Fungal Infections

Swamy - og lecture

Vulvovaginal candidiasis

+common pathogen, labs→ vaginal pH, microscopy, cultures

vaginal pH: normal

pathogen: Candida albicans

Gold standard for diagnosis: microscopy

• budding yeasts

• hyphae

• pseudohyphae

cultures not required

Vulvovaginal candidiasis risk factors

sexual activity

contraeptive agents

antibiotic use

Uncomplicated Vulvovaginal candidiasis characteristics (how many should a patient have?)

+onset, severity, pathogen, health of patient

must have ALL:

sporadic or infrequent

mild-moderate severity

likely pathogen - Candida albicans

not immunocompromised

Complicated Vulvovaginal candidiasis characteristics (how many should a patient have?)

+onset, severity, pathogen, health of patient

must have 1 or more of these:

recurrent disease

severe disease

non-albicans candiasis

diabetes, immunosupression, pregnancy

Uncomplicated Vulvovaginal candidiasis treatment

+medication, duration

duration not critical

preferred: topical azoles x1-7days

or

fluconazole po x1 (avoid systemic)

selection based on patient preference and past experience

Treatment of Complicated Vulvovaginal Candidiasis Treatment

+medications, duration

duration of therapy extended

preferred: topical azaleas x7-14 days

(at least a week)

or

fluconazole by mouth q72 hours x2-3 doses

Treatment of Vulvovaginal Candidiasis Treatment for pregnancy

+which is formulation recommended?

Recommended: topical azoles x7days

• systemic is teratogen

Treatment of Vulvovaginal Candidiasis Treatment for Recurring disease

+definition, treatment and stages (initial→ maintenance), novel agents

Definition: ≥3 episodes in 1 year

Treatment (2 stages)

• initial treatment:

  • Topical azaleas x7-14 days

  • fluconazole PO q72h x3 doses

• maintenance: fluconazole PO x 6 months

Novel Agents: Osteseconazole, ibrexafungerp

Treatment of Vulvovaginal Candidiasis Treatment for Resistant disease

+deifniton, options

definitions: persistently positive yeast cultures and fail to respond to therapy

options: 14 days except ibrex.

• ibrexafungerp PO (only need 2 doses)

• boric acid, intravaginal

• nystatin, intravaginal

• flucytosine, intravgainal (can add amphotericin B)

Oropharyngeal Candidiasis

+pathogen, clinical presentation, diagnosis

pathogen: Candida spp. → mostly C.albicans

clinical presentation:

• white patches on tongue, roof of mouth, or inner cheeks,

• redness or soreness

• cotton-like feeling in mouth

• loss of taste

• cracking/redness at corners of mouth

diagnosis:

• based off presentation, microscopy not usually necessary

• Dysphagia, odynophagia, retrosternal chest pain suggestive of esophageal involvement (esophageal candidiasis)

most opportunistic infection in people with HIV

Oropharyngeal Candidiasis predisposing factors

immunosuppression

immunosuppressive states and medications

things that disrupt normal flora

Treatment of Oropharyngeal Candidiasis for mild infection

topical agents for 7-14 days (require multiple. application bc of short interaction with mucosa)

First line:

Clotrimazole, troche x5qd

Miconazole, mucoadhesive qd

Alt.:

Nystatin, swish and swallow qid

Nystation pastilles qid

Treatment of Oropharyngeal Candidiasis for moderate-severe infection

systemic agents x7-14days

First line: Fluconazole PO qd

Treatment of people with HIV

+duration

systemic agents

• Fluconazoke 7-14 days

alt. topical

ART recommended

Treatment of Fluconazole-Refractory Orophryngeal Candidiasis

+duration

systemic agents for up to 28 days

first line:

• Itraconazole solution

• Posconazole Suspension

  • older formulation.

Esophageal Candidiasis

+clinical presentation, predisposing factors

presentation

• dysphagia, odynophagia, retrosternal chest pain

• usually extensions orophageal candidiasis

predisposing factors: similar to oropharyngeal

• immunosuppression

  immunosuppressive states and medications

  things that disrupt normal flora

Treatment of Esophageal Candidiasis

requires systemic agents

duration is longer: 14-21 days

First Line:

Fluconazole PO x14-21 days

• If cannot take PO:

  • IV FLUCONZAOLE OR IV ECHINOCANDIN

  • transition IV→PO when able

Treatment of Fluconazole-Refractory Esophageal Candidiasis

Itraconzaole oral solution

posaconazole suspension or delayed release tablets

like in Oropharyngeal but can also use:

voriconazole IV or PO

Enchinocandin IV

Amphoteriicn B deoxycholate

Dermatophyte Infections

+common pathogens, common location

pathogens:

• trichophyton spp.

• epidermohyton spp.

• microsporum spp.

locations tend to be keratinous structures of the body

• feet = tine pedis (athletes foot)

• toenails = onchomycosis

• proximal thigh and buttocks - tine curries (jock itch)

• truck/extremities/face = tines corpori’s (ring worm)

• scalp = tinea capris

• beard hair follicles = tine barbae

Dermatophyte Infections Risk Factors

+reservoir for pathogens

prolonged exposure to swear or soaking water

maceration (soaking)

interiginous folds

sharing belongings (combs)

close living quarters

reservoir:

• humans, animals, soil

• contact either a reservoir and have environment for myopic growth (moist conditions)

Dermatophyte Infections Clinical presentation

+skin, nail

infections of skin

• central clearing surrounded by advancing red, scaly, elevated “activated” boarder

infections of the nails

• chalky, dull yellow, or white

• brittle and crumbly

Dermatophyte Infections diagnosis

based on patient history and physical examination

tests:

microscopic examination + KOH

fungal cultures

Dermatophyte Infections treatment - general

+duration, reservation for formulations for which indications

First Line = Topical agents duration = 1-4 weeks

Systemic/Oral agents reserved for:

• tines capitis (head)

• ocychomycosis (toes)

• severe or extensive infection

Dermatophyte Infections treatment - Tinea pedis

+durations, severe cases

(athlete’s foot)

Duration: 1-4 weeks

preferred: daily topicals

• butenafide

• sertaconazole

• luliconazole

• naftifine

severe cases: systemic; duration: 1-4 weeks

• fluconazole PO once weekly

Dermatophyte Infections treatment - Tinea cruris

+duration

(jock itch)

Duration: 1-4 weeks

preferred: topicals

• clotrimazole

• luliconazole

• naftifine

severe cases: 1 week

• Itraconazole

Dermatophyte Infections treatment - Tinea corporis

+duration

(ring worm)

duration: 1-4 weeks

preferred: -azole

severe cases: every 2 weeks

• terbinafine

Dermatophyte Infections treatment - Tinea capitis (scalp)

preferred:

Terbinafide 4-8 weeks

• shampoo in conjunction with oral therapy

Dermatophyte Infections treatment - Onychomycosis

oral preferred: (fingers longer)

first line: Terbinafine

• fingernail: 6 weeks

• toenails: 12 weeks

alt.: Itraconazole

• fingernail: 2 months

• toenail: 12 weeks

alt: fluconazole

• fingernail: 6 months

• toenail: 12 months

topical: duration→ 48 weeks

• cicloopirox 8% nail lacquer

• elfinaconazole 10% topical solution

• tavaborole 5% topical solution

Invasive infection

+pathogens, and how ar they generally acquired

Most acquired via inhalation

pathogens:

• invasive candidiasis

  • acquired via GI tract

  • can also be exogenously (vascular catheters)

• cryptococcosis

• asperigillosis

• mucormycosis

• fusariosis

• endemic mycoses

Risk factors for invasive candidiasis infection

Underlying Disease

• immunocompromising conditions

Surgery (abdominal/ with ICU admission)

Foreign Devices

Colonization (from sites other than blood)

Antibiotic Use

(in previous 10 days or using 2 or more)

• elimination of good flora

Invasive Candidiasis

+diagnosis, acquisition

diagnosis:

• positive cultures from normally sterile sites that invade deep tissues

  • use of non-stertile sites not reliable

    • skin, mouth, sputum, feces, or urine = no treatment

acquisition:

• GI tract

Invasive Candidiasis Empiric Treatment

First Line: Echinocandin agent

Alt:

Fluconazole (non critically ill bs unlikely to have resistance)

or

Lipid formulation of Amphotericin B

Fluconazole Susceptible Candida

Candida albicans

candida tropicalis

candida parapsilos

Invasive Candidiasis Targeted Treatment

for candida: albicans, tropical, parapsilos, glabrata, krusei, auris

When there is a known susceptible to fluconazole or transition to achinocandin to fluconazole

Fluconazole:

• Candida Albicans

• Candida Tropicalis

• Candida Parapsilosis

Echinocandin/Voriconazole:

• Candida Glabrata

• Candida Krusei

Enchinocandin:

• Candida Auris

Invasive Candidiasis duration of therapy

2 weeks after first negative blood culture and resolution of symptoms

Aspergillosis

+species, common diseases, method used to acquire, reqiremnt for disease development

species:

A. fumigates

A. flavis

A.niger

largely due to allergy

acquired by inhalation of spores that reach alveoli or paranasal sinuses

impaired host defenses essential for disease developemnt

Invasive Aspergillosis risk factors

abnormal phagocyte number

abnormal phagocyte function

• high dose corticosteroid

• graft vs host disease

• solid organ transplantation

severe abnormalities in lung functions

• cystic fibrosis, respiratory failure due to flu or COVID-19

Aspergillosis sites of infection

pulmonary

rhionsinutsitis

CNS

heart, joints, bones

Invasive Aspergillosis biomarker

use: Galactomannan

• false positive and negatives may occur

beta -1,3-D-glucan is not specific to Aspergillus

• limited by false positives

Invasive Aspergillosis Treatment

+duration

First Line: Voriconazole

(treat A with V)

alt:

• liposomal amphotericin B

• isavuconazole

• posaconazole

Duration: not well defined

• min. 6-12 weeks

Invasive Aspergillosis Combo Treatment

+when is it used

Voriconazole + Enchinocandin

possible benefit in probably aspergillus

consider in severe disease

Fusariosis

+species, risk factors, manifestations

Species:

F. solani complex

F. oxysporum complex

F. fujikuroi complex

Risk Factors : similar to invasive aspergillosis

• abnormal phagocyte number

  abnormal phagocyte function

  • high dose corticosteroid

  • graft vs host disease

  • solid organ transplantation

  severe abnormalities in lung functions

  • cystic fibrosis, respiratory failure due to flu or COVID-19

• additional prevalence of foreign body, burns

Manifestations

• Fungemia (positive blood cultures)

• cutaneous

• sinusitis

• pneumonia

• disseminated disease

Fusariosis Treatment

+duration

First Line = Voriconazole

alt:

• amphotericin B

• posaconazole

surgical debridement of infective tissue if possible

continue until resolution of symptoms

Mucormycosis

+species, risk factors, clinical presentation

species: Rhizopus spp.

risk factors:

• white cell abnormalities

• metabolic derangements

• breakdown in anatomical barriers

clinical presentations: rapid disease progression and tissue necrosis

• Rhinocerebral

• pulmonary

• rhino-orbital

*listen again*

Mucormycosis Treatment

+alternative, combo?, step down

Source control

• surgical debridement

Drug of choice: Lipsomal Amphotericin B IV!!

• 10mg if brain involvement

alt:

isavuconazole, posacoazole

combo treatment generally not recommended

Step down to PO: isavuconazole, posacoazole and continues until resolution of symptoms