What it is:This chapter is really three unrelated infections that all happen to be superficial fungal disease, bundled together because they're all "outpatient mycology." Vulvovaginal candidiasis (VVC)is a mucosal yeast infection almost every woman gets at least once. Oropharyngeal and esophageal candidiasis (OPC/EC), aka thrush, is a marker of local or systemic immune compromise. Dermatophyte infections(tinea) and onychomycosisare keratin infections of skin, hair, and nails that spread by contact, not by immune failure.
The core problem:Candida species live on and in you already, mucosal surfaces included. Disease happens when the local environment shifts in the yeast's favor (antibiotics wiping out competing bacteria, high estrogen, hyperglycemia, immunosuppression). Dermatophytes, by contrast, aren't normal flora. They arrive from another person, animal, or the soil, and they only survive on dead keratin, which is why they never invade past the skin, hair, or nail in an immunocompetent host.
What you do about it:Match the drug to the site. Mucosal Candida usually falls to a short topical or a single oral azole dose. Keratin infections need a drug that reaches keratin, which usually means oral therapy for hair and nail disease because topical drugs can't penetrate deep enough to cure it.
Organize this whole chapter around one question: is the organism opportunistic flora or an outside invader?Candida overgrowth means you look for what tipped the balance (antibiotics, diabetes, immunosuppression, pregnancy, dentures). Dermatophyte infection means you look for the exposure (locker room floor, an infected pet, a shared comb). That single distinction predicts the workup, the drug class, and the counseling.
C. albicanscauses 80–92% of symptomatic VVC episodes and most OPC. The rest, especially in recurrent VVC, skew toward non-albicans species, mainly C. glabrata, which matters because glabrata is intrinsically less susceptible to azoles. In most symptomatic VVC, no single precipitant is ever found, but recognized triggers include the jump in frequency once someone becomes sexually active, and antibiotic exposure (though this only tips a minority of women into an episode). For OPC, the list of precipitants is longer and more telling: inhaled or systemic steroids, antibiotics, immunosuppressants, chemotherapy or radiotherapy, dentures, xerostomia, smoking, diabetes and other endocrine disease (hypothyroidism, hypoparathyroidism, hypoadrenalism), and primary immunodeficiencies affecting lymphocytes, phagocytes, or IgA.
OPC is the most common opportunistic infection in HIV disease, and it tracks CD4 decline almost linearly. Risk climbs sharply as the CD4 count falls, especially once it drops below 200 cells/mm³, and rises further with a high viral load. An otherwise unexplained new case of thrush in a young adult should always prompt you to think about undiagnosed HIV.
Dermatophytes (genera Trichophyton, Epidermophyton, Microsporum) produce keratinases that let them digest and colonize keratin, so infection is limited strictly to hair, nails, and the stratum corneum of skin. They cannot invade living tissue, which is exactly why a dermatophyte infection almost never becomes systemic in a healthy host, unlike Candida, which can disseminate when host defenses fail. Reservoirs are human, animal, or soil, and transmission follows contact: prolonged moisture or sweating, maceration, intertriginous folds, shared combs or towels, and crowded living quarters like dorms or barracks all raise risk. Superficial cutaneous mycoses affect an estimated 20–25% of people worldwide, making this one of the highest-prevalence diagnoses in the whole handbook.
Every antifungal in this chapter targets one of two things: the fungal cell membrane's sterol, or the fungal cell wall, both of which are different enough from human cells to give a therapeutic window.
| Class | Mechanism | Why it matters clinically |
|---|---|---|
| Azoles(fluconazole, itraconazole, voriconazole, posaconazole, ketoconazole, clotrimazole, miconazole...) | Inhibit fungal lanosterol 14α-demethylase, blocking ergosterol synthesis | Ergosterol is the fungal analog of cholesterol. Deplete it and the membrane malfunctions. Mostly fungistatic, which is why duration and adherence matter more than with fungicidal drugs. |
| Polyenes(nystatin, amphotericin B) | Bind ergosterol directly and punch pores in the membrane | Fungicidal and hard to develop resistance against. Amphotericin also binds human cholesterol somewhat, which is the whole reason it causes nephrotoxicity and infusion reactions. |
| Allylamines(terbinafine, naftifine, butenafine) | Inhibit squalene epoxidase, an earlier step in the same ergosterol pathway | Blocking this step both starves the membrane of ergosterol andlets toxic squalene build up inside the cell, which makes allylamines fungicidal against dermatophytes. That's why terbinafine is the workhorse oral drug for tinea and onychomycosis. |
| Echinocandins(caspofungin, micafungin, anidulafungin) | Inhibit β-(1,3)-D-glucan synthase, a cell wall enzyme | Human cells have no cell wall at all, so this target is uniquely fungal. Excellent safety profile, which is why they're reserved for refractory or invasive Candida rather than first-line mucosal disease. |
| Ciclopirox | Chelates Fe³⁺/Al³⁺ cofactors fungal enzymes need | Broad-spectrum, disrupts membrane transport and metabolism generally. Formulated as a nail lacquer because it doesn't depend on a single narrow target. |
Topical drugs work fine on skin because the stratum corneum is thin and turns over fast. The nail plate is dense, avascular keratin, and a hair follicle sits below the surface, so a topical agent applied on top often can't reach fungicidal concentration at the site of infection. That's the whole reason onychomycosis and tinea capitis need oral therapy (or, for nails, a lacquer applied faithfully for up to a year) while tinea corporis clears with a cream in two weeks.
Intense vulvar itching is the dominant complaint, plus soreness, irritation, burning on urination, and dyspareunia. On exam: erythema, fissuring, a curdy "cottage cheese" discharge, satellite lesions, and edema.
| Type | Who gets it | What it looks like |
|---|---|---|
| Pseudomembranous(classic thrush) | Neonates, HIV or cancer patients, debilitated elderly, broad-spectrum antibiotics or inhaled steroids, dry mouth, smokers | Yellow-white "cottage cheese" or milk-curd plaques over erythema on buccal mucosa, tongue, gums, throat. Rubs off, sometimes leaving a bleeding surface. Tongue can look bald and depapillated. |
| Erythematous (atrophic) | HIV, broad-spectrum antibiotics, inhaled steroids | Painful red mucosa with few or no white plaques, usually dorsal tongue or hard palate. Can be acute or chronic. |
| Hyperplastic (candidal leukoplakia) | Smokers; uncommon in HIV | Thick, white, adherent keratotic plaques on buccal mucosa and lateral tongue that do notscrape off easily. Distinct from oral hairy leukoplakia and can progress to dysplasia or malignancy. |
| Angular cheilitis | HIV, denture wearers | Painful, red, cracking or fissuring lesions at one or both corners of the mouth. |
| Denture stomatitis | Elderly denture wearers with poor hygiene | Red, flat lesions confined to the mucosa under the denture, more often the maxillary plate. |
| Central papillary atrophy(median rhomboid glossitis) | Rare, men 3:1 over women | Rhomboid-shaped atrophic or hypertrophic plaque mid-dorsal tongue. May never fully resolve. |
Hyperplastic candidiasis is the one subtype that can turn into malignancy. A white plaque that won't scrape off, in a smoker, deserves more than a reflexive nystatin prescription.
Usually an extension of OPC downward, though the esophagus can be the only site involved. The distal two-thirdsis the most commonly affected segment. Classic triad is dysphagia, odynophagia, and retrosternal chest pain, though some patients are asymptomatic and a rare few present with epigastric pain instead. Unlike OPC, EC can carry constitutional signslike fever. Advanced disease shows mucosal friability and luminal narrowing; rare complications include perforation and aortoesophageal fistula.
The signature look is central clearing with an advancing red, scaly, elevated "active" border, the ring that gives ringworm its name (despite having nothing to do with worms). Location determines the name: pedis (feet), manuum (hands), cruris (groin), corporis (body), capitis (scalp), barbae (beard area). Pityriasis versicoloris grouped in this chapter's treatment table but is technically caused by Malassezia, a yeast, not a dermatophyte, which is a common source of confusion. Onychomycosisis nail invasion, usually starting distally under the nail plate and spreading proximally, causing thickening, discoloration, and crumbling.
Goal:complete resolution of symptoms. General measures matter regardless of drug choice: remove or correct any identifiable predisposing factor, avoid harsh soaps and perfumes, keep the area clean and dry, skip constrictive clothing and prolonged hot tub use, and skip douching entirely, it doesn't prevent or treat VVC. The evidence for oral lactobacillus is unclear, so don't count on it as monotherapy.
No route, product, or duration beats another for uncomplicated VVC.A single 150 mg oral fluconazole dose is therapeutically equivalent to a 7-day topical azole cream. Duration of therapy isn't critical either, since cure rates across different lengths haven't shown one is significantly better. Pick based on patient preference, cost, and access, not a belief that longer or oral is stronger.
Follow-up:treatment is working if symptoms resolve within 24–48 hourswith no adverse effects. Self-assessment is appropriate for most uncomplicated cases. If symptoms persist or recur, that's the trigger for further testing (culture, species identification) rather than repeating the same empiric therapy blindly.
Goals:clinical cure (elimination of signs and symptoms), rapid symptom relief, prevention of complications without early relapse, and minimizing future recurrences. Secondary goals: minimize toxicity and drug interactions from systemic agents, and maximize adherence by making sure the patient actually understands why and how to take the drug.
General approach:correct whatever's driving it when you can, meaning reassess or hold steroids, chemotherapy, and antimicrobials where feasible, fix oral hygiene, and resolve denture stomatitis. Choosing an agent means weighing adherence, whether the patient has enough saliva to dissolve a topical (a real problem in xerostomia), caries risk from sucrose- or dextrose-containing formulations, drug interactions, comorbidities like liver disease, how severe and where the infection is, and whether long-term suppressive therapy will be needed.
Topical first for OPC, systemic required for EC.Nystatin and clotrimazole are standard first-line for uncomplicated OPC in otherwise healthy adults and infants. Move to systemic therapy when OPC is refractory to topical treatment, the patient can't tolerate topical agents, disease is moderate to severe, or the patient is at high risk for disseminated or invasive candidiasis. Esophageal candidiasis, by contrast, always needs systemic therapy since a topical drug never reaches it.
For patients with frequent or severe recurrences of either OPC or EC, chronic suppressive therapyis recommended. See the dosing table below for the full initial, refractory, and suppressive regimens with their strength-of-evidence grades.
General approach:keep the infected area dry and clean, and limit exposure to the reservoir (treat the pet, stop sharing the towel, dry the shower shoes). Topical therapy is first-line for skin infections.Oral therapy is preferred when disease is extensive or severe, or whenever the infection involves hair (tinea capitis) or nail (onychomycosis), because topical drugs can't penetrate deeply enough to cure those sites (see the pathophysiology unlock above).
A huge, angry patch of tinea corporis still typically responds to topical therapy. A tiny patch of tinea capitis in a child still needs an oral drug. The decision hinges on wherethe infection lives, not how bad it looks.
Duration is the other thing that trips people up here: skin infections clear in one to a few weeks, but nail infections need monthsof therapy (up to 48 weeks for topical nail lacquers, 6–12 weeks for oral terbinafine) because you're waiting for infected keratin to literally grow out, not for the drug to "kill faster."
| Agent | Formulation | Regimen |
|---|---|---|
| Nonprescription topical vaginal | ||
| Butoconazole | 2% cream | 1 applicator × 3 days |
| Clotrimazole | 1% cream | 1 applicator × 1 day |
| 100 mg tablet | 1 tablet × 7 days | |
| 2% cream / 200 mg tablet | 1 applicator or tablet × 3 days | |
| 10% cream / 500 mg tablet | 1 applicator or tablet × 1 day | |
| Miconazolea | 2% cream | 1 applicator × 1 day |
| 100 mg suppository | 1 suppository × 7 days | |
| 200 mg suppository / 1200 mg ovule | × 3 days, or ovule × 1 day | |
| Ticonazole | 2% cream | 1 applicator × 3 days |
| 6.5% cream | 1 applicator × 1 day | |
| Prescription topical | ||
| Nystatin | 100,000 unit vaginal tablet | 1 tablet × 14 days |
| Terconazole | 0.4% cream | 1 applicator × 7 days |
| 0.8% cream | 1 applicator × 3 days | |
| Oral | ||
| Fluconazole | 150 mg tablet | 1 tablet × 1 day no product superior to another |
a FDA warns of possibly increased warfarin effect with concomitant miconazole.
| Agent | Regimen (grade) | Notable side effects |
|---|---|---|
| Clotrimazole troche | 10 mg, dissolve slowly 15–20 min, 5×/day (B-2) | Altered taste, mild nausea, vomiting |
| Nystatin suspension | 100,000 units/mL, 5 mL swish & swallow QID (B-2) | Nausea, vomiting, diarrhea |
| Miconazole buccal tablet | 50 mg mucoadhesive, once daily (A-1) | Diarrhea, headache, nausea, dysgeusia, vomiting |
| Fluconazole | 100–200 mg orally daily (A-1) | GI upset; hepatitis uncommon |
| Itraconazole solution | 200 mg orally daily (A-2) | GI upset; rarely hepatotoxicity, CHF, pulmonary edema with long-term use |
| Posaconazole suspension | 400 mg orally daily with a full meal (A-2) | GI upset, fever, headache; ↑LFTs uncommon |
| Agent | Regimen (grade) |
|---|---|
| Itraconazole solution | 200 mg orally daily (A-3) |
| Voriconazole | 200 mg orally BID (>40 kg), empty stomach (A-3) |
| Posaconazole suspension | 400 mg BID × 3 days, then 400 mg daily × 28 days (A-2) |
| Amphotericin B oral suspension | 1–5 mL swish & swallow QID (B-2) |
| Amphotericin B deoxycholate IV | 0.3–0.7 mg/kg/day (B-2) |
| Caspofungin IV | 50 mg daily (B-2) |
| Micafungin IV | 150 mg daily (B-2) |
| Anidulafungin IV | 200 mg daily (B-2) |
| Agent | Regimen (grade) |
|---|---|
| Fluconazole | 200–400 mg (3–6 mg/kg) orally daily (A-1) |
| Itraconazole solution | 200 mg orally daily (A-3, or A-2 if refractory) |
| Posaconazole suspension | 400 mg orally BID (A-3) |
| Voriconazole | 200 mg orally BID (>40 kg) (A-3) |
| Caspofungin IV | 50 mg daily (B-2) |
| Micafungin IV | 150 mg daily (B-2) |
| Anidulafungin IV | 100 mg day 1, then 50 mg daily (B-2, refractory) |
| Amphotericin B deoxycholate IV or lipid-based | 0.3–0.7 mg/kg/day, or 3–5 mg/kg/day lipid formulation (B-2) |
Voriconazole IV and echinocandins are generally reserved for refractory esophageal disease (A-1). Fluconazole outperforms ketoconazole (A-1); itraconazole solution outperforms the capsule and is better absorbed on an empty stomach (A-1).
| Type | Topical | Oral |
|---|---|---|
| Tinea pedis | Butenafine daily · sertaconazole BID · luliconazole daily · naftifine cream/gel daily | Fluconazole 150 mg once weekly × 1–4 weeks |
| Tinea manuum | Ciclopirox BID | Ketoconazole 200 mg daily × 4 weeks |
| Tinea cruris | Clotrimazole BID · luliconazole daily · naftifine cream daily | Itraconazole 200–400 mg/day × 1 week |
| Tinea corporis | Econazole, ketoconazole cream, luliconazole, naftifine cream (all daily) · miconazole, oxiconazole, sulconazole, terbinafine, tolnaftate, haloprogin (all BID) · triacetin TID | Terbinafine 250 mg/day × 2 weeks |
| Tinea capitis | Shampoo only, as adjunct to oral therapy or for asymptomatic carriers | Terbinafine 250 mg/day × 4–8 weeks |
| Tinea barbae | Ketoconazole twice weekly × 4 weeks · selenium sulfide daily × 2 weeks | Ketoconazole 200 mg/day × 4 weeks · itraconazole 100–200 mg/day × 4–6 weeks · griseofulvin 500 mg/day × 4–6 weeks |
| Pityriasis versicolor (Malassezia, not a true dermatophyte) | Clotrimazole, econazole, ketoconazole, miconazole, oxiconazole (cream only), sulconazole (all daily or BID) · tolnaftate TID · haloprogin BID | Ketoconazole, fluconazole, or itraconazole 200 mg daily × 3–7 days |
| Onychomycosis | Ciclopirox 8% lacquer nightly up to 48 weeks · efinaconazole 10% solution daily × 48 weeks (toenail) · tavaborole 5% solution daily × 48 weeks (toenail) | Terbinafine 250 mg/day × 6 weeks (finger) / 12 weeks (toe) · itraconazole 200 mg BID × 1 wk/month × 2 months (finger), or 200 mg daily × 12 weeks (toe) · fluconazole 50 mg daily or 300 mg weekly × ≥6 months (finger) or 12 months (toe) |
Itraconazole absorption is formulation-dependent and direction-flips between indicationsin this chapter. For OPC, the solutionis preferred and taken on an empty stomach. For onychomycosis, only the capsulehas been studied and it should be taken with foodfor better absorption. Mixing these up is an easy way to lose points, or under-dose a patient.
Azoles cover the majority of regimens in this chapter because they're effective, oral or topical, and generally well tolerated. Fluconazole is the default oral choice for Candida infections, given both as a single 150 mg dose for VVC and as a daily or weekly regimen for OPC, EC, and suppressive therapy. Itraconazole and posaconazole step in for fluconazole-refractory disease or when broader mold coverage matters. Voriconazole is reserved further down the refractory ladder and brings a signature side effect: reversible visual disturbances (altered light perception, photopsia, chromatopsia, photophobia), plus a real risk of hallucinations or confusion, worth flagging before a patient drives home from clinic.
The resistance catch:C. glabrata, more common in recurrent VVC and in patients with repeated azole exposure, is intrinsically less azole-susceptible than C. albicans. A patient who keeps failing fluconazole for recurrent VVC or OPC is a candidate for species identification, not just a longer course of the same drug.
Nystatinis too toxic systemically to give IV, so it's confined to topical and oral (non-absorbed) use, swish-and-swallow suspension or a vaginal tablet. It's a mainstay first-line option for uncomplicated OPC precisely because it stays local and side effects are limited to GI upset.
Amphotericin Bis reserved for refractory mucosal disease or invasive infection. The oral suspension is used for swish-and-swallow refractory OPC (not absorbed, acts locally), while IV amphotericin B deoxycholate is a systemic option for refractory OPC/EC with real toxicity: fever, chills, sweats, nephrotoxicity, electrolyte disturbances, and bone marrow suppression. Lipid-based formulations reduce nephrotoxicity and appear as an alternative for refractory esophageal candidiasis.
Caspofungin, micafungin, and anidulafungin are IV-only and appear in this chapter specifically for fluconazole-refractory OPC and esophageal candidiasis. Because they hit a cell wall target humans don't have, adverse effects are comparatively mild: fever, headache, infusion-related reactions in under 5% (rash, facial swelling, pruritus, vasodilation), hypokalemia, transaminase elevation, anemia, and neutropenia. Anidulafungin uses a loading dose strategy for refractory EC (100 mg day 1, then 50 mg daily) that the other two don't.
Terbinafineis the dominant oral agent for dermatophyte disease (tinea corporis, capitis, and onychomycosis) because it's fungicidal against dermatophytes and accumulates in keratin, letting it keep working after the dosing course ends. Topical allylamines (naftifine, butenafine) and a long list of topical azoles (econazole, oxiconazole, sulconazole, luliconazole, sertaconazole) and other agents (ciclopirox, tolnaftate, haloprogin, triacetin, undecylenic acid) cover the various tinea sites; no single one is clearly superior, and choice mostly comes down to dosing frequency, cost, and formulation.
Griseofulvinonly shows up in this chapter for tinea barbae (500 mg/day × 4–6 weeks), a reminder that it's an older agent that's been largely displaced by terbinafine and the azoles elsewhere but still has a niche.
Ciclopirox 8% lacquer, efinaconazole 10% solution, and tavaborole 5% solution are all applied topically to the nail, daily or nightly, for up to 48 weeks. That timeline isn't about slow killing, it's about waiting for the entire infected nail plate to grow out and be replaced by clean keratin, since a topical agent applied on the surface of an avascular structure penetrates unevenly at best. Cure rates with topical monotherapy are correspondingly modest, which is why extensive or severe onychomycosis usually goes straight to oral therapy instead.
| Population | What changes |
|---|---|
| Complicated VVC(immunocompromised or uncontrolled diabetes) | Treat for 10–14 daysinstead of the standard 1–3 day uncomplicated course. |
| Pregnancy, VVC | Topical imidazole for 7 days.Oral therapy is avoided since higher fluconazole doses have been linked to birth defects. |
| Recurrent VVC | 10-day initial course(e.g., oral fluconazole 150 mg daily), then 6 months of suppressive therapywith oral fluconazole 150 mg once weekly. |
| Frequent/severe recurrent OPC or EC | Chronic suppressive antifungal therapy is recommended (A-1 evidence). |
| HIV / immunocompromised OPC | Lower threshold to move to systemic therapy; recheck for treatment failure sooner given higher risk of progression or dissemination. |
The reflex answer to VVC is often "just give fluconazole 150 mg × 1," but that's wrong in pregnancy. High-dose oral fluconazole carries a birth defect signal, so pregnant patients get a full 7-day topical imidazole course instead.
| Parameter | When | Watching for |
|---|---|---|
| Symptom resolution(VVC) | 24–48 hours after starting therapy | Treatment success; self-assessment is appropriate for uncomplicated cases |
| Symptom resolution(OPC) | 48–72 hours | Improvement can appear early, but the patient still needs to finish the full course to prevent relapse |
| Oral cavity re-exam | End of treatment course, sooner if worsening | Persistent plaques (consider azole resistance, non-albicans species, or reassess predisposing factors) |
| Liver function | With prolonged itraconazole, posaconazole, voriconazole, or ketoconazole use | Hepatotoxicity, transaminase elevation |
| Renal function & electrolytes | During IV amphotericin B deoxycholate therapy | Nephrotoxicity, hypokalemia, hypomagnesemia |
| Visual symptoms | Each visit while on voriconazole | Photopsia, chromatopsia, or other visual disturbance, plus confusion or hallucinations |
| Recurrence pattern | Ongoing, any entity | Whether the patient needs suppressive/maintenance therapy rather than repeated acute courses |
| Nail appearance(onychomycosis) | Every few months during a 6–12 month course | Clear nail growing out from the base confirms response; treatment is judged by regrowth, not by how the diseased tip looks |