Prosthetic joint infection (PJI), also known as peri-prosthetic joint infection, is an acute, sub-acute or chronic infection of a prosthetic joint. It may occur in the period after the joint replacement or many years later. It usually presents as joint pain,

erythema Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology inc ...

(redness of the joint or adjacent area),

joint swelling A joint effusion is the presence of increased intra-articular fluid. It may affect any joint. Commonly it involves the knee (see knee effusion). Diagnostic approach The approach to diagnosis depends on the joint involved. While aspiration o ...

and sometimes formation of a

sinus tract In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hol ...

( a tract connecting the joint space to the outer environment). PJI is estimated to occur in approximately 2% of hip and knee replacements, and up to 4% of revision hip or knee replacements. Other estimates indicate that 1.4-2.5% of all joint replacements worldwide are complicated by PJIs. The incidence is expected to rise significantly in the future as

hip replacements Hip replacement is a surgical procedure in which the hip joint is replaced by a prosthetic implant, that is, a hip prosthesis. Hip replacement surgery can be performed as a total replacement or a hemi/semi(half) replacement. Such joint replaceme ...

and knee replacements become more common. It is usually caused by

aerobic Aerobic means "requiring air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Aerobic respiration, the aerobic process of cellu ...

gram positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain i ...

bacteria, such as Staph epidermidis or

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

but

enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are Gram-positive cocci that often occur in pairs ( diplococci) or short chains, and are difficult to distinguish from streptococci on physical ch ...

species,

gram negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists of ...

organisms and Cutibacterium are also known causes with

fungal A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...

infections being a rare culprit. The definitive diagnosis is isolation of the causative organism from the

synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articul ...

(joint fluid), but signs of inflammation in the joint fluid and imaging may also aid in the diagnosis. The treatment is a combination of systemic

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

debridement Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), or by maggot therapy. In ...

of infectious and

necrotic Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is ...

tissue and local antibiotics applied to the joint space. The bacteria that usually cause prosthetic joint infections commonly form a

biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...

, or a thick slime that is adherent to the artificial joint surface, thus making treatment challenging.

Signs and symptoms

The most common symptom of periprosthetic joint infections is

joint pain Arthralgia () literally means 'joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceutic ...

. Other local symptoms are also present, including

(redness of the joint),

, warmth of the joint, and loosening of the prosthetic joint. A

, or a tract connecting the joint space to the external environment, is more common in chronic PJI, and is definitively diagnostic of PJI. Fever may be present in PJI, but is uncommon.

Cause

Prosthetic joint infections can occur any time after a joint replacement. Early infections (occurring within 4 weeks of a joint replacement) are usually due to Staph aureus,

streptococci ''Streptococcus'' is a genus of gram-positive spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs along a sing ...

enterococci ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are Gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical charac ...

. Whereas late infections (occurring 3 months or later after the joint replacement) are usually due to coagulase negative staphylococcus or cutibacterium. The highest risk of PJI is in the immediate post-operative period, when direct inoculation of bacteria into the joint space may occur during surgery. The risk of PJI is highest in this early period; within 2 years of the joint replacement.

Hematogenous spread Bloodstream infections (BSIs) are infections of blood caused by blood-borne pathogens. The detection of microbes in the blood (most commonly accomplished by blood cultures) is always abnormal. A bloodstream infection is different from sepsis, wh ...

, or infection of a prosthetic joint via direct seeding from a bloodstream infection, may occur at any time after a joint replacement, with the risk being as high as 34% in staph aureus

bacteremia Bloodstream infections (BSIs) are infections of blood caused by blood-borne pathogens. The detection of microbes in the blood (most commonly accomplished by blood cultures) is always abnormal. A bloodstream infection is different from sepsis, wh ...

. An additional possible cause of PJI is from direct spread to the joint from a nearby skin or soft tissue infection, a bone infection (

osteomyelitis Osteomyelitis (OM) is the infectious inflammation of bone marrow. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The feet, spine, and hips are the most commonly involved bones in adults. The cause is ...

), or from more distal spread to the joint from a respiratory tract infection,

gastroenteritis Gastroenteritis, also known as infectious diarrhea, is an inflammation of the Human gastrointestinal tract, gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of ...

,or

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

. Dental procedures may cause a transient bacteremia which can lead to inoculation of the artificial joint and PJI, with strep viridans being the most common causative organism. The most common causes of PJIs are aerobic, gram positive bacteria, including staph aureus and coagulase negative staphylococcus (such as staph epidermidis), which make up greater than 50% of all causes of hip and knee PJIs. With regards to acute PJIs, the most common causative organism is staph aureus (comprising 38% of acute infections) followed by aerobic gram negative bacilli (making up 24% of acute infections). 70% of PJIs are monomicrobial (with a single causative organism identified), whereas 25% of cases are polymicrobial (with multiple causative organisms identified). 3% of PJIs are due to fungal organisms.

Propionibacterium acnes ''Cutibacterium acnes'' (''Propionibacterium acnes'') is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne; it can also cause chronic blepharitis and endophthalmit ...

is the most common cause of shoulder PJIs. Risk factors for PJI include

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

, the presence of a soft tissue infection, or an infection in another part of the body or increased fat tissue around the replaced joint. Surgical factors that may lead to an increased risk of PJIs include

wound dehiscence Wound dehiscence is a surgical complication in which a wound ruptures along a surgical incision. Risk factors include age, collagen disorder such as Ehlers–Danlos syndrome, diabetes, obesity, poor knotting or grabbing of stitches, and traum ...

(unplanned opening of the surgical wound after the surgery) and

hematoma A hematoma, also spelled haematoma, or blood suffusion is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery and may involve blood continuing to seep from broken capillaries. A hematoma is ...

(collection of blood) formation. The presence of multiple artificial joints,

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

PJIs,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

or bacteremia place people at risk for multiple PJIs (either concurrent or subsequent infections). Prolonged operative times, in which the joint is left open to the external environment, determined as greater than 90 minutes in a single study, also increases the risk for PJIs.

Pathophysiology

Prosthetic joint infections are generally difficult to treat as most causative organisms form a biofilm, or a thickly adherent membrane, against the artificial joint surface. The bacteria secrete adhesion proteins which help them attach to each other and to the joint surface. The bacteria then secrete

autoinducer In biology, an autoinducer is a signaling molecule that enables detection and response to changes in the population density of bacterial cells. Synthesized when a bacterium reproduces, autoinducers pass outside the bacterium and into the surround ...

proteins that act as bacterial signals which facilitate the secretion of an intricate extracellular matrix, the biofilm. Biofilms greatly decrease antibiotic penetrance thereby shielding bacteria from the

bacteriocidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their p ...

effects of antibiotics. Biofilms usually take 4 weeks to fully mature.

Granulocytes Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that ...

have decreased

phagocytic Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

activity encountering the biofilm, also allowing the bacteria to persist.

Diagnosis

The presence of a PJI is confirmed when one of the proposed major diagnostic criteria are met: * A sinus tract connecting the joint to the skin * Purulence around the prosthesis * Greater than 2000 leukocytes per μL or greater than 70%

granulocytes Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that ...

in joint fluid analysis * The presence of greater than 23 granulocytes per 10 high powered fields on joint fluid analysis (suggesting acute inflammation) * Microbial growth in a culture of the joint fluid, in at least 2 tissue biopsies (or 1 tissue biopsy if the organism identified is highly virulent) collected from the tissue surrounding the artificial joint or greater than 50

colony forming units In microbiology, a colony-forming unit (CFU, cfu or Cfu) is a unit which estimates the number of microbial cells (bacteria, fungi, viruses etc.) in a sample that are viable, able to multiply via binary fission under the controlled conditions. Coun ...

per mL on culture from

sonification Sonification is the use of non-speech audio to convey information or perceptualize data. Auditory perception has advantages in temporal, spatial, amplitude, and frequency resolution that open possibilities as an alternative or complement to vis ...

fluid from the artificial joint. ** Sonification refers to the process where the prosthetic joint is removed from the body, placed in a liquid medium and then bombarded with ultrasound waves to dislodge any microorganisms that are adhering to the artificial joint. The resulting fluid, the sonicate, is then cultured. **Sonification has superior sensitivity to culture of the joint fluid in the diagnosis of PJI

Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

testing of the joint fluid or sonification fluid may aid in the diagnosis. Skin swabs, sinus tract swabs, swabbing of the artificial joint surface during surgery is not recommended due to the high risk of contaminants and low diagnostic yield (including the risk of contaminants rather than the pathologic organism being cultured). Blood cultures are positive in approximately 25% of cases of PJIs, especially in acute PJI, however, the organism isolated from blood culture does not always correlate to the organisms isolated from the joint fluid, and therefore blood cultures are not diagnostic of PJIs. Routine blood work attempting to identify infection including elevated white blood cells on a

complete blood count A complete blood count (CBC), also known as a full blood count (FBC) or full haemogram (FHG), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blo ...

, elevated inflammatory markers (

erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of in ...

and

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...

) or

procalcitonin Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It arises once preprocalcitonin is cleaved by endopeptidase. It was first identified by Leonard J. Deftos and Bernard A. ...

are not sensitive nor specific in diagnosis PJIs.

Plain radiography Projectional radiography, also known as conventional radiography, is a form of radiography and medical imaging that produces two-dimensional images by X-ray radiation. The image acquisition is generally performed by radiographers, and the images ...

(X-ray) has a low sensitivity and specificity for diagnosing PJI but it may show radiolucent lines around the prosthetic joint, bone breakdown, loosening or migration of the prosthetic joint.

Functional imaging Functional imaging (or physiological imaging) is a medical imaging technique of detecting or measuring changes in metabolism, blood flow, regional chemical composition, and absorption. As opposed to structural imaging, functional imaging center ...

tests such as white blood cell

Scintigraphy Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally a ...

PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bloo ...

may help to identify hypermetabolic areas consistent with infection and aid with the diagnosis.

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

is specific to soft tissue infections, with metal artifact reduction sequence (MARS) MRIs having great utility to aid in the diagnosis of PJIs.

Treatment

Antibiotic treatment alone, without surgical debridement, usually results in treatment failure. Acute infections (in which the biofilm is thought to be immature) are usually treated using the DAIR technique;

, systemic and local antibiotics, and implant retention (the implant is not removed). However, the mobile, easily interchangeable components of the implant are often replaced in the DAIR approach. DAIR is contraindicated if there is a sinus tract, loosening of the prosthesis, or the surgical wound cannot be closed. The microbial cure rate of DAIR is 74%, 49% and 44% in early, sub-acute and late infections respectively. Antibiotic loaded

polymethylmethacrylate Poly(methyl methacrylate) (PMMA) is a synthetic polymer derived from methyl methacrylate. It is a transparent thermoplastic, used as an engineering plastic. PMMA is also known as acrylic, acrylic glass, as well as by the trade names and bran ...

(PMMA) which are placed in the joint are helpful, however these non-resorbable beads may themselves be colonized by bacteria with an associated

, therefore bio-absorbable local antibiotic carriers (calcium sulfate beads, resorbable

gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...

sponges) are preferred. Additionally, more recent studies show that bone grafting can be used as an antibiotic carrier, and impacted bone grafting (IBG) impregnated with antibiotics can achieve much higher local concentrations of antibiotics than the minimum inhibitory concentration (MIC). Chronic PJIs may be treated using 1 stage revisions, where the artificial joint is replaced with a new one during the same surgical procedure, or with a 2-stage revision; in which the infected joint is removed and an antibiotic spacer is placed, this is followed by a second surgery in which a new artificial joint is placed. Two step revisions are associated with increased morbidity, longer hospital stays, longer immobilization time, worse functional outcomes and higher costs. Therefore, for intact, or mostly intact bone and soft tissue, and without a history of joint replacement revisions; a 1 step exchange is the treatment of choice. In the case of hip PJIs both kinds of surgery are equally effective but one-stage surgery results in faster recovery.

Negative pressure wound therapy Negative-pressure wound therapy (NPWT), also known as a vacuum assisted closure (VAC), is a therapeutic technique using a suction pump, tubing, and a dressing to remove excess wound exudate and to promote healing in acute or chronic wounds and ...

is not recommended as the sponges used are often themselves colonized by the biofilm or by new organisms from the environment (including multi-drug resistant organisms). An extended course of antibiotics is required in PJIs, usually 6–12 weeks of antibiotic therapy. Intravenous antibiotics are initially used and then transitioned to oral antibiotics. A strategy of surgical debridement to decrease the bacterial load prior to starting systemic antibiotics is sometimes employed. Common practice involves switching to oral antibiotics after 14 days. Intravenous

ampicillin-sulbactam Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and ...

amoxicillin with clavulanic acid Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of ...

with

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...

added in cases of MRSA is a commonly employed empiric antibiotic treatment strategy. If surgery fails or the PJI persists despite optimal antibiotic therapy, resection arthroplasty of the hip with a pseudarthrosis (

Femoral head ostectomy A femoral head ostectomy is a surgical operation to remove the head and neck from the femur. It is performed to alleviate pain, and is a salvage procedure, reserved for condition where pain can not be alleviated in any other way. It is common in v ...

) is sometimes done. Or in cases of knee PJIs failing treatment; an

arthrodesis Arthrodesis, also known as artificial ankylosis or syndesis, is the artificial induction of joint ossification between two bones by surgery. This is done to relieve intractable pain in a joint which cannot be managed by pain medication, splin ...

(artificial induction of ossification of the knee joint) is done. These are considered last line therapies due to significant disability.

Prevention

Antibiotic prophylaxis Antibiotic prophylaxis refers to, for humans, the prevention of infection complications using antimicrobial therapy (most commonly antibiotics). Antibiotic prophylaxis in domestic animal feed mixes has been employed in America since at least 1970 ...

, or giving small doses of antibiotics as a preventative measure, during the perioperative period (usually less than 60 minutes prior to the start of joint replacements)(usually using second generation

cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotic ...

) is believed to reduce the risk of acute PJIs. Screening for and eradication of MRSA carriage and

chlorhexidine Chlorhexidine is a disinfectant and antiseptic which is used for skin disinfection before surgery and to disinfect surgical instruments. It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and ...

wipes or soap and water skin cleansing prior to surgery may possibly decrease the risk of PJIs. According to the

American Dental Association The American Dental Association (ADA) is an American professional dental association. Established in 1859 and with over 159,000 current members, ADA is the world's largest and oldest national dental association. The organization lobbies on behal ...

: in patients with prosthetic joint implants, prophylactic antibiotics prior to routine dental procedures are generally not recommended in the prevention of PJI. However specific circumstances placing patients at higher risk, as determined by the dentist or other physicians, may warrant antibiotic prophylaxis.

Prognosis

The 5-year mortality after hip PJIs is 21%, which is 4 times that of age adjusted controls. And the 10 year mortality after hip PJIs was 45%, as compared to 29% in people with non-infected hip replacements. 25% of people with PJIs have an unplanned re-operation within 1 year of PJI treatment. Hospital stays are longer in those with knee and hip PJIs as compared to un-infected knee and hip replacement controls; at 5.3 vs 3 days (knee) and 7.6 vs 3.3 days (hip).

Epidemiology

PJIs are the most common cause of knee replacement failures, and the third most common cause of hip replacement failures. As of 2017, 2.1% of hip and 2.3% of knee replacements will at some time develop a PJI. The incidence of PJIs have more than tripled in the last 20 years, with the incidence expected to further increase in the future. This increase is believed to be due to the much greater number of hip and knee arthroplasties being performed presently.

References

{{Reflist Orthopedics Complications of surgical and medical care Infectious diseases