1

Dr. Cheng Tin-sik Dr. Cheng Tin-sik 鄭天錫醫生鄭天錫醫生Specialist in Dermatology & Venereology Specialist in Dermatology & Venereology

(Social Hygiene Service, CHP, DH)(Social Hygiene Service, CHP, DH)

Clinical Assistant Professor (Hon.), CUHKClinical Assistant Professor (Hon.), CUHK

Superficial fungal Superficial fungal infection infection

15 October 201115 October 2011

Superficial fungal Superficial fungal infection infection

15 October 201115 October 2011

Superficial fungal infections

Prevalence: ~ 29.4 million cases Annual economic burden

USD$1,953,000,000 in expenses USD$450,000,000 in indirect costs

Ranked 4th among 22 skin disease groups evaluated in terms of direct costs USD$1.7 billion with 74% of costs attributable to prescription

drugs an estimated average of 4,124,038 ± 202,977 annual visits during

the study period (N.B. 2010: 308 million)

2

• Dermatophyte infection one of the most common human infectious diseases in the

world 3 genera: Trichophyton, Microsporum, Epidermophyton

• Superficial candidosis Involving the skin, nails, and mucous membranes of the mouth

& vagina Candida albicans 80-90%

• Pityriasis versicolor

4

Superficial fungal infection: Dermatophytosis

Clinical features asymmetrical active margin with central

clearing fungal infection elsewhere

Investigation skin scraping nail clipping

microscopy, culture or histology

5

Practical tips for management(Dermatophyte infection)

6

Direct examination

microscopy of skin, nail and hair specimens with 10% KOH simplest cheapest immediate identification of spores and hyphae

e.g. confirms the dx of tinea capitis Differentiates btw endothrix or ectothrix infection

Drawbacks of KOH microscopy Sensitivity:

tinea capitis: 67 to 91% tinea pedis 73.3% (95% CI: 66.3 to 79.5%) Onychomycosis: 80%

Low specificity: 42.5% (36.6 to 48.6%); 72% (onychomycosis) Unable to differentiate between dermatophytic /

Nondermatophytic infections

7Direct examination - Stains

Staining increases sensitivity of direct examination by facilitating the visualization of fungal structures

Stains that can be associated to clearing agents Chlorazol black E (CBE)

stains only the fungal structures & excludes many artefacts KOH–CBE as sensitive as histopathologic analysis using PAS stain

94.3% vs. 98.8%, NS

Blue–Black Ink permanent (Parker Quink) stains fungal elements in deep blue

Congo red binds to polysaccharides of the fungal cell wall, particularly beta-D-glucans

Fluorochromes Calcofluor white

Most convenient binds to chitin may be used in KOH Fungal elements appear blue or green

fluorescence microscope sensitivity significantly higher with calcofluor than with KOH

88% and 72%, respectively, P = 0.0116 (Abdelrahman et al)

Tinea capitis occurs predominantly in prepubertal childrenSource:

infected puppies & kittens close contact with infected children

Usually caused by Trichophyton tonsurans, Microsporum canis, Microsporum audouinii The causative agent varies in different geographical areas.

In the USA and in some cities in the UK, T. tonsurans is the most common cause In Hong Kong, tinea capitis is usually caused by M. canis

Pet exposure: associated with M. canis

8

Tinea capitis Three patterns of invasion:

Ectothrix Arthroconidia found around the hair shaft

Endothrix Arthroconidia within the hair shaft

Favus Hyphae and air spaces found within the hair shafts caused by T. schoenleinii infection

results in a honeycomb destruction of the hair shaft

fluorescence under Wood’s light presence of pteridine

Many species producing a small spore ectothrix pattern T. schoenleinii

9

Tinea capitis

Clinical features: Itch Scalp scaling Irregular, patchy hair loss Lymphadenopathy More severe inflammatory responses:

Erythema Pustules / Pustular boggy masses Crusting Scarring alopecia Id reaction: itchy papules around the outer helix of the ear

10

Tinea capitis Seborrhoeic pattern

dandruff-like scaling on the scalp Prepubertal children p/w suspected seborrhoeic dermatitis

on the scalp: presumed to have tinea capitis until proven otherwise

Black dot pattern patchy alopecia with black stumps of broken hair shaft:

due to breakage of hair near the scalp

Kerion boggy masses covered with pustular folliculitis scarring may ensue afterwards

Favus most frequently caused by T. schoenleinii yellow saucer-shaped adherent crusts made up of hyphae

and spores occur around the hairs

11

Tinea capitis DDx

Seborrhoeic dermatitis scaling of the scalp without significant hair loss

Alopecia areata usually complete alopecia in the affected areas (vs patchy alopecia in T. capitis) little or no scaling or inflammation Exclamation mark hair

Psoriasis usually more scaling is present.

Traction alopecia stress on the hair & hair shaft by tight braiding

Trichotillomania obsessive compulsive disorder of pulling one's own hair hair of various lengths & no scalp involvement

12

scrape affected areas with a blunt scalpel blade to collect affected hairs, broken-off hair stubs, and scalp

scale also pluck hairs from affected areas if possible

not suitable for detecting carriers No abnormal areas to take scrapings

Store at room temperature. No need to refrigerate

If not possible / in an asymptomatic carrier brush with an unused toothbrush or cytobrush

passing the brush through the hair ten times in the affected area

in suspected carriers: different areas of the scalp

send the brush for culture

13

Tinea capitis - Ix

Tinea faciei

Asymmetric erythematous eruption Affecting the glabrous skin of the face the redness & the scaling border usu. less pronounced typical annular pattern frequently absent +/- pustules

Clue: the presence of red borders which are well demarcated and are often serpiginous.

Usually caused by T. rubrum or T. mentagrophytes var. mentagrophytes.

14

Tinea faciei: DDX

Seborrhoeic dermatitis usually symmetrical and the lesions are not well demarcated.

Photodermatitis usually symmetrical sparing areas that are relatively protected from the sun

Perioral and contact dermatitis Rosacea Lupus erythematosus Acne vulgaris Psoriasis

15

Tinea manuum

Diffuse hyperkeratosis of the palms and digits Involvement of palmar creases

Usually affecting only one hand usually in a patient with tinea pedis resulting in ‘two

feet and one hand syndrome’. +/- Tinea unguium of the involved hand Dermatophytes involved:

the same as those for tinea pedis and tinea cruris T. rubrum, T. mentagrophytes, and E. floccosum

16

Tinea manuum

Conditions confused with tinea manuum xerosis, eczema & chronic irritant contact dermatitis

chronic scaling of the palms both palms usually involved & the border not well demarcated

Psoriasis affecting the palms presence of well demarcated scaling plaques occurring

bilaterally plaques more elevated & erythematous +/- lesions of psoriasis in other parts of the body

17

Tinea corporis

dermatophyte infection of the glabrous skin of the trunk and extremities T. rubrum and T. mentagrophytes

Pink-to-red annular or arciform patches and plaques scaly or vesicular borders

expanding peripherally with a tendency for central clearing Inflammatory follicular papules may be present at the active border

18

Majocchi’s granuloma follicular epithelium grossly involved resulting in folliculitis

in the setting of immunosuppression localized (e.g. a potent topical steroid) systemic immunosuppression

Mainly caused by T. rubrum C/F: inflammatory papular, pustular or nodular lesions mainly on the limbs or

face Tinea gladiatorum

transmission of a dermatophyte infection from close skin-to-skin contact of athletes

Tinea incognito Topical steroids modify the presentations of fungal infections

the inflammatory response decreased well defined margins or scaling absent diffuse erythema +/- scales papules and pustules may be found

19

T. corporis: DDx

Nummular eczema the coin-shaped lesions usually multiple & located on the extremities usually no central clearing

Pityriasis rosea The herald patch is frequently mistaken for tinea

Usu. followed by a generalized eruption within a few weeks

Annular psoriasis usually thicker and more scaling than those of fungal infections

Erythema annuulare centrifugum the scale is inside the elevated border

Granuloma annulare no scaling and the border is more indurated

20

21

Tinea cruris

Flexural tinea usu. occurs in the groin N.B. 3 major causes of a groin rash:

tinea cruris, candidiasis, intertrigo Rare in axillae or submammary folds Rare to extend onto the scrotum

Infection from patient’s own feetWell defined patch with leading scaly edgeAsymmetricalMay extend to gluteal fold & buttocks

T. cruris: DDx

Candidiasis Erythrasma Intertrigo Flexural psoriasis Seborrhoeic dermatitis Contact dermatitis Pseudoacanthosis nigricans Hailey-Hailey disease Extramammary Paget’s disease Langerhan’s cell histiocytosis

22

Tinea pedis23

Interdigital type: erythema, scaling and maceration with fissures found in

the web spaces Esp.between the 4th and 5th toes

Moccasin type: diffuse scaling on the soles extending to the sides of the

feet Ulcerative type:

begins in the 2 lateral interdigital spaces extends to the lateral dorsum and the plantar surface of

the arch The lesions of the toe webs are usually macerated and

have scaling borders Vesiculobullous type

vesicular eruptions on the arch or side of the feet are found Pompholyx like lesions on the hands are the classic

dermatophytid reaction

Tinea pedis

Dyshidrotic eczema & contact dermatitis frequently confused with the vesiculopustular type of tinea pedis the vesicles are usually smaller and rarely progress to pustules

Other differential diagnoses eczema, soft corn juvenile plantar dermatosis Erythrasma bacterial infections e.g. pseudomonas

Psoriasis/pustular psoriasis secondary syphilis

24

Tinea unguium25

dermatophytes & non-dermatophytes can cause onychomycosis yeasts or non-dermatophyte moulds: ＜ 10% Dermatophytes: ~90% of cases

Toenail ＞ fingernail infections usually tinea pedis +ve

Tinea unguiumClinical presentations:

26

Distal and lateral subungual onychomycosis (DLSO): Discolouration, subungual hyperkeratosis, distal onycholysis start at

the hyponychium spreading proximally Proximal subungual onychomycosis (PSO):

Invasion of the nail unit under the proximal nail fold and spread distally usually associated with immunosuppressed conditions, e.g. HIV

infection Superficial white onychomycosis (SWO):

Invasion of the superficial layers of the nail plate but do not penetrate it leading to a white, crumbly nail surface

Total dystrophic onychomycosis complete dystrophy of the nail plate

Tinea unguium: specimen collection

Wipe with 70% alcohol before sampling. Superficial infection:

scrape the surface of the nail with scalpel Nail clipping:

sample the full thickness of the nail as proximal as possible Include the scrapings of s/u debris

Put the samples into folded dark paper squares and store at room temperature

27

Tinea unguium: investigations Nail clippings / scrapings x fungal microscopy and culture Positive results:

Dermatophytes: if either microscopy or culture is positive. Candida species: if both microscopy and culture are positive. Non-dermatophytes: if both microscopy and culture are positive on at least two samples taken at different times.

Non-dermatophyte moulds: rare causes of nail infection usually colonize nails as a secondary infection following trauma or an underlying dermatophyte infection.

microscopy of nail specimens with 10% KOH Sensitivity: 80%; Specificity: 72% Unable to differentiate between dermatophytic / Nondermatophytic infections

Culture a few weeks for definite identification Sensitivity: 59%; Specificity: 82%

false negative common culture identification complicated

Based on macroscopic & microscopic morphology and pigmentation dermatophyte isolates from patients on antifungal treatment generally do not show characteristic morphology on culture

High false-negative rates A negative test cannot definitively exclude fungal nail infection. Repeat if clinical suspicion high

Periodic acid schiff (PAS) stain for the presence of dermatophytes higher sensitivity (vs. KOH preparations)

Karimzadegan-Nia et al, 2007; Lawry et al, 2000; Weinberg et al, 2005

28

29Non-dermatophyte moulds

comprise a large group of heterogeneous filamentous fungi usually considered saprophytic under suitable conditions, some of these species may cause true infections

Nail invasion by NDM considered uncommon prevalence rates: ranging from 1.45% to 17.6% only a few species of moulds are regularly identified as causing onychomycosis

Acremonium sp, Aspergillus sp, Fusarium sp, Onychocola canadiensis, Scytalidium sp and Scopulariopsis brevicaulis

NDM: sensitive to cycloheximide use the Sabouraud’s dextrose agar without cycloheximide

The criteria for establishing a diagnosis of NDM nail infection: 1) repeated isolation of the fungus on direct examination of well-sampled specimens 2) repeated positive culture of a species of fungus consistent with the finding on direct microscopic

examination 3) failure to isolate dermatophytes in the culture

30Management of superficial fungal infection: Gerneral

principles

General advice: e.g avoid sharing of towels and clothing; keep the affected areas cool and dry; frequent washing of clothes, linen; etc.

Topical antifungals Advantages of topical antifungals vs oral antifungals

Less risk of adverse effects Fewer drug interactions Laboratory tests not needed to monitor treatment

Prolonged use of a steroid-antifungal cream may not cure the infection May cause striae

Systemic treatment Tinea captitis & tinea unguium severe or extensive disease Failed topical treatment topical treatment may be tried in most other superficial fungal infections.

Topical preparations for fungal infections31

applied to the affected area for 2-4 weeks including a margin of several

centimetres of normal skin Continue for 1 or 2 weeks after

the last visible rash has cleared Azoles

Bifonazole Clotrimazole (Canesten,

Lotremin) Econazole Ketoconazole Miconazole (Daktarin) Sulconazole Tioconazole (Trosyd)

Allylamine Terbinafine Naftifine

Ciclopiroxolamine Polyenes

Nystatin Thiocarbamates

Tolnaftate Tolciclate

Others Whitfield's ointment Undecylenic alkanolamide

Tinea capitis: treatment

A +ve microscopy / +ve culture of skin scrapings recommended before starting treatment

Griseofulvin 500 mg once daily or 250 mg BD; 10-25 mg/kg/d x 8–10/52; standard treatment in the pediatric population

Terbinafine 250 mg once daily x 4/52 not licensed for tinea capitis in the UK FDA approved for children > 4 yr ( < 25 kg: 125 mg/d; 25-35 kg: 187.5mg/d; > 35kg: 250mg/d)

Adjunctive treatment topical antifungal treatment 2x/week

ketoconazole shampoo, selenium sulphide shampoo, or topical terbinafine cream during the first 2 weeks of treatment to reduce transmission.

oral antibiotic e.g. flucloxacillin & an antifungal cream active against Gram (+) organisms (e.g. miconazole, clotrimazole, econazole) For secondary infection

32

Seven studies, 2163 subjects Subgroup analysis

terbinafine was more efficacious than griseofulvin in treating Trichophyton species (1.616; 95% CI = 1.274- 2.051; P < 0.001)

griseofulvin was more efficacious than terbinafine in treating Microsporum species (0.408; 95% CI = 0.254-0.656; P < 0.001)

Both griseofulvin and terbinafine demonstrated good safety profiles in the studies.

33

J Am Acad Dermatol 2011;64:663-70

Tinea capitis: Management of contacts

Contacts screened for clinically silent fungal carriage on the scalp: household members people closely associated with the infected person screening in schools is not necessary

Asymptomatic carriers should be detected and treated Take samples for microscopy and culture Management:

treat with selenium sulphide ketoconazole shampoo povidone iodine shampoo (shown to be more efficacious) people with a heavy growth / high spore count on brush culture

may require oral antifungal treatment

34

Tinea corporis / cruris topical terbinafine (moderate evidence) & topical imidazoles (weak

evidence) Efficacious in the treatment of fungal infections of the groin and body

Insufficient trial evidence: superiority of one preparation over another imidazoles currently the most commonly used topical treatments for fungal infections of the

skin

For inflamed lesions topical antifungal combined with a mildly potent corticosteroid: <= 1 wk Do not give a corticosteroid preparation alone Combination preparation:

beware of the increased risk of adverse effects with topical corticosteroids in occluded areas e.g. groins

35

Tinea pedis: treatment

Allylamines, azoles, butenafine, ciclopiroxolamine, tolciclate & tolnaftate all efficacious relative to placebo in the treatment of tinea pedis

Allylamines greater effectiveness when used for longer

The effectiveness of azoles improved over time No difference in treatment failure rates between any of the individual azoles

allylamines more efficacious than azoles The meta analysis of 8 trials and outcomes from 962 participants supports the finding that

allylamines are more effective than azoles when applied for between 4 to 6 weeks

36

Terbinafine and itraconazole more effective than no treatment (placebo)

Terbinafine (two weeks treatment) more effective than itraconazole (two weeks treatment)

Terbinafine more effective than griseofulvin

No significant difference in effectiveness found between: two weeks of terbinafine vs four weeks of itraconazole fluconazole vs either itraconazole or ketoconazole griseofulvin and ketoconazole different doses of fluconazole

Recommendation: to treat initially with topical azoles and use topical allylamines for azole treatment failures

37

Tinea unguium: treatment Confirm the diagnosis before treatment

positive microscopy or culture

Mild and superficial TU: Superficial onychomycosis Mild distal onychomycosis Lateral onychomycosis

topical tx with amorolfine 5% nail lacquer 6 /12 (fingernail) 9–12 /12 (toenail)

Amorolfine 5% nail lacquer 1x/wk not approved in the USA 6% treatment failure rates found after 1 month of treatment

data collected on a very small sample of people these high rates of success might be unreliable.

38

Tinea unguium: treatment

Ciclopiroxolamine 8% nail lacquer: QD Combining data from 2 trials of ciclopiroxolamine versus placebo:

Treatment failure rates: 61% & 64% for ciclopiroxolamine These outcomes followed long treatment times (48 weeks)

ciclopiroxolamine -> a poor choice for nail infections

Butenafine 2%: treatment failure rate: 20%

Used in combination with oral treatment: increase cure rates No good evidence from randomized controlled trials on other topical

treatments for dermatophyte nail infections: Topical tioconazole / salicylic acid/ undecenoates.

Topical treatments for fungal infections of the skin and nails of the foot. (Review) 22Copyright © 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.

Tinea unguium: treatment Oral terbinafine

250 mg daily: 6/52 for F/N, 12/52 x T/N oral terbinafine may be more effective than oral itraconazole (weak evidence from RCTs) A meta-analysis of 18 studies: a mycological cure rate of 76%.

fewer drug interactions vs. azole antifungals CYP2D6 inhibitor: inc. effect of TCA; Beta blockers & antipsychotics (possible)

adverse effects: usually mild and transient

Oral itraconazole 200 mg bd x 1 wk per pulse, 2 to 3 pulses oral itraconazole may be less effective than oral terbinafine (weak evidence from RCTs) A meta-analysis of 6 studies on pulse itraconazole: mycological cure rate of 63% Pulsed therapy recommended:

no good evidence that it is less effective than continuous therapy; risks of adverse effects may be reduced N.B. this dosing regimen is not licensed

Take with fatty meal/ acidic beverage

40

Pityriasis versicolor

Commensal yeast: Malassezia species occurs most frequently in hot and humid tropical climates

also prevalent in temperate climates Malassezia has an oil requirement for growth

increased incidence in adolescents predilection for sebum-rich areas of the skin use of bath oils and skin lubricants may enhance disease

development Pityriasis versicolor occurs

when the budding yeast form transforms to the mycelial form Various factors implicated:

e.g. hot and humid environment, oily skin and excessive sweating.

41

Multiple white, pink to brown, oval to round coalescing macules and patches mild and fine scaling

mainly found on the seborrhoeic areas especially the upper trunk and shoulders also found on the face, scalp, antecubital fossae, submammary regions and groins

often confluent and quite extensive

Flexural areas: sometimes referred to as ‘inverse’ pityriasis versicolor Associated scale may be shown by scratching of the skin surface Produce chemicals that reduce the pigment in the skin, causing whitish

patches azelaic acid, pityriacitrin and malassezin

ability of the fungus to filter sunlight and the screening effect of tryptophan-dependent metabolites absence of pigmentation in exposed areas

42

Wood's light: a yellow-green fluorescence may be observed in affected

areas due to pityrialactone

Skin scrapings x microscopy (KOH): clusters of yeast cells and long hyphae

like "spaghetti and meatballs“

Malassezia species: difficult to grow in the laboratory scrapings may be reported as "culture negative“ grows best if a lipid such as olive oil added to Littman agar

culture medium

43

Malassezia species

Pityriasis versicolor not considered to be contagious Infection not due to poor hygiene

Inhabit the skin of about 90% of adults without causing harm suppresses the expected immune response to it in some:

allowing it to proliferate & cause a skin disorder often without any inflammatory response.

44

Malassezia Members of the genus Malassezia

formerly classified as Pityrosporum species P. ovale (oval cells) and P. orbiculare (round

cells) Malassezia is the correct name for this

genus Identification of isolates from pityriasis

versicolor (PV) using the new nomenclature: the causal species more likely to be M.

globosa or M. sympodialis Malassezia furfur believed to be the

causal organism of PV prior to the description of the new species in 1996

45

Malassezia furfur

Malassezia sympodialis

Malassezia globosa

Malassezia restricta

Malassezia obtusa

Malassezia slooffiae

Malassezia pachydermatis

Malassezia yamatoensis

Malassezia dermatis

Malassezia nana

Malassezia japonica

Treatment

consider prophylactic treatment e.g. prior to exposure warm humid

environments or sunshine ketoconazole 2% shampoo once daily x a

maximum of 3 days prior to sun exposure limited evidence that weekly or monthly doses of

oral antifungals are effective in preventing recurrence, but optimal regimens have not been established

46

Treat with shampoo Ketoconazole 2% shampoo once-daily to

affected areas for 5/7 Lather and leave it on for 5’ then rinse off

Selenium sulphide 2.5% shampoo once-daily to the affected areas for 7 days. off-label indication may cause skin dryness and irritation Smell: unpleasant Lather and leave it on for 10’ then rinse off

For small affected areas: Imidazole creams 2–3 weeks

e.g. clotrimazole, econazole, ketoconazole, or miconazole

Systemic Treatment: itraconazole 200 mg once daily for 7 days fluconazole 50 mg once daily for 2–4 weeks

(licensed) or a 300 mg dose once weekly for 4 weeks (off-label).

Candidiasis

Cutaneous candidosis less common than dermatophytosis

Candida species capable of producing skin and mucous membrane infections ~200 species

~20 of them associated with human or animal infections e.g. C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei, C.

guilliermondii C. albicans accounting for most of the infections

found among the commensal flora of the diseased skin, mouth, vaginal tract, and gastrointestinal tract

Become a pathogen in predisposed conditions e.g. infancy, pregnancy, occluded sites, diabetes, Cushing’s syndrome,

immunosuppression, imbalance in the normal microbial flora, etc

Predisposing factors: Large skin folds retain heat & moisture:

environment suited for yeast infection E.g. older women with pendulous breasts, obese patients with overhanging skinfolds

Hot, humid weather; tight or abrasive underclothing; DM, poor hygiene. Inflammatory diseases in skinfolds

e.g. psoriasis and the use of topical steroids favour yeast growth within fold areas

48

Rash: red, macerated and well demarcated surrounded by satellite papules and pustules A fringe of moist scale might be found at the border In the skin, pustules are formed

dissect under the stratum corneum peeling it away resulting in a red, denuded/macerated, glistening surface with a long, cigarette paper-like, scaling and advancing border

Pustules rupture to form a superficial collarette of scale

Rash: sore rather than itchy. Usually found in the intertriginous skin folds and other moist, occluded sites

genital area / area covered by diaper flexures, e.g. the groin, axillae, finger & toe webs

In diaper dermatitis caused by Candida bright red plaques in the inguinal and gluteal folds and satellite pustules may be found

Candidal infection is a frequent cause of chronic paronychia manifesting as painful periungual erythema and swelling

associated with secondary nail thickening, ridging and discoloration.

49

Oropharyngeal candidiasis white plaques and pustules on oral mucosal surface

leaving a raw, bleeding base when removed mechanically

Candida balanitis more commonly found in the uncircumcised usually presents with red patches, swelling and tiny pustules

Candida vulvovaginitis usually causing itchiness and soreness, a curd-like discharge, pustules, erythema

and oedema of the vagina and vulva are found Perianal candidiasis:

Pruritus ani & maceration usually found Chronic mucocutaneous candidiasis

associated with a hetererogeneous group of autoimmune, immunologic and endocrinologic diseases characterized by recurrent or persistent superficial candidal infections

due to an impaired cell-mediated immunity against Candida species

50

DDX of cutaneous candidiasis includes tinea, intertrigo, erythrasma, seborrhoeic dermatitis,

psoriasis, etc.

Investigations Microscopy:

pseudohyphae and yeast forms Isolation of the fungus in culture & its identification

In patients with recurrent candidiasis Test for diabetes mellitus & other conditions producing

immunosuppression

51

52

Candidiasis: management

General: drying, weight reduction, air-conditioning

Nystatin cream or topical imidazole cream BD If perianal skin involved: + Nystatin 100,000 units QID for 5/7

oral fluconazole treatment 50 mg daily for 2 weeks Useful in resisitant cases and for extensive or severe candidiasis

THE END

THANK YOU

53