Mikosis Paru/pulmonary mycosis/aspergillosis.pptx

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1. MIKOSIS PARU

2. PENDAHULUAN 01

3. Mikosis Paru Faktor resiko , antara lain: kondisi imunokompromais termasuk HIV, kolonisasi jamur , terpasangnya alat medis invasive, Penggunaan antibiotic jangka Panjang, kortikosteroid sistemik , obat sitostatika , perawatan di ruang intensif Mikosis paru adalah gangguan paru ( termasuk saluran napas) yang disebabkan oleh infeksi / kolonisasi jamur atau reaksi hipersensitif terhadap jamur .

4. Mikosis Paru Endemik (pada daerah / kondisi geografis tertentu ): histoplasmosis, Blastomikosis , Koksidiodomikosis , parakoksidiodomikosis , penisiliosis Paling sering : aspergillosis, pneumonia pneumosistis (PCP), kriptokokosis , histoplasmosis dan kandidosis

5. DIAGNOSIS 02

6. Kriteria Diagnosis Kemudian dikategorikan menjadi istilah : Proven Probable Possible Kriteria diagnosis ditentukan oleh tiga hal : Faktor pejamu gambaran klinis hasil pemeriksaan mikologi .

7. Faktor P ejamu (+) Gambaran K linis (+) Mikologi negatif / tidak dilakukan Faktor pe j a mu (+) + + Gambaran klinis (+) Faktor pe j a mu (+) Gambaran klinis (+) Mikologi (+) + + + + P ossible Pr oven P robable = = = Mikologi (+) Biopsi Jaringan

8. Neutropenia ( netrofil <500/mm selama 10 hari ) Penerima transplantasi sumsum tulang alogenik Penerima terapi kortikosteroid jangka panjang dengan rerata dosis minimal setara prednison 0,3 mg/kg/ hari selama > 3 minggu  Penerima terapi imunosupresan Pasien imunodefisiensi primer berat Penderita penyakit paru kronik (TB paru , PPOK, keganasan rongga thoraks , bronkiektasis , penyakit paru interstitial, dll ) Faktor Pejamu

9. Gambaran Klinis

10. Panah merah : Halo sign Panah tosca: lesi padat Halo sign GB Marshall (2016). Journal of Thoracic Imaging 21(1):76-90 .

11. Air Crescent Sign Low, Qj . (2019). Pulmonary Meliodosis with Air Crescent Sign . International Journal of Case Reports and Clinical Image . Volume 1 (2). https://www.researchgate.net/publication/336823787_Pulmonary_Meliodosis_with_Air_Crescent_Sign

12. Pemeriksaan Mikologi

13. Organism Clinical Manifestations Gold Standard Culture Antigen Testing PCR Comments Aspergillus spp. 1 Respiratory colonization ABPA Aspergilloma IPA Angioinvasion by acute angle, branching septate hyphae on histopathology with positive culture [ 6 ] Sputum BAL BAL GM Serum GM Serum BDG Serum PCR BAL PCR GM is commonly used to aid in diagnosis. Positive serum result should be repeated to confirm. PCR is not widely used in US. Limitations Requires invasive biopsies Limitations May represent infection or colonization; sensitivity is low [ 9 ] Limitations GM low sensitivity, some false positive [ 13 ] BDG non-specific Effect of AF unknown Limitations Single serum test with high sensitivity, repeated serum with high specificity [ 6 ] Effect of AF unknown Mucor Rhino-orbital-cerebral infection Cutaneous Pulmonary Tissue invasion of wide-branching hyphae without septation [ 23 ] Tissue Sputum BAL BAL GM Serum GM Currently unavailable for clinical use GM is not used to diagnose Mucor and is classically negative. Positive GM may help identify co-infection or aide in AF selection. Limitations Requires invasive biopsies Limitations Low sensitivity; takes up to 7 days [ 25 ] Characteristically negative, but may be positive in some sub-species Pemeriksaan berdasarkan organisme

14. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Candida spp. 1 Blood stream infection Deep tissue infection Blood or deep tissue culture [ 6 ] Blood Urine Tissue Serum BDG Mannan/ antimannan IgG T2Candida panel BDG may help rule out IC but lacks the specificity to be used as a stand-alone diagnostic test. Mannan/ anti-mannan IgG is not widely used in the US. T2Candida panel is not widely available. Limitations Blood cultures only positive during candidemia; May require invasive biopsy Limitations Prolonged time to positivity [ 31 ] Limitations BDG is non-specific, should not be used in isolation to make diagnosis [ 6 ] Mannan/ anti-mannan have low sensitivity, but specific [ 32 ] Limitations Only for Candidemia; may remain positive for several days after Candidemia has cleared [ 31 ]

15. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Cryptococcus spp. Pneumonia Meningoencephalitis Culture Direct visualization of narrow budding, encapsulated yeast Sputum BAL CSF Tissue Latex agglutination EIA Lateral flow immunoassay *Can be tested on sputum, BAL, serum, CSF, urine, pleural fluid Currently unavailable for clinical use Antigen testing on serum or CSF is used most to make the diagnosis. Evaluate for CNS disease in immunocompetent patients with neurologic findings and high serum titer Evaluate for CNS disease in all immunocompromised patients Limitations Delayed time to positivity [ 36 ] Limitations Sensitivity dependent upon culture specimen [ 40 ] Limitations False positive RF or other infections [ 35 ]

16. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Histoplasma Chronic pulmonary infection Acute pulmonary infection Disseminated infection Blood, respiratory specimen, or deep tissue culture [ 6 ] Blood Urine Sputum/ BAL Tissue Serum antigen Urine antigen BAL antigen CF Immunodiffusion EIA For isolated pulmonary disease, multiple testing methods are used to aide in diagnosis. Antigen testing is most helpful in disseminated disease. This has improved sensitivity over PCR based testing. Limitations Time consuming; low sensitivity even in disseminated disease Limitations Serum/urine sensitivity around 80% in disseminated disease [ 60 ] Low serum/urine sensitivity in isolated pulmonary disease [ 61 ] High BAL sensitivity [ 62 ] Cross reactivity with other endemic fungi Limitations Antibody testing has modest sensitivity and potential to cross react with other endemic fungi [ 58 ]

17. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Histoplasma Chronic pulmonary infection Acute pulmonary infection Disseminated infection Blood, respiratory specimen, or deep tissue culture [ 6 ] Blood Urine Sputum/ BAL Tissue Serum antigen Urine antigen BAL antigen CF Immunodiffusion EIA For isolated pulmonary disease, multiple testing methods are used to aide in diagnosis. Antigen testing is most helpful in disseminated disease. This has improved sensitivity over PCR based testing. Limitations Time consuming; low sensitivity even in disseminated disease Limitations Serum/urine sensitivity around 80% in disseminated disease [ 60 ] Low serum/urine sensitivity in isolated pulmonary disease [ 61 ] High BAL sensitivity [ 62 ] Cross reactivity with other endemic fungi Limitations Antibody testing has modest sensitivity and potential to cross react with other endemic fungi [ 58 ]

18. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Blastomyces Subacute pulmonary infection Necrotizing pneumonia ARDS Disseminated infection Blood, respiratory specimen, or deep tissue culture [ 6 ] Blood Urine Sputum/ BAL Tissue Urine antigen Serum antigen BAL antigen CF Immunodiffusion EIA EIA to BAD-1 Cultures have a high sensitivity and are very useful in diagnosis. Antibody testing useful in the setting of sub-acute infection manifesting as pulmonary nodules. Limitations High sensitivity but delayed time to positivity Limitations High sensitivity for urine but significant cross reactivity with other endemic fungi [ 70 – 72 ] Lower sensitivity for serum and BAL Limitations Antibody testing has modest sensitivity and potential to cross react with other endemic fungi [ 73 ] EIA to BAD-1 has improved sensitivity and specificity [ 74 ]

19. Pemeriksaan berdasarkan organisme Organism Clinical Manifestations Gold Standard Culture Antigen Testing Molecular Testing Comments Coccidioides Asymptomatic infection Pneumonia Disseminated infection Culture or direct visualization (spherules filled with endospores Blood Urine Sputum/ BAL Tissue Serum antigen Urine antigen CF Immunodiffusion EIA EIA is generally used as screening test with CF or immunodiffusion used for confirmatory testing Limitations Low sensitivity for both culture and direct visualization Limitations Modest sensitivity and high cross reactivity [ 76 ] Limitations EIA has high sensitivity but sensitivity may be slightly reduced immunocompromised populations [ 81 ]

20. TATALAKSANA 3

21. Tatalaksana Dimana obat anti jamur ini dapat berperan sebagai terapi : Profilaksis Empiris pre-emptive (targeted prophylaxis) Definitif

22. Peran OAJ

23. Peran OAJ

24. OAJ Gol. Polien

25. Aktif terhadap infeksi Candida, Cryptococcus. Tidak tersedia di Indonesia OAJ Gol. Flusitosin

26. OAJ Gol. Azol

27. OAJ Gol. ekinokandin

28. Algoritma tatalaksana mikosis paru

29. Anna R, Anwar J, Ahmad H, Arifin N, Elisna Syahrudin , Erlina Burhan, Heidy Agustin, Priyanti Z Supandi . Mikosis Paru . Pedoman diagnosis dan Penatalaksanaan di Indonesia. Perhimpunan Dokter Paru Indonesia. PDPI; Jakarta 2017 Kelly BT, Pennington KM, Limper AH. Advances in the diagnosis of fungal pneumonias. Expert Rev Respir Med. 2020 Jul;14(7):703-714. doi : 10.1080/17476348.2020.1753506. Epub 2020 Apr 21. Low, Qj . (2019). Pulmonary Meliodosis with Air Crescent Sign . International Journal of Case Reports and Clinical Image . Volume 1 (2). https://www.researchgate.net/publication/336823787_Pulmonary_Meliodosis_with_Air_Crescent_Sign GB Marshall (2016). Journal of Thoracic Imaging 21(1):76-90 DAFTAR PUSTAKA

30. TERIMA KASIH

31. Gold standart : biakan specimen maupun biopsy jaringan Selain itu bisa dengan beberapa pendekatan : Pemeriksaan mikologi

32. Menggunakan larutan garam fisiologis+KOH 10% atau tinta india . Bisa dengan pewarnaan Giemsa . Sampel bisa diambil dari sputum, bilasan bronkus , BAL Pemeriksaan Mikroskopis

33. Memiliki nilai diagnostic tinggi untuk diagnosis infeksi jamur tertentu , ex: Biakan darah untuk mendeteksi infeksi Candida dalam darah ( Kandidemia ) Pemeriksaan Biakan jamur

34. Terdiri dari pemeriksaan antibodi dan antigen Pemeriksaan antibody bagus untuk deteksi infeksi jamur kronis Deteksi antigen bisa pada kasu-kasu tertentu , seperti : Antigen cryptococcus pada LCS, antigen Histoplasma dari urin pasien Pemeriksaan Serologis

35. PCR  penggunaan masih terbatas dan belum ada standarisasi Pemeriksaan Molekular