Infection, though an uncommon complication of arthroplasty, may be among the most devastating complications for the patient, as well as for the surgeon. The economic consequences associated with treating periprosthetic infections are substantial. [1, 2, 3]
Revision procedures for infection are associated with a longer operating time, greater blood loss, and more frequent complications, along with increases in the total number of hospitalizations, duration of hospitalization, total number of operations, total hospital costs, and total outpatient visits and charges. When compared with revisions for aseptic loosening or primary total hip arthroplasties (THAs), revisions for sepsis are associated with significantly greater use of hospital and physician resources. 
Currently, the reported infection rate after arthroplasty is about 1%.  Kurtz et al quantified the current and historical incidence of periprosthetic infection associated with hip and knee arthroplasty in the United States using the Nationwide Inpatient Sample, as well as corresponding hospitalization charges and length of stay, and found that the rate of infected knee arthroplasties was 0.92%, significantly greater than the rate of infected hip arthroplasties (0.88%). 
The number of primary and revision procedures has been projected to expand dramatically over the next 25 years  ; accordingly, the infection burden on patients, clinicians, and society as a whole will also increase. The estimated cost of infected revisions is projected to be as high as $1.6 billion by 2020. Methods of preventing, diagnosing, and treating infection must be continually improved in order to reduce the cost and complications of total joint arthroplasty.
There is a need for both improved diagnostic methods and more efficient treatment protocols. Molecular diagnostic methods, such as polymerase chain reaction (PCR) testing, have been associated with high false-positive rates and are still not recommended for routine clinical use. Addressing bone defects during reimplantation is an area that also requires further research.
The problems of conducting randomized studies in the setting of a septic prosthetic failure are a major deterrent to the evolution of treatment protocols. Foolproof intraoperative diagnostic techniques, improved implant designs, and better local antibiotic delivery systems must be developed to face the menace of infection associated with joint replacement surgery.
Gains may be achieved not only by developing newer approaches but also by using currently available approaches more effectively. For example, in one study, culture of samples obtained via sonication of prostheses was more sensitive than conventional periprosthetic-tissue culture for microbiologic diagnosis of prosthetic hip and knee infection, especially in patients who had received antimicrobial therapy within the 14 days preceding surgery. 
In a meta-analysis, antigranulocyte scintigraphy with monoclonal antibodies had a reasonably high discriminating ability with respect to identification of prosthesis infection in patients who underwent total joint arthroplasty. 
The use of cefuroxime-impregnated cement was shown to be effective in the prevention of early-to-intermediate deep infection after primary total knee arthroplasty (TKA) performed with perioperative systemic antibiotic prophylaxis but without any so-called clean-air measures.  This measure may be particularly helpful in developing nations, where more and more arthroplasties are now being performed.
Additional pathogens are being found to cause prosthetic joint infections. A Swiss study drew attention toward infection by Propionibacterium acnes; a median of 10 biopsies, a 14-day incubation period, and histopathologic examination were needed to establish the association. 
Thus, the future of management of arthroplasty-associated infections lies in devising ways to prevent infections, developing investigations that allow early detection, and minimizing both the emergence of new pathogens and the spread of antibiotic resistance among existing pathogens.
Factors influencing the occurrence of arthroplasty-associated infections include the following  :
Debreuve-Theresette et al described the development of a score to asses the endogenous risk of surgical-site infection (SSI) after THA and TKA.  They found the score useful for identifying SSIs but noted that further validation in larger studies would be required.
Immunocompromised status, rheumatoid arthritis, and diabetes mellitus are some of the most important comorbid conditions associated with an increased risk of infection in a patient undergoing arthroplasty.
Malnutrition has been defined by many authors as a total white blood cell (WBC) count lower than 1500/µL and an albumin level lower than 3.5 mg/dL.  Malnourished patients have an increased chance of wound complications.  Hence, it is imperative to build up the patient’s nutritional status before the operation.
chronic urinary tract infection (UTI) and ongoing sepsis in any other part of the body also increase the risk.
Smoking may increase the risk of SSI after total joint arthroplasty. 
Steroid use for an associated condition (eg, inflammatory arthritis or psoriasis) has been associated with increased susceptibility to infection. A previous surgical procedure on the same joint is an independent risk factor that doubles the risk of deep infection in the knee and triples the risk in the hip. [18, 19] Elderly patients and patients with comorbid conditions that require a long time for optimization before surgery are more susceptible to infection as well. 
The number of personnel and the amount of traffic in the OR exert an influence on the incidence of infection. Accordingly, changes in the OR environment have the potential to reduce infection. For example, some people shed a large number of bacteria; they can help decrease the risk of infection by using helmet aspirator suits.
Although various commercial preparations are available for preparing the surgical site, most surgeons prefer the iodophor compounds. Shaving the area is best avoided, but if it is considered essential, it should be done immediately before the procedure. The use of an iodophor-incorporated drape has been proved to decrease infection in arthroplasty patients and is now routine in this setting.
In one study, the use of an iodophor-incorporated drape during 649 TKAs was associated with an infection rate of only 0.5%.  In another study, the use of an iodophor-incorporated drape proved to be significantly better at preventing recolonization of the skin by bacteria than other methods of skin-site preparation were. 
Ultraviolet (UV) light has been employed to decrease the bacterial load in the OR. This measure adds to the cost of the procedure but has not been conclusively shown to produce a decrease in infection risk. 
Use of vertical laminar airflow has been found to yield a significant decrease in the bacterial load in the OR air and thereby decrease the infection rates with THAs. In an important study from the early 1980s, Lidwell et al concluded that laminar airflow systems and body exhaust suits independently reduced surgical infection risk by 50%. 
However, Miner et al, in a 2007 population survey designed to assess the efficacy of laminar flow and body exhaust suits, found no conclusive evidence to support this result.  The cost of laminar airflow systems and body exhaust suits is substantial, adding hundreds of dollars to the expense of each operation and complicating the environment in which the operating team works. The authors concluded that it would be worthwhile to obtain additional evidence about whether these widely used clean-air practices have a meaningful clinical benefit in today’s OR.
A prolonged operating time increases the risk of infection.  In one population-based survey, a prolonged operating time was in fact the only statistically significant risk factor for infection. 
The type of implant used also influences the infection risk. For example, a large hinged knee implant increases the risk of infection. Materials such as polymethylmethacrylate (PMMA), steel, cobalt-chromium (CoCr), and polyethylene (PE) are susceptible to the formation of a biofilm by the infecting organism around the implant, which protects the pathogen from the action of antibiotics. 
The virulence of the infecting organisms is an important factor to consider in planning management. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated organisms. Gram-negative infections are resistant to treatment and are a frequent cause of recurrence after an exchange arthroplasty.  Organisms that can form glycocalyx, methicillin-resistant S aureus (MRSA), group D streptococci, and enterococci are considered highly virulent.
A frequent cause of inability to isolate the organism is empirical antibiotic therapy. Other causes are infections caused by anaerobic organisms and fungi. Trampuz et al reported the frequencies with which different pathogens cause prosthetic joint infections (see Table 1 below). 
Table 1. Microorganisms Causing Prosthetic Joint Infections (Open Table in a new window)
Multiple pathogens (polymicrobial)
Prosthetic joint infections are caused by pathogens living clustered together in biofilm, a highly hydrated extracellular matrix attached to the implant surface. Within the biofilm, the organisms grow either slowly or not at all; consequently, they are resistant to all growth-dependent antibiotics. The bacterial cells of the biofilm organize among themselves, communicate with each other, and behave like a multicellular organism. The biofilm helps the pathogens combat external and internal forces, whether from the host immune system or from antibiotics. 
The Surgical Infection Prevention Project and its Surgical Infection Prevention Guideline Writers Workgroup promoted the following three major interventions to prevent SSIs  :
With increasing frequency, patients are admitted to the hospital on the day of the operation and present to the OR just before their procedure. It is therefore essential to ensure that the institution of safeguards regarding the correct surgical site and the administration of prophylactic antibiotics no more than 1 hour before surgery are implemented as components of an institutional process. 
The cephalosporins cefazolin and cefuroxime are considered to have equal prophylactic efficacy.  Local guidelines that recommend beta-lactam agents as first-line prophylaxis should also recommend alternative drugs for those allergic to penicillin. Available evidence suggests that administering the first dose as near to the incision time as possible will reduce the likelihood of infection, whether superficial or deep.
There remains some controversy regarding the optimal duration of prophylaxis in connection with THA. The US advisory statement recommends that antimicrobial prophylaxis be administered no more than 1 hour before the incision and discontinued within 24 hours after the end of the operation.  However, European guidelines recommend administering a single dose no more than 30 minutes before the incision and advise considering prophylaxis for as long as 24 hours after the operation. [35, 36]
In a Dutch study, superficial and deep SSIs occurred in 2.6% of 1922 THA patients, and the highest odds ratios for infection were found in those who received prophylaxis after incision, those with an American Society of Anesthesiology score of 12, and those in whom the operating time was above the 75th percentile.  Prolonged prophylaxis after the end of the procedure and the use of antibiotic-impregnated cement did not contribute to fewer infections in this study.
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Multiple pathogens (polymicrobial)
Status of Prosthetic Joint Infection
Duration of symptoms <3 wk
absence of sinus tract
susceptibility to antibiotics with activity against surface-adhering microorganisms
Débridement with retention
Intact or only slightly damaged soft tissue
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
• Less morbidity
• Reduced cost
• Improved mechanical stability
• Less complicated technique
• Shorter duration of disability
• Inability to use sensitive antibiotic to mix with cement while fixation
• Major soft tissue or skin defect
• Gram-negative organisms
• Actively discharging sinus or overt purulence
• Ability to identify organisms, determine sensitivities, and give adequate antibiotics before reimplantation
• Ability to repeat debridement if necessary
• Ability to identify and correct other foci of infection and inciting factors
• Technical difficulty resulting from extensive scarring and contracture
• Hardships of resection arthroplasty
• Increased cost and hospital stay
• Delayed rehabilitation
Staphylococcus aureus or coagulase-negative staphylococci
450 mg q12hr
2 g q6hr
For 2 wk, followed by
450 mg q12hr
750 mg q12hr
750 mg q24hr
to 500 mg q12hr
For 2 wk, followed by
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
Streptococcus spp (except S agalactiae)
5 million U q6hr
2 g q24hr
For 2-4 wk, followed by
750-1000 mg q8hr
Enterococcus spp (penicillin-susceptible) and S agalactiae
5 million U q6hr
2 g q4-6hr
For 2-4 wk, followed by
750-1000 mg q8hr
750 g q12hr
Nonfermenters (eg, Pseudomonas aeruginosa)
2 g q8hr
For 2-4 wk, followed by
750 g q12hr
600 mg q6hr
For 2-4 wk, followed by
300 mg q6hr
(without methicillin-resistant staphylococci)
2.2 g q8hr
4.5 g q8hr
500 mg q6hr
1 g q8hr
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).
Rajesh Malhotra, MBBS, MS Professor and Head, Department of Orthopedics, All India Institute of Medical Sciences; Chief, JPN Apex Trauma Centre, India
Disclosure: Nothing to disclose.
Karthik S Murugappan, MBBS, MS(Orth), DNB, MRCS Consulting Surgeon, Department of Orthopedics, Flinders Medical Center, Australia
Disclosure: Nothing to disclose.
William L Jaffe, MD Clinical Professor of Orthopedic Surgery, New York University School of Medicine; Vice Chairman, Department of Orthopedic Surgery, New York University Hospital for Joint Diseases
William L Jaffe, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American College of Surgeons, Eastern Orthopaedic Association, New York Academy of Medicine
Disclosure: Received consulting fee from Stryker Orthopaedics for speaking and teaching.
James J McCarthy, MD, FAAOS, FAAP Associate Professor, Consulting Orthopedic Surgeon, Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health
James J McCarthy, MD, FAAOS, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Orthopaedic Surgeons, American Academy of Pediatrics, American Orthopaedic Association, Limb Lengthening and Reconstruction Society ASAMI-North America, Orthopaedics Overseas, Pediatric Orthopaedic Society of North America, Pennsylvania Medical Society, Pennsylvania Orthopaedic Society, and Philadelphia County Medical Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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