Invasive candidiasis

Invasive candidiasis

Invasive candidiasis

Invasive candidiasis, also known as systemic candidiasis, candidemia or deep organ candidiasis, is an infection that is caused by the Candida fungus.

There are two main types of invasive Candida infections (candidiasis):

  • Candidemia – This is the most common kind of invasive Candida and involves Candida infecting the bloodstream which can lead to issues with a number of body parts and internal problems
  • Deep-seated tissue candidiasis – also known as deep-tissue(organ) candidiasis. This involves Candida infecting internal organs and is also known as a deep organ infection.

In some situations, the terms are used interchangeably as most cases of deep-tissue candidiasis coexist or are a result of a previous candidemia infection.

In order to get a thorough understanding of invasive candidiasis, we will first look at what the condition is as a whole and then go into further detail on the two main types of infection.

The difference between the previously mentioned Candida infections and invasive candidiasis, is that the oral and genital infections are viewed as surface level or superficial conditions and are also the most common infections of the Candida yeast, whereas invasive candidiasis, which comprises of both candidemia and deep-organ candidiasis, are far more severe infections with high mortality rates.

Candidemia has previously been associated with increased hospital stays for patients previously admitted for other underlying conditions (these patients are often infected during their stay in hospital due to their immune systems being compromised) and higher mortality rates and is the most widespread kind of invasive candidiasis. Deep-seated candidiasis is often associated with or secondary to candidemia and despite its severity, little is known about the condition.

Candidemia occurs when Candida enters a patient’s bloodstream, normally via medical equipment during surgery. However, unlike the previously mentioned Candida infections of the throat and mouth (oral thrush) or genital infections (vaginal yeast infections), this form of Candida is a severe infection that is systemic as it may affect the blood, brain, heart, bones, eyes and a number of other body parts of the patient. Candidemia is an infection of the bloodstream with Candida that usually occurs in hospitalised patients.

This is also the case for those who have recently been in hospital or in a healthcare facility like that of a nursing or old-age home. As with other yeast infections, an individual’s risk of this infection developing is increased if they have a weakened immune system, are diabetic, suffer from kidney failure or are taking antibiotics.

Typically, the person who has the infection is already sick with another condition, making the diagnosis more difficult as the symptoms can be misleading. The condition is normally treated orally or intravenously through the use of antifungal medications.

Invasive candidiasis infections encompass a number of different types of severe infections. As stated, there is normally an underlying problem or risk factor such as:

  • The immune system being compromised (immunocompromise)
  • Abdominal surgery
  • Critical illness

Candidiasis that is invasive is often life-threating with a mortality rate as high as 40%.

Diagnosis of invasive candidiasis

It is important that the condition is diagnosed in the initial stages as patients who suffer from the infection over a longer period of time can suffer from further risks and complications.

Antifungal therapy should typically be started if a patient who is at risk has a persistent fever lasting or more than four days despite the use of antibiotics.

The following tests are used in the diagnosis of invasive candidiasis:

Culture tests

  • Blood culture tests can be conducted to detect the presence of Candida overgrowth, however, the results from these tests can often take some time. Fungus can take as long as 30 days to show up. In some cases, the results will be available within a few days. Blood tests are the most common form of diagnosis regarding invasive candidiasis.
  • Culture tests can also be done of the infected tissues or bodily fluids. Here a sample is taken to be examined for fungal infection.
  • A number of rapid tests can also be performed. These are known as rapid diagnostic tests (RDT) that are easy and quick to perform as they are able to detect the antigens associated with candida overgrowth that are present in the blood.

Blood test

Screening tests

  • A CT (computed tomography) scan or an ultrasound can be conducted to detect any abdominal or renal infections.
  • An echocardiography (also known as a cardiac echo) can be conducted to create images of the heart. This is used when cardiac involvement in the infection is suspected.

Other tests

  • An endoscopy can also be conducted to check for intestinal infections (this will be done by means of a biopsy).

Treatment of invasive candidiasis

The type and the dose of the antifungal medication that is used as treatment for invasive candidiasis will depend on the age and immune status of the patient, as well as the severity and location of the infection. Antifungal medication will be the drug of choice in most cases. The most well-known antifungal drug is echinocandin which includes the following brands:

  • Micafungin
  • Anidulafungin
  • Caspofungin
  • Fluconazole

Duration of treatment for invasive candidiasis

In the case of candidemia, the treatment will typically continue for a duration of two weeks and the symptoms have been resolved, with the Candida yeasts no longer being detected in the blood stream. Deep organ candidiasis will normally be treated for a much longer period. 

Types of invasive candidiasis

Candidemia

As previously stated, Candida typically lives on the skin or in the GI (gastrointestinal tract) and does not cause any issues in most people. However, in some cases Candida is able to enter one’s bloodstream and result in a severe infection.

Candida in the bloodstream is the most common kind of invasive candidiasis and is known as candidemia. This condition often results in the patient undergoing lengthy hospital stays with high doctor and medical costs. The prognosis of this infection is often poor as the options of treatment are lacking in their abilities to yield effective treatment.  

The bloodstream infection is often the result of:

  • Major surgery
  • Central venous catheters
  • Broad-spectrum antibiotics
  • IV hyperalimentation – nutrients are administered via a drip
Who is at risk of candidemia?

Healthy individuals very rarely get candidemia. It is commonly found in those who have a current health issue that leads to the suppression of the immune system as this predisposes them to the development of this severe and dangerous infection.

Candidemia is known as one of the most common kinds of infection in people who are currently undergoing hospitalisation for an intestinal surgery or organ transplant. Seeing as the Candida yeast naturally resides on the surface of the skin in the majority of people, if the skin is punctured in some way, this provides the fungus with a direct entry point into the bloodstream. In the case of patients undergoing a central venous catheter, the risk of this infection developing is heightened. A central venous catheter is a tube that is inserted into a main blood vessel for it to deliver certain medications, nutrients or chemotherapy directly to the patient, this creates a route for the fungus as it enters the bloodstream from the skin.

Candidemia may also infect patients who suffer from a weakened immune system that can be due to a number of causes such as ongoing chemotherapy or an organ transplant. Those who have undergone a high dosage of prophylactic broad-spectrum antibiotics in order to rid their body of a certain bacterial antigen are also at risk as this provides Candida with an environment in which to multiply and infect the body. As well as this, those who have received mass doses of corticosteroids (often used to treat asthma) are vulnerable to infection. Finally, candidemia may occur in those who suffer from severe diabetes or have an HIV infection.

Treatment for candidemia

The treatment of candidemia can be complicated as the infection progresses and begins to infect some of the organs such as the eyes, brain, heart and kidneys. The most common kind of Candida species, Candida albicans were originally linked to the development of candidemia. However, recently Candida parapsilosis and Candida glabrata have been causing more infections, some of which have also been noted to be resistant to a number of the most widely used antifungal medications like the Azole drugs.  

The popular antifungal drugs that are usually used for candidemia treatment are:

  • Azoles
  • Echinocandin
  • Polyenes

The medication chosen will depend on the health and age of the patient and the species of Candida causing the infection.

Symptoms for candidemia

An issue with diagnosing candidemia comes in with the lack of exclusive or specific symptoms. However, a few of the symptoms such as chills and fever, as well as general weakness and fatigue are generally associated with the majority of systemic infections.

Patients with candidemia can also suffer from the following:

  • Skin rashes
  • Abdominal pain
  • Muscle aches
  • Vision changes
  • Loss of vision
  • Sustained headaches
  • Other neurological issues

Deep-seated tissue candidiasis

Please note that deep-seated tissue candidiasis is also known as deep-seated candidiasis and deep-organ candidiasis, the terms will be used interchangeably in the information that follows.

Invasive candidiasis is comprised of both candidemia and deep-seated tissue candidiasis. Deep-seated candidiasis is a result of either hematogenous dissemination (spread by the bloodstream) or the direct inoculation of the Candida species to a sterile site, for example, the peritoneal cavity (the space between the abdominal wall and the adjacent abdominal organs).

This kind of candidiasis also infects those who are predisposed through the means of an underlying condition, the immune system being compromised in some way is a leading cause.

Deep-seated tissue candidiasis is something that is being seen more and more in ICUs where patients are severely ill and are therefore predisposed to the condition. It is vital that more research is done on this type of invasive candidiasis as many patients are being misdiagnosed and are often left untreated which can result in the fungal infection progressing, which can, in some cases, end the patient’s life due to the severity of the infection.

Patients in ICU

What is known, and what helps to put this condition into perspective, is that all known episodes of deep-seated candidiasis coexist with or are preceded by candidemia. Bear in mind that as more research is done and more cases are accurately diagnosed and reported, the more information there will be available with more accurate findings.

In both types of invasive candidiasis, the Candida species is seen as an opportunistic pathogen that results in severe infections. As previously mentioned, vaginal and oropharyngeal candidiasis are viewed as ‘superficial’ kinds and do not compromise the survival of the patient. Whereas invasive candidiasis can be life-threatening.

Regardless of the severity of deep-seated candidiasis, apart from the fact that the occurrence of the condition is similar to that of candidemia, very few sources describe deep-seated candidiasis in detail, what is known, however, is that it can be present in any organ, sterile tissue or organ space.

Due to the diagnosis being difficult (diagnosis entail biopsies of the infected areas or blood tests), the estimates regarding the prevalence of the infections are lacking in reliability. Because of this, deep-seated candidiasis can be a condition that is severely underestimated in ICUs (where patients are critically ill and have their immune systems compromised).

Who is at risk of deep-seated tissue candidiasis?

Seeing as the majority of the cases of deep-seated tissue candidiasis have a co-existing or previous candidemia infection, the risk profile for a patient is very similar to that of candidemia. Since candidemia is not a specific clinical entity, the risk probability of a patient is vital for identifying their chance of developing the condition. If a patient undergoes a prolonged stay in ICU, being between seven to ten days, this is one of the highest and most vital risk factors for diagnosis as the condition is seen predominantly in those who are recovering from surgery or another condition in ICU.

The below is a list of risk factors:

  • Previous administration of broad-spectrum antibiotics
  • Abdominal surgery
  • Corticosteroid therapy
  • Previous Candida infection (colonisation) in multiple sites on the body
  • Multiple lumen catheters
  • Peritonitis (inflammation of the lining between the abdominal wall and the covering of the abdominal organs)
  • Use of corticoids or parenteral nutrition
  • Chemotherapy
  • Neutropenia (abnormally low white blood cell count – these form a part of the functioning of the immune system in being able to fight off infections)
Treatment for deep-seated tissue candidiasis

The treatment for deep-seated tissue candidiasis will require an individualised approach for each case. Therefore, the site of infection or the manifestation of the condition will involve antifungal therapy, with the dose and duration of it depending on the type of infection present. These drugs are likely to be administered intravenously or orally and can include brands in one of the following classes of drugs:

  • Azoles
  • Echinocandins
  • Polyenes – The medication known as amphotericin B is a common kind of polyene drug.

There are a number of side effects of the majority of the above systemic antifungal drugs. These can include nausea, vomiting, hepatitis, headaches, kidney- toxicity and even lupus-like symptoms (this is an autoimmune, inflammatory condition wherein the immune system will attack its own tissues resulting in joint pain, fatigue and sometimes brain fog).

Removal of the infection source such as a device (i.e. a catheter) or a drug that is compromising the immune system should also be stopped.

In some cases, surgical debridement (wherein the site of infection is removed) may also be required.

Symptoms of deep-seated tissue candidiasis

The symptoms of deep-seated tissue candidiasis are dependent on the site infected, with the treatment protocols following from this. Thus, each case is different with different symptoms, and the site of infection dictates the physical symptoms.  Some of the symptoms can include:

  • Dysphagia – This is a condition that involves drooling, having a hoarse voice, suffering from heartburn, having pain or difficulty swallowing or regurgitating food.
  • Mucosal and skin lesions
  • Fever
  • Renal shutdown
  • Brain fog – This is also known brain fatigue and may involve moderate to severe episodes of the patient suffering from mental confusion occurring without warning. This often results in a lack of focus, reduced mental ability and poor memory. This condition is often linked to the treatment of Candida with antifungal medications and is also associated with the lupus-like symptoms. Brain fog is typically linked to Candida albicans and Candida die-off during treatment.
Diagnosis for deep-seated tissue candidiasis

It is often difficult for deep-seated candidiasis to be accurately diagnosed, this is due to the blood cultures having a low sensitivity, meaning the results are not always accurate or able to detect the fungus, therefore not all the cases of invasive candidemia are detected.

The issue with deep-seated tissue candidiasis comes in with colonisation (the organisms have spread without causing an infection yet) as patients are often heavily colonised, particularly when they have been treated with broad-spectrum antibiotics. This means that it is difficult to differentiate between infection and colonisation. The infection of Candida, known as candidiasis, is normally secondary to colonisation.

Antifungal treatment is normally the chosen route in combatting the condition, with early diagnosis and accurate treatment associated with a more positive prognosis. Therefore, the diagnosis is dependent on the lab findings from blood and culture tests, however, at present, there is a vital need for more specific markers to be developed in order to make a more accurate diagnosis.

Infection sites of deep-seated tissue candidiasis

Due to deep-seated tissue candidiasis coexisting with or evolving from candidemia, roughly 80% of candidemia cases arise from the fungi having vascular access which often involves the use of central venous catheters. The primary source of entry of candidemia in patients who are non-neutropenic (i.e. who have a normal amount of white blood cells) and develop deep-seated tissue candidiasis may be that of an infected intravenous catheter or infusion fluid being contaminated. However, the peritoneal cavity being infected can also occur after abdominal surgery or trauma.

**My Med Memo – An intravenous catheter is a small, flexible tube that is inserted into a peripheral vein in order for fluids or medication to be administered. A central venous catheter, also known as a central line, is a thin, long and flexible tube that is used over a longer period of time to give fluids, nutrients and blood to the patient, usually when hospitalised.

It is believed that an infected organ is linked to the site that the haematogenous dissemination took place (i.e. the place from which the fungus entered the blood stream and spread) and whether the patient has adequate bone marrow functioning. The bone marrow is responsible for producing the body’s blood cells. White blood cells are involved in the ability of the immune system to protect the body.

Patients who are non-neurotropic and develop deep-seated tissue candidiasis after having abdominal surgery or have had IV catheter-induced phlebitis (trauma to the vein), tend to have myocardial (heart), renal, cerebral (brain), ocular (eyes) and pulmonary (lungs) involvement. Infections of spleen and liver are unusual in these types of patients. Any organ can be contaminated, colonised (where the fungus will spread without causing infection as yet) or infected by Candida.

Some of the most commonly seen infections in ICUs are briefly described below:

  • Gastrointestinal tract, spleen, liver and peritoneum

These infection sites can originate from the Candida fungus moving across the bowel wall, this movement is often facilitated by the decreased functioning ability of the mucosal barrier which is often the case in patients in the ICU.

The GI (gastrointestinal tract) infection of candidemia is often seen in patients who have leukaemia (cancer of the blood).  Candida peritonitis (inflammation of the lining between the abdominal wall and the covering of the abdominal organs), is often seen as a result of a bowel perforation from surgery or trauma.

  • Lung and trachea

Some patients may suffer from fungal pneumonia, although this is very rare. Therefore, Candida pneumonia is not seen very often and is mainly caused by the infection being carried by the blood to the organs (i.e. via haematogenous dissemination). It is often difficult for trachea and lung infections to be diagnosed as screening tests such as CT (computerised tomography) scans cannot be conducted in an ICU and require the patient to be moved.

  • Urinary tract

In as many as 20% of patients in the ICU, Candida has been seen to be isolated in the urinary tract mainly due to bladder catheterisation. Candida infecting the bladder and kidneys is known as Candida pyelonephritis. 

  • Cardiovascular candidiasis

This kind of infection infects the cardiovascular system. If Candida infects the heart, known as Candida myocarditis, it may be compromised by very subtle alterations in the muscle’s functioning, this makes it difficult to detect Candida in the heart. Candida infecting the heart valve, known as Candida endocarditis, has become a real threat to patients who have recently undergone cardiac surgery, specifically when prosthetic valves have been inserted. Endocarditis is the swelling of the heart valve.

  • Central nervous system

Candida meningitis has been seen to affect those who have HIV, neonates (infants) or those who have had neurosurgery (surgery involving the nervous system which includes the brain, nerves and spinal cord). This has a high mortality rate and is often only detected in a post-mortem.

  • Eye

If deep-seated candidiasis infects the eye is can present itself as endophthalmitis and chorioretinitis (inflammatory conditions of the eye). An ophthalmoscopy will need to be conducted that allows the doctor to take a look into the structures of the eye through the use of an ophthalmoscope which is a viewing device with various lenses and a light attached 

On a final note

Deep-seated candidiasis can manifest in a number of different infection sites. Due to the diagnosis being difficult, it is often misdiagnosed or underdiagnosed. On the one end of the scale, this finding presents a threat due to delayed diagnosis and treatment with the appropriate kind of antifungal therapy. On the opposite end, due to the condition being seen in more clinical settings, this can also lead to the over-prescription of antifungal drugs.

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