fungal infection seminar

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Seminar on FUNGAL INFECTIONS:

Seminar on FUNGAL INFECTIONS BY M. Leena M. Pharmacy Pharmacy Practice II semester Vaagdevi College of pharmacy Hanamkonda, MGM-Hospital

contents:

contents Introduction Classification of fungi of medical importance Fungal disease in humans Cutaneous fungal infections Sub-cutaneous fungal infections Systemic fungal infection Conclusion References

Introduction :

Introduction Infectious disease caused by fungi are called mycoses Fungi are eukaryotes, grows predominantly by budding (yeast), or by filamentous extension called hyphae (moulds). They are extremely common organism, widely distributed in nature. Fortunately only a tiny minority causes human disease, although many other are plants and animal pathogen. Fungal infection transmitted by spores or hyphae and normally enter the body through lungs or skin Fungal infection tend to be chronic and often require prolonged chemotherapy. For many years fungal infection considered trivial rather than life threatening In recent years fungal infections have become much more important – immunocompromised people (transplant patients on immunosuppressive drugs, leukaemia, other cancer patients, diabetics, AIDS)

Classification of the fungi of medical importance:

Classification of the fungi of medical importance True yeast Cryptococcus neoformans sacromyces Cerevisiae Yeast like fungi Candida albicans and other Candida species Dimorphic fungi histoplasma capsulatum blastomyces dermatidis Moulds Aspergillus fumigatus and other Aspergillus spceies

Fungal disease in humans:

Fungal disease in humans Cutaneous infections Candidiasis Dermatophytes pityriasis versicolor Sub-cutaneous infections mycetoma (eumycetoma, Actinomycetoma) Systemic infections Histoplasmosis Aspergillosis Blastomycosis Candidiasis Cryptococcosis

Cutaneous fungal infections:

Cutaneous fungal infections Cutaneous fungal infections affect the outer layers of the skin, the nails and hair. The 3 main cutaneous fungal infections are: Candidiasis Dermatophytes Pityriasis versicolor

Candidiasis:

Candidiasis Candidiasis or thrush is a fungal infection (mycosis) of any of the Candida species, of which Candida albicans is the most common. C. albicans is a common yeast-like fungus, found as part of the normal flora of the GIT. Grows best on warm and moist surfaces Other species in the genus Candida such as C. glabrata C. krusei C. trophicalis etc., less common

candidiasis:

candidiasis candidiasis is usually a very localized infection of the skin or mucosal membranes, including the oral cavity (thrush), the pharynx or esophagus, the gastrointestinal tract, the urinary bladder, or the genitalia (vagina, penis). Skin infection and occasionally nail infection may also occur. Candidiasis is the most common fungal infection in patient with AIDS. Oral cavity and esophagus are the two most common clinical manifestations of candidiasis in HIV-infected patients.

Predisposing factors:

Predisposing factors Loss of integrity of skin and mucosae Maceration of skin due to climate or obesity Eczema Dentures Encouragement of local multiplication of Candida Alteration of mucosal flora: antibiotic treatment Hormonal : diabetes, pregnancy Suppression of inflammatory and immune response Specific congenital T lymphocyte defect Leucopenia of any cause Immunosuppressive drugs, including topical corticosteroids Malignancy Human immunodeficiency virus infection

Types of candidiasis:

Types of candidiasis Candidiasis may be divided into the following types: Oral candidiasis (Thrush) Perlèche (Angular cheilitis) Candidal vulvovaginitis Diaper candidiasis Congenital cutaneous candidiasis Perianal candidiasis Candidal paronychia Erosio interdigitalis blastomycetica Chronic mucocuntaneous candidiasis Systemic candidiasis Antibiotic candidiasis (Iatrogenic candidiasis)

Clinical features:

Clinical features Oral thrush: it is a sore mouth, shows white curd like patches of the fungus on the oral mucosa and tongue, which can be scrapped away leaving a raw, tender, bleeding surface behind. Atrophy of the gums and angular stomatitis are common in elderly. Nail infection: may be present as an infection of the sub-cutaneous tissue around and under the nail. Vaginitis: is common form of vaginal infection in women especially those who are diabetic, or pregnant or on oral contraceptive pills. Causes intense pruritus and a thick creamy vaginal discharge, often accompanied by itching. Skin infection: causes an inflamed, itching area of skin with pustules, maceration and fissuring of the skin. Esophageal candidiasis: common in immunocompromised patients, (AIDS), which presents with difficulty and pain on swallowing, and endoscopy is required to confirm diagnosis.

Oral thrush:

Oral thrush White curd Like patches

Candidal nail infection :

Candidal nail infection

Erosio interdigitalis blastomycetica :

Erosio interdigitalis blastomycetica

Investigations :

Investigations Two primary methods to diagnose yeast infections: microscopic examination and culturing. For identification by light microscopy : a scraping or swab of the affected area is placed on a microscope slide. A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves the skin cells but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species. For the culturing method: a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a culture medium. The culture is incubated at 37 °C for several days, to allow development of yeast colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the organism that is causing disease symptoms .

Treatment :

Treatment Oral and vaginal candidiasis may be treated by either topical or systemic antifungal agents 1. Topical antifungal agents falls into two groups: Polyenes Amphotericin B nystatin Imidazoles Clotrimazole Miconazole econazole 2. Systemic antifungal agents are both triazoles Flucanazole itraconazole

Treatment of oral candidiasis:

Treatment of oral candidiasis Step 1: Use topical antifungals Nystatin (1 tablet of 500,000 IU qid): may be sucked or chewed Gentian violet: local application of Gentian violet 1% aqueous solution twice daily for one week M iconazole gel (60 mg qid) Miconazole gum patch (once daily for 7 days) Amphotericin B (10 mg lozenges qid), suck or chew to maintain contact with oral mucosa )

Treatment of candidiasis:

Treatment of candidiasis Step 2: Systemic therapy Recommended when no improvement is seen after 7 days with topical treatment and for all cases of candidiasis 1 st choice — Fluconazole (200 mg loading dose, then 100 mg/day until symptoms have resolved. If fluconazole is not available (affordable) then use Ketoconazole (200-400 mg /day) 2 nd choice — Itraconazole (100 mg bid, dose can be increased to a maximum of 400 mg a day for 10 to 14 days) 3 rd choice — Amphotericin B (I.V.) (0.5-1.5 mg/kg per day) Use intermittent therapy for as long as possible, to delay the emergence of resistant c andida

Treatment of vaginal candidiasis:

Treatment of vaginal candidiasis Fluconazole is effective highly effective in vaginal candidiasis. Dose : 150mg given as a single dose. Itraconazole Dose: 200mg 12 th hourly Clotrimazole 200mg vaginal tablet, one tablet intravaginally for 7 days Mechanism of action of azoles Inhibition of the ergosterol synthesis One of the nitrogen of the azole ring binds to the iron atom of cytochrome P450 and inhibits its activation. and thus impaired the production of ergosterol which is the main component of the cytoplasmic membrane in fungal This mode of action results in number of drug-interaction with these agents.

Drug interaction of anti-fungal gents:

drug Interaction with result Amphotericin B Cyclo-oxygenase 2 inhibitors Any nephrotoxic agent digoxin Increased plasma concentration Enhanced nephrotoxicity Increased digoxin toxicity due to hypokalemia Fluconazole Cox2 inhibitors phenytoin Increased plasma concentration Increased plasma phenytoin concentration Triazoles Ciclosporine statins Reduced plasma concentration Increased risk of myopathy Drug interaction of anti-fungal gents

Dermatophytes :

Dermatophytes Dermatophytosis or tinea - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes. Dermatophytes are keratinophilic - "keratin loving".  Keratin is a major protein found in horns, hooves, nails, hair, and skin. Dermatophytes are classified as anthropophilic (humans), zoophilic (animals) or geophilic (soil) according to their normal habitat. Anthropophilic dermatophytes restricted to human hosts and produce a mild, chronic inflammation. Zoophilic organisms found primarily in animals and cause marked inflammatory reactions in humans who have contact with infected cats, dogs, cattle, horses, birds, or other animals. Geophilic species usually recovered from the soil but occasionally infect humans and animals.

Dermatophytes :

Dermatophytes Three genera of dermatophyte fungi are Trichophyton( infections on skin, hair, and nails) Epidermophyton ( infections on skin and nails ) and Microsporum ( infections on skin and hair ) Severity of ringworm disease depends on (1) strains or species of fungus involved and (2) sensitivity of the host to a particular pathogenic fungus

Clinical manifestations :

Clinical manifestations Clinical manifestations of ringworm infections are called different names on basis of location of infection sites tinea capitis - ringworm infection of the head, scalp, eyebrows, eyelashes tinea favosa - ringworm infection of the scalp (crusty hair) tinea corporis - ringworm infection of the body (smooth skin) tinea cruris - ringworm infection of the groin (jock itch) tinea unguium - ringworm infection of the nails tinea barbae - ringworm infection of the beard tinea manuum - ringworm infection of the hand tinea pedis - ringworm infection of the foot (athlete's foot)

Tinea pedis - Athletes' foot infection :

Tinea pedis - Athletes' foot infection between toes or toe webs (releasing of clear fluid) - 4th and 5th toes are most common Predisposition –warmth and moisture . Secondary bacterial infection, cellulitis, deep soft tissue infection, and sometimes systemic infection can occur. Etiologic agent: T.rubrum,T.mantagrophytes,and Epidermiphyton

Tinea corporis:

Tinea corporis Tinea corporis - body ringworm Generally restricted to stratum corneum of the smooth skin. Produces concentric or ring-like lesions on skin, and in severe cases these are raised and may become inflamed Disease transmitted through infected scales hyphae, also transmitted through direct contact between infected humans or animals, by fomites (any agent such a bedding or clothing capable of retaining a pathogen and transmitting to a new host).

Tinea Unguium:

Tinea Unguium Dermatophytosis of the nail results in thickened, and Discoloured nails.

Tinea Capitis:

Tinea Capitis Dermatophytosis in the scalp presents with itching, skin scaling and inflammation, and patchy hair loss (alopecia)

Diagnosis of dermatophytosis:

Diagnosis of dermatophytosis Note the symptoms. Microscopic examination of slides of skin scrapings, nail scrapings, and hair.  Often tissue suspended in 10 % KOH solution to help clear tissue. Culture test Proper treatment is dependent on diagnosis and prognosis.

Treatment of dermatophytes:

Treatment of dermatophytes Dermatophytes can be treated either topically or systemically. Topical therapy: Small or medium areas of skin infections treated by topical therapy Most commonly used topicla agents are the 1. imidazoles: (clotrimazole, econazole, miconazole,sulconazole and tioconazole) fungistatic MOA: they inhibit C-14 α demethylase (a cytochrome p450 enzyme), thus blocking the demethylation of lanosterol to ergosterol, this disrupts membrane structure and function, and thereby inhibits fungal cell growth. Direction: apply 2to3 times daily, continuing for up to 2 weeks after the leisions have completed. 2. Terbinafine: Drug of choice for treating dermatophytes especially onychomycosis. MOA: terbinafine inhibits fungal squalene epoxidase, thereby decreasing the synthesis of ergosterol ,and also the accumulation of toxic product amount of squalene results in death of fungal cell

Griesofulvin :

Griesofulvin Griesofulvin: the first orally administered treatment for dermatophytosis. Fungistatic Active against only dermatophtye fungi and inactive against all other fungi and bacteria. Dose : 500-1000mg daily, given in one dose or divided dose if required. MOA: cause distruption of the mitotic spindle and inhibition of fungal mitosis. Direction: absorbtion is enhanced if taken with a high-fat meal. In children: it may be given with milk. Treatment for 6 to 12 months Duration of treatment : Skin or hair infection: 4-12 weeks Finger nail infection: 6 months Toe nail infection : more than one year.

Treatment of dermatophytes:

Treatment of dermatophytes Side effects: Mild: headache, gastrointestinal side effects, hypersensitivity reaction. Moderate: exacerbation of acute intermittent porphyria, precipitation of SLE, Contraindicated in pregnancy 3. itraconzaloe: 200mg, daily for 1 week, and terbinafine : 250mg daily for 2 weeks. Pulse therapy of itraconazole for nail infection Itraconazole: 7day course of 200mg twice daily are prescribed at 21-day intervals. Finger nail infection: 2 course Toe nail infection: 3 course.

Tinea (Pityriasis) versicolor :

Tinea (Pityriasis) versicolor Etiologic agent; pityrosporum orbiculare (Malassezia furfur) Common in tropical area, The organism is the member of the normal skin flora. The Yeast grows in stratum corneum of the skin Factors that favours their proliferation are pregnancy, malnutrition, immunosuppression, oral contraceptives and excess of heat and humidity Increased incidence in adolescence and young adulthood. More common during summer

Clinical findings of tinea versicolor:

Clinical findings of tinea versicolor Most leisions begin as multiple small, circuar macules. The macules may darker or lighter than the normal skin Distribution : most common area is trunk, sometimes face forehead, Rarely arms, neck and axila. Facial lesions are more common in children

Tinea versicolor:

Tinea versicolor

Diagnosis :

Diagnosis Diagnosis based on clinical appearance: Culture is not usually required for diagnosis, and since it requires special culture media, is routinely not attempted . Identification of short hypae and budding spores with microscopy confirms diagnosis.

Tenia versicolor:

Tenia versicolor

Treatment :

Treatment Non pharmacologic therapy Sunlight accelerates repigmentation of hypopigmented areas Pharmacological treatment Topical treatment: selenium sulfide2.5% suspension, applied daily for 10mts for 7 consecutive days. Antifungal topical agents: miconazole, clotrimazole Oral treatment: ketoconazole 200mg qd/5days or single 400mg- dose Fluconazole: 400mg single dose Triconazole: 200mg/od/5days

Fungal ear infection:

Fungal ear infection Fungi sometimes infect the external auditory canal, causing otitis externa. Causative organism: various species of Aspergillus (A.niger and A.fumigatus) and Candida albicans and other Candida species Clinical features: pain and itching in the auditory canal with a reduction in hearing due to blockage of the canal. Discharge from the ear. Clinical examination: shows a swollen red canal, and the fungal mycelium is sometimes visible as an amorphous white or grey mass.

Fungal ear infection:

Fungal ear infection Diagnosis: The diagnosis can be made by microscopy and culture of material obtained from the ear. Treatment: topical antifungal agents Nystatin or Amphotericin or Immidazole

Sub-cutaneous mycosis:

Sub-cutaneous mycosis Fungal infections beneath the skin. Infection occurs by implantation of spores or mycelial fragments into a skin wound. Can spread to lymph vessels. Mycetoma: Mycetoma (madhura foot) is a chronic fungal infection of the deep soft tissues and bones. Produced by the members of two groups of organisms classified as Eumycetes and Actinomycetes Clinical features: disease begins as a papule, nodule, or abscess that over months to years progresses slowly to form multiple abscess.

Sub-cutaneous fungal infection :

Sub-cutaneous fungal infection Diagnosis: Confirmed by the demonstration of fungal grains in pus or tissue biopsy. Culture is usually necessary for species identification. Specific antibodies can usually be detected by precipitation. Treatment Rifampicin 4mg/kg daily by mouth (or) Streptomycin 14mg/kg/d (i.m) for 3 months plus oral dapsone 1.5mg/kg 12 th hourly (or) Trimethoprim –sulphamethaxazole- 160/800mg orally, twice a day, for 4-24 months.

Systemic fungal infection:

Systemic fungal infection Histoplasmosis: Histoplasmosis is infection caused by the fungus Histoplasma capsulatum . It occurs mainly in the lungs but can sometimes spread throughout the body. the infection is caused by inhaling spores of the fungus. Most people do not have symptoms, but some feel sick and have a fever and cough, sometimes with difficulty breathing, chest pain. Sometimes the infection spreads, causing the liver, spleen and lymph nodes to enlarge and damaging other organs. Diagnosis Radiological examination may show calcified lesions in the lungs, and spleen. In acute conditions single or multiple soft pulmonary shadows with enlarged tracheobronchial nodes are seen. Antibodies are detected in the sputum or blood sample .

Histoplasmosis :

Histoplasmosis Management: Treatment with Amphotericin B is indicated only in severe condition. Dose: 0.5mg/kg in 500ml of 5%glucose/iv/6 th hourly. Gradually increasing to a maximum of 1.0mg/kg. for up to 3 months or longer. Plasma urea and hemoglobin count falls during the treatment. Severe dysponea in histoplasmosis should be treated with prednisolone 20-4mg daily for a few days. Itraconazole 200-400mg daily can be used in chronic pulmonary histoplasmosis.

Systemic fungal infection-Aspergillosis:

Systemic fungal infection-Aspergillosis Is group of disease caused by a mycotic organism from the genus Asprgillus. Aspergillus usually infects the pulmonary system of the human host, but extra pulmonary systemic infection involving the kidney, and the brain can also occur. Aspergilus can also causes mycetoma, and other superficial mycotic infection. Clinical features: Aspergillus bronchitis, and allergic bronchopulmonary reactions can occur from aspergillus growing in the bronchioles and mucus plugs. Eosinophilia and asthmatic attacks are also common.

Treatment of Aspergillosis:

Treatment of Aspergillosis 1. Amphotericin B: 0.6-1.0mg/kg/iv Adverse effects: nephrotoxicity and hypokalemia, Anemia due to erythropoiesis Peripheral nephropathy (rare) Cardiac failure (due to hypokalemia) 2. Flucytosine: 100-200mg/kg/day/po Mode of action: following uptake by the cell, flucytosine is deaminated to 5-fluro uracil by cytosine deaminase. This in turn incorporated into fungal RNA in place of uracil ,leading to the impairment of protein synthesis Adverse reactions: – Myelosuppression (22%) – Renal insufficiency – Nausea/Vomiting/Diarrhea 3. Ketoconazol: 400mg/od for 6 months 4. Miconazole: 30-60mg/kg/day/iv in 3 divided dose

Blastomycosis :

Blastomycosis Caused by blastomyces dermatidis. Systemic begins in the lungs and lymph nodes and resemble pulmonary tuberculosis. Bones, skin, and the genito urinary tract may also be affected. Treatment: Itraconazole 200-400mg daily, or Ketoconazole 200-400mg daily, or amphotericin 0.5 mg/kg on alternate days.

conclusion:

conclusion Because fungal spores are often present in the air or in the soil, fungal infections usually begin in the lungs or on the skin. Fungal infections are rarely serious unless the immune system is weakened, usually by drugs or disorders. Antifungal drugs may be applied directly to the infected site or, if the infection is serious, taken by mouth or injected Increasing numbers of fungal strains are becoming resistance to current antifungal drugs. toxicity and low efficacy also contribute to the need for better antifungal drugs. A recent development has been the use of combination of antifungal agents to try to improve on the results from single agents.

References :

References Davidson’s principle and practice of Medicine. 18 th edition. Ferri’s Clinical Advisory-2009 Robbins and cotran, Pathologic Basis of Disease 7 th edition Roger Walker, clinical pharmacy and therapeutics 4 th edition Rang and Dale Pharmacology 6th edition Goodman and Gilman’s The pharmacological basis of Therapeutics 10th edition Lippincott’s 4 th edition pharmacology. www.wikipedia.com www.MDconsult.com www.healthology.com