% of total hip and shoulder procedures to < 2% of total knee procedures, but these may be underreported. However, infections have been shown to be the cause of revision surgeries in 14.8% of total hip arthroplasties and 25.2% of total knee arthroplasties, with the total cost of care in revision being approximately $50,000.4,5 Mainstays of treatment have traditionally included intravenous (IV) antibiotics, irrigation, and debridement. Often, orthopedic surgeons perform the initial aspects of the diagnosis and management of these infections. More recently, multidisciplinary approaches have been described for difficult cases, with the departments of orthopedic surgery, plastic surgery, and infectious diseases
Issue Theme Medical Device Infections; Guest Editor, Shayan A. Izaddoost, MD, PhD
working collaboratively. Plastic surgeons, with their expertise in complex wound management, are typically consulted to address associated soft tissue defects and provide coverage of exposed hardware with well-vascularized tissue. This review aims to summarize the growing body of knowledge regarding orthopedic prosthetic infections, with a majority of this information derived through studying joint replacement infections. It will define diagnostic criteria for prosthetic joint infections and discuss management, specifically how they are treated prior to consultation of the plastic surgery team. A second review will discuss the role of the plastic surgeon.
Defining Prosthetic Joint Infection Prosthetic joint infection (PJI) is one of the most devastating complications of prosthetic joint implantation. Until recently, however, no consensus on clinical or laboratory findings defining PJI existed. To that end, multiple professional organizations sought to define PJI to improve diagnosis and subsequent management. The Infectious Diseases Society of America (IDSA) defines PJI as the presence of a sinus tract that communicates with the prosthesis, the presence of purulence surrounding the prosthesis without another known etiology, or two or more intraoperative cultures or a combination of
Copyright © 2016 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0036-1580730. ISSN 1535-2188.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Semin Plast Surg 2016;30:66–72.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
67
PJI hematogenous seeding from skin, soft tissue, urinary, respiratory, or gastrointestinal infections, and the common presentation is that of an acute septic arthritis syndrome with the sudden onset of pain in the setting of simultaneous or recent infection elsewhere.8,12 Similar to early infections, virulent bacteria (i.e., S. aureus, streptococci, gram-negative bacilli) predominate in late infections.9,12
Diagnosis of Prosthetic Joint Infection Prosthetic joint infection should be suspected in any patient presenting with a sinus tract or persistent wound drainage over a joint prosthesis, acute onset of a painful prosthesis, or any chronic painful prosthesis at any time after prosthesis implantation. This is particularly the case in the absence of a pain-free interval in the first few years following implantation or if there is a history of prior wound-healing problems or superficial or deep infection. In those with suspected PJI, a thorough history and physical examination should be obtained, specifically noting the type of prosthesis used, the date of implantation, comorbid conditions, and history of wound-healing complications. Further evaluation should include laboratory studies, such as serum levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), a plain radiograph of the area in question, and diagnostic arthrocentesis for synovial fluid analysis, unless the diagnosis is clear clinically and arthrocentesis would not alter management.8 Erythrocyte sedimentation rate and CRP are nonspecific tests with high false-positive rates and no validated cutoff
Fig. 1 Diagnostic algorithm for prosthetic joint infection developed by the Infectious Diseases Society of America. 8 ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
preoperative aspiration and intraoperative cultures that yield the same organism.8 Similarly, the Musculoskeletal Infection Society (MSIS) recently proposed diagnostic criteria based upon the presence of major and minor criteria (►Fig. 1).9 One major criterion or 4/6 minor criteria are required for definitive diagnosis.10 Prosthetic joint infections and their associated wounds are further characterized by timing and depth of infection, as these factors may affect future management. Deep infections involve the exposure of deep structures (i.e., joint capsule, prosthesis, bone) and mandate immediate and aggressive management. On the other hand, superficial infections are confined to the skin and subcutaneous tissues but can progress to compromise the deep structures if not managed properly.11 Zimmerli and Trampuz classify PJI based upon the timing of symptom onset after implantation with < 3 months, between 3 and 24 months, and > 24 months from index surgery representing early, delayed, and late infections, respectively.9 Early and delayed PJI are the most common biomaterial-related infections and are often the result of perioperative contamination.12 Early infections are often caused by highly virulent microorganisms (i.e., Staphylococcus aureus, gram-negative bacilli like Escherichia coli) and present with local signs of erythema, swelling, pain, and cellulitis, with or without systemic symptoms.8,9,12 Delayed infections frequently present with vague complaints (i.e., chronic pain, prosthesis loosening) without systemic symptoms, and intuitively are caused by less virulent microorganisms like coagulase-negative staphylococci or Propionibacterium acnes.8,9,12 The most common etiology of late
Kaufman et al.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage values to predict PJI.8 However, baseline values may be helpful, and the combination of both negative or both positive values for ESR and CRP together may provide the best positive and negative predictive values for PJI.8 Though plain radiographs lack sensitivity and specificity for diagnosing PJI, they do serve as a good baseline for following diagnostic or therapeutic procedures, especially when compared temporally.8 Radiographic findings suggestive of PJI include the presence of a transcortical sinus tract, prosthesis loosening, or bone resorption—the latter two especially in the case of a chronic infection.8,12 Synovial fluid analysis should include total cell count, differential leukocyte count, and anaerobic and aerobic cultures.8 An aspirate with white blood cell count > 25,000/mm3 or 75% polymorphonuclear leukocytes is diagnostic of infection.13 If the initial diagnostic workup is inconclusive for PJI, intraoperative diagnosis should be pursued.8 Three to six periprosthetic tissue samples or the explanted prosthesis itself should be submitted for aerobic and anaerobic cultures at the time of debridement or prosthesis removal.9 If the patient is medically stable, withholding antibiotics for 2 weeks prior to collecting the intraoperative culture specimens may improve yield (►Table 1).8
Risk Factors and Prevention Device-associated infections are wrought with serious complications and involve complex management; therefore, a strong effort to prevent infection should be undertaken. The International Consensus Meeting on Periprosthetic Joint Infection (ICMPJI) found that the probability of developing a surgical site infection is a direct function of the interaction between three groups: inherent characteristics of the offending bacteria (inoculation load, virulence factors), host immune defenses, and environmental determinants of exposure (size, timing, and location of the surgical wound).9 Preoperatively, patients should be evaluated for the presence of active infections, particularly intraoral infections, and physicians may consider screening for methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). Short-term nasal application of mupirocin for patients colonized with MSSA/MRSA is recommended, as high carriage rates in patients’ anterior nares have been shown to be the
Kaufman et al.
only significant independent risk factor for development of S. aureus surgical-site infections.9 Intraoperatively, efforts to decrease bacterial load include strict adherence to antiseptic principles, sterile intraoperative technique, and appropriate use of perioperative antibiotics. Perioperative IV antibiotic prophylaxis is recommended for all patients undergoing implant placement, with first- or second-generation cephalosporins and vancomycin among the most commonly used.14,15 Laminar flow rooms and body exhaust suits have not been shown to have a lower incidence of surgical-site infections.9,16,17 Various aspects of the prosthesis itself have been scrutinized. The ICMPJI determined that hydroxyapatite coating or the type of prosthesis (cemented vs. uncemented) does not influence the incidence of infection.9 The use of antibiotic-impregnated cement in primary arthroplasty has been shown to result in the lowest rates of revision surgery, and the ICMPJI recommends the use of antibiotic-impregnated polymethylmethacrylate cement in all patients undergoing cemented or hybrid fixation in elective revision arthroplasty and in patients at high risk for PJI (i.e., patients with diabetes mellitus, immunocompromised patients) undergoing elective primary arthroplasty.14 However, this is not recommended in all patients due to cost.9 Postoperative care often includes a short duration of IV antibiotics followed by a prolonged course of oral suppressive antibiotics. Specific recommendations have been detailed previously. Surgeons routinely insert closed suction drains postoperatively, but there is no evidence that these drains improve infection-related outcomes in total knee arthroplasty and total hip arthroplasty.18 The American Academy of Orthopedic Surgeons recommends antimicrobial prophylaxis for patients with prosthetic joints undergoing dental, gastrointestinal, genitourinary, and other invasive procedures.19 Host risk factors play an important role in the development of infections and can be divided into two large subgroups: local and systemic factors. Local factors that increase the risk of PJI include peripheral vascular disease, history of previous surgery, history of irradiation, obesity, local trauma or infection, and presence of excessive foreign bodies. Systemic factors include, but are not limited to, poorly controlled diabetes mellitus (with fasting glucose > 200 mg/dL or hemoglobin A1c > 7%), active liver disease, chronic kidney disease, tobacco use, corticosteroid use, IV drug abuse, advanced age, bleeding diathesis, malnutrition, and severe
Table 1 Prosthetic joint infection diagnostic criteria10 Major criteria
Minor criteria
1. The presence of a sinus tract communicating with the prosthesis 2. A pathogen isolated by culture from at least 2 separate tissue or fluid samples obtained from the affected prosthetic joint.
1. Elevated serum erythrocyte sedimentation rate (> 33 mm/h) and serum C-reactive protein (>10 mg/L) concentration 2. Elevated synovial leukocyte count 3. Elevated synovial neutrophil percentage 4. Presence of purulence in the affected joint 5. Isolation of a microorganism in one culture of periprosthetic tissue or fluid 6. Greater than 5 neutrophils per high-power field in 5 high-power fields observed from histologic analysis of periprosthetic tissue at 400 magnification.
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
68
immunodeficiency. Systemic disease has been demonstrated to compromise the immune system and predispose to bacteremia.11 Although these risk factors impair wound healing and predispose the patient to complicated wound healing, no universally adopted algorithm has been described that delineates a threshold for when an elective procedure should be avoided given the presence of the above risk factors. Ultimately, surgeon discretion dictates when to proceed with surgery; however, effort should be directed to optimize patients medically prior to surgery.
Microbial Biofilms A microbial biofilm is a structured aggregation of microbial cells encased in a self-produced, polymeric matrix that adheres to surfaces.12 The formation of biofilms is intrinsic to the pathogenesis of PJI as the surfaces of many commonly used orthopedic devices (such as titanium, hydroxyapatite, and polymethylmethacrylate cement) are susceptible to colonization by biofilm-forming bacteria, and there is evidence that “aseptic” loosening can be attributed to an underlying biofilm-related infection.12,14 As the biofilm accumulates on an orthopedic implant, it eventually reaches a critical point at which it induces a host inflammatory response with cytokine release that may lead to implant failure.14 It is difficult to diagnose and thus treat biofilm-related infections as it is difficult access the bacteria harbored within the biofilm structure. Few bacteria are present at the surface of the biofilm, and their release from the biofilm is hindered by the extracellular slime. Additionally, the biofilm’s slow metabolic rate renders the bacteria difficult to culture.14 Biofilm-related PJIs are also difficult to treat because these properties make them less susceptible to antibiotics, host defenses, and antiseptics.14 Thus, a high clinical suspicion is necessary to identify a biofilm-related PJI (►Table 2).20 Standard culture methods are insensitive in detecting these infections due to their inability to detect the bacteria growing in the biofilm.12 Techniques that utilize polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) may be used to identify pathogens in chronic/persistent prosthetic joint infections and other biofilm-related infections.12 However, the high cost, heavy reliance on expertise, and lack of primers relevant to diagnosing PJI currently limits routine clinical use of these methods.12 Ultrasound sonification is another technique used to augment the yield of standard microbial culture. In this tech-
Kaufman et al.
nique, ultrasound is directed toward a liquid medium containing the explanted orthopedic implant. In a process called cavitation, ultrasonic waves transmitted through the liquid medium create microscopic air bubbles. The energy released when the microbubbles implode disrupts the biofilm architecture and liberates the trapped bacteria.12 The freed bacteria can subsequently be cultured as discussed in multiple studies demonstrating increased culture sensitivities and detection rates when sonification techniques are utilized.12 Ultrasound sonication remains the standard for the diagnosis of biofilm-related PJI.14 The sensitivity of detecting biofilmrelated PJI is further improved when sonication and PCR techniques are combined.12 Lastly, biofilms can be visualized directly with scanning electron microscopy. Stoodley et al were able to visualize viable bacteria in biofilm in joint fluid, wound tissue, and bone cement collected from an infected joint with consistently negative culture results.21 However, this method is subject to sampling error as a result of its small visual window.14 Additional diagnostic methods, such as serum antibodies to staphylococcal slime polysaccharide antigens and infection-specific radiotracers, are currently being studied as approaches to further increase the sensitivity of biofilm-related PJI detection.14
Orthopedic Management Once a prosthesis-associated infection has been diagnosed, proper management is paramount to eradicate the infection and maximize residual function of the joint. Orthopedic implants perform a multitude of functions from prostheses in joint replacement to plates that stabilize fracture segments. The type of implant guides management. Comprehensive management includes both medical therapy, namely antimicrobial agents, and surgical intervention. Surgical treatment is the gold standard for prosthetic joint infections.22 The extent of surgical intervention exists along a spectrum and can include debridement with retention of the prosthesis, one- or two-stage exchange, resection arthroplasty, joint arthrodesis, and limb amputation.8 Multiple factors are considered when choosing the proper approach including the duration of symptoms; the size, depth, and location of the associated wound, if present; prosthesis stability; the infecting pathogen and its antimicrobial susceptibility pattern; patient medical comorbidities; quality of periprosthetic soft tissues; and patient/surgeon preference.8,11 Regardless of the final decision, successful
Table 2 Possible indicators of a biofilm-related infection20 History of persistent or recurrent joint infection Infection localized to a particular implant site Recalcitrance of infection despite adequate use of appropriate antibiotic therapy (based on antibiotic sensitivity testing of bacterial cultures) Microscopic identification of persistent cell clusters and host inflammatory cells at the same site of infection Culture negative results despite a high degree of clinical suspicion of infection Direct microscopic visualization of a cellular aggregation of matrix-encased bacteria associated with a surface
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
69
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage management of PJI necessitates the early identification of the infection and prompt intervention thereafter.11 The duration of the infection is a common starting point of many PJI treatment algorithms. Acute PJIs, those presenting at < 4 weeks removed from index surgery or an acute hematogenous event, in the setting of a well-fixed prosthesis are routinely managed with debridement and prosthesis retention, as removal of the implant can result in bone loss, blood loss, and increased pain.8,22 Absence of a sinus tract and the susceptibility of the offending organism to oral antibiotics may also drive the decision toward debridement while retaining the prosthesis.22 The joint space is accessed, followed by meticulous debridement of the affected soft tissues (synovium, periarticular muscle), copious irrigation, and exchange of the modular components of the prosthesis.22 Optimal irrigation consists of a minimum of 9 L of an antibioticcontaining solution delivered via pulse lavage, though dilute betadine and sodium hypochlorite solutions have been shown to be as effective as antimicrobial solutions.22 An arthroscopic approach is associated with poorer outcomes.8 A review of 28 studies revealed an average success rate of 51%,22 but greater success has been achieved by adding prolonged oral antibiotics to postoperative care.22 Thus, for staphylococcal infections of total hip, total elbow, total shoulder, and total ankle joint replacements the IDSA recommends 2 to 6 weeks of pathogen-specific IV antibiotics plus rifampin followed by rifampin plus an oral companion antibiotic (ciprofloxacin, levofloxacin) for 3 months. For total knee replacement, 6 months of therapy are recommended.8 Higher failure rates have been observed with MRSA infections, debridement occurring > 2 weeks after presentation, infections with gram-negative organisms, and in wounds with sinus tracts.22 As opposed to acute PJI, chronic PJIs (those presenting at > 4 weeks following index surgery or an inciting hematogenous event) demand implant removal.22 Exchange arthroplasty, the removal and replacement of the prosthesis and all its components, is the gold standard for managing chronic PJI.22,23 It is thought that the pathogenesis of chronic infections involves biofilm-forming bacteria, which are difficult to eradicate with mechanical and chemical debridement alone.22 Exchange arthroplasty can be accomplished via a one- or two-stage approach. Multiple studies have shown no difference in functional outcomes between the two,22 but there are certain indications for each procedure. In direct-exchange arthroplasty, all prosthetic components are removed and replaced in a single operation. The hardware and cement are excised; the devitalized soft tissue and bone are debrided; the joint space is irrigated as described above; and the revision prosthesis is inserted using new instruments.8,22 Antibiotic-loaded cement is commonly used to anchor the revision implant in place, with vancomycin and tobramycin the antibiotics of choice.8,22 These antibiotics may also be tailored based on the susceptibilities of the infecting organism.22 Antibiotic-impregnated bone allograft can be utilized to provide prolonged, local release of antibiotics while also serving as a scaffold for new bone growth.22 A one-stage exchange is offered to relatively healthy patients Seminars in Plastic Surgery
Vol. 30
No. 2/2016
Kaufman et al.
with adequate bone stock and soft tissues and easily treatable infecting pathogens.8 This approach is contraindicated when two previous single-stage exchanges have failed; infection involves the neurovascular bundle; the infecting organism is unknown, highly resistant, or lacks specific antimicrobial therapy; and a draining sinus tract is present.8,22 Directexchange is more cost effective,22 and associated with lower patient morbidity, specifically earlier postoperative mobilization and decreased hospital length-of-stay, when compared with the two-stage technique.8,22 A 2011 decision analysis favored the direct-exchange over the two-stage approach, citing more favorable patient- and surgeon-derived utilities.8 A recent review found the success for direct-exchange arthroplasty ranges from 55% to 100%, with an average of 85%.22 The IDSA also recommends an antibiotic course following the exchange (2–6 weeks of postoperative IV antibiotics plus rifampin followed by 3 months of rifampin plus a companion antibiotic of either ciprofloxacin or levofloxacin).8 A two-stage prosthesis exchange involves removal of the prosthesis and all its components, debridement of devitalized soft tissue, and profuse irrigation, but provides for a “prosthesis holiday” with a temporary antibiotic delivery device inserted instead of another prosthesis.22 This delivery device is often polymethylmethacrylate cement mixed with antibiotics. The antibiotic delivery device serves to locally eradicate infection, and once the device is secured, IV antibiotics are administered for 2 to 6 weeks to provide systemic coverage.22 Common practice in the United States is to observe a 2to 8-week antibiotic holiday after IV antibiotics and before reimplantation.8,22 The ESR and CRP are surrogate markers to evaluate the effectiveness of antibiotic therapy; therefore, prerevision measurements are recommended to establish a baseline.8 Reimplantation is performed when infection is believed to be eliminated based upon clinical judgment. However, this should not be delayed indefinitely as studies have shown that reimplantation occurring > 6 months after the initial surgery results in poorer patient function and may not eradicate infection more effectively than those who undergo reimplantation < 6 months after initial surgery.22 There is no consensus on the need for oral suppressive antibiotics after reimplantation. The two-stage exchange is most often used in the United States in the treatment of chronic PJI associated with prosthesis loosening.8 The ideal patient for the two-stage exchange is a patient with chronic PJI and adequate bone stock who is both medically stable and willing to undergo two procedures8,22; it is the treatment of choice for PJI with sinus tract, difficult-to-treat or resistant organisms, unidentified organisms, and septic PJI.8,22 The two-stage exchange is successful in approximately 90% of patients.22 Resection arthroplasty and amputation are more radical operations. Resection arthroplasty, in which the prosthesis is removed but not replaced,22 has limited indications including patients with massive bone loss, wounds with poor soft tissue coverage, infections caused by highly resistant organisms with no or limited medical therapy, medical conditions precluding major therapy, multiple failed prior reconstructions, and patients who prefer a single definitive
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
70
operation.8,22 It is frequently performed in an effort to avoid amputation in ambulatory patients.8 With regards to the knee, arthrodesis with either intramedullary nail or external fixator placement may follow resection to allow weight bearing.8 Postoperative antimicrobial therapy involves 4 to 6 weeks of IV or highly bioavailable oral antibiotics.8 Success rates are typically lower than staged exchange procedures, possibly attributable to selection bias.8 Amputation should be considered in those with wound-healing problems (prosthetic joint infections), severe bone loss, failure to achieve soft tissue coverage, and failure to control infection via other measures.8 Pathogen-specific antibiotics should be continued for 24 to 48 hours after the amputation, given all infected tissue has been successfully debrided.8 There has been less description of the management of infected internal fixation devices used to stabilize fractures reported in the literature as compared with the management of prosthetic joint infections. Superficial infections without hardware exposure, such as pin-site infections associated with external fixator hardware, can consistently be treated without removal of the hardware.24 Current practice is to debride and irrigate the wound and administer antibiotics to eliminate the infection.25 Recent retrospective studies have demonstrated unexceptional success rates, defined as the achievement of osseous union with the original hardware in place, of 68% and 71% using this approach.25,26 Rightmire et al proposed an approach similar to the two-staged exchange of PJI with implant removal and reimplantation after the infection has been cleared.25 The decision of when to remove this type of hardware is dependent upon many factors, including the duration of infection, duration of hardware exposure (if present), presence of hardware loosening, and location of the hardware.24 Specific values regarding duration of infection and hardware exposure have not been generated, but shorter durations of infection and hardware exposure, typically < 2 weeks, are associated with higher salvage rates.24 Infection with prosthesis loosening is an indication for removal,24 but radiographic evidence of loosening is inconsistent and should not be the sole determinant of management.24 Clinical evidence of loosening, on the other hand, traditionally demands hardware removal in the extremities. Conversely, hardware salvage is generally the preferred management for spinal hardware due to the lack of alternatives to maintain stability and fusion after removal.24 Infection of spinal hardware represents a unique challenge, as instrument removal may lead to progressive deformity. Standard initial management includes early surgical debridement and washout.27 Multiple studies support instrument retention in early postoperative infections.28–32 Though it may be associated with higher rates of recurrent infections, retention may provide enough time for stable fusion to occur, after which the implant can be removed.27 In patients with delayed infection, especially in the setting of stable bony fusion, instrument removal at the time of the initial debridement is indicated. A study by Hedequist et al showed 100% recurrence of infection after implant retention in the setting of a delayed infection,33 whereas six other studies demon-
Kaufman et al.
strated near 100% success rates after debridement and instrument removal.27 However, one should be aware of a significant loss of deformity correction after implant removal, even if stable bony fusion is noted prior to removal.27 When spinal instrumentation is retained, postoperative treatment includes 4 to 6 weeks of IV antibiotics followed by 6 months of oral suppressive therapy, as this has demonstrated superior treatment-failure-free survival than IV therapy alone.29 A shorter treatment course is sufficient when the hardware is removed, as demonstrated by a 100% rate of infection eradication with 2 to 3 days of IV antibiotics and 1 week of cultureguided oral therapy.34 When a biofilm-associated infection is recognized and the implant is retained, the biofilm needs to be addressed to salvage the implant. Rifampin has proven the most effective at reducing the bacterial load of certain biofilms,35 but resistance develops rapidly with rifampin monotherapy.12,35 Combining two or more antibiotics can minimize the emergence of antibiotic resistance and provide synergy to more efficiently treat biofilms.12 In studies of a PJI model in guinea pigs, MRSA biofilms were more effectively treated with combinations of rifampin and either daptomycin or levofloxacin versus rifampin plus vancomycin.36,37 There is no consensus treatment course, but Trampuz and Zimmerli suggest 3 to 6 months of IV antibiotics followed by 2 to 6 weeks of oral antibiotics.38
Conclusion Infections of orthopedic implantable hardware can have devastating consequences. As the number of joint replacement procedures is expected to increase, these complications will continue to be an important public health issue. The focus has turned to prevention, accurate diagnosis, and timely management of these infections. A thorough understanding of the pathophysiology of orthopedic hardware infections is critical to identifying patients who are at risk for these infections and may help prevent them from occurring. In the context of modern multidisciplinary care, it is critical for the plastic surgeon to have a fundamental knowledge of these infections and their medical and surgical management by the orthopedic surgery team prior to their initial encounter to appropriately determine the best reconstructive approach.
References 1 Centers for Disease Control and Prevention. National Hospital
Discharge Survey: 2010 table, procedures by selected patient characteristics - number by procedure category and age. Available at: http://www.cdc.gov/nchs/data/nhds/4procedures/2010pro4_numberprocedureage.pdf. Accessed February 27, 2016 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 Hernández-Vaquero D, Fernández-Fairen M, Torres A, et al. Treatment of periprosthetic infections: an economic analysis. ScientificWorldJournal 2013;2013:821650 4 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 Seminars in Plastic Surgery
Vol. 30
No. 2/2016
71
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage
Orthopedic Prosthetic Infections: Diagnosis and Orthopedic Salvage 5 Bozic KJ, Kurtz SM, Lau E, et al. The epidemiology of revision total
6
7
8
9
10
11
12 13
14
15 16
17
18
19
20
21
knee arthroplasty in the United States. Clin Orthop Relat Res 2010; 468(1):45–51 Bohm ER, Dunbar MJ, Frood JJ, Johnson TM, Morris KA. Rehospitalizations, early revisions, infections, and hospital resource use in the first year after hip and knee arthroplasties. J Arthroplasty 2012;27(2):232–237.e1 Kurtz SM, Ong KL, Schmier J, et al. Future clinical and economic impact of revision total hip and knee arthroplasty. J Bone Joint Surg Am 2007;89(Suppl 3):144–151 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 Parvizi J, Gehrke T, Eds. Proceedings of the International Consensus Meeting on Periprosthetic Joint Infection. 2013. Available at: http://www.msis-na.org/wp-content/themes/msis-temp/pdf/ ism-periprosthetic-joint-information.pdf. Accessed February 27, 2016 Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 2011;469(11): 2992–2994 Gusenoff JA, Hungerford DS, Orlando JC, Nahabedian MY. Outcome and management of infected wounds after total hip arthroplasty. Ann Plast Surg 2002;49(6):587–592 Gbejuade HO, Lovering AM, Webb JC. The role of microbial biofilms in prosthetic joint infections. Acta Orthop 2015;86(2):147–158 Panni AS, Vasso M, Cerciello S, Salgarello M. Wound complications in total knee arthroplasty. Which flap is to be used? With or without retention of prosthesis?. Knee Surg Sports Traumatol Arthrosc 2011;19(7):1060–1068 Deva AK, Adams WP Jr, Vickery K. The role of bacterial biofilms in device-associated infection. Plast Reconstr Surg 2013;132(5): 1319–1328 Rezapoor M, Parvizi J. Prevention of Periprosthetic Joint Infection. J Arthroplasty 2015;30(6):902–907 Der Tavitian J, Ong SM, Taub NA, Taylor GJ. Body-exhaust suit versus occlusive clothing. A randomised, prospective trial using air and wound bacterial counts. J Bone Joint Surg Br 2003;85(4): 490–494 Hooper GJ, Rothwell AG, Frampton C, Wyatt MC. Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry J Bone Joint Surg Br 2011;93(1):85–90 Kosins AM, Scholz T, Cetinkaya M, Evans GRD. Evidence-based value of subcutaneous surgical wound drainage: the largest systematic review and meta-analysis. Plast Reconstr Surg 2013; 132(2):443–450 American Academy of Orthopedic Surgeons. Antibiotic prophylaxis for patients after total joint replacement. Available at: http:// orthodoc.aaos.org/davidgrimmmd/Antibiotic%20Prophylaxis% 20for%20Patients%20after%20Total%20Joint%20Replacement.pdf. Accessed April 5, 2016 Hall-Stoodley L, Stoodley P, Kathju S, et al. Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol Med Microbiol 2012;65(2):127–145 Stoodley P, Nistico L, Johnson S, et al. Direct demonstration of viable Staphylococcus aureus biofilms in an infected total joint
Seminars in Plastic Surgery
Vol. 30
No. 2/2016
22 23
24
25
26
27
28
29
30
31
32
33
34 35
36
37
38
Kaufman et al.
arthroplasty. A case report. J Bone Joint Surg Am 2008;90(8): 1751–1758 Chen AF, Heller S, Parvizi J. Prosthetic joint infections. Surg Clin North Am 2014;94(6):1265–1281 Suda AJ, Cieslik A, Grützner PA, Münzberg M, Heppert V. Flaps for closure of soft tissue defects in infected revision knee arthroplasty. Int Orthop 2014;38(7):1387–1392 Viol A, Pradka SP, Baumeister SP, et al. Soft-tissue defects and exposed hardware: a review of indications for soft-tissue reconstruction and hardware preservation. Plast Reconstr Surg 2009; 123(4):1256–1263 Rightmire E, Zurakowski D, Vrahas M. Acute infections after fracture repair: management with hardware in place. Clin Orthop Relat Res 2008;466(2):466–472 Berkes M, Obremskey WT, Scannell B, Ellington JK, Hymes RA, Bosse M; Southeast Fracture Consortium. Maintenance of hardware after early postoperative infection following fracture internal fixation. J Bone Joint Surg Am 2010;92(4):823–828 Lall RR, Wong AP, Lall RR, Lawton CD, Smith ZA, Dahdaleh NS. Evidence-based management of deep wound infection after spinal instrumentation. J Clin Neurosci 2015;22(2):238–242 Cahill PJ, Warnick DE, Lee MJ, et al. Infection after spinal fusion for pediatric spinal deformity: thirty years of experience at a single institution. Spine 2010;35(12):1211–1217 Kowalski TJ, Berbari EF, Huddleston PM, Steckelberg JM, Mandrekar JN, Osmon DR. The management and outcome of spinal implant infections: contemporary retrospective cohort study. Clin Infect Dis 2007;44(7):913–920 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 Picada R, Winter RB, Lonstein JE, et al. Postoperative deep wound infection in adults after posterior lumbosacral spine fusion with instrumentation: incidence and management. J Spinal Disord 2000;13(1):42–45 Szöke G, Lipton G, Miller F, Dabney K. Wound infection after spinal fusion in children with cerebral palsy. J Pediatr Orthop 1998;18(6): 727–733 Hedequist D, Haugen A, Hresko T, Emans J. Failure of attempted implant retention in spinal deformity delayed surgical site infections. Spine 2009;34(1):60–64 Clark CE, Shufflebarger HL. Late-developing infection in instrumented idiopathic scoliosis. Spine 1999;24(18):1909–1912 Raad I, Hanna H, Jiang Y, et al. Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillinresistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 2007;51(5):1656–1660 John AK, Baldoni D, Haschke M, et al. Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin. Antimicrob Agents Chemother 2009;53(7):2719–2724 Trampuz A, Murphy CK, Rothstein DM, Widmer AF, Landmann R, Zimmerli W. Efficacy of a novel rifamycin derivative, ABI-0043, against Staphylococcus aureus in an experimental model of foreign-body infection. Antimicrob Agents Chemother 2007;51(7): 2540–2545 Trampuz A, Zimmerli W. Antimicrobial agents in orthopaedic surgery: Prophylaxis and treatment. Drugs 2006;66(8): 1089–1105
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
72
