section name header

Info


A. Characteristics of Funginavigator

  1. Eukaryotic single or multicellular organisms
  2. Separate Kingdom of fungi now generally accepted

B. Morphology of Medically Important Organismsnavigator

  1. Yeasts
    1. Exist as discrete cells
    2. Reproduce by asexual budding
  2. Molds
    1. Grow in multicellular filaments (hyphae)
    2. Reproduce by spore formation
  3. Thermally dimorphic fungi
    1. Grow as molds in environment (ambient temperature)
    2. Grow as yeast forms at body temperature

C. Epidermal Mycosesnavigator

  1. Live in stratified squamous epithelium
  2. Candida albicans and other species
    1. Thrush (oral candidiasis), Candidial esophagitis. White, pseudomembranous plaques
    2. Cutaneous candidiasis appears as a "red scalded lesion"; pseudohyphae
    3. Dimorphic only when pathogenic; otherwise yeast forms predominate
    4. C. glabrata and C. krusei are becoming increasingly common
  3. Dermatomycoses
    1. Exist ubiquitously
    2. Includes athlete's foot infection, skin "ringworm", nail infections (Tinea and others)
    3. Organisms posess elastase and keretanase which allow hydrolysis of host epidermis
    4. Rash variable: non-inflamed scaly areas to edematous, vesicular lesions
    5. Typically caused by Tinea species, Trichopyhytum, Epidermophyton, Microspora
    6. Miconazole and tolnaftate (Tinactin®) - cheap and effective without prescription [1]
    7. Terbinafine (Lamisil®) - as effective in 1 week as others in 4 weeks (non-prescription)
    8. Naftifine (Naftin®) - qd application for tinea pedis, others; treat for up to 4 weeks
    9. Butenafine (Mentax®) - qd application x 4 weeks for all forms of tinea, low relapse [2,3]
    10. Ciclopirox (Loprox®) is now also available for topical fungal infections
    11. Terbinafine, fluconazole or itraconazole are well tolerated and very effective for treatment of superficial fungal infections (dermatomycoses and onychomycoses) [5]
  4. Tinea Infections
    1. Tinea Pedis - 70% lifetime prevalence, common infection between pedal digits
    2. Tinea Capitus - scalp infection caused by several organisms; typically age 4-14 years
    3. Tinea Corporis - dermatophyte infection of torso or extremities; includes ringworm
    4. Tinea Cruris - "Jock Itch" dermatophyte infection; bilateral erythrematous pruritc plaques
    5. Tinea (pityriasis) versicolor - well-demarcated sacling patches, variable depigmentation
    6. Tinea nigra - "black rash", one oval-shaped macule or patch, light brown-black
  5. Onychomycosis
    1. Dermatophyte infections of nails, toenails much more common than fingernails
    2. Systemic agents usually more effective than topical agents
    3. Oral agents as for dermatomycoses very effective and well tolerated [5]
    4. Terbinafine (Lamisil®) 250mg po qd for 12 weeks is least expensive, ~75% effective [4]
    5. Fluconazole 150-300mg weekly for 6-12 months is ~90% effective
    6. Itraconazole 200mg po qd for 12 weeks is ~65% effective and well tolerated [6]
    7. Itraconazole may may be given 1 week per month for 3-4 months also effective
    8. Topical terbinafine may be used and is well tolerated (over the counter)
    9. Mycocide NS is a topical anti-fungal with good anti-fungal activity
    10. Ciclopirox 8% (Penlac® lacquer) - effective for fungal paronychia without lunula involvement
    11. Oral griseofulvin (Fulvicin®) no longer recommended
    12. Note: bacterial paronychia (more common in hand than foot) must be treated aggressively
  6. Piedra
    1. Asymptomatic infection of distal portions of hair shaft
    2. Black piedra: disease with dark, hard nodules on scalp hair
    3. White piedra: disease with soft white nodules on axillary or beard hairs

D. Dermal (Subcutaneous) Mycoses: Sporotrichosisnavigator

  1. Spores in large number, predisposed to dissemination to systemic disease
  2. Seen especially in diabetes, T cell deficiency, glucocorticoids [7], and chemotherapy
  3. Easy to culture, see elongated yeast cells, possibly surrounded by capsule material
  4. Skin ulcer, acute central infiltrate and chronic inflammation with granulomas occur
  5. Commonly follow splinter or rose thorn penetration of skin
  6. Treatment Cutaneous: Itraconazole 100-200mg po qd
  7. Treatment Systemic: Itraconazole 200mg po bid

E. Invasive (Deep) Mycoses [8] navigator

  1. Epidemiology
    1. Inhaled forms such as histoplasmosis, coccidiomycosis may affect normal persons
    2. Most invasive infections occur in immunocompromised persons
    3. Stem cell transplant, organ transplant, intensive chemotherapy increase risk
    4. Chronic moderate to high dose glucocorticoids can also increase risk
    5. Overall mortality due to candidal sepsis is decreasing
    6. Overall mortality due to non-candidal organisms is increasing
    7. Aspergillus mortality has increased 4-fold since 1985
    8. Increasing incidence of Scedosporium and Fusarium with limited therapeutic options
  2. Characteristics
    1. Inhalation most common, followed by replication and host response
    2. Other routes of entry with dissemination in immunocompromised persons
    3. Intact cell mediated immunity usually leads to clearance of organism
    4. Granulomatous cell mediated immune response is typical
    5. Dissemination mainly occurs in immunocompromised persons including glucocorticoids [7]
    6. Diagnosis usually requires tissue specimen or bronchoalveolar lavage
    7. Pneumocystis now classified as fungus
    8. Responsible for ~45% of fevers in patients with severe neutropenia and fever [9]
  3. Systemic Candidiasis
    1. Small, white appearing papular lesions someteims present in granulocytopenic patients
    2. Kidneys usually involved in disseminated infection (also liver, spleen and skin)
    3. In normal patients, microabscess formation can occur
    4. C. albicans now represents <50% of isolates from immunocompromised persons
    5. Increase in C. krusei and C. glabrata
    6. Grows well in biofilms on hard surfaces, which are resistant to standard decontamination
    7. Increasing cause of sepsis in intensive care units
    8. Fluconazole prophylaxis has reduced incidence of new C. albicans infections
    9. Non-albicans candida may respond to voriconazole and especially echinocandins
  4. Histoplasmosis
    1. Agent: Histoplasma capsulatum
    2. "Histo" refers to macrophage; "plasma" indicates cytoplasmic residency
    3. Thus, these organisms live in the cytoplasm of macrophages
    4. Produce a TB or "flu" like illness; usually spread through bird feces
    5. Occurs in Southeastern US / Ohio River Valley
  5. Aspirgillosis
    1. Various disease entities including invasive disease and mycetomas
    2. Can cause severe allergies and asthmatic symptoms
    3. Often seen in immunocompromised patients
    4. Most common cause of fungal sinusitis [10]
    5. Most common invasive mold infection associated with glucocorticoids [7]
    6. Treatment with voriconazole or amphotericin or caspofungin [11,12]
  6. Paracoccidiomycosis [13]
    1. Usually treated with itraconazole or amphotericin B
    2. Patients may be severely ill, and should receive amphotericin B
  7. Malassezia Group [14]
    1. Malassezia furfur is a common lipophilic obligate saprophyte in humans
    2. M. furfur has caused nosocomial outbreaks in neonatal intensive care units (ICUs)
    3. Usually found in low birth weight infants receiving lipid rich nutrients
    4. M. pachydermatis has also been found in humans, again in neonates in ICUs
  8. Mucromycosis
    1. Highly resistant, destructive organisms
    2. Usually occurs with immunocompromise, mainly diabetics (~50% of infections)
    3. High glucose due to other insulin resistance and glucocorticoids also predispose [7]
    4. Species include Rhizopus and Mucor
    5. Sinus colonization with invasion to surrounding tissues
    6. Deep bone / soft tissue penetration, often in face
    7. Early symptoms include facial, ocular pain, nasal stuffiness
    8. Black necrotic eschar on nasal turbinates may be seen
    9. Meningitis may occur from progression of deep infections
    10. Invasion to ocular region may lead to visual loss or ocular muscle dysfunction
  9. Pseudoallescheriasis - itraconazole therapy [6]
  10. Penicillium marneffei [15]
    1. Common infection in HIV patients in Southeast Asia
    2. Itraconazole therapy is excellent for treatment and prophylaxis
  11. Resistance to common antifungals is slowly emerging [16]

F. Cryptococcosis [17] navigator

  1. Cryptococcis neoformans
  2. Round organisms in a lucent, "crypt-like" case. Spread from bird feces.
  3. Asymptomatic in some people
  4. Primary pulmonary infection often occurs, often with dissemination
  5. Cryptococcal meningitis is major problem in HIV disease
  6. May cause chronic prostatitis or osteomyelitis

G. Coccidiomycosis [18]navigator

  1. Also called "Valley Fever"
  2. Caused by Coccidioides immitis
    1. Mainly acquired in endemic regions including Southwestern USA, San Joaguin Valley region
    2. Majority of infections are self limited
    3. Only 5-10% of infections lead to any residual sequelae
  3. Disease Types
    1. Majority of patients are asymptomatic
    2. Pulmonary Disease - often mimicking an upper respiratory infection
    3. Skeletal Disease - includes a monoarthritis, bone infections (osteomyelitis)
    4. Skin manifestations may include erythema multiforme or erythema nodosum
    5. Soft Tissue Infection
    6. Meningitis is the most frequent serious complication
    7. Weight loss is a common manifestation of severe disease
  4. High Risk Patients
    1. Diabetics
    2. HIV
    3. Immunosuppressed - glucocorticoids, organ transplant
    4. Chronically debilitated patients
    5. Major outbreak following earthquake due to dissemination from dust spores [19]
  5. Diagnosis
    1. Should be considered in anyone visiting or from the Southwestern USA
    2. Chest radiograph (CXR) may show nodules, interstitial infiltrate, cavitary lesions
    3. Skin testing is positive early in disease, but many patients become anergic
    4. Culture and Fungal Stains are specific but unreliable
    5. Observing spherules in tissue was best method in the past
    6. Commercially available DNA probe now available for definitive diagnosis
    7. Serum antibody titers are useful in mid-disease course (monitor disease progression)
  6. Manifestions of Severe Infections [18]
    1. Loss of body weight >10% of baseline
    2. Intense night sweats persisting >3 weeks
    3. Infiltrates involving >50% of one lung or portions of both lungs
    4. Prominent or persistent hilar lymphadenopathy
    5. Anti-coccidioidal complement fixing antibody titer >1:16
    6. Failure to develop dermal hypersensitivity to coccoidal antigens
    7. Persistence of symptoms >2 months
  7. Treatment Overview
    1. Patients with normal immune systems and mild disease should be monitored
    2. Moderate disease with normal immune status may be monitored or treated
    3. Severe disease should definitevely be treated
    4. Fluconazole or itraconazole for 3-6 months with normal immune status
    5. Itraconazole slightly more effective at 200mg bid for coccidiomycosis than fluconazole [14,20]
    6. Amphotericin B and/or fluconazole for coccidiodal meningitis
  8. Fluconazole [13]
    1. First line therapy for for all coccidiomycosis
    2. Good CSF penetration
    3. Dose 400-800mg po qd 12-18 months for pulmonary and non-meningeal extrapulmonary disease
    4. Dose 400-600mg qd indefinitely for meningitis
    5. Effective in ~75% of patients with coccidioidal meningitis
  9. Itraconazole [6]
    1. Efficacy similar to or slightly better than fluconazole for non-meningeal coccidiomycosis [20]
    2. Dose is 200mg po bid
    3. Must not be used in meningeal disease (poor CSF penetration)
  10. Voriconazole [11,21]
    1. Broad in vitro spectrum agent
    2. Good efficacy in vivo given orally or parenterally
    3. Efficacy nearly as good as liposomal amphotericin B in neutropenic patients with persistent fever
    4. Transient visual changes (~20%) and hallucinations (~5%) are main side effects
    5. Overall well tolerated with minimal infusion-related and kidney toxicities
  11. Amphotericin B
    1. Prior to azole therapies, this was mainstay
    2. Reserved for meningitis infections or relapsed (resistant) cases
    3. Standard formulation (intravenous) is very poorly tolerated
    4. Liposomal amphotericin B is better tolerated and as effective
    5. Intrathecal (with direct port to CSF) for meningitis may be required
    6. Chemical irritation, neurologic deficits are very common
  12. Lifetime therapy with imidazoles may be required in meningeal disease [9]

H. Blastomycosis [22]navigator

  1. Blastomyces dermatitidis - dimorphic fungus, similar to histoplasmosis
  2. Uncommon infection across most geographies
  3. Most cases occur in southeastern, central and mid-Atlantic US, northeastern Canada
  4. Male to female ~10:1
  5. Usually transmitted by inhalation from soild, decomposing vegetation, rotting wood
  6. Usually indolent onset with chronically progressive course
  7. Skin lesions can occur in exposed areas, pimples to encrused or ulcerated lesions
  8. CXR shows nodular infiltrates in ~65% of cases
  9. Diagnosis by culture of sputum, pus, or urine; not usually visible on sputum cytology smear
  10. Treatment
    1. Mild to moderate disease: itraconazole 100-200mg po bid for 6-12 months [6,13]
    2. Immunosuppressed should be treated as severe infection
    3. Amphotericin lipid complex for severe disease

References navigator

  1. Chren MM and Landefeld S. 1994. JAMA. 272(24):1922 abstract
  2. Desnup DH, Galgiani JN, Graybill R, et al. 1996. Ann Intern Med. 124(3):305 abstract
  3. Butenafine. 1997. Med Let. 39(1004):63
  4. Terbinafine. 1996. Med Let. 38(967):10
  5. Chang C, Young-Xu Y, Kurth T, et al. 2007. Am J Med. 120(9):791 abstract
  6. Itraconazole. 1994. Med Let. 36(916):18
  7. Lionakis MS and Kontoyiannis DP. 2003. Lancet. 362(9398):1828 abstract
  8. Patterson TF. 2005. Lancet. 366(9490):1013 abstract
  9. Corey L and Boeckh M. 2002. NEJM. 346(4):222 abstract
  10. DeShazo RD, Chapin K, Swain RE. 1997. NEJM. 337(4):254 abstract
  11. Voriconazole. 2002. Med Let. 44(1135):63 abstract
  12. Caspofungin. 2001. Med Let. 43(1108):58 abstract
  13. Treatment of Fungal Infections. 1996. Med Let. 38(981):72
  14. Chang HJ, Miller HL, Watkins N, et al. 1998. NEJM. 338(11):706 abstract
  15. Supparatpinyo K, Perriens J, Nelson KE, Sirisanthana T. 1998. NEJM. 339(24):1739 abstract
  16. Kontoyiannis DP and Lewis RE. 2002. Lancet. 359(9312):1135 abstract
  17. McGowen K and Mark EJ. 2002. NEJM. 347(7):517 (Case Record) abstract
  18. Galgiani JN. 1999. Ann Intern Med. 130(4):293 abstract
  19. Schneider E, Hajjeh RA, Spiegel RA, et al. 1997. JAMA. 277(11):904 abstract
  20. Galgiani JN, Catanzaro A, Cloud GA, et al. 2000. Ann Intern Med. 133(9):676 abstract
  21. Walsh TJ, Pappas P, Winston DJ, et al. 2002. NEJM. 346(4):225 abstract
  22. Watts B, Argekar P, Saint S, Kauffman CA. 2007. NEJM. 356(14):1456 (Case Record) abstract