Principles of Treatment
In managing a septic prosthetic failure, the goals are to eradicate the infection and to provide a functional limb. The various treatment modalities include long-term antibiotic suppression, débridement, exchange arthroplasty, and arthrodesis (see Table 2 below). [33, 62] Amputation is done as a desperate procedure in case of life-threatening sepsis.
Table 2. Concise Approach to Treatment of Prosthetic Joint Infections (Open Table in a new window)
Status of Prosthetic Joint Infection |
Treatment |
Duration of symptoms < 3 wk and stable implant and absence of sinus tract and susceptibility to antibiotics with activity against surface-adhering microorganisms |
Débridement with retention |
Intact or only slightly damaged soft tissue |
1-stage exchange |
Damaged soft tissue, abscess, or sinus tract |
2-stage exchange with short interval (2-4 wk), spacer |
Microorganism resistant or difficult to treat* |
2-stage exchange with long interval (6-8 wk), no spacer |
Inoperable, debilitated, or bedridden |
Long-term suppressive antimicrobial treatment |
No functional improvement by exchange of implant |
Implant removal without replacement |
The Tsukayama classification of arthroplasty-associated infection into four types (see Classification) can help in formulating the treatment recommendations for the infection. Tsukayama et al based their treatment of infections after total hip arthroplasty (THA) on the clinical presentation—that is, positive intraoperative cultures, early postoperative infection, acute hematogenous infection, or late chronic infection. Treatment protocols have been successfully used for these four clinical settings. [31]
Positive intraoperative culture
Patients who have positive intraoperative cultures can be managed with intravenous (IV) administration of antibiotics for 6 weeks without operative intervention. In these patients, a revision prosthesis has already been implanted for presumed aseptic loosening before the results of the intraoperative cultures become available. Conceivably, this may be a situation for routine use of antibiotic cement in all revisions.
Early postoperative infection
Patients who had an early postoperative infection are managed with débridement, replacement of the polyethylene (PE) insert of the acetabular/tibial component, retention of the prosthesis, and IV administration of antibiotics for 6 weeks.
Removal of the original PE insert permits greater access to the site of the acetabular/tibial component for débridement and removal of a possible nidus of infection. In both the hip and the knee, removal and replacement of the PE liner are frequently necessary to provide access to the complete joint for thorough débridement, and this is the reason why arthroscopic débridement has fallen into disfavor in the knee.
Attempts are made to check the fixation of components manually. There should be no radiologic evidence of loosening. Débridement is tried once or twice, with IV antibiotics administered at an adequate dosage. Although an attempt is generally made to salvage the prosthesis, removal may be warranted in cases where infection is recalcitrant or the implants are loose. Successful results can be attained when the duration of presentation is shorter or when the pathogen is a low-virulence organism.
The success rate of irrigation and débridement in the treatment of early postoperative infection has ranged from 0% to 100%. [63, 64, 65, 66] Nolan et al reported that this procedure was successful for all of six infections diagnosed within 2 weeks after an index THA. [63] In general, it appears that the longer that the infection has been present in the hip, the more difficult it is to eradicate it without removal of the prosthesis.
Acute hematogenous infection
Patients who have an acute hematogenous infection are also managed with débridement, replacement of the PE insert, retention of the prosthesis if it is not loose, and IV administration of antibiotics for 6 weeks.
Late chronic infection
Patients who have a late chronic infection are managed with débridement, removal of all prosthetic components and bone cement, and either a direct one-stage revision [67, 68, 69] or a two-stage exchange (see the images below). [70, 71, 72] Eradication of the infection would entail removal of components in most of these patients, and trying to salvage the prosthesis may be futile.
Exchange Arthroplasty
When exchange is being considered, many important factors must be taken into account. In particular, the host should be evaluated for any problems that may cause a recurrence of infection, including the following [31] :
-
Retained bone cement
-
Previous operations
-
Potential immunocompromise (patients with rheumatoid arthritis, diabetes mellitus, chronic renal insufficiency, or a malignant tumor are considered potentially immunocompromised)
-
Early postoperative infection after arthroplasty without cement
The extent of disability after component removal, the virulence of the infecting organisms, the adequacy of débridement, and the degree to which infection is controlled at local and distant sites are some of the important variables affecting the outcome of an exchange procedure. The literature suggests that infections caused by gram-negative organisms are more difficult to treat than those caused by gram-positive isolates. [73, 74, 75, 76, 77]
Removal of components can be delayed until culture sensitivities are available, unless the patient is in a toxic state. All cement must be carefully removed; image intensification may be necessary to accomplish this. The difficulty of eradicating bacteria adhering to foreign bodies has been well described, [78] as has the need to remove all hardware and cement in the treatment of periprosthetic infections. [64, 66, 77, 79, 80, 81] Periprosthetic tissue should be obtained at the time of prosthesis removal for culture and histologic examination.
If a later exchange is planned, an antibiotic-impregnated spacer or antibiotic beads should be placed after removal of the components (see the image below). An antibiotic-impregnated spacer can be made from antibiotic-loaded cement in the operating room (OR). The spacer maintains limb length and soft-tissue tension and makes the definitive reimplantation procedure easier; however, there is a chance that it may fracture or dislocate.
This device is a “dynamic” spacer, in that it allows movements and avoids muscle wasting. Initial results have been successful. [82, 83] In place of a spacer, some authors prefer to use antibiotic-impregnated beads, made with a mixture of antibiotic and polymethylmethacrylate (PMMA). [84, 85] Antibiotics are also administered IV for 6 weeks, after which time a delayed exchange arthroplasty is performed.
One report described a two-stage exchange arthroplasty technique using an antibiotic-impregnated cement intramedullary nail, which can be easily prepared during surgery and which may provide additional stability to the knee and help it maintain its normal mechanical axis. [86] The advantages claimed for this technique include less pain between prosthesis removal and subsequent reimplantation, less soft-tissue contracture, less scar adhesion, easy removal of the cement intramedullary nail, and successful infection control.
The time interval between removal of the components and implantation of the revision prosthesis varies widely. [87] Typically, the revision is performed 6-12 weeks after the removal of the prosthesis (first stage). The antibiotics should be discontinued 2 weeks before the definitive treatment. Multiple cultures of specimens should be obtained during the revision to confirm the eradication of the infection. The spacer or the tobramycin beads are removed from the joint at that time.
The definitive implants can be either cemented or cementless. Factors reported to be most important in deciding to insert the implant without cement are an age of less than 65 years and thinning of the cortical wall of the femur. [31] A thin cortical wall has been found to be associated with decreased shear strength at the bone-cement interface of revision prostheses. [88] When cemented implants are inserted, antibiotic-impregnated cement (eg, 1.2 g of tobramycin in 40 g of cement) should be used.
Whenever possible, bulky implants are avoided in the knee; a constrained prosthesis is associated with higher rates of infection. Bone defects left after implant removal may have to be treated with large structural allografts. Although some studies have reported increased infection rates with large allografts, the use of such grafts has increased. [89, 90]
Direct vs delayed exchange
A great deal of controversy exists regarding the relative advantages and disadvantages of direct exchange and delayed exchange, each of which has specific merits and the limitations (see Table 3 below).
Table 3. Advantages and Disadvantages of Direct and Delayed Exchange (Open Table in a new window)
Direct Exchange |
Delayed Exchange |
Advantages • Less morbidity • Reduced cost • Improved mechanical stability • Less complicated technique • Shorter duration of disability
Disadvantages • Inability to use sensitive antibiotic to mix with cement while fixation
Contraindications • Immunocompromise • Major soft tissue or skin defect • Gram-negative organisms • Actively discharging sinus or overt purulence |
Advantages • Ability to identify organisms, determine sensitivities, and give adequate antibiotics before reimplantation • Ability to repeat débridement if necessary • Ability to identify and correct other foci of infection and inciting factors
Disadvantages • Technical difficulty resulting from extensive scarring and contracture • Hardships of resection arthroplasty • Increased cost and hospital stay • Delayed rehabilitation |
Good results have been obtained with delayed-exchange arthroplasty in the treatment of chronic infections: the reported success rate has been approximately 85%. [31, 41, 77, 91, 92, 93, 94]
A study from Scotland found the use of "two-in-one" single-stage revision to be an effective option for treating infection after total knee arthroplasty (TKA) and associated bone loss. [95]
Antibiotic Therapy
Selection of appropriate agent
The best choice of antibiotic for staphylococcal infection has been defined. Rifampin should be used against sensitive organisms, always in combination with another drug (preferably a quinolone) to prevent the emergence of resistance. [96, 97] Newer quinolones, such as moxifloxacin, levofloxacin, and gatifloxacin, have better activity in vitro against quinolone-susceptible staphylococci than ciprofloxacin, fleroxacin, and ofloxacin do. [33]
Other drugs tried in combination with rifampin include trimethoprim-sulfamethoxazole, minocycline, and fusidic acid. One study showed good results with the rifampin–fusidic acid combination in staphylococcal infections. [98]
Quinopristin-dalfopristin is active against Enterococcus faecium (including vancomycin-resistant enterococci [VRE]) and S aureus (including methicillin-resistant S aureus [MRSA]) but not against Enterococcus faecalis. In a study of 40 patients with orthopedic infections with MRSA treated with this combination, clinical success was reported in 78% and microbial eradication in 69%. [99]
Daptomycin is active against several gram-positive bacteria, including MRSA, vancomycin-resistant S aureus, and VRE. [100]
Linezolid has been used against MRSA, but long-term administration can lead to reversible optic neuropathy, myelosuppression, and irreversible peripheral neuropathy. [101, 102] Data regarding the combination of linezolid with rifampin are lacking. The use of rifampin may be a concern in countries where tuberculosis is endemic; it could help foster the development of resistance in tubercle bacilli.
Trampuz et al recommended antibiotic regimens for various microbial agents causing periprosthetic infections (see Table 4 below). [33]
Table 4. Antibiotic Regimens for Various Pathogens Causing Prosthetic Infections (Open Table in a new window)
Microorganism |
Antimicrobial Agent1 |
Dosage |
Route |
||
Staphylococcus aureus or coagulase-negative staphylococci |
|||||
Methicillin-susceptible |
Rifampin plus (flu)eloxacillin2 |
450 mg q12hr 2 g q6hr |
PO/IV IV |
||
For 2 wk, followed by |
|||||
Rifampin plus ciprofloxacin or levofloxacin |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr |
PO PO PO PO |
|||
Methicillin-resistant |
For 2 wk, followed by |
||||
|
Rifampin plus ciprofloxacin3 or levofloxacin3 or teicoplanin4 or fusidic acid or trimethoprim-sulfamethoxazole or minocycline |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr 400 mg q24hr 500 mg q8hr 1 forte tablet q8hr 100 mg q12hr |
PO PO PO IV/IM PO PO PO |
||
Streptococcus spp (except S agalactiae) |
Penicillin G3 or ceftriaxone |
5 million U q6hr 2 g q24hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterococcus spp (penicillin-susceptible) and S agalactiae |
Penicillin G or ampicillin or amoxicillin plus aminoglycoside5 |
5 million U q6hr 2 g q4-6hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterobacteriaceae (quinolone-susceptible) |
Ciprofloxacin |
750 g q12hr |
PO |
||
Nonfermenters (eg, Pseudomonas aeruginosa) |
Cefepime or ceftazidime plus aminoglycoside5 |
2 g q8hr |
IV |
||
For 2-4 wk, followed by |
|||||
Ciprofloxacin |
750 g q12hr |
PO |
|||
Anaerobes6 |
Clindamycin |
600 mg q6hr |
PO |
||
For 2-4 wk, followed by |
|||||
Clindamycin |
300 mg q6hr |
PO |
|||
Mixed infections (without methicillin-resistant staphylococci) |
Amoxicillin-clavulanate or piperacillin-tazobactam or imipenem or meropenem |
2.2 g q8hr 4.5 g q8hr 500 mg q6hr 1 g q8hr |
IV IV IV IV |
||
|
For 2-4 wk, followed by individual regimens according to antimicrobial susceptibility |
||||
PO= orally; IV= intravenously; IM= intramuscularly; forte tablet = trimethoprim 160 mg plus sulfamethoxazole 800 mg; MRSA = methicillin-resistant S aureus. 1. If implant retention or one-stage exchange is performed, the total duration of antimicrobial treatment is 3 months for hip prosthesis and 6 months for knee prosthesis. 2. In patients with delayed hypersensitivity, cefazolin (2 g IV q8hr) may be administered. In patients with immediate hypersensitivity, penicillin should be replaced with vancomycin (1 g q12hr). 3. MRSA should not be treated with quinolones, because antimicrobial resistance might emerge during treatment. 4. On the first day of treatment, the teicoplanin dose should be increased to 800 mg IV (loading dose). 5. Aminoglycosides can be administered in a single daily dose. 6. Alternatively, penicillin G (5 million U IV q6hr) or ceftriaxone (2 g IV q24hr) may be used for gram-positive anaerobes (eg, Propionibacterium acnes), and metronidazole (500 mg IV or PO q8hr) for gram-negative anaerobes (eg, Bacteroides spp). |
|||||
Antibiotic-impregnated cement
The use of antibiotic-impregnated cement has greatly altered the delivery of antibiotic to the infection site. The most commonly used antibiotics are tobramycin, vancomycin, and gentamicin. Some antibiotics (eg, lincomycin and tetracycline) are deactivated when mixed with cement. Rifampin forms a black, tacky composite and hence should not be used.
The recommended antibiotic doses vary, depending on whether the cement is being used as beads or spacers or for fixation of implants. For fixation of implants, 1 g of vancomycin or 1.2 g of gentamicin or tobramycin is the ideal dose; for use in spacers or beads, these doses can be doubled.
Options for Special Clinical Situations
Long-term antibiotic suppression
Although there are no strict guidelines regarding the optimal duration and route of antibiotic therapy, IV administration of antibiotics for 6 weeks in doses that achieve a bactericidal concentration of at least 1:8 has proved efficacious in reimplantation protocol studies. A higher drug concentration is needed for bacteria adhering to cement or polyethylene than for suspended bacteria.
Long-term oral antibiotic therapy may be considered in elderly patients who have a short life expectancy and from whom removal of the prosthesis may be extremely difficult. For such therapy to be a worthwhile option, the organism should be of low virulence and susceptible to an oral antibiotic, and the antibiotic should have no serious side effects. Treatment is individualized.
The disadvantages of long-term antibiotic suppression—namely, the emergence of multidrug resistant organisms, the formation of excessive scar tissue, and the progressive loss of bone stock—must be taken into account in the decision-making process.
Arthrodesis
Young patients with a high functional demand and a single joint involvement are ideal candidates for knee arthrodesis. Factors that rule out a revision procedure (eg, loss of extensor mechanism, poor soft-tissue coverage, systemic immune compromise, and highly virulent organisms) also warrant a knee arthrodesis.
Relative contraindications for arthrodesis include bilateral knee disease, ipsilateral ankle or hip disease, severe segmental bone loss, and amputation in the contralateral extremity.
Excision arthroplasty
Excision or resection arthroplasty (the Girdlestone operation, as it is commonly referred to when done in the hip joint) is performed either as a definitive procedure or as a temporizing measure to buy time for infection control before reimplantation.
As a definitive procedure, excision hip arthroplasty is typically successful at controlling the infection, but many patients are unable to walk without assistive devices, and all have a limp. The patient is left with a painless unstable hip. Many patients are unwilling to accept the problems associated with excision arthroplasty and request reimplantation instead. The proximal femur is preserved as much as possible.
Current indications for excision arthroplasty in an infected knee are few but are considered to include inflammatory arthropathy. A study of 26 patients, 11 of whom had rheumatoid arthritis, showed that 89% were free of infection at an average of 5 years after excision arthroplasty. [103] Functional results were suboptimal: only 15 patients were able to walk independently, and all required walking aids. Only five patients had sufficient knee stability to walk without external support; eight required a knee-ankle-foot orthosis, and two used a splint.
Although excision knee arthroplasty usually results in satisfactory resolution of the infection, most patients experience some pain and knee instability and have a limited ability to walk.
Prevention
A systematic review and meta-analysis by Cooper et al compared two different closed incision negative pressure wound therapy (ciNPWT) systems—one with foam dressing (ciNPT-F) and the other with multilayer absorbent dressing (ciNPT-MLA)—against standard of care (SOC) with respect to the incidence of surgical-site infections (SSIs) and surgical-site complications (SSCs) after hip and knee arthroplasties. [104] As compared with SOC, ciNPT-F was found to yield significant reductions in SSI and SSC rates, but ciNPT-MLA was not.
-
Final radiograph after stage II revision.
-
Stage I revision with antibiotic spacer made from mold.
-
Radiograph of 50-year-old patient for whom bipolar arthroplasty was done elsewhere for displaced fracture of neck of femur. Patient came with severe pain hip 1 year after procedure. Severe osteolysis and superior migration of prosthesis are seen.
-
Infected total knee arthroplasty with sinus.
-
Lateral radiograph showing lysis and loosening of prosthesis.
-
Frankly infected tissue around prosthesis.
-
Cement spacer application.
-
Radiograph after stage I revision.
-
Stage II revision. Bone loss at femoral side; allograft used.
-
Astemmed femoral prosthesis and allograft used for bone loss.
-
Final radiograph after stage II revision.
Tables
Microorganism |
Frequency (%) |
Coagulase-negative staphylococci |
30-43 |
Staphylococcus aureus |
12-23 |
Streptococci |
9-10 |
Enterococci |
3-7 |
Gram-negative bacilli |
3-6 |
Anaerobes |
2-4 |
Multiple pathogens (polymicrobial) |
10-12 |
Unknown |
10-11 |
Status of Prosthetic Joint Infection |
Treatment |
Duration of symptoms < 3 wk and stable implant and absence of sinus tract and susceptibility to antibiotics with activity against surface-adhering microorganisms |
Débridement with retention |
Intact or only slightly damaged soft tissue |
1-stage exchange |
Damaged soft tissue, abscess, or sinus tract |
2-stage exchange with short interval (2-4 wk), spacer |
Microorganism resistant or difficult to treat* |
2-stage exchange with long interval (6-8 wk), no spacer |
Inoperable, debilitated, or bedridden |
Long-term suppressive antimicrobial treatment |
No functional improvement by exchange of implant |
Implant removal without replacement |
Direct Exchange |
Delayed Exchange |
Advantages • Less morbidity • Reduced cost • Improved mechanical stability • Less complicated technique • Shorter duration of disability
Disadvantages • Inability to use sensitive antibiotic to mix with cement while fixation
Contraindications • Immunocompromise • Major soft tissue or skin defect • Gram-negative organisms • Actively discharging sinus or overt purulence |
Advantages • Ability to identify organisms, determine sensitivities, and give adequate antibiotics before reimplantation • Ability to repeat débridement if necessary • Ability to identify and correct other foci of infection and inciting factors
Disadvantages • Technical difficulty resulting from extensive scarring and contracture • Hardships of resection arthroplasty • Increased cost and hospital stay • Delayed rehabilitation |
Microorganism |
Antimicrobial Agent1 |
Dosage |
Route |
||
Staphylococcus aureus or coagulase-negative staphylococci |
|||||
Methicillin-susceptible |
Rifampin plus (flu)eloxacillin2 |
450 mg q12hr 2 g q6hr |
PO/IV IV |
||
For 2 wk, followed by |
|||||
Rifampin plus ciprofloxacin or levofloxacin |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr |
PO PO PO PO |
|||
Methicillin-resistant |
For 2 wk, followed by |
||||
|
Rifampin plus ciprofloxacin3 or levofloxacin3 or teicoplanin4 or fusidic acid or trimethoprim-sulfamethoxazole or minocycline |
450 mg q12hr 750 mg q12hr 750 mg q24hr to 500 mg q12hr 400 mg q24hr 500 mg q8hr 1 forte tablet q8hr 100 mg q12hr |
PO PO PO IV/IM PO PO PO |
||
Streptococcus spp (except S agalactiae) |
Penicillin G3 or ceftriaxone |
5 million U q6hr 2 g q24hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterococcus spp (penicillin-susceptible) and S agalactiae |
Penicillin G or ampicillin or amoxicillin plus aminoglycoside5 |
5 million U q6hr 2 g q4-6hr |
IV IV |
||
For 2-4 wk, followed by |
|||||
Amoxicillin |
750-1000 mg q8hr |
PO |
|||
Enterobacteriaceae (quinolone-susceptible) |
Ciprofloxacin |
750 g q12hr |
PO |
||
Nonfermenters (eg, Pseudomonas aeruginosa) |
Cefepime or ceftazidime plus aminoglycoside5 |
2 g q8hr |
IV |
||
For 2-4 wk, followed by |
|||||
Ciprofloxacin |
750 g q12hr |
PO |
|||
Anaerobes6 |
Clindamycin |
600 mg q6hr |
PO |
||
For 2-4 wk, followed by |
|||||
Clindamycin |
300 mg q6hr |
PO |
|||
Mixed infections (without methicillin-resistant staphylococci) |
Amoxicillin-clavulanate or piperacillin-tazobactam or imipenem or meropenem |
2.2 g q8hr 4.5 g q8hr 500 mg q6hr 1 g q8hr |
IV IV IV IV |
||
|
For 2-4 wk, followed by individual regimens according to antimicrobial susceptibility |
||||
PO= orally; IV= intravenously; IM= intramuscularly; forte tablet = trimethoprim 160 mg plus sulfamethoxazole 800 mg; MRSA = methicillin-resistant S aureus. 1. If implant retention or one-stage exchange is performed, the total duration of antimicrobial treatment is 3 months for hip prosthesis and 6 months for knee prosthesis. 2. In patients with delayed hypersensitivity, cefazolin (2 g IV q8hr) may be administered. In patients with immediate hypersensitivity, penicillin should be replaced with vancomycin (1 g q12hr). 3. MRSA should not be treated with quinolones, because antimicrobial resistance might emerge during treatment. 4. On the first day of treatment, the teicoplanin dose should be increased to 800 mg IV (loading dose). 5. Aminoglycosides can be administered in a single daily dose. 6. Alternatively, penicillin G (5 million U IV q6hr) or ceftriaxone (2 g IV q24hr) may be used for gram-positive anaerobes (eg, Propionibacterium acnes), and metronidazole (500 mg IV or PO q8hr) for gram-negative anaerobes (eg, Bacteroides spp). |
|||||
