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167 Cards in this Set

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Define Mycology
The study of Fungi
What are Mycotoxins?
* Mushroom Poisoning
* Some Environmental toxins produced by moulds
- Vomitoxin – produced by Fusarium, etc.
- Aflatoxin – produced by aspergillus flavus
- Ochratoxin – produced by aspergillus, penicillium, and fusarium
- Fumagillan – produced by aspergillus fumagatis
- Trichothecene toxin – produced by Fusarium tricinctum
++ “Yellow Rain” – used as a biological weapon in Vietnam
Vomitoxin
* produced by Fusarium, etc.
* causes vomiting
Aflatoxin
* produced by aspergillus flavus
* High-level aflatoxin exposure produces an acute hepatic necrosis, resulting later in cirrhosis, and/or carcinoma of the liver.
- Acute hepatic failure is manifested by hemorrhage, edema, alteration in digestion, and absorption and/or metabolism of nutrients and mental changes and/or coma.
* No animal species is immune to the acute toxic effects of aflatoxins including humans; however, humans have an extraordinarily high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis.
Ochratoxin
* produced by aspergillus, penicillium, and fusarium
* Ochratoxin A is known to occur in commodities like cereals, coffee, dried fruit and red wine. It is considered a human carcinogen and is of special interest as it can be accumulated in the meat of animals. Thus meat and meat products can be contaminated with this toxin. Exposure to ochratoxins through diet can have can acute toxicity to mammalian kidneys, and may be carcinogenic.
Fumagillan
* produced by aspergillus fumagatis
* Fumagillin is an antibiotic originally used against fungal Nosema apis infections in honeybees.
* Some studies found it to be effective against some myxozoan parasites, including Myxobolus cerebralis, an important parasite of fish; however, in the more rigorous tests required for U.S. Food and Drug Administration approval, it was ineffective.
* Fumagillin can block blood vessel formation by binding to an enzyme called methionine aminopeptidase 2.
Trichothecene toxin
* produced by Fusarium tricinctum
* “Yellow Rain” – used as a biological weapon in Vietnam
* Trichothecenes are a very large family of chemically related mycotoxins produced by various species of Fusarium, , Trichoderma, , , , and Stachybotrys.
* Trichothecenes belong to sesquiterpene compounds.
- These compounds were used in chemical warfare by the Soviet Union on several occasions.
* The most important structural features causing the biological activities of trichothecenes are: the 12,13-epoxy ring, the presence of hydroxyl or acetyl groups at appropriate positions on the trichothecene nucleus and the structure and position of the side-chain.
* They are produced on many different grains like wheat, oats or maize by various Fusarium species such as F. graminearum, F. sporotrichioides, F. poae and F. equiseti.
* The first symptoms exhibited are general discomfort, dry eyes, and drowsiness.
- A red rash appears shortly, starting in blotches and swiftly covering the entire body.
- Symptoms of a classic hemorrhagic fever set in, which include blood-red eyes, vomiting/urinating of blood, nosebleed, and patches of skin ranging from quarter- to A4-sheet size begin to bleed sponateously.
- Brain function is also impaired, with the victim progressing from slurred speech to classic 'fever dreams' to various psychological conditions from Multiple Personality Disorder to Paranoia.
- The victim succumbs to loss of blood, fever, or systemic hyperinfection brought on by the weakened immune system, whichever comes first.
Psilocybin mushrooms
* AKA psychedelic mushrooms
* After ingested, psilocybin is broken down to produce psilocin, which is responsible for the hallucinogenic effects
- Non-toxic
- Lasts 3-7 hours
- Effects variable
What are the 4 Phyla of the Fungal Kingdom?
Zygomycota
Ascomycota
Basidiomycota
Chytridiomycota

Deuteromycota (artificial group – technically not a true phylum)
Examples of Zygomycota
Rhizopus, Mucor, Absidia

Fast growers – “lid lifters”
Examples of Ascomycota
Aspergillus, Histoplasmosis, Blastomycosis, Penicillium

Largest Phylum: contains 80% of all pathogenic fungi
Examples of Basidiomycota
Cryptococcus neoformans
Examples of Chytridiomycota
No pathogens associated with human disease
Examples of Deuteromycota
Coelomycetes

* “Fungi Imperfecti” – only have asexual reproduction
* Some members of ascomycota or more rarely basidiomycota
Fungal Characteristics
* Eukaryotic
* Non-vascular
* Reproduce by utilizing spores
* Sexual and asexual reproduction depending on species and environmental conditions
* Non motile
- Spread by wind, water, contact
* Small nuclei
- Few repetitive DNA
* MORE LIKE HUMANS than plants
- No chlorophyll
Eukaryotic cells typical size vs. Prokaryotic Cell
Eukaryotic cells typically 2 - 100 µM

Prokaryotic Cell Sizes typically between 0.5 - 2 µM
E. coli, 1 µm x 2 µM
Morphology of Pathogenic Fungi
* Filamentous moulds
- Multicellular branching
- Hyphae - thread-like filaments
* Unicellular yeasts
- Ovular or spherical
- Rigid cell walls produced by budding
* Dimorphic fungi
- Exist as either a yeast or mold
- Depending on the pathogen, site of growth, and temperature
* May have capsules (Cryptococcus neoformans) or form biofilms (Candida, Aspergillus, etc.)
Fungal Cell Wall Structure
Major components: proteins, polysaccharides and small amount of lipids
* Polysaccharides
- Mannans (polymer of mannose, predominantly a-linked)
++ N- and O-linked glycosylation can be extensive (e.g., yeasts >200 mannose units per protein molecule).
++ Involved in cell wall porosity.
++Surface component of many yeasts, makes first contact with host.
++ Immunogenic and allerogenic.
++Good target for host defense system.
- Chitin (polymer of N-acetyl glucosamine, b-1,4-linked)
++ Structural component, some on surface.
- Glucan (polymer of glucose, b-linked)
++ Primary structural integrity of wall
++Good antifungal target.
Fungal Cell Membrane
* Cell membrane
- Ergosterol – unique sterol. Similar to cholesterol found in mammalian cell membranes

* Ribosomes
- 80S = 40S + 60S
Fungal Growth Environment
* Aerobic
* Facultative anaerobe
- ATP by aerobic respiration if oxygen is present, but is also capable of switching to fermentation under anaerobic conditions
- Fungi prefer presence of oxygen, but some can live without it
++ Example: Candida growth in the GI tract
Fungal Growth requirements
* Most are obligate aerobes, utilize glucose, require Fe and a lot of water.
* Most are easy to grow, but important exceptions/considerations:
- Tissue forms of Coccidioides immitis and Histoplasma capsulatum require special media.
- Special conditions are required to grow Malassezia furfur
- Loboa loboi and Pneumocystis carinii have not been cultured.
- Cultures are processed in biosafety hood as spores contaminate lab and many are very hazardous to handle.
Fungal Growth: Yeasts
* most replicate by budding and growth curves are similar to bacteria
* Generation times: vary
- Candida albicans generation time ~40 min;
- Cryptococcus neoformans ~2 h
Fungal Growth: Moulds
* grow from apical tip
* Generation times: vary
- Zygomycetes and common Deuteromycete lab contaminants grow rapidly (2-4 days)
- Dimorphic pathogens grow slowly (10 – 21 days)
Fungal Reproduction
* Mitosis (asexual) – spore mediated
- Form a cell division that is an exact copy of the original cell
* Meiosis (sexual)
- Division that reduces the number of chromosomes by half
Fungal Life Cycle
(First half of the life cycle is all asexual reproduction)
1. Hypha produces conidiophore
2. Conidia are released from conidiophore
3. Conidium germinates to produce hyphae
(Step 4 begins the sexual reproduction portion of the life cycle)
4. Vegitative mycellium grows
5. Plasmogamy
6. Karyogamy
7. Meiosis then Mitosis
8. Ascus opens to release ascospores
9. Ascospore germinates to produce hyphae
Are gram stains useful for determining the type of fungus is infecting a given patient?
* Gram Stains are not useful
* Most fungi do not stain with bacteria gram stain medium (Crystal violet dye, red safranin dye)
* Exception – Candida
Fungal cell wall stains
Fungal cell wall stains
* Gomori methenamine-silver (GMS)
* Gridley’s fungas (GF)
* Hematoxylin and eosin (H&E) stain
* Periodic acid-Schiff (PAS) stain
- Stains the polysaccharide in the cell wall
* Calcofluor
* Wet Mount (KOH stain)
* India ink
- CSF stain to detect Cryptococcus neoformans
What is Immunofluorescence?
Fluorescein labeled antibody reacts with fungal antigens in cell wall.
Ex: Direct Fluorescence assay (DFA) for Pneumocystis Carinii (PCP)
Micro Lab Growth Media
Common media
* Sabouraud dextrose agar (Sab agar): common universal medium results in abundant mycelial growth but sporulation may be sparse.
* Sab agar + chloramphenicol + cycloheximide (MycoselTM or Mycobiotic AgarTM)
- Isolation of pathogens from contaminated specimens: dermatophytes, C. albicans, mold phase of dimorphic fungi
- (not good for C. neoformans, other Candida spp., tissue phase of dimorphics, or rapid growers)
* Potato dextrose agar (PDA): sparse growth, but sporulation abundant.
* Special media: there are many, depending on suspected fungus.
Diagnosis of fungal infections
* Stains
* Immunofluorescence
* Blood cultures
- 25-45% of infected patients are positive
The Fungitell beta-D Glucan assay
* Detects B-D-Glucan from the cell walls of some fungi
* Useful for fungi with high levels of (1,3)- beta-D-glucan:


* is indicated for the presumptive diagnosis of invasive fungal disease through detection of elevated levels of (1,3)- beta-D-glucan in serum. Normal human serum contains low levels of (1,3)- beta-D glucan, typically 10 to 40 pg/mL, presumably from commensal yeasts present in the alimentary canal and gastrointestinal tract. However, (1,3)- beta-D-glucan is sloughed from the cell walls during the life cycle of most pathogenic fungi. Thus, monitoring serum for evidence of elevated and rising levels of (1,3)- beta-D-glucan provides a convenient surrogate marker for invasive fungal disease. The Fungitell beta-D Glucan assay detects (1,3)- beta-D-glucan from the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, Pneumocystis jiroveci. The Fungitell beta-D Glucan assay does not detect certain fungal species such as the genus Cryptococcus, which produces very low levels of (1,3)- beta-D-glucan, nor the Zygomycetes, such as Absidia, Mucor, and Rhizopus, which are not known to produce (1,3)- beta-D-glucan. Studies indicate Blastomyces dermatitidis is usually not detected due to little (1,3)- beta-D-glucan produced in the yeast phase.
Galactomannan Assay (Platelia®)
* Useful for diagnosis of invasive aspergillus
* Assay
- Galactomannan is component of the aspergillus cell wall
- Assay detects Aspergillus galactomannan antigen in serum
- 80.7% sensitive and 89.2% specificity

* Potential problems
- Piperacillin/Tazobactam causes false positive
- Other fungi may react (Penicillium, Alternaria, etc)
- Current anti-fungal therapy may reduce sensitivity of assay
Germ Tube Test
* Differentiates C. albicans from non-albicans species
- A. A small portion of an isolated colony of the yeast to be tested is suspended in a test tube containing 0.5 ml of rabbit or human plasma or serum.
- B. The test tube is inoculated and incubated at 35C for no longer than 2 hours.
- C. A drop of the yeast-serum suspension is placed on a microscope slide, overlaid with a coverslip, and examined microscopically for the presence of germ tubes.
PNA FISH™ C. albicans detection
* C. albicans PNA FISH™
- Qualitative nucleic acid hybridization assay intended for identification of Candida albicans from blood cultures.
- Rapid identification of C. albicans on smears made directly from Yeast-positive blood culture bottles
- 2.5 hour fluorescence in situ hybridization (FISH) assay uses fluorescently labeled peptide nucleic acid (PNA) probes that target the species-specific ribosomal RNA (rRNA) of C. albicans. 
- Results are visualized using fluorescence microscopy. 
++ Green fluorescing cells indicates C. albicans while no fluorescence indicates another species is present in the positive blood culture.
Candida albicans Screen
* Detects b-galactosaminidase & L-proline aminopeptidase enzymes in C. albicans
* A positive reaction for b-galactosaminidase is indicated by yellow color development after the addition of the first reagent. A positive reaction for L-proline aminopeptidase is indicated by a pink to red color development after the addition of the second reagent.
* C. albicans should test positive for both enzymes.
Why do Antifungal Susceptibility Testing? (AST)
* To correlate in vitro MIC data with clinical outcome so as to predict the likely outcome of therapy

* To monitor the development of resistance

* To predict the therapeutic potential of investigational agents
Current Methodologies for Antifungal Susceptibility Testing
Broth dilution
- Clinical and Laboratory Standards Institute (CLSI): Methods for yeast and mould testing available.
- Colorimetric: A reagent (e.g. Alamar blue or XTT) added to enhance clarity of endpoint.

Agar based
- Etest stable gradient of drug on a plastic strip is transferred to agar.
- BioMIC disk-diffusion assay
Where are we in AST?
* Yeast (Candida)
- Establishment of standard method for AST is completed
- Relevant drugs
++ fluconazole, itraconazole, 5-fluorocytosine, amphotericin B, voriconazole
- In vitro - in vivo correlation established
- Interpretive breakpoints proposed
Colorimetric Method for Yeast Testing
* Broth dilution method with addition of Alamar blue reagent

* Color changes from blue to red in the presence of growing yeast

* Recently approved by FDA

* - Read positive control well
- Record MIC as first blue well
++ Compare to positive control well
++Read color change; do not read turbidity in wells
Etest
* Advantages: Ease of use and low cost

* Available for clinical use for yeast testing; procedure for molds is under investigation

* Studies demonstrate Etest has good correlation with broth dilution MIC results

* Like broth dilution, MICs for azoles are sometimes difficult to interpret due to the trailing endpoint
Susceptibility Breakpoints
* Susceptible (S)

* Susceptible Dose Dependent (SDD)

* Resistant (R)
Fluconazole
< or = 8.0 Susceptible 97% chance of success
16-32 Susceptible-dose dependen 82 * chance of success
> or = 64 Resistant 60% chance of success.
Itraconazole
<or = 0.12 Susceptible 90% chance of success
0.25-0.5 Susceptible-dose dependent 63% chance of success
> or = 1.0 Resistant 53^ chance of success.
Flucytosine
<4.0 Susceptible 90% chance of success rate.
8.0-16 Intermediate NA
> or = 32 Resistant NA
Yeasts
* Round or oval
* Smooth flat colonies
* Reproduce by budding
* Examples
- Candida
- Cryptococcus
Moulds
* Composed of tubular structures called hyphae
* Grow by branching and longitudinal extension
* Typically appear fuzzy
* Examples
- Aspergillus
- Mucormycoses
Dimorphic Fungi
* Grow in the host as yeast like forms, but grow at room temperature in-vitro as moulds
* Examples
- Histoplasmosis
- Blastomycosis
- Sporotrichosis
- Coccidioidomycosis
- Paracoccidioidomycosis
- Chromoblastomycosis
Healthy People get Fungal Infections?
* Fungal Infections have always been a problem
- Dermatophytoses
++ Most common of all infectious diseases
++ Ring worm, athlete’s foot, jock itch
* Candidiasis
- Mucocutaneous disease
++ Yeast infections
- Disseminated disease (now more common)
* United States Endemic mycoses
- Coccidioidomycoses - Desert SW
- Histoplasmosis - Ohio-Mississippi Valley regions
- Blastomycosis
- Ohio-Mississippi Valley regions and North and east of that region
Fungal infections in Immunosuppressed Patients
* Substantial increase in the incidence of deep mycoses and the range of fungi that can cause potentially fatal disease
- Human Immunodeficiency Virus (HIV) epidemic
- Increasing use of immunosuppressive drugs

* About 20 new species of fungus are found to cause infections each year
Factors Contributing to Fungal Infections
* Exposure to the fungus
* Inoculum delivered during the exposure
* Virulence of the fungus
* Host’s immune status
- Underlying disease
- Immunosuppressive therapy
* Prior exposure to the fungus
Reasons for Increase in Infection
* Advances in medical technology
- Organ and bone marrow transplant
- HIV/AIDS
- Cytotoxic chemotherapy
- Use of indwelling venous catheters
- Increased use of potent broad spectrum antibiotics
Risk Factors for Invasive Fungal Disease
* Neutropenia
* Central venous catheters
* Parenteral Nutrition
* Renal Replacement therapy in the ICU
* Broad-spectrum antibiotics
* Prosthetic devices
* Immunosuppressive therapy or disease states
- Chemotherapy agent, dose, duration
- Radiotherapy
- Corticosteroids
- HIV, BMT, Organ Transplantation, etc.
* Others
- High APACHE II or III score
- Fungal Colonization
- Recent surgery
++ Organ transplant, GI tract
- Concomitant bacterial infections
- Cancers/Hematologic malignancies
- CMV disease
- Hospital environment
- Mucositis
Primary Invasive Pathogens (e.g. The ones you need to Know)
* Primary Mycoses
- Histoplasmosis, Coccidioidomycosis, Cryptococcosis, Blastomycosis, Paracoccidioidomycosis, Sporotrichosis
* Opportunistic fungi
- Candida albicans, Aspergillus sp., Trichosporon, Candida glabrata, Fusarium, Alternaria, Mucor, Pneumocystis
Portals of Entry
* Exogenous Inhalation
- Soil
- Animal excretions
* Skin
- IV catheters, burns, surgery, or trauma
* Endogenous flora
- Skin, GI, GU, or respiratory tract
- Candida albicans found in 20%-30% of humans
Types of Fungal Infection
* Superficial mycoses
Outermost skin and hair
* Cutaneous mycoses
Deep epidermis, nails

* Subcutaneous mycoses
Dermis, Beneath the skin
* Systemic mycoses
Deep within body
* Opportunistic mycoses
Unsually from an immunocompomised
Mycoses Fungal infections can be classified into:
* Superficial: hair, nail, and skin
- Dermatophytosis: tinea barbae, tinea capitis, tinea corporis, tinea cruris, tinea favus, tinea nigra, tinea pedis, tinea unguium
- Piedra (both white and black)
- Pityriasis versicolor

* Subcutaneous: caused by moulds, usually acquired through traumatic implantation
- Chromoblastomycosis
- Phaeohyphomycosis
- Sporotrichosis
- Lobomycosis
Fungal Diseases, Superficial mycoses
Ex: Tinea versicolor or pityriasis versicolor
Malassezia furfur or M. pachydermatis
Fungal Diseases Cutaneous
Ex: Onychomycosis (tinea unguium)
Fungal Diseases Systemic Mycosis
Ex: Candidemia, Aspergillosis, Mucormycosis
Fungal Diseases Opportunistic Fungal Infections
Ex: Cryptococcus, Pneumocystis (PCP)
Complications of fungal disease
Types of Serious Systemic Infections
Fungemia (Sepsis)
Endocarditis
Peritonitis
Septic arthritis
CNS
Infection Rate for Fungal infections
Nosocomial fungal infections
9.9% of all bloodstream isolates
Candida spp. responsible for 72%
Candida albicans accounts for 55% of fungi
Fungal Infection Rates
* Wide Variability - Very dependent on Patient Population

* 35% in 111 patients who stayed >4 days in trauma ICU

* 2% in 435 patients admitted to medical or surgical ICUs
Candida Morbidity and Mortality
* Responsible for most fungal infections
* 4th leading cause of nosocomial bloodstream infections
* High rate of attributable mortality
* Up to 38% reported
* Prolonged hospitalization
VVC Epidemiology
AGE is the key factor:
* Rare before menarche
* Incidence increases dramatically around 20yo
* By 25 years of age ~50% of college women will have experienced at least 1 episode
* Peak incidence 30-40 years of age
Microbiology of VVC
* Most cases caused by C. albicans (85%-90%)
* Remainder are Candida glabrata and other non-albicans
* Candida species are normal flora of the skin and vagina
* Asymptomatic colonization 10-20% of women
* VVC is caused by overgrowth of C. albicans and other non-albicans species
* Yeast grows as oval budding yeast cells or as a chain of cells (pseudohyphae)
* Symptomatic clinical infection occurs with excessive growth of yeast
* Disruption of normal vaginal ecology or host immunity can predispose to vaginal yeast infections
Risk Factors for VVC
* Dramatic increase around the time women become sexually active (NOT an STD)
* Oral-genital contact
* Oral contraceptives – (Older higher dose versions)
* Spermicides, diaphragms, intrauterine devices
* **Antibiotic use **
* Diet:excessive carbohydrates
* Douching
* Tight-fitting clothing
Clinical Presentation/Symptoms of VVC
* Vulvar pruritis (ITCH)
* Thick, white, curdy vaginal discharge ("cottage cheese-like")
* Erythema, irritation, erythematous "satellite" lesion
* External dysuria and dyspareunia
Diagnosis of VVC
* History, signs and symptoms
- Typically a self diagnosis
* Visualization of pseudohyphae (mycelia) and/or budding yeast (conidia) on KOH or saline wet prep
* pH normal (4.0 to 4.5)
- If pH > 4.5, consider concurrent BV or trichomoniasis infection
* Cultures not useful for routine diagnosis
Classification of VVC: Uncomplicated VVC
* Sporadic or infrequent vulvovaginal candidiasis
- Or -
* Mild-to-moderate vulvovaginal candidiasis
- Or -
* Likely to be C. albicans
- Or -
* Non-immunocompromised women
Classification of VVC:
Complicated VVC
* Recurrent vulvovaginal candidiasis (RVVC)
- Or -
* Severe vulvovaginal candidiasis
- Or -
* Non-albicans candidiasis
- Or -
* Women with uncontrolled diabetes, debilitation, or immunosuppression or those who are pregnant
Uncomplicated VVC
* Mild to moderate signs and symptoms
* Non-recurrent
* 75% of women have at least one episode
* Responds to short course regimen
* Treatment
Remove any predisposing factors
Pharmacologic agents
? Pro-biotics (lactobacillus acidophilus)
CDC-Recommended OTC Treatment Regimens
Butoconazole 2% cream, 5 g intravaginally for 3 days†
Butoconazole 2% sustained release cream, 5 g single intravaginally application
Clotrimazole 1% cream 5 g intravaginally for 7 days†
Clotrimazole 100 mg vaginal tablet for 7 days
Clotrimazole 100 mg vaginal tablet, 2 tablets for 3 days
Clotrimazole 500 mg vaginal tablet, 1 tablet in a single application
Miconazole 2% cream 5 g intravaginally for 7 days†
Miconazole 100 mg vaginal suppository, 1 suppository for 7 days†
Miconazole 200 mg vaginal suppository, 1 suppository for 3 days†
Ticonazole 6.5% cream 5 g intravaginally in a single application†
Ticonazole 300 mg ovule x 1 day
Prescription Treatment Options
* Topical
- Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
- Econazole 150 mg tablet daily x 3 days
- Fenticonazole 2% cream 1 applicator x 7 days
- Terconazole 0.4% cream 5 g intravaginally for 7 days
- Terconazole 0.8% cream 5 g intravaginally for 3 days
- Terconazole 80 mg vaginal suppository, 1 suppository for 3 days

* Oral agents:
- Fluconazole 150 mg oral tablet, 1 tablet in a single dose
- Itraconazole 200 mg BID x 1 day
- Ketoconazole 200 mg BID x 5 days
Cure Rates for uncomplicated VVC
* 80-95% with topical or oral azoles
* 70-90% with nystatin preparations
Referral for uncomplicated VVC
* Symptoms should resolve within 24-48 hours
* If symptoms persist, then further testing is needed for actual diagnosis and evaluation of treatment options
Complicated VVC
* Recurrent (RVVC) Four or more episodes in one year
* Severe
- Edema
- Excoriation/fissure formation
* Non-albicans candidiasis
* Compromised host
* Pregnancy
Complicated VVC Treatment
* Recurrent VVC (RVVC)
- Increase length of therapy:
++ 7-14 days of topical therapy, or
++ 150 mg oral dose of fluconozole repeated 3 days later
- If 14 days not effective, can continue until symptoms resolve or negative cultures
- Maintenance regimens x 6 months
++ Clotrimazole 500 mg vaginally qweek
++ Fluconazole 100 mg po qweek
++ Ketoconazole 100 mg daily
++ Itraconazole 400 mg monthly

* Severe VVC
- 7-14 days of topical therapy, or
- 150 mg oral dose of fluconozole repeated in 72 hours
* Non-albicans
- Optimal treatment unknown
- 7-14 days non-fluconozole therapy
- 600 mg boric acid in gelatin capsule vaginally once a day for 14 days
++ Maintenance – twice weekly
- Flucytosine cream 1000mg nightly x 7d

* Immunocompromised host
- 7-14 days of topical therapy
Candidal Intertrigo
Inflammatory condition of two closely opposed skin surfaces (intertriginous area)
Etiology and Risk Factors for Candidal Intertrigo
* Warm moist environment of skin folds is ideal for Candida growth
* Skin friction caused by obesity, clothing that chafes skin, activities that promote skin and skin rubbing
* Moisture within skin folds due to obesity, occlusive clothing, hyperhidosis, exposure to moisture
* Interference with immune response allowing fungal growth: Diabetes, topical and systemic corticosteroids, Antibiotics, HIV, chemotherapy, immunosuppressant medications, sugar (bakers)
Common infection sites for Candidal Intertrigo
Common infection sites
* Inguinal folds
* Axillae
* Scrotum
* Intergluteal folds
* Inframammary folds
* Web spaces of the toes and fingers
* Abdominal folds
Clinical Presentation of Candidal Intertrigo
* Erythematous plaques and erosions
- Peripheral scaling
- Erythematous satellite pustules
* Pruritic and Painful if significant skin breakdown
Candida Pathogens involved in Candidal Intertrigo
* Candida albicans most common
* Non-albicans less frequent (tropicalis, krusei, glabrata, parapsilosis, lusitaniae, guillermondii, etc)
Candidal Intertrigo Diagnosis
* Generally a clinical diagnosis
* Potassium hydroxide (KOH) stain of skin scrapings
Treatment of Candidal Intertrigo
* Eliminate predisposing factors
- Weight loss, Diabetes control
* Topical antifungal agents
- Creams, powders
++ Nystatin, miconazole, clotrimazole, ketoconazole
* Drying agents
- Powders, some solutions
++ Talcum powder, corn starch
++Aluminum acetate (Domeboro’s solution), gentian violet, potassium permanganate
++ Antifungal powders double as antifungal therapy and drying agent
- Drying agent monotherapy typically after adequate antifungal treatment
Treatment Controversy with Candidal Intertrigo:

To add or not to add a topical corticosteroid?
* Helps with itching, pain, and burning
* Avoid moderate and high potency corticosteroids
- Can worsen candidiasis and increase fungal growth
Treatment Controversy with Candidal Intertrigo:

Systemic antifungals
Effective, but rarely necessary
Use if patient fails topical therapy
Epidemiology/Microbiology of Oropharyngeal and Esophageal Candidiasis
Oropharyngeal candidiasis
Commonly known as “Thrush”
Esophageal candidiasis
AIDS defining illness, Immunocompromised
Candida colonizes oral cavity in 30-60%
Predominately C. albicans
Increase in non-albicans in immunocompromised
Most common opportunistic infection
Risk Factors for Oropharyngeal and Esophageal Candidiasis
* Exogenous
Steroids
Antibiotics
Dentures
Xerostomia (Dry mouth)
Smoking
Disruption of oral mucosa

* Disease states
Immunosuppressed
Neonates
Elderly
HIV/AIDS
Diabetes
Malignancies
Malnutrition
Presentation/Symptoms Oropharyngeal and Esophageal Candidiasis
* Symptoms
- Maybe none
- Painful, burning, metallic taste, dysphagia
* Signs
- Diffuse erythema and white patches on oral mucosa and tongue
* Laboratory tests
- Scrape lesion and examine under microscope
- Do not culture – does not distinguish between colonization and infection
Localized and Uncomplicated Treatment of Oropharyngeal Candidiasis
* Uncomplicated localized infection (mouth)
- Clotrimazole 10 mg troche
++ Hold in mouth for 15-20 minutes 4-5 times a day x 7-14 days
- Nystatin 100,000 units/ml suspension
++ 5 ml swish and swallow QID x 7-14 days
- Amphotericin B suspension
++ 5 ml swish and swallow QID x 7-14 days
Systemic Treatment of Oropharyngeal and Esophageal Candidiasis
* Systemic therapy is not typically first line for uncomplicated for oropharyngeal candidiasis; but if disease is extensive, the patient is at high risk for disseminated disease, or if it is refractory to topical agents then systemic agents must be considered
- Common problem populations
++ HIV infected, Immunosuppressed (e.g. neutropenic)
++ Fluconazole 100-200 mg/day can be used

* Esophageal candidiasis (higher doses)
- Fluconazole (first line) 200-400mg/day
- Itraconazole
- Ketoconazole
- Amphotericin B
HIV Infected patients with Oropharyngeal and Esophageal Candidiasis
Esophageal candidiasis
* Lower cure rates
* May be infected with more resistant candida
- Fluconazole resistance becoming problematic
- May have to use alternative agents (Caspofungin, voriconazole, posaconazole, Ampho-B)
* Need higher doses and longer durations: Typically a minimum of 14 days of therapy
Prophylaxis of Oropharyngeal and Esophageal Candidiasis
* Primary prophylaxis not routinely recommended
- Nystatin suspension is frequently utilized in hospitalized patients, especially those on mechanical ventilation
* Secondary prophylaxis
- Consider in patients with multiple recurrent episodes
* Prophylactic agents
- Fluconazole
- Itraconazole
Monitoring Outcomes for Oropharyngeal and Esophageal Candidiasis
* Relief of symptoms (2-3 days)
- Will not eradicate candida in most cases
- Re-evaluate therapy if >5-7 days without improvement
* Drug interactions
* Side effects
Fungal Pathogens(Dermatophytes) involved in infections of the skin, hair and nails
* Come from other humans, animals, or soil

* Penetrate keratinized tissues (e.g. skin) or other areas connected to epidermis such as hair and nails

* Infections can occur at any skin site, but they are most common on the feet, groin, scalp, and nails
Risk Factors for mycotic infections of the skin, hair and nails
Prolonged exposure to sweaty clothes
Failure to bathe regularly
Multiple skin folds (obesity)
Sedentary life style
Confinement to bed
Dermatophytes
* Fungal organism genera

- Trichophyton: Trichophyton rubrum

- Epidermophyton

- Microsporum
Diagnosis of mycotic infections of the skin, hair and nails
* Red, scaly, elevated border
* Nails – yellow or white, brittle and flaking
* Laboratory tests
- Potassium hydroxide (KOH) and microscope
Define Tinea
Dermatophyte infection of the skin
Types of Tinea
Tinea pedis
“Athletes foot”
Tinea manuum
Palmar surface of hands
Tinea cruris
“Jock itch”
Tinea corporis
Skin of trunk and extremities
Tinea capitis
Scalp, hair follicles, and adjacent skin
Tinea barbae
Hairs and follicles of beard
Pityriasis versicolor
Hyper or hypopigmented scaly patches
Treatment of Tinea infections
* Keep infected area dry and clean
* Topical agents preferred
* Oral therapy if infection is extensive or severe when treating tinea capitis or onychomycosis
Topical Tinea Treatments
Butenafine
Ciclopirox
Clotrimazole
Econazole
Haloprogen
Ketoconazole
Miconazole
Naftifine
Oxiconazole
Sulconazole
Terbinafine
Tolnaftate
Triacetin
Undecylenic acid
Systemic Treatment for Tinea infections
For Severe or widespread infection (e.g. Tinea capitis)
Fluconazole
Ketoconazole
Itraconazole
Terbinafine
Griseofulvin
Onychomycosis (Tinea unguium)
* Infection of the nail
- Accounts for 50% of nail problems
* Trichophyton rubrum
- Pathogen in > 90% of cases
* Higher risk patients
- > 40 yo, familial history, smoking, peripheral vascular disease, diabetes, HIV
Diagnosis
Microscopy of nail scrapings to look for fungal hyphae
KOH stain
Systemic Therapy for Onychomycosis
* Terbinafine
* Itraconazole
* Both terbinafine and itraconzole have good lipophilic and keratinophilic properties = good penetration into nail
- Drug half-life in nail ~ 80 days
* Duration
- ~ 3 months
* Cure rates
- Terbinafine 60-80%
- Itraconazole 32-68%
Adverse effects of Terbinafine
N/V, diarrhea, dyspepsia, nausea, abdominal pain
Rash
HA
Taste disturbances
Hepatotoxicity (rare cases of liver failure and death)
Monitor LFTs
Drug interactions with Terbinafine
Potent CYP 2D6 inhibitor
Topical Therapies for Onychomycosis (Tinea unguium)
Ciclopirox (Penlac)
Whitfield’s ointment (salicylic and benzoic acid compound)
Amorolfine (Loceryl®) nail lacquer
Tioconazole (Trosyd®) nail solution
Castellani’s paint (magenta and resorcinol)
Salicylic acid (Phytex®) paint (considered, but not recommended)
Undecenoates (Monphytol®) paint
Naftifine
Tolnaftate
Other antifungal creams (although generally not effective)

Ask your compounding pharmacist for other options!
Echinocandins Spectrum of Activity
* Fungicical
* Very effective against Candida
- All types
- No cross-R with azoles or amphotericin B
* Very active against Aspergillus

* That is really it. Echinocandins: Candida and Aspergillus.
Mechanism of Resistance that limits the spectrum of activity of echinocandins
Primary Resistance: LIMITS SPECTRUM
Cryptococcus, Zygomycetes, Fusarium, scedosporium, trichosporon (they don’t have large amount of the glucan strands in their cells)
Secondary Resistance to echinocandins
*** FKS1 encodes glucan synthase (this is the one to know)
* GNS1 encodes an enzyme involved in fatty acid elongation
Drug Interactions with Caspofungin
* Decreases tacrolimus AUC by 20% and Cmax by 16%
*** Cyclosporine increases caspofungin AUC by 35% (MOST IMPORTANT)
** Inducers (rifampin, carbamazepine, etc.) decrease caspofungin concentrations (Give 70mg of caspofungin daily)
Drug Interactions with Anidulafungin
** Cyclosporine increases anidulafungin AUC by 22%
* LEAST INTERACTIONS – no brainer agent
No significant effect on other drugs
Drug Interactions with Micafungin
* Mild CYP3A inhibitor - MOST DDIs
- Increases sirolimus AUC by 21%
- Increases nifedipine AUC 18% and Cmax 42%
- Cyclosporine increases micafungin AUC by 17%
TARGETS for antifungal activity
* Ergosterol (Cell membrane)
Drug-ergosterol interaction
Inhibition of ergosterol synthesis

* RNA/EF3 (Nucleic acid/protein synthesis)
Incorporation of 5-FU into RNA
Inhibition of EF3

* Glucan/Chitin (Cell wall)
Inhibition of glucan / chitin synthesis
Endemic Mycosis Pathogens
* Dimorphic Fungi - Grows as mold in ambient temperatures and as yeast in body

* Histoplasmosis
* Coccidioidomycosis
* Blastomycosis
Histoplasmosis
H. capsulatum
* Dimorphic fungus
* Nitrogen rich soil
- Bats, pigeons, chickens
- Caves, attics, old buildings
* Ohio and Mississippi river valleys
- >90% of residents may be affected
* Transmission
- Spores travel via air currents
* Inhalation of dust-borne microconidia
Pathogenesis of Histoplasmosis
* 2-3 days after inhaled conidia germinate releasing yeast forms that start multiplying
* Days 9-15 macrophages start ingesting organism
- Transported to lymph nodes, spleen, liver
* 2-4 months
- Tissue granulomas form causing necrosis
* Several years
- Granulomas become encapsulated and calcified trapping yeast within the necrotic tissue
- Yeast are no longer able to proliferate
Presentation Histoplasmosis
* Depends on patient and pathogen
- Immunocompromised vs. immune competent
- Inoculum size, exposure to an enclosed area, and duration of exposure
* Acute and chronic manifestations
- Unusual inflammatory response
++ Pericarditis, Rheumatologic syndromes
- Chronic mediastinal inflammation, fibrosis, broncholithiasis, enlarged parenchymal granulomas
Signs and Symptoms of Histoplasmosis
* Majority of patients
- Mild or asymptomatic pulmonary symptoms
- Higher inoculums
++ Flulike symptoms, fever, chills, headache, myalgia, non-productive cough
* Acute Pulmonary Infection
- Majority of patients, generally self-limiting
- Diffuse pulmonary infection may cause hypoxemia and require mechanical ventilation

* Chronic Pulmonary Infection
- Patients with underlying pulmonary abnormalities (e.g. emphysema)
- Chronic pulmonary symptoms
- Disease progresses over years in 25-30% of patients
- Patients may be ill for 10-20 years with waxing and waning symptoms
Histoplasmosis in Immunocompromised Hosts
Disseminated Infection
Untreated mortality of 83-93%
Blood stream infections, CNS disease, endocarditis, etc.
Enlargement of spleen, liver, lymph nodes
Diagnosis of Histoplasmosis
* Blood smears
- Budding yeasts
* Clinical cultures
* Antigen and antibody tests
* Skin testing
Histoplasmosis Therapy
* Generally not required in asymptomatic or mild disease
* Give therapy for:
- Severe hypoxia
- Diffuse pulmonary disease
- Chronic pulmonary disease
- Immunosuppressed host
Blastomycosis
B. dermatitidis
Dimorphic fungus
Warm moist soil containing decayed vegetation, decomposed wood, and pigeon feces
Increased risk with outdoor occupations that have exposure to soil, etc.
Southeastern and south central United States, Midwest and great lakes region
Inhalation of conidia
Blastomycosis Manifestations
* Acute Pulmonary
- Fever, malaise, weight loss, night sweats, chest pain, and productive cough

* Chronic Pulmonary
- Symptoms similar to acute
- May appear 1-3 years after primary pneumonia resolves
* Disseminated
- Can include all organs (skin, bone, joints, GU, etc.) and CNS
- May appear 1-3 years after pulmonary symptoms resolve
Diagnosis of Blastomycosis
Microscopic (KOH)
Yeast
Treatment of Blastomycosis
* Generally not required in asymptomatic or mild disease
* Give therapy for:
- Severe hypoxia
- Diffuse pulmonary disease
- Disseminated/extrapulmonary disease
- Immunosuppressed host
Coccidiodomycosis
C. immitis
* Dimorphic fungus

* Hot, dry, sandy, and alkaline soil
Become airborne when soil is disturbed

* Southwestern and western United States, Mexico, and South America

* Inhalation of conidia
Clinical Presentation of Coccidiodomycosis
* Asymptomatic disease in 60%
* Fever, cough, HA, sore throat, myalgias, fatigue
* Rash
* Valley Fever
* Pulmonary infection
- Acute and Chronic
++ Necrosis of pulmonary tissue with scaring
* Diffuse maculopapular rash
* Valley Fever (25%)
- erythema of the upper trunk and extremities with diffuse joint aches or fever
* Persistent cough, fever, and weight loss
* Dissemination (< 1% of patients)
Skin, lymph nodes, bone, meninges, spleen, liver, kidney, adrenal gland, etc.
Risk Factors for severe disseminated disease with Coccidiodomycosis
Race
Filipinos>African Americans> Native Americans> Hispanics> Asians
Pregnancy
Immunosuppression
HIV, Steroids, Chemotherapy
Male > Female
Neonates
Patients with A or AB blood types
Diagnosis of Coccidiomycosis
* Microscopic examination
- Tissues or secretions

* Sputum cultures
* CSF fluid (CNS infections)
- Antibodies (IgG, IgM)
* Skin tests
Therapy for Coccidiomycosis
* Generally not required in asymptomatic or mild disease
* Give therapy for:
- Severe infection
- Diffuse disease
- Immunosuppressed host
Treatment of Histoplasmosis, Blastomycosis, or Coccidioidomycosis:
Acute Pulmonary Infection
* Severe - Amphotericin B 0.7 mg/kg/d ± prednisone x 2 weeks followed by itraconazole
* Moderate - Itraconazole 200 mg BID
* Duration ≥ 6 months
Treatment of Histoplasmosis, Blastomycosis, or Coccidioidomycosis:
Chronic Pulmonary Infection
* Itraconazole 200-400mg qd x 12-24 months
* Alternatives
- Amphotericin B 0.7mg/kg/d
- Ketaconazole or fluconazole 200-800mg/d x 1 year
Treatment of Histoplasmosis, Blastomycosis, or Coccidioidomycosis:
Disseminated Infection (Typically an immunocompromised host)
* Life threatening
- Amphotericin 0.7-1mg/kg/d x 1-3 months then itraconazole 200-400mg qd for 6-18 months
* Non-life threatening
- Itraconazole 200-400mg/d x 6-18 months
- Alternative - Fluconazole 400-800mg/d, but resistance may develop
What about Newer Therapies in Histoplasmosis, Blastomycosis, or Coccidioidomycosis?
* No clinical studies, but some have activity
- Lipid and Liposomal Amphotericin B
- Considered alternative to regular Ampho-B deoxycholate formulation
- New Azoles - Have activity
- Enchinocandins will likely not be effective (In-vitro killing data does not look great in comparison to amphotericin B)
Suppressive Therapy for Histoplasmosis, Blastomycosis, or Coccidioidomycosis
* Immunocompromised
- Itraconazole 200 mg daily

* Without suppressive therapy relapse rates range from 50-90%
* Follow closely for relapse
- Monitor antigen levels every 3-6 months
Monitoring for Histoplasmosis, Blastomycosis, or Coccidioidomycosis
* Improved signs and symptoms
* Resolution of radiologic, serologic, and microbiologic parameters
* Drug-Drug interactions
* Toxicities
Sporotrichosis
AKA Rose Gardener’s Disease

* Pathogen
- Sporothrix schenckii (dimorphic)
* Epidemiology
- Tropical or temperate climates
Presentation of Sporotrichosis
* Incubation: 1-3 weeks
* Inoculation
- Spores multiply at lesion site caused by thorn or other plant material
- Spores are carried by lymph fluid
* Painless ulcerating nodules in a linear pattern
Treatment for Sporotrichosis
* Topical agents
- Potassium iodide (SSKI), terbinafine
* Generalized or more severe infections
- Amphotericin B or Itraconazole

* Newer azoles? work just fine just no great data
* NO Echninocandins (not effective)
Global hot spots for TB infection
Asia, SE Asia
Africa
Mexico
 Caribean
 Central America
 Soviet Union (former)
US Hot spots for TB infection
 Prisons
 NY City
 Other ports of entry: California, Florida, Georgia, Illinois, New Jersey, Texas
 Most prevent among the foreign born
List groups of patients with a high risk for developing TB
 Minority race
 Ages 25-44 most common
 <2 and > 65 more at risk
 Men more than women (= if under 15 yo)
 Immunosuppressed: HIV, Cancer, Renal disease, Long-term oral corticosteroid use, anything else leading to immunosuppression
Describe 2-3 public health strategies relating to tuberculosis
 DOTS: The five elements of the DOTS strategy:
 Sustainable government commitment
 Quality assurance of sputum microscopy
 Standardized short-course treatment (including direct observation of therapy)
 Regular supply of drugs
 Establishment of reporting and recording systems (2,3).
 Federal Tuberculosis Task Force Plan in Response to the Institute of Medicine Report, Ending Neglect: The Elimination of Tuberculosis in the United States
 Ensure available clinical and public health services to provide continuous quality care for TB patients.
 Improve and optimize follow-up of immigrants and refugees arriving in the U.S. with suspected TB.
 Improve and ensure the quality of tuberculosis examinations conducted by overseas panel physicians and domestic civil surgeons.
 Facilitate continuity of care for prisoners and INS detainees across correctional facilities and communities in the U.S. and Mexico and elsewhere.
 Continue to ensure TB medications are available and at federal pricing via the Department of Veterans Affairs national contract.
 Develop improved engineering techniques to prevent TB transmission.
How often do most types of mycobacteria replicate?
mycobacterium double every 20 hours.
Describe laboratory characteristics of mycobacteria and how they differ from those of bacteria
o Appearance: MYCOBACTERIUM: Slender bacillus, 1-4 microns long, straight or slightly curved, stain RED with carbol-fuschin staining(will not gram-stain) BACTERIA: Gram stain
o Growth: MYCOBACTERIUM: slow ~20 hours to double BACTERIA: fast, ~ 30 mins to double
• Nontuberculous Mycobacteria (NTM): List other mycobacterial organisms that lead to disease in humans.
o Mycobacterium kansasii
o Mycobacterium fortuitum
o Mycobacteruym avian complex (MAC)
Explain the Agar Method of susceptibility testing and list pros and cons
Characteristics:
- PROPORTION METHOD: this method reports any resistance as a "percent" resistance, meaning that X% of the organisms growing on the plate are demonstrating resistance. PLEASE NOTE: even ONE percent is considered resistant!

Pro(s):
- Cheap! $
- Low-tech (Therefore good for use in developing countries)

Con(s):
- Qualitative (S or R)
- Slow (because mycobacteria grow slowly!) - can take 3-6 weeks to get a good result
Explain the Radiometric Method (ie BACTEC, Becton-Dickson, Sparks, MD)of susceptibility testing and list pros and cons
Characteristics:
- Uses 7H12 Broth as the media
- Detects radiolabelled CO2 given off by the mycobacteria

Pro(s):
- Quantitative (gives a true MIC value...
- Faster than agar (9-14 days)

Con(s):
- More expensive - $$
- Newer methods now available
Explain the Nucleic Acid Probeof susceptibility testing and list pros and cons
Characteristics:
- uses a DNA probe to measure the complementary rRNA of replicating mycobacteria

Pro(s):
- Great for identifying the exact species (ie, is it M. tuberculosis, M. chelonae, etc), which can then allow for the correct therapy!
- Also expensive! - $$-$$$
Con(s):
Explain how TB is transmitted
 Person to person transmission through respiratory droplets (cough or sneeze)
 Droplet nuclei are created, each containing 1 to 3 organisms, and are dispersed in the air
 30% of people who have prolonged contact with a TB infected patient will contract TB
 Patients with rare laryngeal TB can spread TB just by talking
Compare and contrast the difference between TB infection and TB disease
A Person with Latent TB Infection:
- Has no symptoms
- Does not feel sick
- Cannot spread TB
- Has skin test or blood test positive for TB infection
- Normal chest X-ray and negative sputum smear
- Needs treatment for latent TB infection to prevent active disease

A Person with TB Disease
- Has symptoms:
++ bad cough for 3 or more weeks
++ chest pain
++ coughing up blood or sputum
++ weakness or fatigue
++ weight loss
++ no appetite
++ fever, chills, night sweats
- Feels sick
- May spread TB
- Has a skin or blood test positive for TB
- may have an abnormal chest X-ray or positive sputum smear or culture
- Needs treatment to treat active TB disease
o Nontuberculous Mycobacteria (NTM): Compare and contrast the pathophysiology of disease caused by NTM organisms versus that of Mycobacterium tuberculosis
 NTM can cause bad disease, too!
 The only real difference is that disease due to NTM is NOT considered communicable.
Describe differences in the pathophysiology of TB in the face of HIV.
Symptoms
- HIV negative: fever, jweight loss, cough
- HIV positive: Fever may be low-grade or absent

Site of Infection:
- HIV negative: Anywhere, but most commonly in the apices of the lungs
- HIV positive: Anywhere, but more commonly EXTRA - pulmonary

Lab tests:
- HIV negative: Mild Increase in WBC, with mostly lymphocytes
- HIV positive: Low number of T lymphocytes

Radiography (CXR)
- HIV negative: Infiltrates mostly in apices of upper lobes, but also anywhere. Cavities = classic sign of TB
- HIV positive: Rarely are cavities seen
Widespread cloudy infiltrate or there may be no radiographic findings
o Nontuberculous Mycobacteria (NTM): Compare and contrast the pathophysiology of disease caused by NTM organisms versus that of Mycobacterium tuberculosis
 NTM can cause bad disease, too!
 The only real difference is that disease due to NTM is NOT considered communicable.
Describe differences in the pathophysiology of TB in the face of HIV.
Symptoms
- HIV negative: fever, jweight loss, cough
- HIV positive: Fever may be low-grade or absent

Site of Infection:
- HIV negative: Anywhere, but most commonly in the apices of the lungs
- HIV positive: Anywhere, but more commonly EXTRA - pulmonary

Lab tests:
- HIV negative: Mild Increase in WBC, with mostly lymphocytes
- HIV positive: Low number of T lymphocytes

Radiography (CXR)
- HIV negative: Infiltrates mostly in apices of upper lobes, but also anywhere. Cavities = classic sign of TB
- HIV positive: Rarely are cavities seen
Widespread cloudy infiltrate or there may be no radiographic findings
Discuss key tests (lab and clinical) used in the diagnosis of TB infection and disease
o Tuberculin Skin Test (PPD- tuberculin purified protein derivative)
 When an infected patient is injected with PPD, and if they have been exposed to MTB, it mounts a response of activated lymphocytes, macrophages, etc at the injection site.
 At this time, if the skin test is positive, a wheel or induration should form.
o Clinical Presentation of TB Disease
 S/sxns: Fever, weight loss, cough
 Mild increase in WBC with mostly lymphocytes
 CXR - Infiltrates mostly in apices of upper lobes, but also anywhere. Cavities = classic sign of TB
o Sputum Smear/Culture Info
 the revised definition of a new sputum smear-positive pulmonary TB case is based on the presence of at least one acid fast bacilli (AFB+) in at least one sputum...
 The more AFB seen, the more contagious the patient is.
 A patient can be smear negative, but still end up being culture positive. If so, that means there were too few organisms to show up under the microscope (ie by "smear"), but there are enough organisms to grow in a culture.
 It is from this culture test that drug susceptibility can be identified.
Goals of TB therapy
•Rapid identification of a new TB case
•Initiation of specific anti-TB treatment
•Resolve signs and symptoms
•Achieve non-infectious state!
•Adherence to the treatment regimen
•Cure of the patient ASAP
Provide a drug regimen to treat patients recently exposed to TB and those with latent tuberculosis infection (LTBI).
Izoniazid 300 mg qd x 9 months
Provide a drug regimen to treat drug susceptible TB
Initial phase:
Isoniazid 300 mg, Rifampin 600 mg, pyrazinamide1g-2g (wt based), and ethambutol 800 - 1600 mg (weight based) daily x 8 weeks

Continuation phase:
Isoniazid, rifampin daily x 18 weeks
Provide a drug regimen to treat drug resistant TB
No preferred regimen
Take patients drug exposure into account
Test for susceptibility
Treat with 4 or more drugs
Never add just one drug to a failing regimen
There are two tests used to evaluate the efficacy of a TB regimen. What are they and how often should they be checked to assure proper TB treatment?
Smears: If smear positive, check smears Q 1-2 weeks until smear negative x 2 (consecutively). Then you may check them less frequently.

Culture: Obtain these monthly until smear negative.
Describe how drug resistance to tuberculosis can develop with treatment errors
* When treating TB, it is critical to avoid monotherapy.

* NEVER add a single drug to a failing regimen!!!
- This amounts to Monotherapy

When these principles are ignored, developement of drug resistance is much greater.
Advise on potential treatment differences in an HIV positive patient
* Regimens are similar but longer in duration (9 months minimum, max not defined)
* Intermittent regimens are not recommended
* Oral drugs may not be absorbed well in the HIV positive patient