invasive fungal infections seminar1.pptx

infectious diseases

1. Invasive Fungal Infections Presenter Dr. Meron (IMR3) Moderator Dr. Anteneh (Consultant Internist and ID Subspecialist) 07-Sep-25

2. Outline Introduction Epidemiology Invasive candidiasis Invasive aspergllosis Mucormycosis Reference 07-Sep-25

3. Introduction Fungal pathogens cause a wide range of infections in humans, from superficial to disfiguring, allergic syndromes, and life-threatening invasive infections Fungi are a major cause of mortality in humans Fungi have an estimated 1.5 million deaths annually 07-Sep-25

4. Fungi as a public health problem C ontinuous increase in the population of individuals at risk of fungal infections G rowing global threat of multidrug-resistant fungal strains U navailability of recently introduced novel antifungal drugs Poor access to essential diagnostics 07-Sep-25

5. Fungi morphology Yeasts A re typically round or oval F orm smooth, flat colonies R eproduce by budding Molds A re composed of tubular structures called hyphae Form colonies which appear fuzzy G row by branching and longitudinal extension Dimorphic Fungi C an grow either as a yeast or as a mold Histoplasma , Coccidioides , Blastomycosis 07-Sep-25

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7. Invasive fungal infections I nvasive fungal infections are serious and potentially life-threatening diseases caused by fungi that invade tissues and organs These infections can be caused by various fungal species, including Candida , Aspergillus, Cryptococcus, and others They require prompt diagnosis and therapy as well as early specialist consultation 07-Sep-25

8. Invasive Candidiasis In 1861, Zenker described the first well documented case of deep-seated Candida Increasing incidence since 1940s Secondary to the widespread use of antibiotics was introduced Fourth most common organisms recovered from blood of hospitalized patients 07-Sep-25

9. Candida organisms Yeasts G row well in routine blood culture bottles Form smooth, creamy white, glistening colonies A rapid identification of C. albicans can be made by Germ tube test 07-Sep-25

10. Invasive candidiasis Candida are normal commensals of humans Commonly found on skin, GIT, sputum, female GUT Normally not pathogenic in humans until immune compromised There are more than 150 species of Candida B ut only a small percentage are frequent pathogens They are C. albicans , C. krusei , C. parapsilosis , C. tropicalis , C. pseudotropicalis , C. dubliniensis , C. auris and C . glabrata 07-Sep-25

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12. Candida epidemiology Oropharyngeal candidiasis O ne of the most prevalent opportunistic infections in the advanced HIV disease Vulvovaginal candidiasis E stimated to affect 75% of women at least once during their lives Latest estimates suggest that over 1 , 565,000 people are affected by invasive candidiasis every year Overall , Candida  spp account for more than 85% of all cases of fungaemia in Europe and the USA 07-Sep-25

13. Changing epidemiology 07-Sep-25

14. Pathogenesis Virulence factors include Biofilm formation Switch from yeast to hyphal phase Secretion of A spartyl proteases and phospholipases capable of directly damaging tissue Candidalysin , a cytolytic peptide toxin secreted by C. albicans critical for mucosal epithelial damage Host factor CARD9 deficiency 07-Sep-25

15. Clinical manifestations 07-Sep-25

16. Candidemia Describes the presence of  Candida  species in the blood M anifestations vary from minimal fever to a full-blown sepsis syndrome Clinical clues pointing to possible hematogenous spread are C haracteristic eye lesions ( chorioretinitis with or without vitritis ) S kin lesions   07-Sep-25

17. Deep Organ Involvement CNS candidiasis Present as meningitis or with multiple micro abscesses Common in premature neonates, after craniotomy and with ventricular drainage device CSF= neutrophilic predominant, low glucose, high protein = 1,3-beta-D-glucan can be detected Candida Endocarditis In patients with risk factor(prosthetic valve, injection drug use) Arterial embolization is more common 07-Sep-25

18. Deep Organ Involvement Hepatosplenic candidiasis Present with RUQ tenderness , hepatomegaly, splenomegaly, nausea, vomiting, and anorexia E levated serum ALP concentration I maging showing hypodense nodular lesions in the liver and/or spleen Ocular candidiasis Candida Arthritis Candida Osteomyelitis 07-Sep-25

19. DIAGNOSIS Culture and stain of biopsy material Biopsy leads to a definitive diagnosis Punch biopsies of skin or tissue biopsy will show Microabscesses B udding yeasts and often hyphae or pseudohyphae Blood culture 2-3 sets with each 20 mL blood volume should be collected  Sensitivity= 40 – 60% 07-Sep-25

20. Serologic biomarkers Beta-D- glucan assay   U seful for diagnosis of invasive candidiasis Is a pan fungal assay and not specific for  Candida Can be done from CSF in suspected CNS  Candida   infection Combination of serum mannan antigen and anti- mannan antibody assays M oderately recommended 07-Sep-25

21. Serologic biomarkers T2Candida FDA approved for the detection of candidemia   Can detect C . albicans ,  C. tropicalis ,  C. parapsilosis , and C. glabrata /C. krusei Can detect as few as 1 to 3 CFU/mL from a blood within 3-5 hrs S ensitivity of 89% A ntifungal treatment could reduce the sensitivity but to a lesser amount than that seen for blood cultures 07-Sep-25

22. Diagnosis PCR Have greater sensitivity for deep seated candedemia Better yield when combined with blood culture Species identification P eptide nucleic acid fluorescence in situ hybridization ( PNA-FISH) M atrix-assisted laser desorption ionization-time of flight mass spectrometry ( MALDI-TOF MS ) 07-Sep-25

23. Clinical evaluation Detailed physical examination for metastatic foci Routine ophthalmologic examination for all patients with candidemia Routine echocardiography is not warranted for patients with candidemia Should be done in patients with persistently positive blood cultures and with predisposing conditions (prior IE or injection drug use) 07-Sep-25

24. Treatment Treatment of candidemia consists of  Early and appropriate antifungal therapy T argeted source control C entral venous catheter removal or abscess drainage Blood cultures should be performed daily or every other day Echinocandins are the recommended treatment of candidemia Alternative options include Triazoles fluconazole, itraconazole , voriconazole , and posaconazole Amphotericin B 07-Sep-25

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29. Empiric fungal treatment E mpiric antifungal therapy should be considered in critically ill patients with persistent, unexplained fever and risk factors for invasive candidiasis Discontinuation of empiric antifungal therapy is reasonable  for Patients who receive empiric antifungal therapy but do not respond after 4-5 days and H ave no evidence of invasive candidiasis (a negative serum beta-D- glucan assay) 07-Sep-25

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32. OUTCOMES Untreated , candidemia has a mortality rate of 60%- 100% With treatment, the mortality is approximately 25 to 40 percent Factors associated with increased mortality include H igher APACHE II scores Treatment delay Inadequate fluconazole   dosing I nfection with an echinocandin -resistant strain R etention of a central venous catheter I ncreasing age U se of immunosuppressive therapy 07-Sep-25

33. Invasive A spergillosis (IA) IA remains a major cause of morbidity and mortality in the immunosuppressed population Aspergillosis is infection is caused by hyaline mold Aspergillus I nclude more than 250 species in 8 subgenera Aspergillosis causes syndromes range from Colonization such as Aspergilloma A llergic responses to Aspergillus , including ABPA Invasive infections , from chronic necrotizing pneumonia to invasive pulmonary aspergillosis and other invasive syndromes 07-Sep-25

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36. Invasive Aspergillosis (IA) There is a dramatic increase in the number of patients affected Aspergillus is ubiquitous worldwide Found in soil, water, food, and air Hosts with normal pulmonary host defenses rarely develop disease There is increasing incidence for non invasive species causing invasive infection 07-Sep-25

37. Risk factors Traditiona l factors include Severe and prolonged neutropenia Recipient of HSCT or SOT Immunosuppressive drugs AIDS S evere illness requiring ICU stay S evere influenza, COVID-19, or RSV infection Chronic granulomatous disease New risk factors S evere liver disease Malnutrition A dvanced diabetes mellitus C hronic obstructive pulmonary disease (COPD ) S olid tumors 07-Sep-25

38. Clinical manifestation I nvasive aspergillosis can be manifested as a spectrum of diseases Involving predominantly the airways ( tracheobronchitis ) or lung D isseminated disease, involving the CNS and other organs Invasive pulmonary aspergillosis Acute progressive infection that occurs in immunocompromised patients The classic triad in neutropenic patients is Fever, pleuritic chest pain, and hemoptysis 07-Sep-25

39. Invasive pulmonary aspergillosis Imaging with chest CT-scan Lung nodule/s, with or without “ halo sign ” Patchy or segmental consolidation Peribronchial infiltrates Air-crescent sign Pleural effusion and pneumothorax 07-Sep-25

40. Tracheobronchitis   Reported most commonly in L ung transplant recipients, hematologic malignancies, and HIV infection Present with prominent dyspnea, cough, and wheezing Chest imaging may be Show airway thickening, patchy infiltrates, consolidation, or centrilobular nodules There are 3 different patterns of presentation Pseudomembranous, ulcerative or obstructive 07-Sep-25

41. Disseminated infection Occurs secondary to H ematogenous spread to distant sites or C ontiguous extension from the lung C omplication associated with an extremely high mortality( >90 %) Can cause endophthalmitis , osteomyelitis, endocarditis or involve the GIT 07-Sep-25

42. Disseminated infection Rhinosinusitis Present with nasal congestion, fever, and facial and eye pain MRI show soft tissue lesions and focal enhancement of the sinus lining  Cerebral Aspergillosis Associated with the highest mortality of IA syndromes (>90%) Estimated to occur in 10% to 20% of all cases of IA The clinical presentation is nonspecific On CT of the brain the appearance is similar to other infectious causes of brain abscess Confirmation of the diagnosis requires biopsy 07-Sep-25

43. Diagnosis Culture-based methods Respiratory samples are needed to diagnose IPA The isolation of Aspergillus from respiratory sample can represent colonization Bronchoscopy examination is recommended For observation of the affected region and it enables targeted sampling T o obtain BAL fluid Species identification with MALDI-TOF or PCR 07-Sep-25

44. Diagnosis Histopathologic examination Using Gomori methenamine silver or periodic acid-Schiff stain Organisms are shown as N arrow (3 to 6 microns wide), septated hyaline hyphae with dichotomous acute angle (45°) branching 07-Sep-25

45. Serum biomarkers Aspergillus antigen (Galactomannan) A polysaccharide in the cell walls of fungi, including Aspergillus Serum cutoff ≥ 0.5 has Sensitivity of 56–89 % and specificity of 67–99 % respectively Used as a monitoring therapeutic response tool 1,3 -d- glucan Cut-off of ≥80 pg /mL has a sensitivity and specificity of 80% and 63–81%, respectively 07-Sep-25

46. Treatment Early and definitive diagnosis as well as early initiation of antifungal therapy shows better outcome Mortality rates can reach >75 % in severely immunosuppressed patients Antifungal agents active against aspergillus are Polyenes, azoles, and echinocandins 07-Sep-25

47. Antifungal therapy Monotherapy with  voriconazole is first line of treatment Combination treatment recommended for patients with S everely immunocompromised patients with disseminated infections Infections caused by resistant Aspergillus spp. or mixed molds H igh azole resistance rates areas (>10%), especially in severely ill patients Lacking response to monotherapy 07-Sep-25

48. Antifungal therapy Alternative options Posaconazole and isavuconazole Liposomal amphotericin B Salvage therapy  In patients with refractory disease despite antifungal monotherapy Options are Change antifungal to another drug class (Liposomal amphotericin B) Combination therapy with voriconazole   plus  an echinocandin   07-Sep-25

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50. Duration of treatment The minimum duration of therapy is 6 to 12 weeks  Antifungal therapy is generally continued until all signs and symptoms of the infection have resolved When combination therapy with an azole and an echinocandin is used, we suggest continuing both medications for two weeks before transitioning to monotherapy 07-Sep-25

51. Surgery Surgery is recommended for localized infections that are easily accessible for debridement Indicated for Rhinosinusitis Primary cutaneous infection Pulmonary infection with A single pulmonary lesion and recurrent hemoptysis or bacterial superinfection  L esions contiguous to the great vessels or pericardium Endocarditis   Osteomyelitis and septic arthritis 07-Sep-25

52. Prophylaxis 07-Sep-25

53. Mucormycosis Mucormycosis is a serious fungal infection caused by molds called mucormycetes M anifested by a variety of different syndromes in humans, particularly in immunocompromised patients and those with diabetes mellitus Devastating rhino-orbital-cerebral and pulmonary infections are the most common syndromes The genera most commonly found in human are Rhizopus ,  Mucor , and  Rhizomucor 07-Sep-25

54. RISK FACTORS Diabetes mellitus, particularly DKA Treatment with glucocorticoids Immunosuppressed patients Hematologic malignancies, HSCT, SOT, AIDS Treatment with  deferoxamine Iron overload Recent coronavirus disease 2019 (COVID-19) infection Injection drug use Trauma/burns Malnutrition 07-Sep-25

55. CLINICAL PRESENTATION Mucormycosis is characterized by infarction and necrosis of host tissues that results from invasion of the vasculature by hyphae The pace is usually fast Rhino-orbital-cerebral mucormycosis The most common presentation   P resents as acute sinusitis F ever , nasal congestion, purulent nasal discharge, headache, and sinus pain A black eschar may be visible in the nasal mucosa, palate, or skin overlying the orbit  07-Sep-25

56. CLINICAL PRESENTATION Pulmonary mucormycosis A rapidly progressive infection that occurs after inhalation of spores into the bronchioles and alveoli Gastrointestinal mucormycosis Stomach is the commonest site affected Cutaneous mucormycosis Almost always associated with trauma or wounds Can be natural disaster-associated or combat-associated   Disseminated mucormycosis is rare 07-Sep-25

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58. DIAGNOSIS D iagnosis relies on histopathology with culture confirmation The hyphae are broad , irregularly branched , and have rare septations Negative for serum biomarkers B-D glucan or galactomannan PCR 07-Sep-25

59. DIAGNOSIS Chest imaging Most common abnormalities are F ocal consolidation, masses, pleural effusions, or multiple nodules A halo sign  Reversed halo signs more common in mucormycosis Cavitary lesions with or without air crescent signs are unusual 07-Sep-25

60. TREATMENT Combination of starting antifungal therapy as soon as possible and aggressive surgical debridement of involved tissues, whenever feasible Aggressive surgical debridement   A ssociated with improved survival Antifungal therapy     Early antifungal therapy improves outcome The preferred initial antifungal treatment is   liposomal amphoter i cin B Maintenance therapy with isavuconazole or posaconazole   07-Sep-25

61. TREATMENT Combination therapy should be considered in P atients who are worsening after at least one week of high-dose liposomal amphoter i cin B  therapy (10 mg/kg daily) Options for combination are Posaconazole , isavuconazole Use an echinocandin as the second line agent 07-Sep-25

62. Outcome Even with treatment, mortality is very high H ighest for disseminated (96 percent), pulmonary (60 to 87 percent), and cerebral (62 to 79 percent) infection Early aggressive surgical intervention and initiation of antifungal treatment is very crucial 07-Sep-25

63. References Mendel, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th Edition IDSA guideline 2016 for the management of invasive aspergillosis and Candidiasis Harrison’s principles of internal medicine, 21 st edition UPTODATE 07-Sep-25

64. Thank you! 07-Sep-25