When it comes to prescription medications being used to treat fungal infections most of my regular readers will be aware that I am quite critical of these particular treatment methods and most certainly of any anti-fungal drug ending in ‘zole.’ However there is one anti-fungal medication which, although it is by no means without drawbacks, does have a good track record in treating fungal infections.
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Nystatin, which was originally called Fungicidin, was developed back in the 1950s by Elizabeth Lee Hazen and Rachel Fuller Brown after it was isolated from the bacteria streptomyces noursei, and has been in constant use since. Nystatin was even recommended as the preferred treatment for fungal infections by the then renown world authority, Dr William Crook, back in the 1980s.
One of the possible reasons for the continuing popularity of Nystatin compared to that of most modern pharmaceutical treatments is due to its rather more gentle action and the fact that it is less easily absorbed through both the intestinal tract and skin which leaves the user with far fewer side-effects to cope with. The more subtle performance of Nystatin compared to the aggressive ‘zole’ drugs is so significant that many clinicians, even today, believe that it is actually a natural preparation. It is also routinely used in patients with severely compromised immune conditions, such as those with AIDs or patients undergoing chemotherapy treatment, not only as a treatment, but also as a preventative. This is very important because for patients with already compromised immune conditions because for them fungal overgrowth can result fatally. Such an invasion of Candida is what is known as being ‘systemic.’ This means because the body has little or no defense mechanisms, the fungi have literally traveled around the body and set up infections which can become life-threatening. This is particularly so in the case of Candida, which I have discussed in other articles as being the most opportunistic of yeasts, making the body of an already compromised patient an ideal target.
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However, Nystatin is not without side-effects, despite the fact it is less easily absorbed through mucous membranes including that of the skin and intestinal wall. Some clinicians even believe that it cannot be absorbed at all, but the science indicates that this is not in fact correct. But, because its permeability is limited then this allows the medication to be made available in a variety of forms, which include:
- Liquid (Oral suspension)
- Powder (for external application)
- Lozenges (Pastilles)
- Creams and Ointments
- Vaginal Pessaries
Although Nystatin is both fungistatic, which means it inhibits the growth of fungi, it is also an extremely effective fungicidal, which means it kills the actual Candida cells. The way in which it works is to specifically target the cell walls of fungi. It does this by attaching itself to a component of the cell wall which is called ergosterol. Nystatin then destroys this component which has the overall effect of killing the cell entirely. Since ergosterol is actually unique to the cells of fungi, then this is why Nystatin has a specific action and other damage, which can be caused by more broadly acting drugs, is limited.
However although I can appreciated the effectiveness of Nystatin when used as an treatment against internal yeast overgrowth, I am a little more dubious about the ability of this drug to treat external infections. The powders, creams and ointments which are available for treating conditions such as Athlete’s Foot, work in exactly the same way as the ingested medications. However when, as often happens, such infections consistently recur I strongly suspect that this is not due to the ineffectiveness of the treatment, but that the external infection actually has an internal cause.
Herxheimer Reaction (Die-off) and Nystatin
At the commencement of my career I was no different to any other clinician of the era and prescribed Nystatin regularly. Although my patients experienced no side-effects with the external treatments (though the recurrence incidence rate was rather high) I began to notice that the patients who ingested Nystatin often experienced side-effects ranging in severity from mere inconvenience to actually debilitating. I now consider that what many of these patients were experiencing was a condition known as Herxheimer’s Reaction, or what is more commonly referred to today as, Die-off. This is where the body has to try and cope with a large amount of toxins which are released as cells die-off (apoptosis) after aggressive drug induced treatments.
What is peculiar to fungi and specifically Candida albicans is that we know the cell walls of this yeast contain what is known as mannan. This is essentially a defense mechanism of the fungi and it is also an antigen which means it triggers the stimulation of the auto-immune system of the body. When large amounts of Candida are killed the antigen is released and so can trigger a violent auto immune reaction. Candida also releases another toxin when it dies and this one can actually cause toxins to be released into the bloodstream as it breaks through the tight-junctions of the intestinal wall.
As you can see, although it might initially appear to be a good thing to kill off large amounts of Candida very quickly, this can often have a very severe adverse effect. I state throughout my site that the way to reduce Candida back into manageable numbers is to approach it thoroughly but slowly and gently rather than aggressively. Even with Nystatin, which is considered by most clinicians to be the least aggressive anti-fungal medication, precisely because it is specific to fungi and is effective, it can in itself cause problems if not prescribed responsibly.
Dr William Crook was a great advocate of Nystatin, and, more surprisingly of the symptoms of die-off. Where I agree with Dr Crook is when he said in his book, The Yeast Connection, “As long as Nystatin can cause symptoms then it is is probably killing Candida,” which is quite likely true because the symptoms are actually reflective of high levels of apoptosis. Where I disagree with Dr Crook however is when he goes on to suggest that patients should take Nystatin at increasingly higher dosages to kill the infection at deeper levels.
My beliefs are formulated around the fact that simply because symptoms of die-off are reflective that Nystatin is working, a lack of symptoms doesn’t mean that it isn’t. What a lack of side-effect symptoms mean is that the Candida is being killed off at a rate which doesn’t negatively affect the body. Providing a patient’s symptoms are improving then it simply is not necessary to give such high dosages of Nystatin that the drug induces die-off effects. For many people the symptoms of die-off are not only unpleasant but they can be extremely severe and range from headaches, chills, night-sweats, anxiety, depression, fatigue, aching muscles, vomiting, diarrhea and skin rashes. Often the onset of these symptoms begins shortly after treatment commences and, at best, could be described as those of a severe flu.
Because of the way in which Nystatin works and it being specific, not to say spectacularly effective, in targeting fungi, then the problems can start as soon as the product is swallowed. It begins by clearing Candida from the mouth and all the way through to the colon, so it is unsurprising that many patients suffer severely from die-off when ingesting this particular drug in high quantities.
I have stopped recommending internal Nystatin treatments simply due to the problems my patients experienced when taking it. This is not to say that I do not recommend the drug, simply that I believe it has to be taken in smaller rather than larger doses, to limit the side-effects while still remaining effective. If I were to recommend any dosage of Nystatin I would start with either 1 tablet or 1 unit of liquid suspension per day and to build up the dosage gradually, but only IF the symptoms of Candida overgrowth were not diminishing in intensity. If the symptoms are diminishing, albeit slowly, then there is every reason to believe that the low dosage of Nystatin is doing its job without producing any unwanted side-effects.
Who Can Take Nystatin?
It is important to distinguish between the type of Candida infection any particular patient has, in addition to taking into consideration the personal circumstances of the patient when assessing who is suitable for Nystatin treatment. Most patients with Candida either have a topical or cutaneous infection, which means one which is on the exterior of the body, or a localized internal infection, such as oral thrush or one located in the digestive tract. For patients such as these then for the majority of the time, Nystatin is considered to be safe, with very few side-effects although, as I have already discussed, die-off can be an issue with those receiving treatments which are ingested.
Side-effects of Nystatin in patients receiving treatment for a localized infection, if they present at all, can include:
- Gastrointestinal issues – including stomach cramps, nausea, vomiting, diarrhea.
- Skin Responses – primarily an inflammatory contact reaction
- Hypersensitivity to Nystatin
When it comes to age-ranges for Nystatin treatment there are, unsurprisingly few restrictions. In fact research has established that it is safe to use in age groups ranging from neonates through to the elderly. There have never been any recorded deaths from Nystatin treatment.
There is however one usual caution: Because Nystatin has not been researched with regard to pregnant women or nursing mothers, the effect on baby is unknown. Therefore it is wise to take your clinician’s advice if you come into either of these two groups and are considering taking Nystatin.
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Systemic Candida Infections
When it comes to systemic Candidiasis however, which I touched upon earlier as being when Candida sets up infections after it has traveled through the body, the problems of treating with Nystatin become much more complicated. This is primarily due to the fact that, precisely because the absorption of Nystatin through the intestinal tract is poor, it cannot effectively reach the organs affected. In cases such as these Candida is treated with the ‘zole’ drugs, which usually include:
- Fluconazole (Diflucan)
- Itraconazole (Sporanox)
- Fungizone (amphotericin B)
I must remind readers however that systemic infections are usually secondary to severe primary illnesses and most patients receiving treatment will either be hospitalized or under the care of a hospital. However to give you an idea of what can occur when Candida becomes systemic, here are a few areas of the body which can be affected:
- Dialysis related Peritoneal Candidiasis
- Central Nervous System (CNS) Candidasis related to neurosurgery
- Candida endophthalmitis (eye)
- Billary Candidiasis (Gallbladder)
- Cardiac Candidiasis (Heart)
- Candida Osteomyelitis (Joints and bones)
- Candida Pneumonia (Lungs)
- Fungal Mass (fungus balls) urinary tract (bladder)
- Hepatosplenic Candidiasis
- Pancreatic Candidiasis
Nystatin and Its Alternative Uses
Surprisingly Nystatin has proven to be useful in respect not only of other health conditions but also in fields completely distinct from the world of medicine. Within it, non-fungal related ear infections have been treated successfully with Nystatin in patients with Meniere’s Disease (Leong et al 2014) and also auto-immune related inner ear diseases (Nelson 1993). More surprisingly though has been its usefulness in other fields entirely and these include:
- Using Nystatin to protect and preserve artwork being denatured by fungi and molds
- In the laboratory for measuring cellular currents
- By molecular biologists in a range of testing techniques
Nil-Response to Nystatin?
Many patients quite rightly ask what to do if they find symptoms do not go into remission when taking Nystatin. Although a nil response is rare, it does happen and this could be for one of several reasons:
- Concomitant Condition
If could be that the patient has another condition running alongside the Candida which needs investigation and treatment.
- Aggravating Medications
It should always be remembered that even if someone is aware that they have a co-existing condition treatment for it may be compromising the Nystatin medication. For instance, antibiotics may simply be inducing further Candidiasis and even the oral contraceptive pill can have this effect without the patient realizing.
- Inaccurate Dosage
It is possible that the dosage you have been prescribed is too small to positively affect the Candida. Discuss changing the dose with your clinician.
Most patients suffering from Candida do respond positively to the drug. If you are still suffering symptoms and have seen no improvement at all, consider discussing the possibility of investigating another cause with your clinician.
- Resistant Strain
Some strains of Candida are more resistant to treatment than others. Discuss the possibility of this with your clinician.
What Dosage Should I Take?
As I mentioned earlier it is far better to start with smaller doses and build up the amounts if necessary, than to battle the effects of die-off if too much Nystatin is given. I would suggest the following initial dosages and if these prove effective then they can be maintained until the condition is cleared:
Oral Thrush: 1 tablet or lozenge daily. Equally one dose of liquid suspension which can also be used as a mouth wash or gargle.
Cutaneous Candida (Topical Infections): Apply cream, powder or ointment between 1-3 times daily.
Intestinal Candida: Liquid suspension, tablets or lozenge taken once per day.
If however, symptoms persist on the lower dosages, then with regard to the ingested medications they may be slowly increased to 3 times the amounts stated.
How Long Does It Take for Nystatin to Work?
Undoubtedly response time depends on the severity of the infection and its location, however most patients begin to see a remission of symptoms between 24-48 hours after commencing treatment. Often patients see an easing of symptoms prior to this time, particularly in cases of cutaneous Candida, and, less frequently, improvements take longer than 48 hours.