Interview

Epidemiologically speaking…

As risk factors increase, so will the nosocomial fungal infections. Dr Ben de Pauw, Professor of Medicine, Radbound University Nijmegen Medical Centre, the Netherlands talks to Aashruti Kak about the nature of the infections and the medicines in use

What percent of the total nosocomial infections do fungal infections account for?

On an average, fungal infections are now at number four on the list of nosocomial infections in an Intensive Care Unit (ICU) with very sick patients. If the hospitals don't have very sick patients, it has to do with more intensive treatment, which also goes hand in hand with more intensive diagnosis.

What is the mortality rate?

The mortality rate in fungal infections is really very high, especially when you don't diagnose them. They are 100 percent curable if the underlying disease is curable. We all carry fungus with us all the time. It is only because of our strong defence system we have intact mucosa, intact skin, and we have competent immune cells that keep the fungus out. As long as the defence system is healthy, there can be no problem. But, if a patient falls ill, the defence system goes down. If the patient is down with serious diseases like cancer, autoimmune diseases, and others contracted during organ transplants, the medication that he/she is given to treat those diseases enable the incidence of a fungal infection to shoot suddenly from eight or nine percent to 50 percent.

Why do nosocomial infections occur?

In the nosocomial infections, the fungus usually becomes apparent when one starts to treat a patient for an underlying disease. When that happens, the immunity of the patient is compromised temporarily and that's when the fungus gets to the patient. A big issue is lowering the defence of the patient. If you operate on a patient's guts, you open them, and that is a big risk factor for a fungal infection. And if you give patients corticosteroids or any other immunosuppressive drugs, or cytostatic drugs, then you lower the defences of that patient and the fungus can prop up. You can only suppress the fungus with an anti-fungus as the natural defence system has to come back in action to get rid of it. If the natural defence system does not come back, the patient dies.

What are the most common fungal pathogens that you find in a hospital?

The most common is Candida, which shows up mostly in the throat infections that are seen after taking antibiotics. It lives on the skin and in the mucosa along with the bacteria, and if you wipe out the bacteria with antibiotics, the fungus gets more space to grow. But it is different when the fungus is outside the body. Candida infections of the vagina in women are the most horrible and the most fatal. These are mostly related to the use of antibiotics and oral contraceptives that change the immune system. The moment you open the body with knives, when you damage the system by using chemotherapy or put a line in the body, the fungus gets a chance to get in. The second most common pathogen is Aspergillus. It occurs in certain patient groups with immunocompromised conditions like haematological malignancies.

Is there a difference in the pathogens in different geographical areas?

It is only in Candida that there is a difference in species. In Brazil, for instance, C albicans and C tropicalis are the most frequent in occurrence, whereas in Europe, the United States and in other colder states, C glabrata is the next most prevalent and is an increasingly important pathogen with increase in the age of patients and in oncology patients. C tropicalis is more dangerous than C glabrata, as it has the habit of penetrating into the tissues leading to really serious infections, due to which the mortality rate is also really high. Globally, C albicans is the most frequently occurring pathogen in immunocompromised patients, whereas in India, C tropicalis reigns. C parapsilosis is the next most frequently occurring pathogen that thrives on the skin, and is mostly associated with intravascular devices, hyperalimentation, or prosthetic devices. It is predominant in neonatal age groups, along with C albicans. In Aspergillus, A fumigatus is globally the most commonly occurring pathogen, followed by A flavus. But, in India, A flavus is the most common cause of all forms of aspergillosis.

Currently, which drug seems to be the most suitable to fight these infections?

Of all the anti-fungals, the most important drug is fluconazole. It is a simple drug with very less side-effects and has reasonably good activity and is very effective. There is increasing news of combination drug therapy with candins and azoles. This is being used globally but is not formally recommended as an indication. It is a trimedication of the established efficacy of the common drugs, like caspofungin is for Candida and Aspergillus infections; there is no activity against mucormycosis and cryptococcossis. The other drugs, voriconazole and amphoterecin-B, do have activity against Candida, Aspergillus, and to a lesser extent against mucormycosis and cryptococcossis. Fluconazole is active against cryptococosis and Candida, but not against aspergillosis and mucormycosis. People are not satisfied with the current drugs so they are combining several medications to make one super-drug. There is no scientific evidence that a combination helps, moreover, it is very expensive. So far, some of the C albicans, C krusei and some others have become resistant to fluconazole.

Are there any new drugs coming in the market?

There are two more candidates coming apart from caspofungin (anidulafungin and micafungin), and there is a new azole (ravuconazole) coming up from the voriconazole group. In pre-clinical testing, isavuconazole (a novel water-soluble, broad-spectrum antifungal) and posiconazole (a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients) are the two drugs. Posiconazole is used for prophylaxis but is only an oral drug and has never been tested well.

So in the next five years there are not going to be any revolutionary drug coming, apart from these two. I don't think that the company will invest in the further development of posiconazole, they are selling it for prophylaxis and they do not have enough sales to invest in clinical trials. That is one of the main problems that the anti-fungal drug development is facing. Manufacturers are ready to develop and sell them, putting them for testing, so it is up to the big companies to do their part.

Has the segment of invasive fungal infections been getting enough attraction from the Pharma industry?

Over the last three to four years, Gilead Sciences, California, has invested money in anti-fungal drugs. Isavuconazole is being worked on by a very small company in Switzerland by the name of Basilea Pharmaceuticals, which will sell it to a big company once it has proven that it works. Currently, they are holding Phase III trials for the drug. In India, there are only two companies that are working towards the development of anti-fungal drugs-Merck Sharp and Dohme Pharmaceuticals (wholly owned subsidiary of Merck) that developed Cancidas (caspofungin), and Pfizer, which came up with Vfend (voriconazole) and Eraxis (anidulafungin).

What are the major concerns plaguing the segment?

The antifungal drug segment is an increasing part of the medication requirements but not all hospitals stock it. If you are doing an organ transplant or a bone marrow transplant, you need access to such drugs. It has already become a pandemic because everybody seems to have it. If you take a look at autopsies, 70-80 percent of the patients that have been treated for something, have died because of these infections. If not the absolute cause, then these infections have contributed to other diseases. There is a dire need for improvements in both diagnosis and therapy of these infections.

aashruti.kak@expressindia.com