Fungal Infections

Alessandro DianaNovember 22th 2007

alessandro.diana@ne.ch

Topics

AspergillosisCandidiasisCryptococcosisHistoplasmosisCoccidioidomycosisBlastomyocosisSporotrichosisPneumocystis jiroveci

Aspergillosis - Aspergillus

Very common:compost heaps, airbone dustUsually affects thelungs and sinusesLess often: veryagressive, spreadtroughout the lungs andbloostream to brain andkidneys

Aspergillosis – Symptoms & Diagnosis

May cause nosymptoms (fungus ballRx)Reapeted coughing upof blood (severebleeding)FeverChest painDifficulty breathing

Aspergillosis - Symptoms & Diagnosis

Can affect deepertissues:

1. Renal failure2. Liver failure3. Shock4. Delirium5. Bood clots6. Death can occur quickly

Chest x-rayComputed tomography(CT)Whenever possible : send material to a laboratory to confirmidentification!

Aspergillosis- Prognosis & Treatment

When present in a sinus or single spot in he lung progresses SLOWLYRequires treatment, but no immediate dangerIf infection widespread: patient is seriously ill

VoriconazoleAmphotericin bItraconazoleCapsofungin

Aspergillosis- Prognosis & Treatment

If fungus balls grow nearlungs blood vesselsremoved surgicallySinuses aspergillosisremoved surgicallyEar canal infection

scraping out the fungusand topics antifungal drops

Immune malfunction

Frequency of aspergillosis

Immune hyper-reactivity

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Acute invasiveaspergillosis

Aspergilloma

Allergic aspergillosisAllergic sinusitis

Normal immune function Courtesy: Prof. A. Gervaix

Candidiasis – Candida species

Normally present on the skin, intestinal tract and genital region.Can cause infection of the skin or the mucous membranes of the mouth or vagina (immunocompetent)

Candidiasis – Symptoms & Diagnosis

These infections are more common in patients with:

1. Cancer2. AIDS3. Diabetes4. Pregnant women

Candidiasis – Symptoms & Diagnosis

Candidiasis also commonwith patients who are given antibioticsPatients with a weakend immune system developcandidiasis that spreadstrough the bloodstream to other part of the body

Candidiasis – Symptoms & Diagnosis

Infection of the mouth (trush) causes creamy, white and painful patches inside the mouthPatches in the esophagus cause pain with swallowing

Candidiasis – Symptoms & Diagnosis

Endocarditis causes:1. Fever2. Heart murmur3. Spleen enlargement

Candidiasis – Symptoms & Diagnosis

Ophtalmic infection (Retinitis)

1. Blindness- Candidemia and kidney

infection1. Fever2. Very low pressure

(shock)3. Decrease urine

production

Congenital Cutaneous Candida (CCC)

Usually self limited diseaseSome experts : treatment (fluconazole) highlyrecommended for prematures < 1000 g

Candidiasis – Symptoms & Diagnosis

To confirm the diagnosis: identify the fungi

1. Skin sample2. Blood culture3. Spinal culture

cultured on the fungi « milieu »

Candidiasis – Prognosis & Treatment

Skin infectionTopical ttt: clotrimotazoleMouth infection (trush)Topical nystatin

supsensionVulvovaginal candidiasisTopical vaginal cream OR fluconazole 12 mg/kg (max 150 mg x1.

Candidiasis – Prognosis & Treatment

Endocarditis

Retinitis

Candidemia (blood infection)

Kidney infection

Cryptococcosis – Symptoms & Diagnosis

Cryptococcus neoformansInfection relatevely rare until AIDS epidemicsSometimes infects peoplewith:

1. Hodgkin’s disease2. Sarcoidosis3. Long term corticosteroids

treatment

Cryptococcosis – Symptoms & Diagnosis

Cryptococcosisproduces mild and vague symptomsMeningitis: headache & confusionLung infection: cough, aching chest (!) or poorsymptomaticSkin: nodules

Cryptococcosis – Prognosis & Treatment

Immunocompetent patients withcryptococcosis in a small part of their lung usually do not require anytreatment.Patient with weakened immune system or severedisease:Fluconazole, Am-B, flucytosine

Histoplasmosis – Symptoms & Diagnosis

Histoplasma capsulatumInfection occurs mainly in the lungs!Spores present in the soilFarmers are most likely to inhale the sporesPatients with AIDS are prone to develophistoplasmosis

Histoplasmosis – Symptoms & Diagnosis

Most people withhistoplasmosis do not have any symptomsHowever 3 forms do cause symptoms:

1. Acute h.2. Progressive

disseminated h.3. Chronic cavitary h.

Histoplasmosis – Symptoms & Diagnosis

Acute:3-21 days. Patient feelssick, fever, coughing.Self limited disease (2-6 weeks)Progressive disseminated:Does not normally affect healthy adults!Patients with weakened immune system (AIDS,…)

Spleen, liver and lymph nodesmay enlarge

If adrenal glands damaged: Addison!!!

Without treatment: fatal in 90% ofpeople!

Chronique cavitaryLung infection. Developsgradually ove several weeksLund damages or fungal invasion may cause death.

Histoplasmosis – Prognosis & Treatment

Acute: usually notreatment Progressive disseminated:Amphotericin B or itraconazoleChronic cavitary:Amphotericin B or itraconazole

Coccidioidomycosis– Symptoms & Diagnosis

Coccidioides immitisSouthwest US, Central America, South AmericaInfection occurs mainly in the lungs! Spores present in the soilFarmers are most likely to inhale the sporesPatients with AIDS are prone to develop histoplasmosis

Coccidioidomycosis– Symptoms & Diagnosis

Most people with acute primary infection have nosymptoms.If so, symptoms appear 1-3 weeks after infectionCough, fever, chills, chest pain, shortness of breathCough may producesputum and/or blood

Some people develop1. Conjuntivitis2. Arthritis3. Skin nodules

Coccidioidomycosis– Prognosis & Treatment

Acute primary infection typically goes awaywithout treatment.For lung disease:fluconazole (oral)Amphotericin B givenwith the progressive form of the disease

Blastomycosis– Symptoms & Diagnosis

Blastomyces dermatitidisSpores enter the body

trough the airwaysLungs primarily affectedMost infections occur in the U.S (Southwest andMissisipi River valley)

Blastomycosis– Symptoms & Diagnosis

Fever, chills, drenchingsweats.Chest painCough, difficultybreathingLung infection progresses slowly

When blastomycosisspreads it affects manyareas of the body (skin, bones andgenitourinary tract.

Blastomycosis– Prognosis & Treatment

Amphotericine B or itraconazole (oral)With ttt the patient willfeel better quickly, but ttt must be continued for months (2-6)

Sporotrichosis– Symptoms & Diagnosis

Sporothrix schenckii Grows on rosebushes, barberry bushes andother mulches.Farmers, gardeners are usually infected from a small puncture wound.

Sporotrichosis– Symptoms & Diagnosis

Infection starts on a finger as a small nontenderbump the slowly enlargesand forms a sore.Spreads through thelymphatic vessels, forming nodules and sores alongthe way.Usually no othersymptoms

Infection of the lungs causes penumoniaUsually in patients withother lung diseases (emphysema)Joint infection producesswelling and pain

Sporotrichosis– Prognosis & Treatment

Skin infection: itraconazoleLung & bone infection:itraconazole or Amphotericin B

Pneumocystis jiroveci– Symptoms & Diagnosis

From the time of itsdiscovery, until late in the 1980s, Pneumocystis cariniiwas widely thought to be a protozoan. The organism that causes human PCP is now namedPneumocystis jiroveci

Pneumocystis jiroveci– Prognosis & Treatment

TMP/SMX 15-20 mg/Kg/div q8H IV x 2 wks orPentamidine isethionate 4 mg/kg/d IVUse steroids for more severedisease

Choosing among antifungal agents:Amphotericin B

Polyene antifungal antibiotic (1960)The most broad spectrumantifungal for clinical useRenal dysfunction: decreasedglomerular filtration + tubularnephropathyDecrased toxicity with lipid formulation (higher cost)Nystatin for topical useAction on the membrane

Choosing among antifungal agents:Azoles

Azoles are fungistaticKetoconazole (1981)Fluconazole, active againstbroader ranger of fungi (Cryptococcus, Coccidioides, Histoplasma)Despite many resistances in non-albicans Candida, fluconazoneremains the safest systemicantifungal agent of most Candida infectionsToxicity unusual (hepatic)

Choosing among antifungal agents:Azoles

Itraconazole: active againstbroader range (fungi & moulds) including Aspergillus

Voriconazole: the most recenttriaole FDA approved (May 2002)Although not FDA.approved in < 12 yrs, published suggest superiorefficacy in the treatment of fver and neutropenia and in ttt of invasice Aspergillus infections in adults

Choosing among antifungal agents:Echinocandins

New class of systemic agents approved in 2001Inhibit the glucan synthesis (cellwall formation)Capsofungin: active against most Candida species and Aspergillus.Little data in childrenGiven a site of activity, combination therapyis beingactively investigatedMicafungin (2005) under study in pediatric population

Choosing among antifungal agents:Flucytosine

Inhibits fungal proteinsynthesis by replacing uracilwith 5-flurouracil in fungalRNA.Also inhibits thymidylate

synthetase via 5-fluorodeoxy-uridine monophosphate and thusinterferes with fungal DNA synthesis

Preferred therapy for specific fungalpathogens

Therapy CommentsAspergillosis Voriconazole 14 mg/kg/d IV, PO

400 mg/d bid in children 2-12 yrs (6 weeks)Alternative: AmB LP 5-10 mg/kg/d IVItraconazole (PO IV) for less severe (non CNS) disease

Treat for tissue invasion, NOT colonizationPorvides better response than AmB

Candidiasis(disseminated infection)

AmB-LP 3-5 mg/kg/d IVFluconazole 6-12 mg/kg/d IV, PO x 2-4 wksKg/d PO div q 6H

For immune-compromised children start with AmBas some Candida are R to fluconazole (C. Kruzei)

Candidiasis(urinary infection)

Fluconazole 3-6 mg/ once daily IV or PO x 7 days

Removing catheter, il present may lead to a spontaneous cure in normal hostCheck for upper UTI

Candidiasis- oropharyngeal

Clotrimazole 10 mg PO 4-5 times /dX 7 days; or fluconazole 3-6 mg/kg

AmB IV or capsofungin or fluconazole IV for severe disease or febrile neutropenic patients

Adapted from Nelson’s Pocket Book of Pediatric Antimicrobial Therapy, 2006-2007

Preferred therapy for specific fungal pathogensTherapy Comments

Cryptococcosis Pulmonary disease :Fluconazole 10-12 mg/lk/d IV, PO q24H x 6-12 wks or AmB-LP 3-5 mg/kg/d q 24HMeningitis: AmB LP 3-5 mg/kg/d q 24H AND flucytosine 100 mg/kg/d PO div q 6H y 6 wks OR fluconazole 10-12 mg/kg/d IV, PO q 24H x 6 wks

Monitor flucytosine concentrations to keep peaks less than 80-100 to prevent neutropenia

Coccidioidomycosis Pulmonary disease : AmB LP 3-5 mg/kg/d q 24H OR Fluconazole 6-12 mg/lk/d IV, PO q24H Meningitis: Fluconazole 12 mg/lk/d IV, PO q24H Osteomyelitis : itraconazole 5-10 mg/kg/d q 24H

Mild pulmonary disease does not require therapy in the normal host

Watch for relapse up to 1-2 yrs after therapy

Histoplasmosis AmB LP 3-5 mg/kg/d q 24H OR itraconazole 5 mg/kg/d q 24 H x 6-12 wks

Mild disease may not require therapy

Pneumocystisjirevocipneumonia

Serious disease : TMP/SMX 15-20 mg/kd/d div q 8H OR pentamidine4mg/kg/d x 2 wks

Use steroids for more severe disease

Adapted from Nelson’s Pocket Book of Pediatric Antimicrobial Therapy, 2006-2007

Thank your for your attention