Fungal Infections. Alessandro Diana November 22th 2007

Transcription

1 Fungal Infections Alessandro Diana November 22th 2007

2 Topics Aspergillosis Candidiasis Cryptococcosis Histoplasmosis Coccidioidomycosis Blastomyocosis Sporotrichosis Pneumocystis jiroveci

3 Aspergillosis - Aspergillus Very common:compost heaps, airbone dust Usually affects the lungs and sinuses Less often: very agressive, spread troughout the lungs and bloostream to brain and kidneys

4 Aspergillosis Symptoms & Diagnosis May cause no symptoms (fungus ball Rx) Reapeted coughing up of blood (severe bleeding) Fever Chest pain Difficulty breathing

5 Aspergillosis - Symptoms & Diagnosis Can affect deeper tissues: 1. Renal failure 2. Liver failure 3. Shock 4. Delirium 5. Bood clots 6. Death can occur quickly Chest x-ray Computed tomography (CT) Whenever possible : send material to a laboratory to confirm identification!

6 Aspergillosis- Prognosis & Treatment When present in a sinus or single spot in he lung progresses SLOWLY Requires treatment, but no immediate danger If infection widespread: patient is seriously ill Voriconazole Amphotericin b Itraconazole Capsofungin

7 Aspergillosis- Prognosis & Treatment If fungus balls grow near lungs blood vessels removed surgically Sinuses aspergillosis removed surgically Ear canal infection scraping out the fungus and topics antifungal drops

8 Acute invasive aspergillosis Allergic aspergillosis Allergic sinusitis Frequency of aspergillosis Frequency of aspergillosis Immune malfunction Aspergilloma Normal immune function Immune hyper-reactivity Courtesy: Prof. A. Gervaix

9 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)

10 Candidiasis Symptoms & Diagnosis These infections are more common in patients with: 1. Cancer 2. AIDS 3. Diabetes 4. Pregnant women

11 Candidiasis Symptoms & Diagnosis Candidiasis also common with patients who are given antibiotics Patients with a weakend immune system develop candidiasis that spreads trough the bloodstream to other part of the body

12 Candidiasis Symptoms & Diagnosis Infection of the mouth (trush) causes creamy, white and painful patches inside the mouth Patches in the esophagus cause pain with swallowing

13 Candidiasis Symptoms & Diagnosis Endocarditis causes: 1. Fever 2. Heart murmur 3. Spleen enlargement

14 Candidiasis Symptoms & Diagnosis Ophtalmic infection (Retinitis) 1. Blindness - Candidemia and kidney infection 1. Fever 2. Very low pressure (shock) 3. Decrease urine production

15 Congenital Cutaneous Candida (CCC) Usually self limited disease Some experts : treatment (fluconazole) highly recommended for prematures < 1000 g

16 Candidiasis Symptoms & Diagnosis To confirm the diagnosis: identify the fungi 1. Skin sample 2. Blood culture 3. Spinal culture cultured on the fungi «milieu»

17 Candidiasis Prognosis & Treatment Skin infection Topical ttt: clotrimotazole Mouth infection (trush) Topical nystatin supsension Vulvovaginal candidiasis Topical vaginal cream OR fluconazole 12 mg/kg (max 150 mg x1.

18 Candidiasis Prognosis & Treatment Endocarditis Retinitis Candidemia (blood infection) Kidney infection

19 Cryptococcosis Symptoms & Diagnosis Cryptococcus neoformans Infection relatevely rare until AIDS epidemics Sometimes infects people with: 1. Hodgkin s disease 2. Sarcoidosis 3. Long term corticosteroids treatment

20 Cryptococcosis Symptoms & Diagnosis Cryptococcosis produces mild and vague symptoms Meningitis: headache & confusion Lung infection: cough, aching chest (!) or poor symptomatic Skin: nodules

21 Cryptococcosis Prognosis & Treatment Immunocompetent patients with cryptococcosis in a small part of their lung usually do not require any treatment. Patient with weakened immune system or severe disease: Fluconazole, Am-B, flucytosine

22 Histoplasmosis Symptoms & Diagnosis Histoplasma capsulatum Infection occurs mainly in the lungs! Spores present in the soil Farmers are most likely to inhale the spores Patients with AIDS are prone to develop histoplasmosis

23 Histoplasmosis Symptoms & Diagnosis Most people with histoplasmosis do not have any symptoms However 3 forms do cause symptoms: 1. Acute h. 2. Progressive disseminated h. 3. Chronic cavitary h.

24 Histoplasmosis Symptoms & Diagnosis Acute: 3-21 days. Patient feels sick, 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 nodes may enlarge If adrenal glands damaged: Addison!!! Without treatment: fatal in 90% of people! Chronique cavitary Lung infection. Develops gradually ove several weeks Lund damages or fungal invasion may cause death.

25 Histoplasmosis Prognosis & Treatment Acute: usually no treatment Progressive disseminated: Amphotericin B or itraconazole Chronic cavitary: Amphotericin B or itraconazole

26 Coccidioidomycosis Symptoms & Diagnosis Coccidioides immitis Southwest US, Central America, South America Infection occurs mainly in the lungs! Spores present in the soil Farmers are most likely to inhale the spores Patients with AIDS are prone to develop histoplasmosis

27 Coccidioidomycosis Symptoms & Diagnosis Most people with acute primary infection have no symptoms. If so, symptoms appear 1-3 weeks after infection Cough, fever, chills, chest pain, shortness of breath Cough may produce sputum and/or blood Some people develop 1. Conjuntivitis 2. Arthritis 3. Skin nodules

28 Coccidioidomycosis Prognosis & Treatment Acute primary infection typically goes away without treatment. For lung disease: fluconazole (oral) Amphotericin B given with the progressive form of the disease

29 Blastomycosis Symptoms & Diagnosis Blastomyces dermatitidis Spores enter the body trough the airways Lungs primarily affected Most infections occur in the U.S (Southwest and Missisipi River valley)

30 Blastomycosis Symptoms & Diagnosis Fever, chills, drenching sweats. Chest pain Cough, difficulty breathing Lung infection progresses slowly When blastomycosis spreads it affects many areas of the body (skin, bones and genitourinary tract.

31 Blastomycosis Prognosis & Treatment Amphotericine B or itraconazole (oral) With ttt the patient will feel better quickly, but ttt must be continued for months (2-6)

32 Sporotrichosis Symptoms & Diagnosis Sporothrix schenckii Grows on rosebushes, barberry bushes and other mulches. Farmers, gardeners are usually infected from a small puncture wound.

33 Sporotrichosis Symptoms & Diagnosis Infection starts on a finger as a small nontender bump the slowly enlarges and forms a sore. Spreads through the lymphatic vessels, forming nodules and sores along the way. Usually no other symptoms Infection of the lungs causes penumonia Usually in patients with other lung diseases (emphysema) Joint infection produces swelling and pain

34 Sporotrichosis Prognosis & Treatment Skin infection: itraconazole Lung & bone infection: itraconazole or Amphotericin B

35 Pneumocystis jiroveci Symptoms & Diagnosis From the time of its discovery, until late in the 1980s, Pneumocystis carinii was widely thought to be a protozoan. The organism that causes human PCP is now named Pneumocystis jiroveci

36 Pneumocystis jiroveci Prognosis & Treatment TMP/SMX mg/kg/div q8h IV x 2 wks or Pentamidine isethionate 4 mg/kg/d IV Use steroids for more severe disease

37 Choosing among antifungal agents: Polyene antifungal antibiotic (1960) The most broad spectrum antifungal for clinical use Renal dysfunction: decreased glomerular filtration + tubular nephropathy Decrased toxicity with lipid formulation (higher cost) Nystatin for topical use Action on the membrane Amphotericin B

38 Choosing among antifungal agents: Azoles are fungistatic Ketoconazole (1981) Fluconazole, active against broader ranger of fungi (Cryptococcus, Coccidioides, Histoplasma) Despite many resistances in nonalbicans Candida, fluconazone remains the safest systemic antifungal agent of most Candida infections Toxicity unusual (hepatic) Azoles

39 Choosing among antifungal agents: Itraconazole: active against broader range (fungi & moulds) including Aspergillus Azoles Voriconazole: the most recent triaole FDA approved (May 2002) Although not FDA.approved in < 12 yrs, published suggest superior efficacy in the treatment of fver and neutropenia and in ttt of invasice Aspergillus infections in adults

40 Choosing among antifungal agents: New class of systemic agents approved in 2001 Inhibit the glucan synthesis (cell wall formation) Capsofungin: active against most Candida species and Aspergillus. Little data in children Given a site of activity, combination therapyis being actively investigated Micafungin (2005) under study in pediatric population Echinocandins

41 Choosing among antifungal agents: Inhibits fungal protein synthesis by replacing uracil with 5-flurouracil in fungal RNA. Also inhibits thymidylate synthetase via 5- fluorodeoxy-uridine monophosphate and thus interferes with fungal DNA synthesis Flucytosine

42 Preferred therapy for specific fungal pathogens Aspergillosis Candidiasis (disseminated infection) Candidiasis (urinary infection) Candidiasis - oropharyngeal Therapy 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 IV Itraconazole (PO IV) for less severe (non CNS) disease AmB-LP 3-5 mg/kg/d IV Fluconazole 6-12 mg/kg/d IV, PO x 2-4 wks Kg/d PO div q 6H Fluconazole 3-6 mg/ once daily IV or PO x 7 days Clotrimazole 10 mg PO 4-5 times /d X 7 days; or fluconazole 3-6 mg/kg Comments Treat for tissue invasion, NOT colonization Porvides better response than AmB For immune-compromised children start with AmB as some Candida are R to fluconazole (C. Kruzei) Removing catheter, il present may lead to a spontaneous cure in normal host Check for upper UTI AmB IV or capsofungin or fluconazole IV for severe disease or febrile neutropenic patients Adapted from Nelson s Pocket Book of Pediatric Antimicrobial Therapy,

43 Preferred therapy for specific fungal pathogens Therapy Cryptococcosis Pulmonary disease :Fluconazole mg/lk/d IV, PO q24h x 6-12 wks or AmB- LP 3-5 mg/kg/d q 24H Meningitis: AmB LP 3-5 mg/kg/d q 24H AND flucytosine 100 mg/kg/d PO div q 6H y 6 wks OR fluconazole mg/kg/d IV, PO q 24H x 6 wks 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 Comments Monitor flucytosine concentrations to keep peaks less than to prevent neutropenia 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 Pneumocystis jirevoci pneumonia Serious disease : TMP/SMX mg/kd/d div q 8H OR pentamidine 4mg/kg/d x 2 wks Use steroids for more severe disease Adapted from Nelson s Pocket Book of Pediatric Antimicrobial Therapy,

44 Thank your for your attention