Parasitology & Mycology 2024/2025 Lecture Script PDF
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Medical University of Lodz
2024
Medical University of Lodz
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This document provides a lecture script on parasitology and mycology for second-year DMD students. It covers the characteristic features of fungi, their reproduction, different types of spores, and various fungal diseases.
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Department of Biology and Parasitology Medical University of Lodz Parasitology & Mycology 2024/2025 IInd year DMD Lecture – script MYCOLOGY Characte...
Department of Biology and Parasitology Medical University of Lodz Parasitology & Mycology 2024/2025 IInd year DMD Lecture – script MYCOLOGY Characteristic features of fungi Chitin and chitosan in the cell wall; Glycogen - reserve material; No chlorophyll; Nutrition on the basis of primary osmotrophy (Heterotrophy); The body in the form of mycelium, budding cells, slime; Construction of the thallus; Huge reproductive capabilities (creation of diasporas); The dominance of conidial stages (vegetative) and independence from sexual stages; The ability to join the form of conidial in parasexual cycles; Trends in the loss of sexuality; Plasticity and expansiveness - the enzymatic activity; Life expectancy (spores); Saprotrophy; Tolerance to changes in physical conditions. Fungi reproduce by the formation of spores which may be sexual or asexual (Figure 1). Some fungi produce both types of spores, so they have full life cycle called holomorphy. The form of the fungus sexual spores or organs used in sexual reproduction is called the teleomorph, and the form producing asexual spores – the anamorph. Both forms of the same fungus can have different names (e.g. Candida krusei – anamorph, and Issatchenkia orientalis – teleomorph). From clinical specimens mostly anamorphs are isolated. Types of spores sexual asexual zygospores sporangiospores conidia ascospores (conidiospores) basidiospores chlamydospores Figure 1. Types of fungal spores. Sexual spores include: ▪ Zygospore - a thick-walled spore of fungi of phyllum Zygomycota, that is formed by union of two similar sexual cells, usually serves as a resting spore, typical for: Mucor sp., Rhizopus sp., Absidia sp. ▪ Ascospore - a spore of fungi of phyllum Ascomycota, that is formed as an endospore in structure called acus, typical for: Saccharomyces sp., Pichia sp., Issatchenkia sp. ▪ Basidiospore - a spore of fungi of phyllum Basidiomycota, that is formed as an egzospore on structure called basidium, typical for: Rhodosporidium sp., Filobasidiella sp. Asexual spores include: ▪ Sporangiospore - a spore of fungi of phyllum Zygomycota, that is formed as an endospore in structure called sporangium on sporangophiore, typical for: Mucor sp., Rhizopus sp., Absidia sp. ▪ conidium/conidiospore: 1 - blastoconidium/blastospore – spore formed by budding, e.g. Candida sp., Saccharomyces sp. - aleuroconidium/aleurospore - spore formed directly on hyphae, two types: large, multicelled macroconidia and small, unicelled microconidia, e.g. Microsporum sp., Trichophyton sp. - phialoconidium/phialospore – spore formed on structure called conidiophore, e.g. Aspergillus sp., Penicillium sp., Scopulariopsis sp. - arthroconidium/arthrospore – spore formed by disintegration of hyphae, e.g. Geotrichum sp., Trichosporon sp. ▪ Chlamydospore - a the thick-walled big resting spore of several kinds of fungi: Zygomycota, Ascomycota and Basidiomycota formed intercalary or terminaly, typical for: Mucor sp., Candida sp., Trichophyton sp. Types of fungal diseases: - mycoallergies - resulting from hypersensitivity to fungal antigens, e.g. inhaled fungal spores - mycotoxicoses - resulting from ingestion of fungal toxins in contaminated food or of poisonous mushrooms - mycoses - resulting from invasion of living tissue by a fungus Fungi are major causes of human diseases, especially in immunocompromised persons (e.g. after transplantation, with AIDS or cancer, undergoing chemotherapy, hospitalized with other serious underlying conditions), among whom they may cause significant mortality. In medical mycology fungi were functionally divided into three major groups: yeast: yeast (formerly subdivided into yeast and yeast like fungi)- fungi whose main propagation form is budding, belonging to different clusters, and various classes for both Ascomycota and Basidiomycota, e.g. Saccharomyces cerevisiae, Issatchenkia orientalis/Candida krusei, Filobasidiella neoformans/Cryptococcus neoformans, Candida albicans dimorphic fungi - represent different anatomical forms depending on the temperature, e.g. Blastomyces dermatidis, Paracoccidioides brasiliensis, Histoplasma capsulatum molds fungi belonging to different taxonomic groups (Zygomycota, Ascomycota and Basidiomycota) with a very well- formed aerial mycelium growing on different substrates, natural and artificial; widespread in the environment; characterized by enormous reproductive capability, e.g. Aspergillus fumigatus, Mucor racemosus dermatophytes filamentous fungi belonging to Ascomycota; cause a variety of superficial mycoses: dermatomycoses (fungal infections of the skin and mucous membranes) and onychomycosis (nail fungal infections); characterized by the ability to degrade keratin, e.g. Trichophyton rubrum, Microsporum gypseum. Definition of potentially pathogenic fungi: Potentially pathogenic fungi are those which are capable of growth and development of human body temperature, and survival under reduced oxidation - reduction potential which prevails in injured and diseased tissues. Colonization of human body by fungi: immunocompetent persons with no symptoms of infection skin – 5-10% oral cavity– 10-50% digestive tract– 10-40% vagina – 5-55% patients of risk groups skin – 60% oral cavity– 50-96% esophagus and stomach – 43-60% duodenum – 6-36% large intenstine – 38-45% Globally, over 300 million people are afflicted with a serious fungal infection and 25 milllion are at high risk of dying or losing their sight. Common fungal disease problems: Skin, hair and nails fungal infections: ~ 1 billion people Vulvovaginal candidiasis: ~70% of women, especially during pregnancy and ~135 million with repeated episodes Fungal asthma: 10-25 million adults, ~2 million children Fungal keratitis (front of eye infection): 1.0-1.5 million per year Chronic pulmonary aspergillosis (often after tuberculosis): ~3 million affected 2 WHO fungal priority pathogens list (WHO FPPL) Biosafety classification BSL 1 – saprobionts or plant pathogens present in the niches of invertebrates; they cause conicidal, superficial, non-invasive and mild infections BSL 2 – they mainly occupy ecological niches of invertebrates, have the ability to survive in the tissues of vertebrates; cause deep, opportunistic infections in patients with severely impaired immunity, and surface infections in immunocompetent individuals BSL 3 – common pathogens, potentially capable of causing severe deep infections in immunocompetent individuals Types of mycoses: 1. Classification based on route of acquisition a. Exogenous mycoses – infections caused by fungi present in the environment; routes of entry for exogenous fungi include airborne, cutaneous or percutaneous b. Endogenous mycoses - involves colonization by a member of the normal commensal flora or reactivation of a previous infection 2. Classification based on site Mycoses are classified depending on the type and degree of tissue involvement and the host response to the pathogen. a. Superficial mycoses b. Cutaneous mycoses c. Subcutaneous mycoses d. Systemic mycoses - without fungemia - with fungemia Superficial mycoses - limited to the superficial surfaces of the skin and hair shaft. No living tissue is invaded and there is no cellular response from the host. They are of cosmetic importance only and patients are often unaware of their condition. The fungi causing such infections include: Malassezia furfur, Trichosporon spp.[1,2] Cutaneous mycoses - infections of the keratinized layer of the skin, hair or nails. No living tissue is invaded, however a variety of pathological changes occur in the host because of the presence of the infectious agent and its metabolic products. Symptoms include itching, scaling, ringlike patches of the skin, broken hair, thickened and discoloured nails. The fungi causing such infections include: Candida spp., Geotrichum spp., Aspergillus spp., Scopulariopsis spp., dermatophytes (Microsporum, Trichophyton, Epidermophyton).[1,2] Subcutaneous mycoses - involve the deeper layers of the skin (cornea, muscle, connective tissue); chronic, localized infections following the traumatic implantation of the aetiological agent. The causative fungi (a broad spectrum) are all soil saprophytes whose ability to adapt to the tissue environment and elicit disease is extremely variable. Such mycoses usually remain localized and rarely disseminate systemically. They cause abscess formation, ulcers and sinus tracts draining. The fungi causing such infections include: Fusarium spp., Alternaria spp., Cladosporium spp., Rhizopus spp., Mucor spp.[1,2] 3 Dimorphic systemic mycoses (endemic mycoses) - caused by fungal pathogens which can overcome the defences of the healthy human host by changing their morphological form. They are geographically restricted and the primary site of infection is the lung (following the inhalation of conidia), with subsequent dissemination to other organs and tissues. The fungi causing such infections include: Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Penicillium marneffei. Opportunistic systemic mycoses - occur almost exclusively in debilitated (immunosuppressed) patients whose normal defence mechanisms are impaired, or in individuals who carry implanted prosthetic devices or vascular catheters. The organisms involved are cosmopolitan fungi (human commensals or occurring in the environment) which have a low virulence (except Cryptococcus neoformans). Generally they cause infection when there are disruptions in the protective barriers of the skin and mucous membranes or when defects in the host immune system allow them to penetrate, colonize, and reproduce in the host. The fungi causing such infections include: Candida spp., Cryptococcus spp., Aspergillus spp., Rhizopus spp., Mucor spp., Penicillium spp., Fusarium spp., Scopulariopsis spp. 3. Classification based on virulence a. Primary mycoses – infections in normal, apparently immunocompetent hosts; the primary pathogens have relatively well-defined geographic ranges (endemic); e. g. coccidioidomycosis (Coccidioides immitis), histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis). Primary pathogens may exist in two forms (dimorphism) - they have a saprobic phase (in soil or decaying vegetation) and a parasitic phase (in host). b. Opportunistic mycoses - diseases in individuals with compromised host defense mechanisms; the opportunistic fungi are ubiquitous; e.g. candidosis or candidiasis (Candida spp.), aspergillosis (Aspergillus spp.), zygomycosis (Rhizopus spp., Absidia spp., Mucor spp.); cryptococcosis (Cryptococcus sp.). Primary pathogens may also serve as opportunistic, causing more severe forms of each mycosis. Reservoirs of fungi potentially pathogenic to humans: soil air water plants: plant organs (fruits, seeds), secretions of plants (rubber, juices) plankton animals: invertebrates and vertebrates including humans (skin, organs, body fluids) Routes of entry of fungi into human organism: mouth, nose, ear canal, eyeball, rectum skin damage damage to the mucous membranes, cornea during catheterisation or surgical treatments inhalation The transmission of potentially pathogenic fungi for humans: humans - humans humans - animals humans - environment Risk groups for fungal infections: immunocompromised individuals people suffering from tumours treated with radiotherapy and chemotherapy organ transplant recipients new-borns with low birth weight patients of intensive care units elder people adolescent children (10 - 15 years) pregnant women Risk factors for fungal infections: 1. Endogenous a. Physiological infancy old age pregnancy b. Pathological diabetes tuberculosis 4 failure of the immune system cancer diseases of the endocrine system genetic disease 2. Exogenous injuries (burns, frostbite) surgery catheterisation long-term antibiotic therapy immunosuppression contraceptives iatrogenic factors (related to the development of medicine) 3. Environmental urbanization industrialization anthropopression diet lifestyle Factors affecting the development of asymptomatic infection in symptomatic mycosis 1. Infection of the organism by fungi 2. Features of pathogenicity of strains colonizing organism 3. Risk factors for candidiasis occurring in the host organism 4. Condition of the host immune system 5. The interaction - the fungus – the host - the fungus – natural microbiota Factors affecting the invasion of Candida spp. into the mucous membrane or skin 1. The proliferation of fungi - an intensive cell proliferation of Candida spp. 2. Dimorphism / phenotypic variability - a form hyphal is more pathogenic than yeast 3. Adherence - the ability to adhere to host cells (epithelial cells, phagocytes) 4. Enzymatic activity - secretion of hydrolytic enzymes 5. Molecular mimicry - the variability of surface antigen expression Virulence factors of Candida albicans Stages of candidosis pathogenesis ORAL CAVITY CANDIDIASIS/CANDIDOSIS Etiological factors: Candida albicans Candida tropicalis 5 Candida glabrata Candida parapsilosis Candida guilliermondIi Candida dubliniensis Candida kefyr Candida krusei The prevalence of fungi in the oral cavity ranges from 34% to nearly 100% of those examined. The detection rate of fungi is on average 83.4%. In individual dental diagnoses: inflammation of the gums (gingivitis) 71% chronic periodontitis (periodontitis chronica) 73% inflammation of the tongue (glossitis) 82% aggressive periodontitis (periodontitis aggressiva) 88% prosthetic stomatitis (stomatitis prothetica) 92% leukoplakia 96% Factors predisposing to oral mycosis Local factors Reduction of saliva flow Epithelial changes Changes in the composition of the microbiota High-carbohydrate diet Systemic factors Hormonal disorders Diabetes Hypothyroidism Hyperparathyroidism Adrenal insufficiency Iron or folic acid deficiencies Immunosuppression Medicines Immune deficiencies Leukocyte function disorders Classification of oral candidiasis Primary candidiasis Fungal lesions occur only in the oral cavity (pseudomembranous, erythematous, hyperplastic candidiasis) and perioral tissues Clinical forms: Acute (erythematous, pseudomembranous) Chronic (erythematous, pseudomembranous, hyperplastic) Others (prosthetic stomatopathy, angular cheilitis and medial rhomboid glossitis) Usually in adults Secondary candidiasis Fungal lesions are found in the mouth, skin and other mucous membranes (mucocutaneous syndromes) It occurs in many disease syndromes: chronic mucocutaneous candidiasis endocrinopathies severe combined immunodeficiency syndromes chronic granulomatous syndromes acquired immunodeficiency syndromes (HIV+) and AIDS It can appear at any age Oral candidiasis - forms Pseudomembranous form: acute form extensive white or white-cream lesions and caseous coatings located on the mucous membrane of the mouth and tongue lesions after removal from the mucosa surface leave inflammatory, red, bleeding erosions usually in children and infants (thrush) and adults with debilitating diseases Symptoms: feeling of dryness and burning, taste disturbances, loss of appetite, difficulty swallowing Atrophic form (erythematous): acute or chronic form 6 characterized by redness of the oral cavity resulting from vascularization or hyperemia of the mucous membrane, disappearance of filiform papillae on the dorsum of the tongue, epithelial atrophy, drying of the mucous membrane usually in people taking antibiotics and steroids, heavy smokers and people wearing dentures (extensive erythema, epithelial atrophy) Symptoms: soreness and burning sensation in the mouth Hyperplastic form: chronic form lesions of chronic, transparent or white, palpable, rough plaques, located on the mucous membrane of the cheeks, less often on the tongue tongue furrowed, with a white coating usually as a complication of existing lesions changes imitate cancer Systemic mycoses MYCOSIS OF THE GASTROINTESTINAL TRACT - opportunistic infections in: bacterial diseases, diabetes, CD4 lymphocyte deficiency, hypothyroidism, parathyroidism, adrenal glands, etc., hematological diseases, viral diseases - symptoms: change in bowel movement rhythm, bloating, itching in the anus, poor alcohol tolerance, bleeding from the gastrointestinal tract, iron and zinc deficiencies, other (recurrent vaginal or penis mycosis, skin rashes, chronic fatigue syndrome, chronic urinary tract infections, chronic headaches) MYCOSIS OF THE RESPIRATORY SYSTEM - Symptoms: - septic fever in at-risk patients that does not respond to standard antibiotic treatment - acute pneumonia, with an atypical clinical picture, which does not improve despite the use of antibiotics - chronic pneumonia, with gradual deterioration of the patient's condition, leading to the destruction of the body (hemoptysis, low-grade fever, radiological changes in the chest) - long-term exacerbations of COPD, despite treatment with antibiotics and steroids - "mold asthma" - severe course of bronchial asthma - presence of tightness in the cavities in the course of lung diseases (emphysema, tuberculosis, sarcoidosis, pneumoconiosis, bronchiectasis) - transient pulmonary infiltrates with eosinophilia ("farmer's lung", corkosis) - transient pulmonary infiltrates in people with cystic fibrosis or bronchial asthma with progressive fibrotic parenchymal changes MYCOSIS OF THE NERVOUS SYSTEM - Symptoms: - most often a form of chronic meningitis - non-specific symptoms: headaches, apathy, low-grade fever, progressive cachexia, vomiting, nausea, visual disturbances, - personality changes - meningeal symptoms - congestive disc at the bottom of the eye - paralysis of the cranial nerves - Clinical syndromes of CNS mycoses - meningitis – Cryptococcus, Coccidioides, Exserohilum, Candida, Histoplasma - meningoencephalitis – Cryptococcus, Coccidioides, Candida - brain abscesses – Aspergillus, Candida, Mucoromycetes, Blastomyces, Coccidioides, Histoplasma - rhino-cerebral – Mucor, Rhizopus, Absidia, Rhizomucor, Syncephalastrum - skull base syndromes - Aspergillus - ischemic stroke – Mucoromycetes, Aspergillus MUCORMYCOSIS = ZYGOMYCOSIS – infection due to fungi of family Mucoraceae (phylum Zygomycota): - Rhizopus sp. - Absidia sp. - Mucor sp. - Rhizomucor sp. - Cunninhamella sp. Mucormycosis: rhinocerebral mucormycosis with involvement of the upper respiratory tract and brain lung’s mucormycosis 7 gastrointestinal mucormycosis skin mucormycosis disseminated mucormycosis Patients at increased risk of rhino-orbito-cerebral form: o with diabetes (especially in cases of ketoacidosis): 58.9-86.7% o with hematological disease: 13.3-22% o after transplants o with inflammation of the gastric mucosa and intestines o with kidney diseases Immunocompetent patients (without identified risk factor: 24% Mortality rate: 30-97% Symptoms of rhino-orbital-cerebral mucormycosis: o headache, mainly around the face o periorbital swelling, often with loss of vision, fever, double vision o runny nose - black discharge from the nose, necrotic changes in the nasal cavity o ulcers and perforation of the palate o decreased mental functions o ischemic stroke with neutrophilic infiltration and invasion of cerebral blood vessels ASPERGILLOSIS - infection due to fungi of genus Aspergillus (phylum Ascomycota) - Aspergillus fumigatus - Aspergillus flavus - Aspergillus niger - Aspergillus nidulans - Aspergillus terreus Aspergillosis is the most common invasive mould infection throughout the world, which may be caused by inhalation of conidia from the air. Aspergillosis: aspergillosis of the respiratory system (nasopharynx, sinuses, lungs) - pneumonia - aspergilloma – colonization of pre-existing cavities - mould-asthma cerebral aspergillosis primary and secondary skin aspergillosis endocarditis osteomyelitis endophtalmitis disseminated aspergillosis Aspergillosis of Central Nervous System: granulomatous tumors in the brain (increase in intracranial pressure) meningitis and blockage of small vessels (ischemic or haemorrhagic stroke) CANDIDOSIS/CANDIDIASIS - infection due to fungi of genus Candida (phylum Ascomycota): - Candida albicans - Candida dubliniensis - Candida tropicalis - Candida glabrata - Candida parapsilosis - Candida krusei - Candida lusitaniae - Candida lipolityca Candida spp. are the most common of the opportunistic fungal pathogens, frequently colonizing the gastrointestinal mucosa that may invade deep tissues of many organs (the liver, spleen, kidneys, heart, brain) through the bloodstream. Candidiasis: candidemia disseminated candidiasis: acute or chronic candidiasis of the respiratory system, trachea, bronchus and lungs endocarditis, myocarditis and pericarditis meningitis, encephalitis endophtalmitis and chorioretinitis esophagitis peritonitis 8 lower urinary tract and/or renal candidiasis disseminated candidiasis of drug addicts Clinical forms of oral candidiasis: acute pseudomembranous form - "oral thrush" acute form of erythematous chronic atrophic form chronic hyperplastic form inflammation of the mouth corners Vaginal candidiasis: 75% of women have had fungal vaginosis at least once in their lifetime most women will have at least one symptomatic episode of vaginal and vulvar fungal infection 5-55% of women are asymptomatic carriers of fungi of the genus Candida 10-20% suffer from complicated vaginal candidiasis 40-50% are treated for recurrent vaginal candidiasis 30% of pregnant women suffer from vaginal candidiasis temporary or permanent vaginal carrier of yeast such as Candida is estimated at 6-30% Symptoms: vaginal discharge itching pain in the vulva area, in the vaginal vestibule, in the vagina swelling and redness of the vulva and vagina erosions vaginal contents are abundant, thick, whitish, purulent, yellowish or brown CRYPTOCOCCOSIS - infection due to fungi of genus Cryptococcus (phylum Basidiomycota): - Cryptococcus neoformans - Cryptococcus gatti - Cryptococcus albidus - Cryptococcus ater - Cryptococcus humicola - Cryptococcus laurentii - Cryptococcus terreus - Cryptococcus uniguttulatus C. neoformans causes infections throughout the world in immunocompetent and immunocompromised individuals. Infections of immunosupressed hosts are much more frequent and severe. The most common risk for cryptococcosis caused by C. neoformans is AIDS. The environmental source of C. neoformans are birds’ (mainly pigeons) nests and droppings and also soil. C. gattii is endemic to tropical parts of North and South America, Africa and Australia. The environmental reservoirs of C. gattii are various trees (e.g. eucalyptus). Infections caused by this species are more often reported in immunocompetent patients than in the immunocompromised. Infection with Cryptococcus sp. proceeds via inhalation and subsequent dissemination to the central nervous system to cause meningoencephalitis. Cryptococcosis: meningitis and encephalitis pneumonia skin lesions osteomyelitis prostatitis disseminated cryptococcosis Central nervous system cryptococcosis - cryptococcal meningitis and encephalitis - Symptoms of cryptococcal meningitis: mental disorders convulsions ischemic stroke atypical symptoms: o paralysis of lower limbs o photophobia o confusion o creating neologisms, linguistic errors, confusing the meaning of words 9 ANTIFUNGAL DRUGS USED IN ORAL CAVITY TREATMENT Rules of treatment: elimination of fungi from all foci administration of different form of this same drug in dependence of localization of changes local application of the drugs a few times per day choise of suitable doses of drugs of general action manegement for 4 weeks, in case of invasive mycosis and nail mycosis even up to 18 months Laboratory analysis before and after using oral antifungal drugs: morphology urine analysis liver function tests pregnancy test Evaluation of results of treatment after 1st and 8th week: 1. Recover regression of sings and symptoms negative cultures 2. Improvement partial regression of signs and symptoms negative cultures 3. No improvement signs and symptoms still present positive cultures Species resistant to antifungal drugs Reasons for fungi resistance: polimorphism of fungi structure and composition of cell membrane and cell wall enzymatic activity location of fungi in low vascularized area and necrotic changes Antimycotic drug resistance mechanisms 1 – changed drug target (enzyme) 2 – over production of enzymes 3 – actively pumped out by efflux pump 4 – drug is not absorbed inside the cell 5 – changed methabolic pathway 6 – activity of drug-degradating enzyme inside the cell 7 – activity of drug degradating enzyme outside the cel 10 Mycosis type Antifungal drug Form of drug oral cavity and pharynx mycosis amphotericin B tablets clotrimazole lozenges chlorhexidine chlorchinaldol oral cavity and pharynx mycosis nystatin oral gel miconazol oral cavity and pharynx mycosis amphotericin B suspension/ solution for inhalation natamycine nystatin clotrimazole fluconazole ketoconazole miconazole oral cavity and pharynx mycosis chlorhexidine solution to gargle mycoses of nose, sinus and larynx amphotericin B nose drops natamycine suspension/soliution for inhalation nystatin clotrimazole flucytosine miconazole otomycosis amphotericin B drops natamycine ointment clotrimazole flucytosine miconazole econazol The treatment scheme of oral candidosis (oral trush) – Polish recommendations Ist line drugs: – Nystatin (suspension): adults – 100 000-500 000 units every 6 hours children – 100 000 units every 6 hours IInd line drugs: – Fluconazole (tablets) adults – 200 mg (first 24 hours) 100 mg (next 6 days) children – 6 mg/kg of body weight (first 24 hours) 3 mg/kg of body weight (next 6 days) Solution used to disinfection of orthodontic apparatus and prothesis: pertlenon chloramine B chlorhexidine The treatment scheme of oral candidosis - CDC recommendations mild to moderate infections – usually an antifungal medicine applied to the inside of the mouth for 7 to 14 days. clotrimazole, miconazole, or nystatin. severe infections – Ist line drug: fluconazole - oraly or intravenously – IInd line drug: different antifungal The treatment scheme of oral candidosis - Canadian Dental Association, acc. J Can Dent Assoc 2013;79:d122 Non-pharmaceutical Management (local treatment) – Denture-wearing patients: 11 Clean the denture and avoid wearing it overnight. Soak the denture in a dilute solution of bleach (1 tsp for 8 oz of water) or in chlorhexidine gluconate 0.12% and rinse thoroughly before reinsertion in the mouth. – Dry mouth patients: Ensure adequate hydration and chew xylitol sugar-free gum to improve saliva flow. – Angular cheilitis patients: Avoid licking the lesions as this will further superinfect them with salivary bacteria. Discard all lip balm or lipstick currently in use to avoid reinoculation with the infectious agent. – Steroid inhaler users: Brush and rinse the palate after each inhalation. Refer patient to the pharmacist to review the proper aerosol inhalation technique and consider the need for inhaler chamber (spacer) and alternative metered- dose inhaler device, if needed. Pharmaceutical Management (topical antifungal treatment) – Clotrimazole (10 mg oral troches): Dissolve 1 troche in oral cavity 5 times a day. – Nystatin oral suspension (100 000 U/mL): rinse 5 cc q.i.d. for 2 minutes and expectorate. Caution: commercial preparation might contain cariogenic sweeteners. – Non-prescription treatments (clotrimazole: 1% cream or nystatin: 100 000 U/g cream or ointment): Angular cheilitis patients: Apply a thin layer to the inner and outer corner of mouth q.i.d. after meals. Denture-wearing patients: Apply a thin layer to the tissue side of the denture and the infected oral mucosa q.i.d. after meals. 12