Treatment of Infections Associated with Surgical Implants
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《新英格兰医药杂志》
About half of the 2 million cases of nosocomial infection that occur each year in the United States are associated with indwelling devices. Although less common than infections related to catheters, infections associated with surgical implants are generally more difficult to manage because they require a longer period of antibiotic therapy and repeated surgical procedures.1,2 In 2002, the Multidisciplinary Alliance against Device-Related Infections (www.maadrialliance.org) was established to organize groups of experts to develop guidelines for treatment. The four objectives of this review of infections associated with a variety of surgical implants are to describe the clinical and economic effects, address diagnostic challenges, discuss the general principles of medical and surgical treatment, and analyze implant-specific therapeutic approaches.
Clinical and Economic Consequences
Infections that are associated with a variety of surgical implants have clinical and economic consequences (Table 1). Mortality attributable to such infections is highest among patients with cardiovascular implants, particularly prosthetic heart valves and aortic grafts. Infections associated with orthopedic devices and ventricular shunts often result in serious disabilities. Although infections of mammary and penile implants are rarely life-threatening, they can cause major disfigurement and psychological trauma. The average rates of infection listed in Table 1 are for initially inserted implants, which are less likely than replacement implants to become infected.2 The nature and the number of stages of surgical intervention vary according to the type of implant. Except for combination pacemaker–defibrillator systems, the cost of an implant itself usually constitutes a small fraction of the overall cost of treating implant-associated infections.
Table 1. Clinical and Economic Consequences of Infections Associated with Surgical Implants.
Diagnostic Challenges
Some, but not all, postoperative wound infections affect the surgical implant.21 However, bacterial colonization of surgical implants does not necessarily indicate infection. In fact, most colonized implants do not become infected. The ultimate proof of implant-associated infection requires the presence of clinical manifestations, intraoperative signs of infection adjacent to the implant, and the growth of pathogens in cultures of surgical specimens. To help obviate the need to operate on a patient who may not have an implant-associated infection, one can rely on certain microbiologic and imaging studies that are implant-specific. Although bacteremia is the hallmark of prosthetic-valve endocarditis and some infections associated with vascular grafts, blood cultures are negative in most cases of infection associated with pacemaker–defibrillator systems (unless endocarditis is present), ventricular assist devices, orthopedic devices, ventricular shunts, mammary implants, and penile implants.
Nonoperative cultures of local body fluids vary in their sensitivity for detecting infections associated with implants. For example, a culture of cerebrospinal fluid from a ventricular shunt has a sensitivity greater than 90 percent, whereas a culture of fluid from a prosthetic joint space, obtained by percutaneous aspiration, has a sensitivity of less than 50 percent. A transesophageal echocardiogram is much more sensitive than a transthoracic echocardiogram in identifying vegetations around prosthetic heart valves and pacemaker leads. Infection associated with vascular grafts can be diagnosed with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), or, in the case of an aortoenteric fistula, esophagogastroduodenoscopy.22 Since nuclear scans can yield false positive results up to a few months after surgical placement of orthopedic devices, CT and MRI scans are more reliable in diagnosing infection. Figure 1 shows some clinical, radiologic, and microscopical findings that can help in the diagnosis of implant-related infections.
Figure 1. Clinical, Radiologic, and Microscopical Findings in Patients with Implant-Related Infections.
Panel A shows the clinical presentation of a penile implant that became infected with Staphylococcus epidermidis and eroded through the scrotum (arrow). (Photograph courtesy of Dr. Timothy Boone.) In Panel B, the roentgenographic finding of radiolucent lines (arrows) at the cement–bone interface around a hip prosthesis that had been implanted six months earlier raises the possibility of infection, which was confirmed by the intraoperative finding of purulent material around the hip implant. (Radiograph courtesy of Dr. Glenn Landon.) Panel C is a confocal scanning laser microscopical image of the biofilm surrounding a urologic device. It shows bacterial DNA (Enterococcus faecalis), stained blue (DRAQ5, x1000), and carbohydrate material, stained green (SYTOX green, x1000). (Image courtesy of Dr. Barbara Trautner.)
General Principles of Treatment
The essential factor in the evolution and persistence of infection is the formation of biofilm around implanted devices.23 Soon after insertion, a conditioning layer composed of host-derived adhesins (including fibrinogen, fibronectin, and collagen) forms on the surface of the implant and invites the adherence of free-floating (planktonic) organisms. Bacterial cell division, recruitment of additional planktonic organisms, and secretion of bacterial products (such as the glycocalyx) follow. A three-dimensional structure of biofilm finally evolves that contains complex communities of tightly attached (sessile) bacteria. These bacteria display cell-to-cell signaling and exist within a polymer matrix containing fluid channels that allow for the flow of nutrients and waste.24 Possible reasons for the reduced susceptibility of biofilm-embedded organisms to antibiotic agents, as compared with their free-floating counterparts, include a slow rate of bacterial growth within the biofilm, inhibition of antimicrobial activity by biofilm substances, and poor penetration of the biofilm by antibiotics.
The most important clinical objectives in treating infections associated with surgical implants are to cure the infection, prevent its recurrence, preserve body function, and reduce the risk of death. In most cases, these objectives can be achieved with both antibiotic therapy and surgical intervention. Table 2 summarizes the general principles of the medical and surgical treatment of infections that are associated with surgical implants. About two thirds of infections are caused by either Staphylococcus aureus or coagulase-negative staphylococci. Methicillin-resistant staphylococci are variably susceptible to older antibiotics (doxycycline, trimethoprim–sulfamethoxazole, quinolones, and clindamycin), and they are almost universally sensitive to the newer agent linezolid, but the clinical efficacy of these drugs for the treatment of infections associated with surgical implants has not been prospectively compared with the efficacy of vancomycin.
Table 2. General Principles of the Medical and Surgical Treatment of Infections Associated with Surgical Implants.
Most implants that are infected by S. aureus or candida require surgical removal (Table 2). Patients with an established response to medical therapy for an implant infection caused by the less virulent coagulase-negative staphylococci may not require surgery to remove the implant. If a decision is made to remove the infected implant, complete extraction of all components is essential, if surgically feasible, regardless of the type of infecting organism. Although surgical removal of the infected implant is generally associated with a better outcome than is retention of the infected implant, medical treatment alone may be warranted in patients who are at high risk for intraoperative or postoperative complications.
Implant-Specific Therapeutic Approaches
Prosthetic Heart Valves
Although relatively uncommon, prosthetic-valve endocarditis is life-threatening, with mortality exceeding 30 percent.4 Curing prosthetic-valve endocarditis may require a combination of antibiotic therapy and surgical intervention. Medical therapy consists of a six-week course of systemic bactericidal antibiotics. Bacteriostatic antibiotics, such as clindamycin, should not be used for the treatment of staphylococcal endocarditis. Although in-hospital mortality is generally higher among medically treated patients than among patients who undergo surgery (46 percent vs. 24 percent), this difference in mortality almost disappears when patients who are treated medically simply because they are considered to be too sick for curative treatment are excluded from the analysis.25 However, a recurrence of endocarditis, which warrants surgery, is more likely in medically treated patients.25 Patients with aortic paravalvular abscesses, particularly those caused by S. aureus, have a very poor prognosis when treated medically.26
Clinical practice dictates surgical replacement of almost all prosthetic valves infected by S. aureus or candida. Surgical intervention may not be required in patients infected by coagulase-negative staphylococci that have already responded to antibiotic therapy. Regardless of the causative pathogen, cardiac complications (e.g., congestive heart failure, conduction abnormalities, paravalvular abscesses, valve dehiscence, and serious peripheral embolization) necessitate the surgical replacement of the infected prosthesis. Since emergency surgery is associated with high mortality,27 it is essential that surgery be performed before patients become hemodynamically unstable. Central nervous system complications may be aggravated by cardiopulmonary bypass and postoperative anticoagulation, and if valve replacement is indicated in patients with such complications, surgery is delayed for 10 days or even a few weeks, until their neurologic condition stabilizes.3 Figure 2 shows the therapeutic quandary that may evolve in the context of surgical treatment of prosthetic-valve endocarditis due to S. aureus, a condition associated with high mortality.3,28,29
Figure 2. Surgical Management of Prosthetic-Valve Endocarditis Due to Staphylococcus aureus.
Patients with prosthetic heart valves receive long-term oral anticoagulant therapy, and it is prudent to consider a particular patient's circumstances in making decisions about when to stop anticoagulation before surgical replacement of the infected valve and when and at what dose to restart it postoperatively. Warfarin is usually stopped at least two days before nonemergency surgical replacement, but in the case of an emergency procedure, anticoagulation should be reversed rapidly with fresh-frozen plasma. Anticoagulation is usually reinitiated (typically at a dose lower than the preoperative dose, because of the postoperative depletion of coagulation factors) about four to seven days after surgery to reduce the risk of bleeding — a risk that is particularly high around the time of removal of the epicardial pacemaker (a few days postoperatively).
Vascular Grafts
The three major types of prosthetic vascular grafts (arteriovenous, femoropopliteal, and aortic) differ with regard to the associated rates of infection and the most pertinent complications.30 More than 5 percent of arteriovenous grafts become infected, necessitating another means of access to ensure uninterrupted hemodialysis. Infection occurs in about 4 percent of femoropopliteal grafts and can result in limb loss. Although infection of aortic grafts is the least likely (the rate of infection is about 2 percent), this complication is lethal in almost 90 percent of cases.
A combination of medical and surgical treatment is used for most infected vascular grafts. The duration of antibiotic therapy is determined by the presence of septicemia (treated with systemic antibiotics for six weeks) or an abscess. Surgical intervention is tailored to the condition of the patient and the type of graft, and in many cases alternatives to traditional therapeutic approaches need to be considered.5,31 Combined vascular reconstruction and adjunctive tissue transfer is often necessary in patients with tissue defects.
No prospective studies have compared the various surgical treatments of infections associated with different types of vascular grafts. Traditional treatment of infected arteriovenous grafts is performed in two stages: the infected graft is removed before a new polytetrafluoroethylene graft or fistula is placed elsewhere, with interim placement of a dialysis catheter until the new graft or fistula matures, in four to six weeks.32 A new therapeutic approach that has recently been developed consists of inserting a new polyurethane graft that can be used immediately, thereby obviating the need for a temporary dialysis catheter. In patients with limited venous access, a one-stage procedure to remove the infected graft and replace it with a cryopreserved human allograft can be performed.33 (The Food and Drug Administration has expressed concern about the validation of methods used to prevent microbial contamination of allograft tissue and has limited the distribution of some cryopreserved grafts, pending implementation of certain preventive procedures.) This approach to the treatment of infected grafts results in a relatively low incidence of reinfection and a rate of graft patency similar to that with the placement of prosthetic grafts.
Surgical management of infected femoropopliteal grafts usually consists of a one-stage procedure for graft excision and revascularization with autologous venous conduits, prosthetic grafts, or cryopreserved homografts.34 In patients with a favorable risk–benefit ratio for surgical intervention, infections of aortic grafts are treated with either axillofemoral bypass grafting, followed by excision of the infected graft,35 or graft excision plus in situ replacement with cryopreserved homografts,7 autologous vascular conduits, or if the infecting organism has low virulence (such as coagulase-negative staphylococci), prosthetic grafts.31
Pacemaker–Defibrillator Systems
The combined medical and surgical treatment of infections of pacemakers is similar to that of pacemaker–defibrillator systems.8,36 Patients with clinical infection of the pulse-generator pocket without bloodstream infection receive systemic antibiotics for 10 to 14 days, whereas patients with lead-associated endocarditis receive a 6-week course of systemic antibiotics. The mainstay of surgical management is a two-stage approach that consists initially of complete removal of the entire implanted system, including the cardiac leads (by means of laser-assisted extraction, if needed), even in patients with clinical infection of only the pocket, because their cardiac leads may already be colonized. Although rare instances of curing the infection with antibiotics alone have been reported,37 recurrence of infection is generally more likely in patients treated with antibiotics alone, or with antibiotics plus removal of only the generator, than in patients who undergo extraction of the whole system.38 Before the new implant is placed, the cardiac rhythm can be controlled either by a temporary transvenous pacemaker (exchanged every 5 to 10 days) or by cardiac medications; patients with a history of ventricular fibrillation may wear an external defibrillator vest at home. The new implant is placed on the contralateral side as early as 10 to 14 days after removal of the implanted system in patients with infection of the pulse-generator pocket and as late as 6 weeks in those with endocarditis.
Left Ventricular Assist Devices
In patients with left ventricular assist devices, infection can develop in the percutaneously placed drive line, the generator pocket, and the bloodstream.39 Although potentially serious, these infections do not decrease the likelihood of successful transplantation.40 Infection is often initiated by mechanical disruption of the interface between the tissue and the drive line and is manifested as drainage that may defy treatment with antibiotics alone and may require surgical excision or revision of the exit site. Since left ventricular assist devices are considered life-sustaining,10 explanting or replacing the entire infected device before a heart becomes available for transplantation is a risky, if not impossible, option.
Joint Prostheses
The four possible surgical approaches for the treatment of infected joint prostheses are débridement plus retention of the prosthesis, removal of the infected implant without replacement, one-stage replacement, and two-stage replacement.13,14,41,42,43,44 The two-stage replacement approach results in higher cure rates and yields better function than one-stage replacement. In the first stage, the infected implant is removed and a biodegradable (polylactic acid or polyglycolic acid) or nonbiodegradable (polymethylmethacrylate) antimicrobial carrier is placed. After the patient completes a six-week course of systemic antibiotics, a new joint prosthesis is placed. In patients who have undergone multiple surgical procedures for the treatment of infection with particularly virulent organisms, arthrodesis may be necessary.
A single prospective, randomized, double-blind, placebo-controlled trial compared two treatment approaches, both intended to salvage the implant, in patients who had infections associated with joint prostheses or fracture-fixation devices.16 Among patients who had a mechanically stable implant, whose symptoms had lasted three weeks or less, and who had undergone adequate surgical débridement, the cure rate with three to six months of systemic therapy with ciprofloxacin and rifampin was 100 percent, as compared with a 58 percent cure rate with ciprofloxacin and placebo. Since most failures in the placebo group were associated with the emergence of resistance to ciprofloxacin during therapy, combining rifampin with ciprofloxacin also helped provide protection against the evolution of ciprofloxacin resistance. The results of this trial16 and other, differently designed studies13,14,42,43 provide the basis for a therapeutic algorithm for the treatment of staphylococcal infections of joint prostheses (Figure 3).
Figure 3. Management of Joint Prosthesis–Related Infection Caused by Staphylococcus aureus or Coagulase-Negative Staphylococci.
Fracture-Fixation Devices
Infections of fracture-fixation devices that involve bone are treated with a 6-week course of systemic antibiotics, whereas 10 to 14 days of antibiotic therapy are sufficient for superficial infections. The nature of the surgical intervention in patients with infected fracture-fixation devices depends on the type of device, the presence or absence of bone union, and the patient's underlying condition.45 Infection of intramedullary nails is often associated with nonunion of bone and requires removal of the infected nail, insertion of external-fixation pins, and if necessary, subsequent insertion of a replacement nail. Surgical treatment of infection of external-fixation pins usually consists of a single procedure to remove the infected pins and, if bone union has not occurred, either insert new pins at a distant site or fuse the bones. Attempts can be made to salvage infected fracture-fixation devices in carefully selected patients by using a prolonged course of systemic antibiotics12,14,16,43 (Figure 3).
Ventricular Shunts
Infected ventricular shunts are surgically managed in two stages.46 The infected shunt is removed, and an external ventricular catheter is contemporaneously inserted to drain cerebrospinal fluid and monitor intracranial pressure. The external ventricular catheter is usually replaced every 5 to 10 days to prevent ventriculitis,47 and systemic antibiotics are given for 10 to 14 days. Repeated analysis of cerebrospinal fluid is performed to ensure sterility before a new ventricular shunt is inserted, preferably on the contralateral side and usually within two weeks after the initial surgery.48
Mammary Implants
Management of an infected mammary implant usually entails a two-stage replacement procedure.19 The first surgery involves removal of the infected implant and débridement of the capsule surrounding it. A 10-to-14-day course of systemic antibiotics is administered to cover the infecting pathogen (or pathogens). A few months later, the contralateral implant is removed, and a new pair of mammary implants is inserted to replace the original pair and to achieve symmetry.
Inflatable Penile Implants
There is a universal consensus on the need for surgical removal of infected penile implants. However, there are diverging views about the stages of surgical management. Although a single-stage replacement has been advocated for use in carefully selected patients,49 the preferred approach is a two-stage replacement.20 First, the infected implant is removed, and a malleable penile prosthesis is inserted to preserve space in the corpora cavernosa. For uncomplicated infections, a 10-to-14-day course of systemic antibiotics is given. Four to six months later, a new inflatable penile implant is inserted in place of the malleable prosthesis.
Source Information
From the Center for Prostheses Infection and the Infectious Disease Section, Veterans Affairs Medical Center and Baylor College of Medicine, Houston.
Address reprint requests to Dr. Darouiche at the Center for Prostheses Infection, Baylor College of Medicine, 1333 Moursund Ave., Suite A221, Houston, TX 77030, or at rdarouiche@aol.com.
References
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Klug D, Lacroix D, Savoye C, et al. Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management. Circulation 1997;95:2098-2107.
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Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;345:1435-1443.
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Stein A, Bataille JF, Drancourt M, et al. Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole). Antimicrob Agents Chemother 1998;42:3086-3091.
Tattevin P, Cremieux A-C, Pottier P, Huten D, Carbon C. Prosthetic joint infection: when can prosthesis salvage be considered? Clin Infect Dis 1999;29:292-295.
Widmer AF. New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis 2001;33:Suppl 2:S94-S106.
Boxma H, Broekhuizen T, Patka P, Oosting H. Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch Trauma Trial. Lancet 1996;347:1133-1137.
Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. JAMA 1998;279:1537-1541.
Cochrane DD, Kestle J. Ventricular shunting for hydrocephalus in children: patients, procedures, surgeons and institutions in English Canada, 1989-2001. Eur J Pediatr Surg 2002;12:Suppl 1:S6-S11.
Naradzay JF, Browne BJ, Rolnick MA, Doherty RJ. Cerebral ventricular shunts. J Emerg Med 1999;17:311-322.
Gabriel SE, Woods JE, O'Fallon WM, Beard CM, Kurland LT, Melton LJ III. Complications leading to surgery after breast implantation. N Engl J Med 1997;336:677-682.
Wilson SK, Delk JR II. Inflatable penile implant infection: predisposing factors and treatment suggestions. J Urol 1995;153:659-661.
Darouiche RO. Antimicrobial approaches for preventing infections associated with surgical implants. Clin Infect Dis 2003;36:1284-1289.
Sierra J, Kalangos A, Faidutti B, Christenson JT. Aorto-enteric fistula is a serious complication to aortic surgery: modern trends in diagnosis and therapy. Cardiovasc Surg 2003;11:185-188.
Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999;284:1318-1322.
Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002;15:167-193.
Akowuah EF, Davies W, Oliver S, et al. Prosthetic valve endocarditis: early and late outcome following medical or surgical treatment. Heart 2003;89:269-272.
Lerakis S, Robert Taylor W, Lynch M, et al. The role of transesophageal echocardiography in the diagnosis and management of patients with aortic perivalvular abscesses. Am J Med Sci 2001;321:152-155.
Sasaki Y, Isobe F, Kinugasa S, et al. Early and late outcomes after reoperation for prosthetic valve endocarditis. Jpn J Thorac Cardiovasc Surg 2001;49:224-229.
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Wallace SM, Walton BI, Kharbanda RK, Hardy R, Wilson AP, Swanton RH. Mortality from infective endocarditis: clinical predictors of outcome. Heart 2002;88:53-60.
Reilly L. Aortic graft infection: evolution in management. Cardiovasc Surg 2002;10:372-377.
Darling RC III, Resnikoff M, Kreienberg PB, et al. Alternative approach for management of infected aortic grafts. J Vasc Surg 1997;25:106-112.
Lentino JR, Baddour LM, Wray M, Wong ES, Yu VL. Staphylococcus aureus and other bacteremias in hemodialysis patients: antibiotic therapy and surgical removal of access site. Infection 2000;28:355-360.
Lin PH, Brinkman WT, Terramani TT, Lumsden AB. Management of infected hemodialysis access grafts using cryopreserved human vein allografts. Am J Surg 2002;184:31-36.
Chiesa R, Astore D, Piccolo G, et al. Fresh and cryopreserved arterial homografts in the treatment of prosthetic graft infections: experience of the Italian Collaborative Vascular Homograft Group. Ann Vasc Surg 1998;12:457-462.
Yeager RA, Taylor LM Jr, Moneta GL, et al. Improved results with conventional management of infrarenal aortic infection. J Vasc Surg 1999;30:76-83.
Wunderly D, Maloney J, Edel T, McHenry M, McCarthy PM. Infections in implantable cardioverter defibrillator patients. Pacing Clin Electrophysiol 1990;13:1360-1364.
Turkisher V, Priel I, Dan M. Successful management of an infected implantable cardioverter defibrillator with oral antibiotics and without removal of the device. Pacing Clin Electrophysiol 1997;20:2268-2270.
Mela T, McGovern BA, Garan H, et al. Long-term infection rates associated with the pectoral versus abdominal approach to cardioverter-defibrillator implants. Am J Cardiol 2001;88:750-753.
Goldstein DJ, Oz MC, Rose EA. Implantable left ventricular assist devices. N Engl J Med 1998;339:1522-1533.
Sinha P, Chen JM, Flannery M, Scully BE, Oz ME, Edwards NM. Infections during left ventricular assist device support do not affect posttransplant outcomes. Circulation 2000;102:Suppl III:III-194.
Brandt CM, Sistrunk WW, Duffy MC, et al. Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis 1997;24:914-919.
Crockarell JR, Hanssen AD, Osmon DR, Morrey BF. Treatment of infection with debridement and retention of the components following hip arthroplasty. J Bone Joint Surg Am 1998;80:1306-1313.
Segreti J, Nelson JA, Trenholme GM. Prolonged suppressive antibiotic therapy for infected orthopedic prostheses. Clin Infect Dis 1998;27:711-713.
Meehan AM, Osmon DR, Duffy MCT, Hanssen AD, Keating MR. Outcome of penicillin-susceptible streptococcal prosthetic joint infection treated with debridement and retention of the prosthesis. Clin Infect Dis 2003;36:845-849.
Grimer RJ, Belthur M, Chandrasekar C, Carter SR, Tillman RM. Two-stage revision for infected endoprostheses used in tumor surgery. Clin Orthop 2002;395:193-203.
Whitehead WE, Kestle JRW. The treatment of cerebrospinal fluid shunt infections: results from a practice survey of the American Society of Pediatric Neurosurgeons. Pediatr Neurosurg 2001;35:205-210.
Kulkarni AV, Rabin D, Lamberti-Pasculli M, Drake JM. Repeat cerebrospinal fluid shunt infection in children. Pediatr Neurosurg 2001;35:66-71.
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Mulcahy JJ. Surgical management of penile prosthesis complications. Int J Impot Res 2000;12:Suppl 4:S108-S111.
Related Letters:
Infections Associated with Surgical Implants
Deysine M., Roy-Chaudhury P., Munda R., Kreismann E., Mitsutake K., Niwaya K., Darouiche R. O.(Rabih O. Darouiche, M.D.)
Clinical and Economic Consequences
Infections that are associated with a variety of surgical implants have clinical and economic consequences (Table 1). Mortality attributable to such infections is highest among patients with cardiovascular implants, particularly prosthetic heart valves and aortic grafts. Infections associated with orthopedic devices and ventricular shunts often result in serious disabilities. Although infections of mammary and penile implants are rarely life-threatening, they can cause major disfigurement and psychological trauma. The average rates of infection listed in Table 1 are for initially inserted implants, which are less likely than replacement implants to become infected.2 The nature and the number of stages of surgical intervention vary according to the type of implant. Except for combination pacemaker–defibrillator systems, the cost of an implant itself usually constitutes a small fraction of the overall cost of treating implant-associated infections.
Table 1. Clinical and Economic Consequences of Infections Associated with Surgical Implants.
Diagnostic Challenges
Some, but not all, postoperative wound infections affect the surgical implant.21 However, bacterial colonization of surgical implants does not necessarily indicate infection. In fact, most colonized implants do not become infected. The ultimate proof of implant-associated infection requires the presence of clinical manifestations, intraoperative signs of infection adjacent to the implant, and the growth of pathogens in cultures of surgical specimens. To help obviate the need to operate on a patient who may not have an implant-associated infection, one can rely on certain microbiologic and imaging studies that are implant-specific. Although bacteremia is the hallmark of prosthetic-valve endocarditis and some infections associated with vascular grafts, blood cultures are negative in most cases of infection associated with pacemaker–defibrillator systems (unless endocarditis is present), ventricular assist devices, orthopedic devices, ventricular shunts, mammary implants, and penile implants.
Nonoperative cultures of local body fluids vary in their sensitivity for detecting infections associated with implants. For example, a culture of cerebrospinal fluid from a ventricular shunt has a sensitivity greater than 90 percent, whereas a culture of fluid from a prosthetic joint space, obtained by percutaneous aspiration, has a sensitivity of less than 50 percent. A transesophageal echocardiogram is much more sensitive than a transthoracic echocardiogram in identifying vegetations around prosthetic heart valves and pacemaker leads. Infection associated with vascular grafts can be diagnosed with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), or, in the case of an aortoenteric fistula, esophagogastroduodenoscopy.22 Since nuclear scans can yield false positive results up to a few months after surgical placement of orthopedic devices, CT and MRI scans are more reliable in diagnosing infection. Figure 1 shows some clinical, radiologic, and microscopical findings that can help in the diagnosis of implant-related infections.
Figure 1. Clinical, Radiologic, and Microscopical Findings in Patients with Implant-Related Infections.
Panel A shows the clinical presentation of a penile implant that became infected with Staphylococcus epidermidis and eroded through the scrotum (arrow). (Photograph courtesy of Dr. Timothy Boone.) In Panel B, the roentgenographic finding of radiolucent lines (arrows) at the cement–bone interface around a hip prosthesis that had been implanted six months earlier raises the possibility of infection, which was confirmed by the intraoperative finding of purulent material around the hip implant. (Radiograph courtesy of Dr. Glenn Landon.) Panel C is a confocal scanning laser microscopical image of the biofilm surrounding a urologic device. It shows bacterial DNA (Enterococcus faecalis), stained blue (DRAQ5, x1000), and carbohydrate material, stained green (SYTOX green, x1000). (Image courtesy of Dr. Barbara Trautner.)
General Principles of Treatment
The essential factor in the evolution and persistence of infection is the formation of biofilm around implanted devices.23 Soon after insertion, a conditioning layer composed of host-derived adhesins (including fibrinogen, fibronectin, and collagen) forms on the surface of the implant and invites the adherence of free-floating (planktonic) organisms. Bacterial cell division, recruitment of additional planktonic organisms, and secretion of bacterial products (such as the glycocalyx) follow. A three-dimensional structure of biofilm finally evolves that contains complex communities of tightly attached (sessile) bacteria. These bacteria display cell-to-cell signaling and exist within a polymer matrix containing fluid channels that allow for the flow of nutrients and waste.24 Possible reasons for the reduced susceptibility of biofilm-embedded organisms to antibiotic agents, as compared with their free-floating counterparts, include a slow rate of bacterial growth within the biofilm, inhibition of antimicrobial activity by biofilm substances, and poor penetration of the biofilm by antibiotics.
The most important clinical objectives in treating infections associated with surgical implants are to cure the infection, prevent its recurrence, preserve body function, and reduce the risk of death. In most cases, these objectives can be achieved with both antibiotic therapy and surgical intervention. Table 2 summarizes the general principles of the medical and surgical treatment of infections that are associated with surgical implants. About two thirds of infections are caused by either Staphylococcus aureus or coagulase-negative staphylococci. Methicillin-resistant staphylococci are variably susceptible to older antibiotics (doxycycline, trimethoprim–sulfamethoxazole, quinolones, and clindamycin), and they are almost universally sensitive to the newer agent linezolid, but the clinical efficacy of these drugs for the treatment of infections associated with surgical implants has not been prospectively compared with the efficacy of vancomycin.
Table 2. General Principles of the Medical and Surgical Treatment of Infections Associated with Surgical Implants.
Most implants that are infected by S. aureus or candida require surgical removal (Table 2). Patients with an established response to medical therapy for an implant infection caused by the less virulent coagulase-negative staphylococci may not require surgery to remove the implant. If a decision is made to remove the infected implant, complete extraction of all components is essential, if surgically feasible, regardless of the type of infecting organism. Although surgical removal of the infected implant is generally associated with a better outcome than is retention of the infected implant, medical treatment alone may be warranted in patients who are at high risk for intraoperative or postoperative complications.
Implant-Specific Therapeutic Approaches
Prosthetic Heart Valves
Although relatively uncommon, prosthetic-valve endocarditis is life-threatening, with mortality exceeding 30 percent.4 Curing prosthetic-valve endocarditis may require a combination of antibiotic therapy and surgical intervention. Medical therapy consists of a six-week course of systemic bactericidal antibiotics. Bacteriostatic antibiotics, such as clindamycin, should not be used for the treatment of staphylococcal endocarditis. Although in-hospital mortality is generally higher among medically treated patients than among patients who undergo surgery (46 percent vs. 24 percent), this difference in mortality almost disappears when patients who are treated medically simply because they are considered to be too sick for curative treatment are excluded from the analysis.25 However, a recurrence of endocarditis, which warrants surgery, is more likely in medically treated patients.25 Patients with aortic paravalvular abscesses, particularly those caused by S. aureus, have a very poor prognosis when treated medically.26
Clinical practice dictates surgical replacement of almost all prosthetic valves infected by S. aureus or candida. Surgical intervention may not be required in patients infected by coagulase-negative staphylococci that have already responded to antibiotic therapy. Regardless of the causative pathogen, cardiac complications (e.g., congestive heart failure, conduction abnormalities, paravalvular abscesses, valve dehiscence, and serious peripheral embolization) necessitate the surgical replacement of the infected prosthesis. Since emergency surgery is associated with high mortality,27 it is essential that surgery be performed before patients become hemodynamically unstable. Central nervous system complications may be aggravated by cardiopulmonary bypass and postoperative anticoagulation, and if valve replacement is indicated in patients with such complications, surgery is delayed for 10 days or even a few weeks, until their neurologic condition stabilizes.3 Figure 2 shows the therapeutic quandary that may evolve in the context of surgical treatment of prosthetic-valve endocarditis due to S. aureus, a condition associated with high mortality.3,28,29
Figure 2. Surgical Management of Prosthetic-Valve Endocarditis Due to Staphylococcus aureus.
Patients with prosthetic heart valves receive long-term oral anticoagulant therapy, and it is prudent to consider a particular patient's circumstances in making decisions about when to stop anticoagulation before surgical replacement of the infected valve and when and at what dose to restart it postoperatively. Warfarin is usually stopped at least two days before nonemergency surgical replacement, but in the case of an emergency procedure, anticoagulation should be reversed rapidly with fresh-frozen plasma. Anticoagulation is usually reinitiated (typically at a dose lower than the preoperative dose, because of the postoperative depletion of coagulation factors) about four to seven days after surgery to reduce the risk of bleeding — a risk that is particularly high around the time of removal of the epicardial pacemaker (a few days postoperatively).
Vascular Grafts
The three major types of prosthetic vascular grafts (arteriovenous, femoropopliteal, and aortic) differ with regard to the associated rates of infection and the most pertinent complications.30 More than 5 percent of arteriovenous grafts become infected, necessitating another means of access to ensure uninterrupted hemodialysis. Infection occurs in about 4 percent of femoropopliteal grafts and can result in limb loss. Although infection of aortic grafts is the least likely (the rate of infection is about 2 percent), this complication is lethal in almost 90 percent of cases.
A combination of medical and surgical treatment is used for most infected vascular grafts. The duration of antibiotic therapy is determined by the presence of septicemia (treated with systemic antibiotics for six weeks) or an abscess. Surgical intervention is tailored to the condition of the patient and the type of graft, and in many cases alternatives to traditional therapeutic approaches need to be considered.5,31 Combined vascular reconstruction and adjunctive tissue transfer is often necessary in patients with tissue defects.
No prospective studies have compared the various surgical treatments of infections associated with different types of vascular grafts. Traditional treatment of infected arteriovenous grafts is performed in two stages: the infected graft is removed before a new polytetrafluoroethylene graft or fistula is placed elsewhere, with interim placement of a dialysis catheter until the new graft or fistula matures, in four to six weeks.32 A new therapeutic approach that has recently been developed consists of inserting a new polyurethane graft that can be used immediately, thereby obviating the need for a temporary dialysis catheter. In patients with limited venous access, a one-stage procedure to remove the infected graft and replace it with a cryopreserved human allograft can be performed.33 (The Food and Drug Administration has expressed concern about the validation of methods used to prevent microbial contamination of allograft tissue and has limited the distribution of some cryopreserved grafts, pending implementation of certain preventive procedures.) This approach to the treatment of infected grafts results in a relatively low incidence of reinfection and a rate of graft patency similar to that with the placement of prosthetic grafts.
Surgical management of infected femoropopliteal grafts usually consists of a one-stage procedure for graft excision and revascularization with autologous venous conduits, prosthetic grafts, or cryopreserved homografts.34 In patients with a favorable risk–benefit ratio for surgical intervention, infections of aortic grafts are treated with either axillofemoral bypass grafting, followed by excision of the infected graft,35 or graft excision plus in situ replacement with cryopreserved homografts,7 autologous vascular conduits, or if the infecting organism has low virulence (such as coagulase-negative staphylococci), prosthetic grafts.31
Pacemaker–Defibrillator Systems
The combined medical and surgical treatment of infections of pacemakers is similar to that of pacemaker–defibrillator systems.8,36 Patients with clinical infection of the pulse-generator pocket without bloodstream infection receive systemic antibiotics for 10 to 14 days, whereas patients with lead-associated endocarditis receive a 6-week course of systemic antibiotics. The mainstay of surgical management is a two-stage approach that consists initially of complete removal of the entire implanted system, including the cardiac leads (by means of laser-assisted extraction, if needed), even in patients with clinical infection of only the pocket, because their cardiac leads may already be colonized. Although rare instances of curing the infection with antibiotics alone have been reported,37 recurrence of infection is generally more likely in patients treated with antibiotics alone, or with antibiotics plus removal of only the generator, than in patients who undergo extraction of the whole system.38 Before the new implant is placed, the cardiac rhythm can be controlled either by a temporary transvenous pacemaker (exchanged every 5 to 10 days) or by cardiac medications; patients with a history of ventricular fibrillation may wear an external defibrillator vest at home. The new implant is placed on the contralateral side as early as 10 to 14 days after removal of the implanted system in patients with infection of the pulse-generator pocket and as late as 6 weeks in those with endocarditis.
Left Ventricular Assist Devices
In patients with left ventricular assist devices, infection can develop in the percutaneously placed drive line, the generator pocket, and the bloodstream.39 Although potentially serious, these infections do not decrease the likelihood of successful transplantation.40 Infection is often initiated by mechanical disruption of the interface between the tissue and the drive line and is manifested as drainage that may defy treatment with antibiotics alone and may require surgical excision or revision of the exit site. Since left ventricular assist devices are considered life-sustaining,10 explanting or replacing the entire infected device before a heart becomes available for transplantation is a risky, if not impossible, option.
Joint Prostheses
The four possible surgical approaches for the treatment of infected joint prostheses are débridement plus retention of the prosthesis, removal of the infected implant without replacement, one-stage replacement, and two-stage replacement.13,14,41,42,43,44 The two-stage replacement approach results in higher cure rates and yields better function than one-stage replacement. In the first stage, the infected implant is removed and a biodegradable (polylactic acid or polyglycolic acid) or nonbiodegradable (polymethylmethacrylate) antimicrobial carrier is placed. After the patient completes a six-week course of systemic antibiotics, a new joint prosthesis is placed. In patients who have undergone multiple surgical procedures for the treatment of infection with particularly virulent organisms, arthrodesis may be necessary.
A single prospective, randomized, double-blind, placebo-controlled trial compared two treatment approaches, both intended to salvage the implant, in patients who had infections associated with joint prostheses or fracture-fixation devices.16 Among patients who had a mechanically stable implant, whose symptoms had lasted three weeks or less, and who had undergone adequate surgical débridement, the cure rate with three to six months of systemic therapy with ciprofloxacin and rifampin was 100 percent, as compared with a 58 percent cure rate with ciprofloxacin and placebo. Since most failures in the placebo group were associated with the emergence of resistance to ciprofloxacin during therapy, combining rifampin with ciprofloxacin also helped provide protection against the evolution of ciprofloxacin resistance. The results of this trial16 and other, differently designed studies13,14,42,43 provide the basis for a therapeutic algorithm for the treatment of staphylococcal infections of joint prostheses (Figure 3).
Figure 3. Management of Joint Prosthesis–Related Infection Caused by Staphylococcus aureus or Coagulase-Negative Staphylococci.
Fracture-Fixation Devices
Infections of fracture-fixation devices that involve bone are treated with a 6-week course of systemic antibiotics, whereas 10 to 14 days of antibiotic therapy are sufficient for superficial infections. The nature of the surgical intervention in patients with infected fracture-fixation devices depends on the type of device, the presence or absence of bone union, and the patient's underlying condition.45 Infection of intramedullary nails is often associated with nonunion of bone and requires removal of the infected nail, insertion of external-fixation pins, and if necessary, subsequent insertion of a replacement nail. Surgical treatment of infection of external-fixation pins usually consists of a single procedure to remove the infected pins and, if bone union has not occurred, either insert new pins at a distant site or fuse the bones. Attempts can be made to salvage infected fracture-fixation devices in carefully selected patients by using a prolonged course of systemic antibiotics12,14,16,43 (Figure 3).
Ventricular Shunts
Infected ventricular shunts are surgically managed in two stages.46 The infected shunt is removed, and an external ventricular catheter is contemporaneously inserted to drain cerebrospinal fluid and monitor intracranial pressure. The external ventricular catheter is usually replaced every 5 to 10 days to prevent ventriculitis,47 and systemic antibiotics are given for 10 to 14 days. Repeated analysis of cerebrospinal fluid is performed to ensure sterility before a new ventricular shunt is inserted, preferably on the contralateral side and usually within two weeks after the initial surgery.48
Mammary Implants
Management of an infected mammary implant usually entails a two-stage replacement procedure.19 The first surgery involves removal of the infected implant and débridement of the capsule surrounding it. A 10-to-14-day course of systemic antibiotics is administered to cover the infecting pathogen (or pathogens). A few months later, the contralateral implant is removed, and a new pair of mammary implants is inserted to replace the original pair and to achieve symmetry.
Inflatable Penile Implants
There is a universal consensus on the need for surgical removal of infected penile implants. However, there are diverging views about the stages of surgical management. Although a single-stage replacement has been advocated for use in carefully selected patients,49 the preferred approach is a two-stage replacement.20 First, the infected implant is removed, and a malleable penile prosthesis is inserted to preserve space in the corpora cavernosa. For uncomplicated infections, a 10-to-14-day course of systemic antibiotics is given. Four to six months later, a new inflatable penile implant is inserted in place of the malleable prosthesis.
Source Information
From the Center for Prostheses Infection and the Infectious Disease Section, Veterans Affairs Medical Center and Baylor College of Medicine, Houston.
Address reprint requests to Dr. Darouiche at the Center for Prostheses Infection, Baylor College of Medicine, 1333 Moursund Ave., Suite A221, Houston, TX 77030, or at rdarouiche@aol.com.
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Related Letters:
Infections Associated with Surgical Implants
Deysine M., Roy-Chaudhury P., Munda R., Kreismann E., Mitsutake K., Niwaya K., Darouiche R. O.(Rabih O. Darouiche, M.D.)