Nystatin chemical structure
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Nystatin

Nystatin is a polyene antimycotic drug. Nystatin is considered a "clean" drug as it has no proven side effects. Candida spp. are sensitive to nystatin. more...

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Uses

Cutaneous, vaginal, mucosal and esophageal Candida infections can be treated with nystatin. Cryptococcus is also sensitive to nystatin. In the UK its license for treating neonatal oral thrush is restricted to those over the age of one month (miconazole is an appropriate alternative for younger babies).

Nystatin is often used as prophylaxis in patients who are at risk for fungal infections, such as AIDS patients with a low CD4+ count and patients receiving chemotherapy.

It is prescribed in units, with doses varying from 100,000 (for oral infections) to 1 million (for intestinal ones). As it is not absorbed from the gut, it is safe for oral use and does not have probelms of drug interactions.

Method of action

Like amphotericin B and natamycin, nystatin binds to ergosterol, the main component of the fungal cell membrane. When present in sufficient concentrations, it forms a pore in the membrane that leads to K+ leakage and death of the fungus. As mammals do not have ergosterol-based cell membranes, the drug only affects fungi.

Origin

Like many other antimycotics and antibiotics, nystatin is itself a fungal product. It was isolated from Streptomyces noursei in 1950 by Elizabeth Lee Haxen and Rachel Fuller Brown, who were doing research for the Division of Laboratories and Research of the New York State Department of Health. The soil sample where they discovered nystatin, was from the garden of Hazen's friends called Nourses, therefore the strain was called noursei. Hazen and Brown named nystatin after the New York State Public Health Department.

Brand names

  • Nystan® (oral tablets, topical ointment, and pessaries, Bristol-Myers Squibb)
  • Infestat®
  • Nystamont®
  • Nystop® (topical powder, Paddock)
  • Nystex®
  • Mykinac®
  • Nysert® (vaginal suppositories, Procter & Gamble)
  • Nystaform® (topical ointment, combined with iodochlorhydroxyquine and hydrocortisone; Bayer)
  • Nilstat® (vaginal tablet, Lederle)
  • Korostatin® (vaginal tablets, Holland Rantos)
  • Mycostatin® (vaginal tablets, Bristol-Myers Squibb)
  • Mycolog-II® (topical ointment, combined with triamcinolone; Apothecon)
  • Mytrex® (topical ointment, combined with triamcinolone)
  • Mykacet® (topical ointment, combined with triamcinolone)
  • Myco-Triacet II® (topical ointment, combined with triamcinolone)

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Effectively diagnosing and treating Candida
From Townsend Letter for Doctors and Patients, 10/1/05 by Jacob Teitelbaum

Everyone's immune system has strengths as well as weaknesses. Some people never get colds but have frequent bouts of athlete's foot or other skin fungal infections. Others never get fungal infections but tend to get colds. Many people seem to have a diminished ability to fight off fungal infections.

[ILLUSTRATION OMITTED]

Fungi are very complex organisms and can cause difficulties to many mechanisms. It is suspected that fungal overgrowth may suppress the body's immune system. The body may also develop allergic reactions to components of the yeast.

This allergic reaction was suggested in a study that connected the fungal organism Candida albicans with allergic skin dermatitis (eczema). This study was published in The Journal of Clinical Experimental Allergy in 1993. It found that there is a significant correlation between the body having antibodies to Candida albicans and allergic dermatitis or eczema. In addition, we have found that unexplained rashes that have lasted for many years often clear up with antifungal treatment. Many physicians feel that yeast overgrowth causes a generalized suppression of the immune system. In other words, once the yeast gets the upper hand, it sets up a cycle that further suppresses the body's defenses. Interestingly, a recent Mayo Clinic study showed that most cases of chronic sinusitis seem to be associated with a reaction to yeast in the sinuses--something that holistic physicians have proposed for many years. Nonetheless, it is important to remember that yeast are also normal members of the body's "zoo." They live in balance with bacteria--some of which are helpful and healthy, and some of which are detrimental and unhealthy. The problems begin when this harmonious balance shifts and the yeast begin to overgrow.

Many things can prompt yeast to overgrow. One of the most common causes is frequent antibiotic use. Antibiotics kill off the good bacteria in the bowel along with the bad bacteria. When this happens, the yeast no longer have competition and begin to overgrow. The body is often able to rebalance itself after one or several courses of antibiotics, but after repeated or long-term courses--and especially if the body has an underlying immune dysfunction--the yeast can get the upper hand.

Other factors are also important. Studies have shown that animals that are sleep-deprived and/or have increased sugar intake develop bowel yeast overgrowth. Many physicians feel that eating sugar stimulates yeast overgrowth in people as well. Sugar is food for yeast. Yeasts ferment sugar in order to grow and multiply. Yeast overgrowth due to the overuse of sugar also seems to cause immune suppression, which facilitates bacterial infections, which then require even more antibiotic use. Poor sleep also results in marked suppression of the immune function.

Diagnosing Yeast Overgrowth

There are no definitive tests for yeast overgrowth that will distinguish yeast overgrowth from normal yeast growth in the body. In my experience, however, using Dr. William Crook's yeast questionnaire is still the most reliable way to tell if a person is at risk of yeast overgrowth. If the symptom score is over 140 points, I recommend treatment. Another option is to suspect yeast in those with chronic sinusitis or spastic colon, anyone with chronic fatigue or pain who has been on recurrent or long-term antibiotics (especially tetracycline for acne), or those who intermittently have painful sores in different parts of the mouth that last for about ten days (aphthous ulcers) which persist after nutritional support. In our experience, most people who have irritable bowel syndrome (spastic colon) or chronic sinusitis, have yeast overgrowth in both of these--usually resolved with proper therapies including antifungals.

Treating Yeast Overgrowth

A number of very effective methods can be used to take care of a yeast problem. Some involve dietary changes and supplements, others prescription medications. Combining both approaches may be more effective than any one method alone.

Natural Yeast Treatments

Primary among the methods for treating yeast overgrowth is avoiding sugar and other sweets. Patients can often enjoy one or two pieces of fruit a day, but should not consume such concentrated sugar sources as juices, corn syrup, jellies, pastry, candy, or honey. They need to stay far away from soft drinks, which have 10 to 12 teaspoons of sugar in every twelve ounces. This amount of sugar has been shown to markedly suppress immune function for several hours.

Using stevia as a sweetener is a wonderful substitute for sugar. Stevia is safe and natural, and patients can use all they want. Many Stevia brands are bitter, and therefore I recommend the one made by Body Ecology (1-800-4Stevia--they even have cookbooks available for using stevia.) or the Stevita brand. Although more expensive, xylitol (which also decreases osteoporosis) and inositol (which is also very helpful for anxiety) are also excellent sugar substitutes and look and taste just like sugar. When telling people to eliminate sugar, I generally add the three magic words "Except for Chocolate." This improves compliance considerably. I also let them know that "they can have their cake and eat it too" by using the sugar-free chocolates. Some brands are awful, but the Russell Stover brand has dozens of types of chocolates which taste excellent. The main downside of the sugar free chocolates is that the sweetener maltitol can sometimes cause gas and diarrhea.

When stopping sweets, the patient should be prepared to have withdrawal symptoms for about one week. Several excellent books have been written on the yeast controversy and offer additional dietary methods to try. One of the best is The Yeast Connection and the Woman by the late Dr. Crook, a physician who has done a spectacular job of advancing our understanding of yeast overgrowth.

Many people have found that acidophilus--that is, milk bacteria, a healthy type of bacteria for the bowel--helps restore balance in the bowel. Acidophilus is found in yogurt with live and active yogurt cultures. Indeed, eating one cup of yogurt a day can markedly diminish the frequency of recurrent vaginal yeast infections. Unfortunately, many acidophilus products do not have anywhere near the label claim, and the acidophilus is destroyed upon contact with stomach acid. Because of this, I recommend using acidophilus that is in an enteric coated "pearl." This delivery mechanism does not dissolve until it reaches an alkaline environment, protecting the acidophilus from acid as it goes through the stomach. In addition, it eliminates the need to refrigerate the acidophilus. The form that I use in my practice is called Probiotic Pearls by Integrative Therapeutics. I recommend that patients take two pearls twice a day for five months. This supplies over 6 billion bacteria daily (the pearls actually have been a much higher level than the label claim). If patients are on antibiotics (not anti-fungals), I recommend that they take the acidophilus at least three to six hours away from the antibiotic dose.

Natural remedies can also be very helpful as antifungals. Unfortunately, when individual treatments are taken in a high enough dose to be effective, they often cause reflux and indigestion. Because of this, I prefer to use the products that combine a mix of natural antifungals at lower dosing. One excellent one is Phytostan (also by Integrative Therapeutics) which contains Pau D'Arco bark (Tabebuia impetiginosa) 100 mg, Undecylenic acid 100 mg, Caprylic acid 75 mg, Grapefruit fruit extract (Citrus paradisi) 40:1 25 mg, Rosemary aerial parts oil (Rosmarinus officinalis) 4:1 1.5 mg, and Thyme aerial parts oil (Thymus vulgaris) 4:1 1.5 mg. In my own "test tube studies," this combination was almost as effective as the medication Diflucan. Another natural product which did very well was Citricidal (grapefruit seed extract) at higher dose. For the Phytostan I use two tablets twice a day for five months. For the Citricidal (use the tablets not the liquid) I use 200 mg twice a day for five months. They can be used together. If nausea occurs with either of them, I would lower the dose.

Medical Treatments for Yeast Overgrowth

Nystatin, an antifungal medication, has been helpful in the treatment of yeast overgrowth. Unfortunately, some fungi seem to be resistant to nystatin. In addition, nystatin is poorly absorbed, which means that it has little impact on the yeast outside of the bowel.

Other antifungal medications, such as Diflucan and Sporanox, seem to be effective systemically (throughout the body) but they have three main drawbacks. First, they are expensive, costing more than $450 to $900 for a two-month course. Fortunately, however, Diflucan recently went generic and is now available for only $40 for 42 tablets of 200 mg each. For patients without insurance, a mail-order pharmacy called Consumers Pharmacy (323-461-3606) has the lowest prices I have found on prescription medications. Second, any effective antifungal can initially make the symptoms of yeast infection worse. In addition, although it is uncommon, Diflucan and Sporanox can also cause liver inflammation. If patients are taking Diflucan or Sporanox for more than six to twelve weeks, I would consider intermittently doing blood tests to check liver function--specifically, checking blood levels of alanine aminotransferase (ALT) and aspartate transaminase (AST). If they have preexisting active liver disease, you should be cautious about using Diflucan or Sporanox--or not use them at all. I do recommend that patients take 200 milligrams of lipoic acid a day whenever they take Sporanox or Diflucan. This is a natural supplement that helps to protect and heal the liver. For that matter, I also strongly recommend lipoic acid for anyone with active liver disease (for example, hepatitis), at doses up to 1,000 to 3,000 milligrams a day, as it may prevent and/or help treat cirrhosis.

Further Yeast Treatment Recommendations

As noted above, if symptoms of yeast overgrowth are caused by an allergic or sensitivity reaction to the yeast body parts, symptoms may flare up when mass quantities of the yeast are suddenly killed off. This is called a yeast die-off reaction. If patients get this reaction, start their treatment with acidophilus pearls and a sugar-free diet for a few weeks, followed by Phytostan and/or Citricidal before beginning nystatin. Give the nystatin in tablet or powder form. The powdered forms need to be refrigerated and Kronos Pharmacy (800-723-7455) has excellent prices on one million unit nystatin capsules. I generally recommend beginning with 500,000 international units a day for one to three days, and increasing the dosage by 500,000 international units every one to three days (slower if yeast die-off is a problem) until the patient is taking 1,000,000 international units two to four times a day. Give this dosage for five to eight months. (If they develop nausea, reduce the dosage.) One month after beginning the nystatin, I add 200 milligrams of Diflucan or Sporanox every morning for six weeks. If symptoms flare, give just 100 milligrams each morning for the first three to fourteen days. If symptoms recur after the patient stops the Diflucan or Sporanox, I recommend continuing the medication for an additional six weeks (or longer if needed) at 200 milligrams a day.

Sporanox should be taken with food. If it is taken alone, its absorption is greatly reduced. When the patient is taking Diflucan or Sporanox, they should not use cholesterol-lowering medications in the pravastatin (Mevacor) family, which also includes Baycol, Lescol, Lipitor, Pravachol, and Zocor (all of these can also flare fibromyalgia pain even when not combined with Diflucan/Sporanox). Also, antacid medications such as cimetidine (Tagamet), nizatidine (Axid), ranitidine (Zantac), and famotidine (Pepcid) prevent the proper absorption of Sporanox. At the high price of Sporanox per dose, you will want the patient to absorb every last bit of the medication. If they need to be on an antacid medication, you should use Diflucan instead of Sporanox. Unfortunately, the antifungal terbinafine (Lamisil) does not seem to work very well for Candida yeast overgrowth.

Many books on yeast overgrowth, including Dr. Crook's, advise readers to avoid all yeast in the diet. This advice is based on the theory that an allergic reaction to yeast is the cause of the problem. In my experience, trying to avoid all yeast in foods often results in a nutritionally inadequate diet and little benefit. Although a subset of patients does appear to have true allergies to the yeast in their food, they account for a small percent of my patients with suspected yeast overgrowth. These people may benefit from the stricter diet recommended in Dr. Crook's book. Interestingly, once adrenal insufficiency and yeast overgrowth are treated, most people find that their allergies and sensitivities to yeast and other food products seem to improve or disappear.

Nutritional deficiencies such as low zinc or low selenium may also decrease resistance to yeast overgrowth. A good multivitamin supplement should take care of these deficiencies. The one that I recommend for all of my patients for overall nutritional support is the Energy Revitalization System Vitamin Powder (also by Integrative Therapeutics), which replaces 35 tablets of supplements with one good tasting drink each day.

The best thing patients can do to combat yeast overgrowth is to try to avoid it in the first place. When they get an infection, immediately begin treating it naturally. Hopefully, you will be able to prevent it from turning into a bacterial infection that might require an antibiotic. In my experience the most effective immune stimulant for fighting infections is a Thymulin mimic called ProBoost (from Klabin Marketing -- 800-933-9440). This is an incredibly popular product with my patients, who use it sublingually at the first sign of any infection. If patients find, however, that they must take an antibiotic, all is not lost. They can still lessen the severity of yeast overgrowth by avoiding sweets and by taking nystatin plus either taking acidophilus pearls (not within three to six hours of an antibiotic) or by eating one cup of yogurt with live and active acidophilus cultures daily. Don't use the yogurt (or milk) if they have sinusitis or pneumonia, because the milk protein causes mucus to thicken and makes it hard for the body to fight these infections.

What If the Yeast Comes Back?

It is normal for yeast symptoms to resolve after treatment. After six weeks on the Sporanox or Diflucan, most people feel a lot better. However, symptoms may recur soon after they stop taking the antifungal. If this happens, I would continue the Sporanox or Diflucan for another six weeks or for as long as is needed to keep the symptoms at bay. More frequently, people feel better after treatment and stay feeling fairly well for a period of six to twenty-four months. At that time, it is common to see a recurrence of symptoms, especially if they are eating too much sugar or are taking antibiotics.

The best marker that I have found for recurrent yeast overgrowth is a return of bowel symptoms, with gas, bloating, and/or diarrhea or constipation. If these symptoms persist for more than two weeks, especially if there is also even a mild worsening of the CFIDS/FMS symptoms, it is very reasonable to retreat them empirically with six weeks of nystatin and perhaps Sporanox or Diflucan. In addition, I would also resume treatment if there is a recurrence of vaginal yeast or sinus infections. If a second round of treatment resolves the symptoms, you may opt to repeat this regimen as often as is needed, usually every six to twenty-four months. By using some of the natural remedies listed earlier in this chapter, however, you may be able to avoid repeated use of antifungals and the possible risk of patients becoming resistant to them.

Some people find that they need to stay on the antifungals for extended periods of time--years, in some cases--or the symptoms recur. If this is necessary, I add the natural remedies. I do, however, also use prescription medications when needed. The main risk of long-term use of the antifungals Sporanox and Diflucan is liver inflammation. As mentioned earlier, if these medications are used for extended periods, liver function should be monitored. Consider checking the ALT and AST liver tests (also called the SGOT and SGPT test) every three to six months and anytime that a severe flulike feeling or worsening of symptoms occurs. In addition, it is very important to take 200 milligrams of lipoic acid a day as long as they are on the medication. Although I am not aware of any studies on using lipoic acid with antifungals, I have seen no worrisome liver tests in patients using this natural substance while taking these antifungals. As an alternative, instead of taking the antifungals every day, many people find they can get long-term suppression of the yeast by taking 200 milligrams of Sporanox or Diflucan twice a day, one day each week (for example, each Sunday).

Treating fungal overgrowth is one of the most important parts of treating chronic fatigue syndrome, fibromyalgia/myofascial pain syndrome, chronic sinusitis, and spastic colon. Although controversial, I think you'll find that treating it effectively in your practice will be a dramatic benefit to your patients!

Jacob Teitelbaum, MD is director of the Annapolis Research Center for Effective CFS/Fibromyalgia Therapies, which sees patients with CFS/FMS from all over the world (410-573-5389; www.EndFatigue.com) and author of the best selling book From Fatigued to Fantastic! and Three Steps To Happiness! Healing Through Joy. His newest book Pain Free 1-2-3! has just been released. CD sets of his workshops on effective CFS/Fibromyalgia therapies and pain management for both prescribing and non-prescribing practitioners are available at www.vitality101.com. He accepts no money from any company whose products he recommends and 100% of his royalties for products he makes is donated to charity.

by Jacob Teitelbaum, MD

410-573-5389 * www.Vitality101.com.

COPYRIGHT 2005 The Townsend Letter Group
COPYRIGHT 2005 Gale Group

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