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  • Writer's pictureDr. Koralla Raja Meghanadh

Mucormycosis/black fungus treatment – Amphotericin B injection, Isavuconazole, Posaconazole

Updated: May 2, 2023


Mucormycosis or black fungus is a disease that spreads aggressively and requires treatment aggressively.


Mucormycosis comes under the fulminant type of fungal sinusitis, which comes under invasive fungal sinusitis. It is a super fast express version of invasive that spreads through the blood vessels. Mucormycosis's initial symptoms and Invasive fungal sinusitis symptoms are the same, but the pace at which symptoms develop in black fungus is fast that it is easy to differentiate them.


Treatment on suspicion

When a patient comes in with at least one symptom of mucormycosis, an ENT doctor performs a nasal endoscopy. If he finds a black material inside the nose, he will immediately scrape it and send it for culture and biopsy. Without waiting for the test results to confirm, he will start with the test dose of Amphotericin B or Isavuconazole and proceed further, assuming that the patient has mucormycosis. The antifungal medication will curb the fungus growth. Waiting for the test results can alter the patient's fate due to the rapid growth of fungus.


For normal invasive fungal sinusitis, Dr. K. R. Meghanadh suggests antifungal medication even if takes years to heal. He would not opt for debridements even in extreme cases of invasive fungal sinusitis. But, the progress of the fulminant disease is so fast that he goes on a full-on aggressive mode with the treatment that will consist of extensive debridements.


Mucormycosis/black fungus treatment


Black fungus treatment involves two steps.

  1. Debridement surgery

  2. Treatment with antifungals

The antifungal treatment and debridements should go hand in hand to save the patient.


Skipping either debridements or antifungal treatment is not an option.

Debridements


What is debridement?

The fungus attacks tissue and starts eating the tissue, and replaces the tissue. As much as possible fungus-infected tissues and tissues that are replaced with fungus must be removed by surgery.

debridement, black fungus treatment, treatment of mucormycosis, mucormycosis treatment, amphotericin b injection

The surgical procedure to remove infected tissues is called debridement.

What tissues need to be removed for the treatment of mucormycosis

Suppose the fungus attacks the tissue, but the tissue is viable( the tissue is attacked by the fungus but still working and not yet eaten up by fungus and still has a blood supply and nerves working), then this type of tissue needs treatment with antifungals through intravenous root or tablets. A surgeon will not remove the viable infected tissues.


However, suppose the infected tissue is not vital, a doctor might choose to remove the non-vital tissue even if it is partially or even doubtfully infected. This removal could decrease the unnecessary fungal load.


Debridements might include removal of eyes and jaw bone too.


Why do we need debridements?

Why are debridements important in treating black fungus?

The antifungals used for the treatment of mucormycosis are potent. They can have severe side effects on the human body compared to other drugs.


The quantity of antifungal medication given to the patient is directly proportional to the amount of fungus in the body.


So, the amount of fungus left out in the body during debridement will determine the dosage of antifungals.


So, debridements need to be done carefully for the best results.


How many surgeries or debridements will be required for black fungus treatment?

Any ENT surgeon or doctor can not give you an exact number of surgeries required for a particular patient. It depends on the patient’s immunity, doctor’s skill, experience, and patient’s luck.


As per Dr. K. R. Meghanadh, a minimum of 3 surgeries will be required for a patient, and the number can go up from there with no limit. The highest number of debridement surgeries Dr. K. R. Meghanadh has done on a patient is 20. In the future, this number could go higher.


After an adequately done surgery, the remaining fungus will replace the leftover infected tissues and spread to new tissues after 2 to 3 days while giving antifungal medication and also till the critical effective dose of antifungal medication is attained.


So, the treatment involves multiple debridements done every day or on alternate days to remove the growing infection.


If the infection gets under excellent control, the debridement can be done once in 3 to 4 days.


Antifungal treatment for black fungus

Depending on a patient’s immunity, mucormycosis can double up in a few hours. Potent antifungals can only control this rapid growth.


As mentioned in the above section, the partially infected working vital tissues left out in the debridement procedure also must be treated with antifungals.


We do have many antifungals available. However, all do not have action on the mucormycosis infection.


The antifungals that can be used for the treatment of black fungus are

  1. Amphotericin B

  2. Isavuconazole

  3. Posaconazole

All the 3 antifungal medications have different mechanisms of action.


Amphotericin B Injection

Treatment using Amphotericin B is the gold-standard treatment for mucormycosis and is available only in injection form.


To treat the patient judiciously and choose the right medicine, a doctor needs to know the fundamentals of different Amphotericin B compounds and their mechanism of action.


How is Amphotericin made?

Amphotericin is a naturally occurring substance formed by a bacteria called Streptomyces nodosus.


Amphotericin has the property of killing a majority of the fungi.


There are many variants of Amphotericin. The raw product obtained from Streptomyces nodosus is a mix of all the variants.


The Amphotericin obtained from Streptomyces nodus bacteria consists of many types of Amphotericin. This raw Amphotericin mixture is harmful to the human body.


Types of Amphotericin

There are many variants of Amphotericin called Amphotericin A, Amphotericin B, Amphotericin C, Amphotericin X, etc.


Amphotericin B is very active against fungi and can help humans fight a fungal infection.


However, Amphotericin C and Amphotericin X are the ones that are toxic to the human body.

Amphotericin A is ineffective.


How is Amphotericin B derived?

Streptomyces nodosus bacteria produce natural Amphotericin that contains Amphotericin B and other variants of Amphotericin. Amphotericin C & Amphotericin X are toxic to the human body and hence need to be filtered out along with the ineffective Amphotericin A.


Lyophilization is the process used to filter out other variants of Amphotericin B out of raw Amphotericin.


The quality of the final product, i.e., Amphotericin B, entirely depends on the lyophilization process.


The side effects of the medicine are directly proportional to the purity of the Amphotericin B given.


The purity varies from company to company and batch to batch. Per the law, filtered Amphotericin B needs to be 99% pure, but few brands sometimes achieve 99.9% purity.


The batch with 99.9% purity, if used to make Amphotericin B Deoxycholate, gives the best results for most patients.


Types of Amphotericin B compounds and their mechanism of action


Multiple compounds are made with filtered Amphotericin B obtained from actinomycete Streptomyces nodosus’ produce.


We have mainly three types of Amphotericin B compounds

  1. Amphotericin B Deoxycholate (AMBDOC) or Conventional Amphotericin B

  2. Amphotericin liposomal

  3. Amphotericin B lipid complex


Amphotericin B Deoxycholate or AMBDOC or Conventional Amphotericin B

Amphotericin B Deoxycholate (AMBDOC), or Conventional Amphotericin B, is a pure form of Amphotericin B combined with deoxycholate salt.


AMBDOC would be the most effective for fulminant fungal infection treatment among the available options if Amphotericin B used to make the compound is in its purest form.

Amphotericin B Deoxycholate or Conventional Amphotericin or AMBDOC - mucormycosis treatment

Conventional Amphotericin B dosage

A test dose must always be given to the patient and then offered at a dose of 1 to 2 milligrams per kilogram of body weight, up to a cumulative dose of 1.5 to 3 grams per kilogram, depending on how much fungus is left out in the tissues after series of debridements.


Conventional Amphotericin b side effects

There could be side effects like reduced hemoglobin, calcium, and potassium. Patients can often have a fever, chills, vomiting sensation, and loose motions that need to be corrected by additional medication.


The way Amphotericin B is made can have a big impact on whether someone experiences side effects. Dr. K. R. Meghanadh and their team have noticed that this can vary not only between different companies but also between different batches made by the same company. Sometimes, patients who receive test doses from a particular batch may experience serious side effects, meaning other doses from that same batch must be thrown away. On the other hand, there have been cases where batches with very few side effects and the best results have been found.


Amphotericin liposomal

Another way of making the formula safe is tagging with liposomes, i.e., lipoproteins.


These proteins do not have any pharmacological effect on the body, making Amphotericin B inactive on the body cells.


So, Amphotericin B, tagged with liposomal protein, will not act on the human body and eliminates the chance of side effects.


Whereas the black fungus can take liposomal Amphotericin B and divide it into liposomes protein and Amphotericin B. Amphotericin B ends up killing the fungus.


liposomal amphotericin b - black fungus treatment

Amphotericin B toxicity happens secondarily in the body after its action on the fungus. Human cells cannot take liposomal Amphotericin hence they initially escape from the drug action. But, after killing the fungus, the remaining Amphotericin B separated from liposomal molecules can enter the body and will give a reaction.


Amphotericin B lipid complex(Amphotericin BLC) & Amphotericin emulsion

Similarly, we have another compound along with fats. Lipids are fats. They have a different kind of action when compared to the other two types and are safer. 5 to 6 Amphotericin B molecules are combined with a fat molecule to form an emulsion. So, the emulsion is a bigger molecule.


A simple Amphotericin B molecule gets diffused from the blood vessel into the tissue easily, whereas the larger emulsion molecules cannot diffuse from the normal blood vessels to tissues. So, the medicine will stay in the blood and not go into tissues, so side effects are less. Whenever there is an infection in tissue, there will be a certain amount of inflammation at the end of the blood vessels connected to the tissue, i.e., the blood vessels expand, and the pores to the tissues will also expand. So, the blood vessels make the medicine permeable and reach the tissue. So, the drug reaches the infected parts of the body only. As this medicine goes to the infected areas, the side effects are less.


The con with the Amphotericin B lipid complex is it doesn’t reach tissues with minor infections. As the infection will be less, the inflammation could be less, and the blood vessels might not have expanded enough for the medicine to reach the targeted area. Due to this flaw, Amphotericin BLC is less effective when compared to other compounds.


Conclusion about Amphotericin B compounds

Any variant other than AMBDOC must be given in higher doses to a patient.


For example, in a scenario where 50mg AMBDOC is required, we will need 500mg of liposomal Amphotericin B.


How is Amphotericin B used?

So far oral form of Amphotericin B is not developed. We give these intravenously only.


After giving one to two doses, the vein through which the medicine is sent will inflame in a lot of pain. The inflammation of these veins due to the drug is called local reaction. So, we have to change the vein every 2 to 3 doses. After using the vein for 2 to 3 doses, it might be blocked and cannot be used for the next 10 to 15 days. So, we tend to go for a central venous line, i.e., put a central line in the major vein in the neck, arm, or leg. A central venous line can be used for 10 to 12 days comfortably without causing pain to the patient. The possibility of local reactions is relatively less when we use the central venous line.


Amphoteric B can have side effects on kidneys and decrease calcium and magnesium levels. So, we need to supplement calcium and magnesium at the same time. We must not increase the total fluid given to the body. This requires experienced physicians and supporting staff as well.


Amphotericin B Deoxycholate injection with good purity best treats mucormycosis in a general scenario.


Isavuconazole

Isavuconazole has action closer to Amphotericin B. But, it is not as effective as Amphotericin B anyhow much safer.


Posaconazole for mucormycosis

Posaconazole’s action is much lighter than Amphotericin B.


Posaconazole is good for the maintenance of the therapy only.

Posconazole cannot replace Amphotericin B like Isavukonazole. After removing 99.9% of the fungus, 0.1% only can be tackled with Posaconazole. Else, Isavuconazole can be used depending on the patient’s budget.


Posaconazole and Isavuconazole are available in the form of injections, capsules, or syrups. The side effects are almost nil, but the lever functions must be monitored.


NOTE:

  • All the medications, capsules, and syrup medications must be used under a registered medical practitioner's guidance.

  • Amphotericin B or Isavuconazole, which will be initially given in the IV form, must be given in an ICU only and must be started with a test dosage.

  • This article cannot be used as a prescription by a patient. Mucormycosis is not a disease that can be treated at home.

  • This article is insufficient for a doctor to take as a guide. There is a lot more learning that a doctor needs to do before prescribing a patient.


Who can get treatment for black fungus?


Late-stage mucormycosis patients might not be treated, as the chances of recovery are low.


Primarily if mucormycosis has spread to the brain., The chances of recovery are almost zero, making death inevitable.


If the infection has spread to multiple parts of the face, then the survival chances drop down very low.


When a patient reaches out to the doctor late, the doctor will not treat the patient as it can give unnecessary hope to the patient and family members. Mucormycosis treatment can be very aggressive and expensive, and the low chances of survival will not make sense to treat the patient.


The standards followed for deciding whether the patient is worthy of treatment might differ from doctor to doctor.


To understand the curability of black fungus at various stages, we recommend reading our article "Is mucormycosis completely curable?"


Mucormycosis treatment cost


Mucormycosis treatment costs can vary, and no doctor or hospital can give you a precise estimate before the patient is fully treated.


It depends on three factors mainly.


  1. Recovery rate or immunity of the patient

  2. Doctor’s expertise If the doctor is experienced in treating black fungus, the treatment and recovery can be over quickly, bringing down the cost. The chances of recurrence will also be low then.

  3. Complications If the fungus has spread to the eye or jawbone, the removal will cost extra bucks.

Mucormycosis treatment is very costly due to many reasons.

  1. Multiple surgeries Debridement surgeries for mucormycosis are in particular quoted higher than similar surgeries as the reusable equipment will need multiple sterilizations during and after the surgery. These multiple sterilizations will bring down the life of the equipment. In fact, during the Post-COVID-19 Mucormycosis outbreak in India, there was a shortage of reusable equipment used in black fungus surgeries.

  2. Medication

  3. Long stay at the hospital, i.e., for 15 to 40 days

  4. ICU Bed charges Antifungal medicines like Amphotericin B in IV form must be given in an ICU, as the patient can react and might need immediate care. The patient might occupy an ICU bed for 8 hours daily just for the medication. patient’s

Mucormycosis treatment cost in India

As mentioned earlier, the mucormycosis cost varies from patient to patient depending on various factors.

Mucormycosis treatment costs in India should generally range from INR 10,00,000 to 18,00,000.

This cost can also increase if the recurrence of mucormycosis occurs.


Black fungus treatment at home

Black fungus or mucormycosis treatment cannot be done at home. It doesn't have any home remedies to treat or slow it down.


This is not normal fungus sinusitis that can be treated with medications. It needs surgeries, not one but multiple. A patient needs to stay for 15 to 40 days in a hospital.


It involves powerful antifungals and surgeries. Even the antifungals need to be given in an ICU, and many parameters must be checked.


Black fungus treatment requires an experienced ENT doctor and a well-experienced supporting staff.


We need to rush to an ENT doctor when we find the symptoms in high-risk people who can get black fungus.


The black fungus survival rate

If not treated black fungus survival rate is zero, and death is inevitable.


If treated in late stages, i.e., the fungus has spread to the brain, two eyes, or multiple facial organs, then the survival rate is almost 1%. Most doctors will deny

treatment at this stage, as the possibility of recovery is only written in books, and most of them haven't been seen in recent times as this is a very rare disease.


If treated on suspicion in the early stages, i.e., when the patient has shown only the first symptom, then the survival rate can be as high as 90%. The first symptom is always severe facial pain.


As you can see, the survival rate varies in a huge range, but the main problem is that it takes just a few weeks to reach from 90% to 1%.


The takeaway is high-risk patients who can get black fungus need to be aware of the first symptom and should reach an ENT doctor as soon as they have doubt. Then there will be a very high chance of survival, and recovery will also be quicker.


FAQs

How long is treatment for mucormycosis?

The treatment for mucormycosis typically involves hospitalization lasting between 15 and 45 days, during which a series of debridement surgeries are performed, and potent antifungal medications are administered in the ICU. Following the treatment given under expertise, patients will require oral antifungal medication, such as Posaconazole, for a few additional days at home.

However, the duration of treatment may differ depending on individual factors, such as the severity of the fungal infection, the timing of treatment initiation, the patient's immune system, and the medical team's experience and expertise.

Mucormycosis may recur, necessitating the repetition of the aforementioned treatment.


How do you treat black fungus at home?

We can't treat black fungus at home.


It is crucial to seek treatment from an ENT doctor as soon as possible to ensure the best possible outcome.


Black fungus or mucormycosis disease is characterized by the rapid spread of a fungus that can reach the brain within a few weeks and lead to fatal outcomes. The probability of survival is considerably lower during the late stages of the disease. Consequently, delaying treatment and trying home remedies can elevate the risk of complications and reduce the likelihood of surviving the infection.


Can mucormycosis heal without surgery?

No, mucormycosis can't heal without surgery. The removal of non-vital infected tissues is necessary.


Antifungal medications used for treating the fungus can cause severe side effects if given in high dosages, and the dosage depends on the amount of fungus present in the body. As a result, surgeries play a crucial role in reducing the fungal load in the body.


What surgery is done for mucormycosis?

Debridement surgeries are done for mucormycosis. It's worth noting that several surgeries may be needed to address this condition. Dr. K. R. Meghanadh says, "When it comes to treating mucormycosis, a minimum of three debridement surgeries are necessary. However, it's worth noting that the number of surgeries required can vary significantly depending on the severity of the case. In my experience, the highest number of debridement surgeries I have performed on a single patient was 20. However, it's essential to acknowledge that the number of surgeries required depends not only on the patient's condition but also on a surgeon's expertise and experience. The maximum number of surgeries should not be a point of pride for a surgeon. I hope that my highest number of surgeries done on a patient doesn't repeat or go any higher" The reason for this is that the fungus can grow at an alarming rate, making it tough to tackle with just powerful antifungal medications. Unfortunately, our bodies can't handle high dosages of these medications without putting ourselves at risk. That's why surgeries are performed to remove any partially and fully infected tissues and organs to reduce the amount of fungus in our bodies. By doing so, the antifungals can work effectively as the amount of fungus in the body decreases.


Please read the above section about debridement surgeries for mucormycosis for more details.


What increases the absorption of posaconazole?

Azithromycin can increase the absorption of posaconazole by 25 to 50 percent. This can help us reduce the dosage of posaconazole by 70%. Dr. K. R. Meghanadh used this trick when this drug was scarce.


Why is amphotericin B so toxic to humans?

Technically Amphotericin B is not so toxic to humans, but an impure Amphotericin B can have side effects.


Amphotericin B is derived from Amphotericin, which contains A, B, C, and X. A and B are non-toxic, while C and X are harmful. Improper extraction of Amphotericin B may result in trace amounts of C and X that can harm the human body.


Can Amphotericin B cure black fungus?

Amphotericin B or any antifungal alone cannot cure black fungus. However, antifungals play a major irreplaceable role in the process.


Treating black fungus requires a combination of surgeries to remove infected tissues and powerful antifungal drugs to control the further growth of the fungus.


Three anti-fungal medications can fight black fungus.

  1. Amphotericin B

  2. Isavuconazole

  3. Posaconazole


Isavuconazole is a newer drug, while Posaconazole is taken orally for after-hospital care.


Amphotericin B is a well-established medication for treating black fungus. Its effectiveness is so trusted that its compound Amphotericin B Deoxycholate is considered a gold standard for treating mucormycosis.

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