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Mucosal Candidiasis Medication

  • Author: Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC); Chief Editor: William D James, MD  more...
 
Updated: Feb 12, 2016
 

Medication Summary

Antifungal treatment may be necessary for the treatment of candidiasis.

Fluconazole and HIV infection

Fluconazole has been active against oral candidosis in HIV disease and produces remission within approximately 1 week. Fluconazole has gained preference mainly because it is rapidly effective, has a long half-life, and lacks serious adverse effects. Fluconazole 100 mg qd is more effective against oropharyngeal candidosis in HIV infection than nystatin 500,000 U qid or clotrimazole troche 10 mg 5 times per day.

Maintenance therapy or intermittent therapy with fluconazole is essential to prevent relapse after cessation of treatment; 50 mg qd prevents recurrence of candidosis as does 150 mg/wk. It appears that a regime of 50 mg/d (single-dose therapy) of fluconazole for 2-3 wk may be adequate to prevent or suppress candidosis in patients infected with HIV.

Patients undergoing therapy for metastatic malignancy were assigned randomly to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidosis developed in only 2% of patients receiving fluconazole but in 28% of patients receiving placebo. These favorable results indicate that fluconazole should be evaluated as antifungal prophylaxis in patients at greatest risk of developing serious fungal infections, such as transplant patients or those receiving chemotherapy for malignant diseases.

Fluconazole prophylaxis reduces not only the chance of candidosis in HIV disease but also mycoses such as cryptococcosis. Fluconazole also has been used successfully to treat some patients with acute cryptococcal meningitis in uncontrolled trials, although the time to elimination of the organism in cerebrospinal fluid (CSF) was slower than with amphotericin B.

Fluconazole was not as effective in treating cryptococcal meningitis as amphotericin B and flucytosine in a patient with HIV disease; however, fluconazole may be considered in patients with clinically mild disease. Initial use of amphotericin B and flucytosine followed by fluconazole to prevent relapse may be considered. Prevention of recurrent cryptococcal meningitis with daily fluconazole is effective and better tolerated than weekly amphotericin. While amphotericin has been standard therapy, fluconazole recently has been effective in treating patients infected with HIV with coccidioidomycosis.

Chronic hyperplastic candidiasis

Topical applications of 0.18% isotretinoin may be efficacious.[22]

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Antifungals

Class Summary

Currently available azoles are imidazoles (eg, clotrimazole, miconazole, econazole, ketoconazole) and triazoles (eg, fluconazole, itraconazole), which are synthetic antifungals with broad-spectrum activity against a number of yeasts and fungi including candidal organisms. They are fungistatic and expensive. They inhibit fungal cytochrome P450-dependent enzymes, which are essential catalysts for the 14-demethylation of lanosterol in sterol biosynthesis and block synthesis of ergosterol, the principal sterol in fungal cell membranes. One adverse effect of azoles is accumulation of precursors of ergosterol, which may have effects on their own.

Diazoles (eg, ketoconazole, miconazole) have more effect on mammalian cytochromes than do triazoles (eg, fluconazole, itraconazole) and tend to have more severe adverse effects. None of the azoles is entirely benign. Hepatotoxicity may be common to all of them, and the potential for endocrine toxicities exists, particularly at high doses. As with any new agent, novel toxicities may be discovered.

Azoles are effective antifungals, but resistance increasingly is reported. Development of cross-resistance of C albicans to different azoles during treatment with a single azole derivative has been described.

The triazole voriconazole has activity against fluconazole-resistant C albicans.

Clotrimazole (Lotrimin, Mycelex, Femizole, Gyne-Lotrimin)

 

Clotrimazole is a broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate the diagnosis if no clinical improvement is seen after 4 weeks. It is used as a topical agent only because of GI and neurologic toxicity. As a 10-mg troche used 5 times/day, clotrimazole is effective against oral candidiasis in some patients who are immunocompromised. It is less effective than other azoles in patients with HIV infection.

Miconazole (Absorbine, Femizole, Lotrimin, Monistat, Maximum Strength Desenex)

 

Miconazole is for topical treatment of candidosis such as angular stomatitis. Miconazole lacquer is effective for treatment of chronic atrophic candidosis; chewing gum may be effective against intraoral candidosis. It is available for parenteral use against systemic mycoses, but the injection contains polyethoxylate castor oil, which may provoke allergic reactions.

Econazole (Spectazole)

 

Econazole is effective in cutaneous infections. It interferes with RNA and protein synthesis and metabolism. Econazole disrupts fungal cell wall membrane permeability, causing fungal cell death.

Ketoconazole (Nizoral)

 

Ketoconazole is the first imidazole agent capable of achieving therapeutic blood levels when given orally. It is used in the treatment of CMC and candidosis in patients who are immunocompromised.

The cream form can be used to treat angular stomatitis. Oral ketoconazole can be effective for treatment of severe oral and esophageal candidosis, but patient compliance often is poor because of the taste of the drug. Failures also may be related to drug malabsorption, ketoconazole-resistant strains of C albicans, or adverse effects. It should be taken with food since gastric acid is essential for dissolution and absorption, but absorption is variable and adverse effects are common.

Acidic pH is required for drug absorption, which can be enhanced by taking the drug with orange juice, a carbonated beverage, or glutamic acid. Ketoconazole is poorly absorbed from an empty stomach or with concurrent use of medications, such as cimetidine, ranitidine, and other antacids. It is poorly absorbed in patients with AIDS because of gastric atrophy and reduced acid production.

Fluconazole (Diflucan)

 

Fluconazole inhibits fungal ergosterol production essential in cell wall formation by inhibiting the cytochrome c-dependent demethylation step in the formation of ergosterol. It has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Adhesion of candidal organisms to epithelial cells, widely recognized as an essential step in the process of candidal colonization and subsequent infection, is inhibited significantly.

Since fluconazole is secreted in saliva in high concentrations, it is tempting to speculate that it may interfere with the synthesis or structure of candidal receptors on buccal epithelial cells.

Fluconazole is active against most C albicans, although resistance may appear, but it is less active against non-C albicans species. It tends to be active against Candida parapsilosis and Candida tropicalis, but is less active against Candida glabrata, and is not active against C krusei.

Fluconazole is well absorbed from the gut, even in the absence of acidity of the stomach. It can penetrate into other body fluids, including CSF. Oral absorption is rapid and almost complete within 2 hours. The plasma half-life is approximately 30 hours. Intravenous preparations are available for patients who cannot take medication orally.

Fluconazole appears to undergo relatively little metabolism in the body; elimination is predominantly renal. With normal renal function, the serum half-life is approximately 30 hours. The concentration of the drug in CSF is estimated to be from 50-90% of plasma concentration, suggesting that fluconazole is given best daily and penetrates into CSF and urine in high concentrations. It enters saliva, although salivary levels are higher and persist longer after use of an oral suspension, compared with oral use.

Fluconazole is effective in patients with chronic atrophic oral candidosis, particularly when administered concurrently with an oral antiseptic such as chlorhexidine. For patients with CMC in whom relapse after initial remission is expected, a dose of 50 mg produces clinical and mycologic responses in approximately 10 days.

It is active against oral candidosis in HIV disease and produces remission within approximately 1 week.

Itraconazole (Sporanox)

 

Itraconazole is an orally active triazole that inhibits ergosterol biosynthesis in fungal cell. It has a long half-life and fewer adverse effects than ketoconazole but is expensive and eliminated hepatically.

Itraconazole is well absorbed and achieves good distribution in the body and may be more active than ketoconazole. Absorption is impaired when gastric acid is reduced or when antacid, rifampicin, or phenytoin is given. It may interact with terfenadine, astemizole, and cisapride to produce dysrhythmias and to increase the activity of anticoagulants, cyclosporin, midazolam, and sulfonylureas. Adverse effects have included altered liver function (hepatotoxicity is less than that of ketoconazole) and hypokalemia with hypertension resulting from accumulation of steroids with an aldosteronelike activity, mild leukopenia, nausea, epigastric pain, headache, and edema.

It is available in 50- and 100-mg capsules and 10-mg/mL oral solution. Administering 100-200 mg/d for 2 weeks gives good clinical and laboratory results compared with ketoconazole and clotrimazole. GI absorption is reduced in HIV disease.

The availability of oral solution may offer advantages over capsules because it acts topically and is easier to swallow for patients with oral candidosis and to administer by nasogastric tube.

Itraconazole is active against all candidal species; therefore, it may be indicated in patients who are immunocompromised and in whom other antifungals may predispose to selection and overgrowth of resistant species. It has been successful at a dose of 200 mg/d for 4 weeks in the treatment of candidosis. Absorption from the GI tract in persons with HIV infection is approximately one half that in healthy individuals. A dose of 100 mg PO qd or bid probably is as effective as fluconazole. It is available for topical use as a solution. A dose of 200 mg qd is more effective than clotrimazole or ketoconazole.

Voriconazole (Vfend)

 

Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. It is a triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

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Contributor Information and Disclosures
Author

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) Emeritus Professor, University College London; Visiting Professor, Universities of Athens, BPP, Edinburgh, Granada, Helsinki and Plymouth

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) is a member of the following medical societies: Academy of Medical Sciences, British Society for Oral Medicine, European Association for Oral Medicine, International Academy of Oral Oncology, International Association for Dental Research, International Association for Oral and Maxillofacial Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Franklin Flowers, MD Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

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Pseudomembranous candidosis.
Erythematous candidosis in HIV/AIDS.
Denture-related stomatitis; a common form of oral candidiasis. From Scully C, Flint SF, Bagan JV, Porter SR, Moos K. Atlas of Oral and Maxillofacial Diseases. 2010. Informa, London.
Angular stomatitis; a common form of oral candidiasis, typically seen in patients with denture-related stomatitis, especially those in whom the denture needs adjustment. In others, it may be a sign of diabetes, nutritional deficiency, or immune defect.
Multifocal candidosis; lingual lesions.
Chronic hyperplastic candidosis; typically affects the tongue dorsum or the commissures of the lips; potentially malignant.
 
 
 
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