About
Learn More
Resource for Patients
What is PJI?
▼
Replacement of joints with a prosthesis can occur because of certain fractures and injuries, and general degeneration of the joint and joint cartilage because of illness, medications and age-related wear and tear. When cartilage in peoples’ joints such as knees or hips wear out, it can be very painful, as bone rubs on bone without any cushioning and have a high impact on the movement. This may be movement needed for work, leisure activities, exercise or to do daily activities such as home and self-care.
One way to help restore joint function and lessen pain, is to replace the degenerated joint with a prosthetic or artificial joint. The artificial joint is made of metal or ceramic material and is usually lined with a special type of plastic called polyethylene.
The operation is called a “joint replacement” or “arthroplasty”. This operation is done for fixing both knees and hips.
In most cases these operations are very successful, and the artificial joint can last for many years. There about one million people in Australia walking around with a joint replacement, and a similar number in many other countries of the world.
However, in a small number of people, about 1-3% after a joint replacement, the artificial joint gets infected – we call this a “prosthetic joint infection” or PJI for short. PJI is defined as an infection caused by the presence of a microorganism (germ) growing in and on a joint prosthesis (artificial joint) and the adjacent tissue. It is also referred to as a periprosthetic infection.
This can happen in the weeks and months after the replacement surgery and can also occur many years after surgery. A PJI is quite debilitating and can cause pain, swelling, and stiffness of the joint.
These infections are harder to cure than most infections because the artificial joint is a foreign body with no blood supply of its own. This means that antibiotics and the immune system can’t always kill the germs causing the infection. These germs have an ability to stick onto and hide on the plastic, metal or the bone around the artificial joint. They can form a thin layer or coating which is called a biofilm. This biofilm acts as a sanctuary for the germs. A place for the germs to hide and continue to grow. Making it hard to both treat and completely kill.
One way to help restore joint function and lessen pain, is to replace the degenerated joint with a prosthetic or artificial joint. The artificial joint is made of metal or ceramic material and is usually lined with a special type of plastic called polyethylene.
The operation is called a “joint replacement” or “arthroplasty”. This operation is done for fixing both knees and hips.
In most cases these operations are very successful, and the artificial joint can last for many years. There about one million people in Australia walking around with a joint replacement, and a similar number in many other countries of the world.
However, in a small number of people, about 1-3% after a joint replacement, the artificial joint gets infected – we call this a “prosthetic joint infection” or PJI for short. PJI is defined as an infection caused by the presence of a microorganism (germ) growing in and on a joint prosthesis (artificial joint) and the adjacent tissue. It is also referred to as a periprosthetic infection.
This can happen in the weeks and months after the replacement surgery and can also occur many years after surgery. A PJI is quite debilitating and can cause pain, swelling, and stiffness of the joint.
These infections are harder to cure than most infections because the artificial joint is a foreign body with no blood supply of its own. This means that antibiotics and the immune system can’t always kill the germs causing the infection. These germs have an ability to stick onto and hide on the plastic, metal or the bone around the artificial joint. They can form a thin layer or coating which is called a biofilm. This biofilm acts as a sanctuary for the germs. A place for the germs to hide and continue to grow. Making it hard to both treat and completely kill.
PJI Treatments
▼
An infection in prosthetic or artificial joint called a prosthetic joint infection (PJI) are usually treated with a combination of surgery and antibiotics. These treatments are used to help clean the joint and to fight and kill the germ causing the infection.
Surgical Treatments
▼
DAIR: One of the most common types of surgery used for a PJI is called “debridement, antibiotics, and implant retention surgery” or “DAIR” for short. In a “DAIR” operation, after the patient is anaesthetised, we open the affected joint space and clean out as much of the infection as we can but leave the original artificial joint in place. Cleaning out all pus and infected tissue or bone is called “debridement”. Easily removable parts of the artificial joint are often replaced with new ones, but we leave most of the artificial joint in place. That is why it is called “implant retention”.
REVISION: The other common type of surgery is called a “revision”. Like a DAIR, in a revision, we open and clean out the joint space, but instead of leaving the artificial joint in place, we remove all the components of the prosthesis and replace them with new ones.
This type of surgery can be done in one stage (the old one is removed, and the new one is put in at the same operation), or in two stages. In a two-stage revision, the infected artificial joint components are removed and replaced with a temporary joint replacement made of special medical cement containing antibiotics, this is the 1st stage of the operation. The 2nd stage can happen weeks to months later, at this 2nd stage operation the temporary joint is removed, and a new permanent artificial joint is implanted.
Whether it’s a one stage or a two-stage revision, the main feature of a revision is that the infected artificial joint is completely removed, but in a DAIR it is left in place.
There are pros and cons to each of these operations.
A DAIR takes a shorter time for the surgeon to do and may have a lower chance of complications such as bleeding. However, it can also have a lower chance of completely killing the germ and curing the infection. This is because some bacteria can hide on and in the artificial joint that is left in place.
A revision operation, where the old joint is replaced with a new one, is thought to have a higher chance of getting rid of the infection completely, but this might require an extra operation and might have a higher chance of complications.
The surgical treatments commonly used are not new and all have been proven to be effective for PJI. However, we don’t know for sure which type of surgery is best or more effective which is why the ROADMAP trial is comparing treatments for PJI.
REVISION: The other common type of surgery is called a “revision”. Like a DAIR, in a revision, we open and clean out the joint space, but instead of leaving the artificial joint in place, we remove all the components of the prosthesis and replace them with new ones.
This type of surgery can be done in one stage (the old one is removed, and the new one is put in at the same operation), or in two stages. In a two-stage revision, the infected artificial joint components are removed and replaced with a temporary joint replacement made of special medical cement containing antibiotics, this is the 1st stage of the operation. The 2nd stage can happen weeks to months later, at this 2nd stage operation the temporary joint is removed, and a new permanent artificial joint is implanted.
Whether it’s a one stage or a two-stage revision, the main feature of a revision is that the infected artificial joint is completely removed, but in a DAIR it is left in place.
There are pros and cons to each of these operations.
A DAIR takes a shorter time for the surgeon to do and may have a lower chance of complications such as bleeding. However, it can also have a lower chance of completely killing the germ and curing the infection. This is because some bacteria can hide on and in the artificial joint that is left in place.
A revision operation, where the old joint is replaced with a new one, is thought to have a higher chance of getting rid of the infection completely, but this might require an extra operation and might have a higher chance of complications.
The surgical treatments commonly used are not new and all have been proven to be effective for PJI. However, we don’t know for sure which type of surgery is best or more effective which is why the ROADMAP trial is comparing treatments for PJI.
Antibiotic Treatments
▼
Antibiotics are commonly used to treat infections and can be given for different periods of times and as needed to kill the germs that are causing the infection. Antibiotics come in many forms and can be given as an intravenous drip or tablets and capsule. When antibiotics are used to treat PJI they will be often given whilst the patient is in hospital and delivered via an antibiotic intravenous drip. After a few days or weeks these will be changed over to antibiotic tablets or capsules, which the patient can take by mouth.
The type of antibiotic, or combination of antibiotics that are used are chosen based upon the type of infection and based on what germs are causing the infection, what antibiotics the laboratory results show kill the germs. In choosing antibiotics, patient medical history including any antibiotic allergies, reactions or preferences are also considered. Commonly used antibiotics include vancomycin, cefazolin and flucloxacillin but there are many others.
In PJI, an antibiotic called “rifampicin” is often used as part of the antibiotic treatment plan in combination with other antibiotics to cure PJI infections. Lab experiments using bacteria on agar plates and in animals with infections suggest that rifampicin may be better than other antibiotics to kill the germs in or on an artificial joint. There have been two small past randomised clinical trials of rifampicin for prosthetic joint infection – one showed that rifampicin worked better than other antibiotics, and the other showed no benefit of adding rifampicin. The ROADMAP trial will systematically look at the use of Rifampicin in addition to other antibiotics in a large, randomised trial to answer the question about whether the use of rifampicin is beneficial.
The type of antibiotic, or combination of antibiotics that are used are chosen based upon the type of infection and based on what germs are causing the infection, what antibiotics the laboratory results show kill the germs. In choosing antibiotics, patient medical history including any antibiotic allergies, reactions or preferences are also considered. Commonly used antibiotics include vancomycin, cefazolin and flucloxacillin but there are many others.
In PJI, an antibiotic called “rifampicin” is often used as part of the antibiotic treatment plan in combination with other antibiotics to cure PJI infections. Lab experiments using bacteria on agar plates and in animals with infections suggest that rifampicin may be better than other antibiotics to kill the germs in or on an artificial joint. There have been two small past randomised clinical trials of rifampicin for prosthetic joint infection – one showed that rifampicin worked better than other antibiotics, and the other showed no benefit of adding rifampicin. The ROADMAP trial will systematically look at the use of Rifampicin in addition to other antibiotics in a large, randomised trial to answer the question about whether the use of rifampicin is beneficial.
Antibiotic Duration
▼
Antibiotics work by killing the bacteria or germ that’s causing an infection, it can take different times to achieve this goal. Antibiotics may also be given as a prophylactic or preventative treatment to help reduce the risk of infection due to medical history or surgery.
When surgery is performed to help treat and cure PJI, it is common for antibiotics to be prescribed. These can be prescribed post-surgical treatment and in-between surgeries if multiple surgeries are planned. The duration of how long antibiotics need to be given is not clear with some people taking short courses of antibiotic over a few days to six weeks and other over extended periods of 12 weeks and more if needed.
If you have a two-stage operation, it is common to give at least six weeks of antibiotics between the first stage operation and the 2nd stage where a new artificial joint is put in. Sometimes there might be several months between the first and second stage. The time between the operations and the duration of antibiotics between the two stages will be decided by your treating Doctors based on the type of surgery you have had, the number of surgeries that are planned and based on your medical history and history of past infections.
When surgery is performed to help treat and cure PJI, it is common for antibiotics to be prescribed. These can be prescribed post-surgical treatment and in-between surgeries if multiple surgeries are planned. The duration of how long antibiotics need to be given is not clear with some people taking short courses of antibiotic over a few days to six weeks and other over extended periods of 12 weeks and more if needed.
If you have a two-stage operation, it is common to give at least six weeks of antibiotics between the first stage operation and the 2nd stage where a new artificial joint is put in. Sometimes there might be several months between the first and second stage. The time between the operations and the duration of antibiotics between the two stages will be decided by your treating Doctors based on the type of surgery you have had, the number of surgeries that are planned and based on your medical history and history of past infections.
Antibiotic Side Effects
▼
Most people don’t get any side effects from antibiotics as they are generally safe, but occasionally people do. The most common side effect can be indigestion, nausea, and diarrhoea. Other rare reactions include low blood counts, and irritation to the veins, liver or kidneys, and allergic reactions, such as rash. Giving longer courses of antibiotics may mean it is more likely for you to develop side effects, but this is not always the case.
Doctors can help to manage these side effects if they do occur, management may involve changing the antibiotic type, changing the time the antibiotic is taken and whether it is taken with food or not. In some cases, other medications can be given to help with nausea and diarrhoea. It is important to keep your treating Doctors informed about any reactions so they can offer some help.
Doctors can help to manage these side effects if they do occur, management may involve changing the antibiotic type, changing the time the antibiotic is taken and whether it is taken with food or not. In some cases, other medications can be given to help with nausea and diarrhoea. It is important to keep your treating Doctors informed about any reactions so they can offer some help.
Adaptive Platform Trials
▼
Randomised controlled trials (RCTs) are the gold-standard method for generating evidence to show benefits of new therapies or interventions. The limitations to traditional RCTs are that they can be slow to answer questions and are limited to the number of questions they are able to answer. To address some of the limitations of traditional RCTs, adaptive platform trials (APTs) have been developed.
APTs aim to answer multiple questions in a disease area through an established infrastructure and the use of a master protocol. As the trial progresses, APTs are designed to analyse accumulating data at specific intervals as patients are enrolled. The interim analyses are used to determine if there is sufficient data to say the question being looked at has been answered (according to the pre-defined rules), this may be when the intervention is superior, no different or inferior to the standard treatment (or the control). Interventions that are shown to be better than the current standard treatment can then become the control and new interventions can be included in the trial.
APTs can also include other within-trial adaptation to increase their efficiency. Traditional RCTs will randomise patients to a pre-defined ratio of control to intervention (often this is 1:1). APTs can pre-specify the use of response-adaptive randomization (RAR), whereby if a treatment appears to be performing better in the interim analyses, more patients can be randomised to this arm. Bayesian statistical modelling can also be used to analyse the data accumulated and to give better estimates of the outcomes by considering data that has been collected to that point and any prior data available.
The infrastructure developed for APTs can continue to enrol patients if there are ongoing research questions to answer. In traditional RCTs, the sample size is calculated before the study begins recruitment and is based on the estimated effect of the intervention. This sample size could be underestimated and result in the trial enrolling insufficient patients to answer the question or could be overestimated, which means the trial could have answered the question earlier and saved considerable time, money and potentially patients being exposed to an inferior treatment. In contrast, APTs have the capacity to stop recruitment to interventions once a stopping rule is met, or to keep enrolling until such a stopping rule is met. APTs also have the capacity to have continuing enrolment if new research questions become apparent, such as when a new treatment has become available since the trial was initiated.
APTs aim to answer multiple questions in a disease area through an established infrastructure and the use of a master protocol. As the trial progresses, APTs are designed to analyse accumulating data at specific intervals as patients are enrolled. The interim analyses are used to determine if there is sufficient data to say the question being looked at has been answered (according to the pre-defined rules), this may be when the intervention is superior, no different or inferior to the standard treatment (or the control). Interventions that are shown to be better than the current standard treatment can then become the control and new interventions can be included in the trial.
APTs can also include other within-trial adaptation to increase their efficiency. Traditional RCTs will randomise patients to a pre-defined ratio of control to intervention (often this is 1:1). APTs can pre-specify the use of response-adaptive randomization (RAR), whereby if a treatment appears to be performing better in the interim analyses, more patients can be randomised to this arm. Bayesian statistical modelling can also be used to analyse the data accumulated and to give better estimates of the outcomes by considering data that has been collected to that point and any prior data available.
The infrastructure developed for APTs can continue to enrol patients if there are ongoing research questions to answer. In traditional RCTs, the sample size is calculated before the study begins recruitment and is based on the estimated effect of the intervention. This sample size could be underestimated and result in the trial enrolling insufficient patients to answer the question or could be overestimated, which means the trial could have answered the question earlier and saved considerable time, money and potentially patients being exposed to an inferior treatment. In contrast, APTs have the capacity to stop recruitment to interventions once a stopping rule is met, or to keep enrolling until such a stopping rule is met. APTs also have the capacity to have continuing enrolment if new research questions become apparent, such as when a new treatment has become available since the trial was initiated.
