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Fungal Infections Cheat Sheet by

Cheat sheet for fungal infections of the feet and commonly used drug prescriptions.

Tinea Pedis

1. Acute Vesicular
T.ment­agr­ophytes and sometimes E.floc­cosum
 
Small vesicles, vesicu­lop­ustules and/or blisters typically seen near instep.
 
Treatment: Topical anti-f­ungal
2. Chronic Papulo­squ­amous
T.ruburm, sometimes T.ment­agr­ophytes
 
Often assoc. with hereditary palmop­lantar kerato­derma
 
Thick, boggy yellow to brown hyperk­era­tosis with peripheral scaling and/or fissures.
 
Usually bilateral. Charac­terized by a moccas­in-like distri­bution. Hands may be infected as well. most common pattern is for both feet and one hand to be involved. When both hands and feet are infected, T.ment­agr­ophytes is the organism
 
Treatment: Debrid­ement, topical anti-f­ungal and urea based emollient. May need oral
3. Chronic Interd­igital
T.ment­agr­ophytes and sometimes T.rubrum and E.floc­cosum
 
Fissuring, scaling, and maceration in the toes spaces.
 
Hyperh­idrosis is typically the cause
 
Treatment: Wash and DRY in between toes. Can use cotton balls to place in between toes to absorb moisture. Can use Drysol products for feet and shoes. Can use alcohol spray to dry out area. If wear boots, use boot dryer to prevent moisture. Use sprays not cream. If use cream, needs to be completely rubbed in. Clean shoes and change socks every day.
4. Acute Ulcerative
T.ment­agr­ophytes and can be compli­cated by grm- bacteria
 
Presents with macera­tion, weeping, and ulceration of the sole with assoc. white hyperk­era­tosis and odour
 
Need to rule our secondary infection by bacterial cultures and gram stains.
 
Treatment: Oral antibi­otics and topical anti-f­ungal
Most commonly caused by T. rubrum, T.ment­agr­oph­ytes. E.floc­cosum

Diagnosis of Mycolo­gical Conditions

Clinical Presen­tation
KOH micros­copic evaluation
Nail or skin clipped and placed in 10% KOH solution. Observe under microscope for septa and branching hyphae
Fungal Cultures
Sabour­aud's dextrose agar most common fungal mediym
Biopsy
Only used when concerned about malign­ancy. Can be examined with periodic acid schiff
Dermat­ophytes are group of fungi capable of colonizing kerati­nized tissues such as the stratum corneum, nails and hair. They use keratin as a source of nutrients.
Three Genera of Dermat­oph­ytes: 1) Micros­porum 2) Tricho­phyton 3) Epider­mop­hyton

Deep Fungal Infections

Majocchi's Granuloma
caused by T.rubrum
 
Starts as a fungal follic­ulitis and spreads into the dermis where it forms an inflam­matory nodule
 
clinic­ally, there is a erythe­matous plaque with indistinct borders and no central clearing
 
Oral therapy is necessary
Sporot­ric­hosis
Secondary to sporothrix schenckii
 
introduced into the dermis trauma­tically from thorns or splinters with the conidia
 
Happens in gardeners
 
Starts as a papule that becomes a painless ulcer with a ragged undermined red border. May follow lymphatics so wont respond to a topical.
 
Tx: potassium iodide PO, Amphot­ericine B IV, PO itraco­nazole or terbin­afine
Chromo­bla­sto­mycosis
Caused by species pf phialo­phora, fonsecaea and clados­porium
 
Nodule develops and ulcerates followed by scales, crust and scarring and keloid formation
 
Tx: local heat, same as for sporot­ric­hosis. Need to consult with infectious disease specialist

Polyenes- Inhibitors of Fungal Membrane Stability

MOA of Nystatin:
Binds to ergosterol and produced channe­ls/­pores that alter fungal membrane permea­bility -> leakage of cell contents -> cell death
Nystatin Cream
mitte: 15g or 30g tube or 450g jar, sig: apply to affected areas of skin on feet twice a day for four weeks
 
uses: candida infections (and to lesser extent dermat­ophyte infect­ions) of the skin and mucosa

Echino­can­dins- Inhibitors of Fungal Wall Synthesis

MOA
Target fungal cell wall synthesis by inhibiting synthesis of B-(1,3)-D glucans (a key component in the fungal cell wall). Disruption of cell wall integrity -> osmotic stress -> lysis of fungal cell -> fungal cell death
Ciclopirox (Topical)
1% cream, mitte: 45g tube sig: applied twice a day to affected areas of skin for 4 weeks. Good for dermat­ophyte and candida infections of the skin
 
1% lotion (loprox) mitte: 60ml bottle sig: applied twice a day to affected areas of skin for 4 weeks
 
Nail Lacquer 8% (Penlac) mitte: 6.6ml bottle with brush applicator sig: apply once a day to all affected nails for 6-9 months. Remove build up with alcohol or nail polish remover every 7-10 days. Loprox and penlac are good for skin and nails
 
MOA: Chelates metal ions in fungal membrane which increase fungal cell membrane permea­bility (inhibits membrane transfer system by interr­upting na/K/A­TPase) -> fungal cell death
 
Effective against some bacteria
 
exerts anti inflam­matory activity by inhibiting 5-lipo­xyg­enase and COX enzymes
Tolnaftate
topical: OTC powder (tinac­tin), gel and cream. unknown MO. Good for tinea versic­olour and mild dermat­ophytes infections of skin
Undecy­cline Acid
topical: OTC power (desenex), cream, spray (tolcylen) Unknown MOA. Used as preven­tative or adjunct. Uses: candida and mild dermat­ophyte infections of skin
Routine debrid­ement will help decrease fungal load and help with drug penetr­ation !!
  

Tinea Ungium/ Onychm­ycosis

Caused by:
E.floc­cosum, T.rubrum, T.ment­agr­ophytes
Toe nail infections may seem chronic and resistant to therapy due to:
1. Footgear occlusion
 
2. Nail trauma
 
3. Decreased circul­ation
 
4. Endogenous re-inf­ection

Other Fungal Infections

Candid­iasis
candida albicans is a yeast fungus
 
Clinical manife­sta­tions: Intert­rigo, OM, tinea pedis, follic­ulitis, paronychia
Candidal Paronychia
Treatment for 4-6 weeks w/ topical imidaz­oles, nystatin, ciclopirox or terbin­afine
Tinea Versic­olour
Caused by Malassezia furfur (yeast)
 
charac­terized by hypopi­gmented and/or hyperp­igm­ented macules w/ a fine scale localized to the trunk and thighs
 
Usually found in lipic rich areas and releases an acid that impacts melanin
 
Tx: topical azole cream/­sha­mpoo, terbin­afine gel, selenium sulfid­e,c­icl­oppirox
 
Oral Tx: flucon­azole, itraco­nazole. Oral terbin­afine is not effective

PREVENTION

1. Keep skin intact (prote­cted)
2. Prevent excessive moisture- don't let skin get excess­ively wet, change socks and wet shoes. Dry thoroughly after shower
3. Avoid contam­ina­tion- wear shower shoes. Put socks on first, disinfect shoes and bathtub

Inhibitors of the Ergosterol Synthesis Pathway

Allyla­mines

MOA:
Inhibit squalene epoxidase and prevents formation of lanosterol from squalene. lanosterol is needed for production of ergosterol which is needed for normal structure and function of plasma membrane. Accumu­lation of squalene which is a toxic metabolite will occur, making these drugs fungicidal
Oral Terbin­afine
Hepatic CYP metabo­lism, renal excretion (inact­ive). Highly lipid soluble so penetrates through nails. However, benefits do not outweigh risk for tx of OM.
 
Pulse dosing is effective as it is less overall drug so better on liver and less costly
Topical Terbin­afine:
1% cream or gel or 1% spray, mitte: 15g or 30g, tube or 30ml for spray sig: apply to affected areas of skin on feet once or twice a day
 
Uses: tinea pedis (demat­oph­ytes), tinea corporis, tinea cruris
Oral Terbin­afine:
Daily dosing: 250mg tablets mitte: 84 tablets sig: one tablet po daily for 12 weeks (LFT and CBC baseline lab tests with repeat at 4-6 weeks)
 
Pulse dosing: 250mg tablets, mitter: 42 tablets sig: two tables po daily for 1 week followed by 3 weeks off for three months then mitte 7 tablets sig: one tablet po daily for 7-21 days
 
Uses: OM, tinea pedis(­der­mat­oph­yte­s)/­cap­iti­s/c­rur­is/­cor­poris, and systemic fungal and candida infections
 
Contra­ind­icated in pts with liver disease or renal impairment
 
side effects: Hepato­tox­icity, neutro­penia, GI upset, skin reactions, taste/­smell distur­bances, renal and liver function impairment
Allylamine Hepato­tox­icity:
increase in serum transa­minase levels, sympto­matic liver injury occurs rarely, majority of cases resolve within 3-6mos of stopping meds
Allylamine Intera­ctions
warfarin and other CYP metabolism drugs, cimeti­dine, azole antifu­ngals, TCAs, SSRI, beta blockers, opioids, MAO inhibi­tors, anti-a­rry­thmics (ie digoxin),
 

Types of Onycho­mycosis

1. Distal Subungal Onycho­mycosis
Most common OM and most common organism is T.rubrum
 
Fungal penetrates distal hypony­chium or lateral nail fold region
 
Starts with subungual debris, yellowing and onycho­lysis
 
After many years, kerati­niz­ation of the distal nail bed occurs with loss of the nail grooves. Proximal nail plate then appears as a thick mound w/ neglected care, a ram's horn deformity develops
 
non dermat­ophytes such as asperg­illus niger can also cause OM (ddx is pseudo­monas infection)
2. Proximal Subungual Onycho­mycosis
Occurs secondary to fungi entering the proximal nail fold and then the matrix and nail plate.
 
infection involves the nail plate but the nail surface is intact
 
Debris develops under nail plate then onycho­lysis. Nail appears white and fluid may accumulate under nail
3. White Superf­icial Onycho­myo­cosis
Due to T.ment­agr­ophytes
 
Fungi infect the superf­icial nail plate. Nails are dry, soft, powdery white
 
Topical may work early on as it is on the nail plate
4. Candidal Onycho­mycosis
Caused by candida albicans
 
Nails are thick, white-­yellow or yellow­-brown
 
entire nail plate is involved often with parony­chia, inflam­mation and toe tip vesicu­lation
Compli­cations
Permanent nal matrix or nail bed changes, subungual ulcera­tion, secondary bacterial infection, possibly gangrene

Azoles

MOA:
Inhibit 14a-sterol demeth­ylase and prevent formation of ergosterol by preventing lanosterol conversion to ergost­erol. Fungis­tatic
Clotri­mazole (Topical)
1% cream mitte: 15g or 30g tubes or 500g tub sig: apply to affected areas on feet twice a day for four weeks.
 
Uses: superf­icial fungal and candida infections of stratum corneum and squamous mucosa (not good for hair and nails)
Miconazole(Topical)
2% cream or 2% spray mitte: 30g tube or 85g cans for spray sig: apple to affected areas twice a day for four weeks
 
uses: same as clotri­mazole
Ketoco­nazole(Topical)
2% cream mitte: 30g tube sig: apply to affected areas once-twice a day for 4 weeks.
 
uses: same as above
Efinac­onazole (Jublia) (Topical)
10% cream, applied daily to nails with no need to remove excess product
 
uses: DLSO, AE: dermatitis and vesicles on applic­ation sites
 
Gold standard for topical tx of OM
-Azoles inhibit hepatic P450 enzymes therefore drug to drug intera­ctions are an important consid­eration whenever they are used.
-Topical azoles are better for candida infections and are less expensive whereas allyla­mines are better against common dermat­ophytes but are more expensive
 

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  • Published: 11th April, 2022

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