Fungal infection presentation by mohamed salah.pptx

Fungal infection management

1. FUNGAL AND VIRAL INFECTION IN ICU BY Dr. MOHAMED SALAH SHARAF MBBCH, AL-AZHAR UNIVERSITY

2. INVASIVE FUNGEMIA A Forgotten visitor in General ICU practice 1

3. Increased Incidence of I nvasive Fungal Infections. Changes in treatments Hematopoietic stem cell and organ transplantation. invasive chemotherapy for malignancy. P rolonged survival with HIV. Changes in hosts M edical progress inside and outside ICU. Aging, sicker population on life-sustaining therapies. We will exclude Immuno-comporamised patients ( HIV patient, Post transplantation patients) 3

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5. Candida Harmless inhibitants of the skin and mucous membranes of all humans. Normal immune system keeps candida on body surface 5

6. Main defense mechanisms against candida S kin and mucous membrane integrity. P resence of normal bacterial flora. P hagocytosis K illing , mostly in polymorphonuclear cells. T- cells (CD4) 6

7. IDSA There are at least 15 distinct Candida species that cause human diseases, but >90% of invasive disease is caused by the 5 most common pathogenes , C. albicans , C.glabrata , C. tropicalis , C. parapsilosis and C. krusei . Significant infections due to these organisms are generally referred to as invasive candidiasis. 7

8. 250,000 / year 4 th common blood stream infections in ICUs N Engl J Med 2015;373:1445-56. > 50,000 deaths/ year 8

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10. 43 years old male, stab wound to abdomen Arrives in shock Sigmoid colon injury with fecal contamination Splenic laceration Hypothermia and acidosis 2.5 liters combined blood loss from trauma and surgery 10 Case study

11. - Arterial, cvc , and urinary catheters placed, intubated PIP-TAZ 4.5 gram iv on route to OR Exploratory laparotomy Splenectomy Sigmoid colectomy and colostomy 8u PRBCs, 6uFFP, 12u PLTs intraoperative Pt. kept on PIP-TAZ & Flagyl postop. 11 Course

12. - Third postop. Day, fever persist, high WBCs Still ventilated, CXR few scattered infiltrates Full sepsis workup was sent. CT abdomen,,No collection. Surgical sample culture E. Coli (?ESPL) PIP-TAZ changed to imipenem & teicoplanin 12 Post-OP Course

13. - Fever persists, now end of day 4 Awake and lethargic Abdominal exam : typical post-op Hemodynamics : became unstable Become oliguric Still ventilated,, Do U Like to Evaluate for invasive fungal infection or not yet ??? If YES ……… HOW ?? 13 Post-OP Course

14. Please don’t forget to look for… 14

15. Immunosuppression including steroids. Neutropenia. Broad spectrum antibiotics. ICU stay >4-5 DAYS . TPN . APACHE score >20. Hemodialysis /filtaration. CVC . Major abdominal surgery. B urns > 50 % . P erforation of digestive tract. Risk factors of invasive candidiasis C olonization of multiple body sites. Urinary tract surgery in presence of candiduria. 15

16. Diagnostic Tools 16 Colonization index Candida Score Laboratory diagnosis Prediction Rule C C L P

17. COLONIZATION INDEX 17

18. CANDIDA SCORE 18

19. Clinical Predictive Rule 19

20. Laboratory Diagnosis: 20 Microbiology Methods: Recovery of candida species from sterile sites ex. Blood, peritoneal fluid) is a diagnostic of invasive candidiasis) Recovery from multiple Non-sterile sites is a highly suggestive of invasive candidiasis ) in the high risk patient. Blood culture is positive in less than 50 % of patients with autopsy proven IC . - Serological Methods: - Early diagnosis ex. 1,3 beta D glucan assay. - Histopathologic Methods:

21. Diagnostic Dilemma 21 Clinical Setting: NONSPECIFIC, ONLY risk factors Radiology: Helpful more for Aspergillus . Cultures : Low yield and longer time PCR Assay: Not widely available . 1-3 Beta D Glucan Assay : ???? Galactomannan Assay : For Aspergillus .

22. NOW for this patient: 22 WILL ADD VANCOMYCIN instead of TEICOPLANIN WILL CHANGE IMIPENEM WILL START ANTIFUNGAL WAIT FOR RESULTS OF LABS

23. Nosocomial Bloodstream Infections in US Hospitals: 1995-2002 23

24. 24 Empiric antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis & no other known cause of fever. • Should be based on clinical assessment of risk factors, surrogate markers for invasive candidiasis, and/or culture data from non-sterile sites. (strong recommendation; moderate-quality evidence)

25. 25 • Empiric antifungal therapy should be started as soon as possible in patients who have the above risk factors and who have clinical signs of septic shock. (strong recommendation; moderate-quality evidence)

26. - The panel recommends not starting empirical antifungal therapy in patients without septic shock and MOF (strong recommendation, low quality of evidence ) ESCIM/ESCMID task force on practical management of invasive candidiasis in critically ill patient 2019 26

27. • If Candida infection is suspected, treatment will need to be initiated empirically without delay on the basis of individual patient risk factors (before a definitive diagnosis is made *) CCM 2008,2012 • For adults with sepsis or septic shock at high risk of fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy. CCM 2021 * Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 27

28. Early treatment critical to good outcome in candidaemia 28

29. FLUCONAZOLE L- AMPHOB . ECHINOCANDIN 5-FLUCYTOSINE WHICH ANTIFUNGAL WILL BE UR CHOICE 29

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31. General Pattern of Susceptibility of Candida spp. 31

32. 32 • Preferred empiric therapy for suspected candidiasis in non- neutropenic CRITICALLY ILL patients in the intensive care unit (ICU) is an ECHINOCANDIN . ( caspofungin : loading dose of 70 mg, then 50 mg daily; micafungin : 100 mg daily; anidulafungin : loading dose of 200 mg, then 100 mg daily) ( strong recommendation; moderate-quality

33. 33 • Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, is an acceptable alternative for patients who have had no recent azole exposure and are not colonized with azole-resistant Candida species. ( strong recommendation; moderate-quality evidence). • Lipid formulation AmB , 3-5 mg/kg daily, is an alternative if there is intolerance to other antifungal agents. ( strong recommendation; low-quality evidence).

34. - The panel recommends that echinocandins should be used as the first treatment option in critically ill patients with septic shock and MOF. ( weak recommendation, low quality of evidence). ESCIM/ESCMID task force on practical management of invasive candidiasis in critically ill patient 2019 34

35. -• The panel recommends that fluconazole should be considered the first treatment option for critically ill patients with low severity of disease (i.e. without septic shock and/or MOF) in settings with low fuconazole resistance. (strong recommendation, low quality of evidence). ESCIM/ESCMID task force on practical management of invasive candidiasis in critically ill patient 2019 35

36. DURATION ?? 36

37. 37 Recommended duration of empiric therapy for suspected invasive candidiasis in those patients who improve is 2 weeks, the same as for treatment of documented candidemia (weak recommendation; low-quality evidence)

38. Extending Therapy for Invasive Candidiasis 38

39. Back to our patient :- REMOVE CVC OR NOT ?? • Central venous catheters (CVCs) should be removed as early as possible in the course of candidemia when the source is presumed to be the CVC and the catheter can be removed safely; this decision should be individualized for each patient. (strong recommendation; moderate-quality evidence). 39

40. • The panel recommends that adequate source control (catheter removal, appropriate drainage, surgical control) should be performed early, if clinically feasible, in every critically ill patient with IC. (strong recommendation, moderate quality of evidence) ESCIM/ESCMID task force on practical management of invasive candidiasis in critically ill patient 2019 40

41. Biofilms interfere in Antibiotic Therapy • M.O growing in a biofilm are highly resistant to antibiotics, up to 1,000 times more resistant than the same bacteria not growing in a biofilm. Standard antibiotic therapy is often useless and the only recourse may be to remove contaminated implant. 41

42. • Have you ever slipped on a wet stone in a creek? -Certainly - and it was biofilm that you slipped on • Have you an aquarium and do you clean its walls? -If you do, what you wipe from them is the biofilm formed by algae • Do you clean your teeth regularly? -by doing this you remove the biofilm called dental plaque Three examples of biofilm 42

43. • Phagocytes are unable to effectively engulf a bacterium growing within a biofilm. • This causes the phagocyte to release large amounts of pro-inflammatory enzymes and cytokines, leading to inflammation and destruction of nearby tissues . Fungal biofilm on CVCs could act as a reservoir for re-infection and necessitate catheter withdrawal. Biofilms - Protects from Phagocytosis 43

44. • Echinocandins are the most active agents against Candida biofilms in in-vitro & in-vivo models . • The MIC profiles of echinocandins in sessile cells are higher than in planktonic cells . • AmB -L had a good anti-biofilm effect when used at high doses . Emilio Bouza et al : Antibiotics 2015, 4, 1-17 ; Activity of antifungals against Candida biofilm 44

45. Acute Invasive Aspergillosis 45

46. Invasive Aspergillosis Underlying Diseases 46

47. - Reduce immunosuppresion , restore immunity if possible • Start antifungal therapy promptly ??? • Polyenes • Mould -active azoles • Echinocandins • Consider surgical resection of infected tissue in certain situations Treatment principles 47

48. Preferred therapy: • Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients • Alternative Agents: - Liposomal AmB therapy could be considered as alternative primary therapy in rare patients (with C.I). IDSA Aspergillus Treatment Guidelines for Primary Therapy of Invasive Aspergillosis 48

49. Nivoix et al, Clin Infect Dis 2008;47:1176 Impact of voriconazole in real life for invasive aspergillosis 49

50. •Invasive fungal infections are mostly opportunistic •Take advantage of breach in host defense •Candida is the most common invasive fungal pathogen in hospitalized patients •Part of endogenous flora • Portal of entry: skin, mucosa •Fever is often the only manifestation •Usually disseminates via bloodstream •Early recognition and effective treatment is key to saving lifes . TAKE A HOME MESSAGE 50

51. • Aspergillus is much less common but even more deadly • Airborne • Portal of entry: nasal passages, respiratory tract • Pneumonia , sinusitis usual presentation • Voriconazole is the drug of choice. TAKE A HOME MESSAGE 51