Fungal infection in Intensive care unit.pptx

Its about fungal infection in critical care with antifungals drugs. with mechanism and drug dose

1. Candida infection in ICU

2. Overview Types of fungi. Drugs Candida Introduction Mechanism of Invasion Predisposing factors Diagnosis Treatment Candida auris Take away points. 9/18/2024 Candida infections in ICU 2

3. Classification based on morphology Yeast – Oval spherical. Grow by budding. Ex Candida, Cryptococccus ,   Molds - Hyphae tubular or filamentous morphology, grow by branching & Longitudinal extension. Septataed – A spergillus ,  Aseptate hyphae - Mucor   mycosis and Zygomycetes . 9/18/2024 Candida infections in ICU 3

4. Classification based on structure Dimorphic Fungi- Grow as Filaments at ambient temperatures. Grow as Yeast at human body temperatures. Histoplasma , Blastomyces . 9/18/2024 Candida infections in ICU 4

5. Antifungals MoA 9/18/2024 Candida infections in ICU 5

6. Antifungals Type - MoA Agents Dose Notes Polyenes - bind to ergesterol in fungal cell wall led to leakage and cell death Deoxycholate / conventional dAmB 0.5 – 1.5 mg/kg day Rasistance to Candida lusitaniae , C. Guillermondii . S/E – Decrease K, Mg, Nephrotoxicity Lipid complex ABLC; 5 mg /kg/day Liposomal LAmB (Low renal toxicity) 3 – 5 mg/kg/day Echinocandins - inhibit Beta (1,3)-D- Glucan Synthase, component of fungal cell wall. Caspofungin 70 mg loading than 50 mg OD Fungicidal for candida , fungistatic for Aspergillus S/E Liver toxicity, pruritus, leucipenia , neutropenia, anemia , Hypokalemia Anidulafungin 200 mg iv than 100 mg OD Micafungin 100mg od 9/18/2024 Candida infections in ICU 6

7. Antifungals Type - MoA Agents Dose Notes Azoles - Inhibition 14- α demethylase enzyme. Inhibiting ergosterol synthesis in ER of fungal cell Fungistatic S/E - Hepatotoxicity Fluconazole High bioavailability LD 12 mg/kg on day 1, than 6 mg/kg per day Not Active against glabrata , krusei and auris . S/E Prolonged Qtc Voriconazole 6 mg/kg loading BD, then 4 mg/kg bd Activity to C. Glabrata , C. krusei S/E : visual disturbance transient, Avoid in SEVERE RENAL INSUFFCIENCY ( cyclodextrin ) Isavuconazole 200 mg tds 6 doses. Then 200 mg daily. No adjustment in Renal Failure Posaconazole 300 mg IV BD LD on day 1 f/b 300 mg IV OD Used for candida but not Candidemia Flucytosine - Conversion of 5FU which is toxic to fungal wall Use in Candidal meningitis. 50-150 mg/kg/d PO q6hr. Given with AmB S/E - Bone marrow depression, Hepatotoxicity 9/18/2024 Candida infections in ICU 7

8. Selecting antifungal according to site of action Echinocandins do not penetrate into CNS, Urinary TRACT and VITREOUS fluid Voriconazole and posaconazole have poor Urinary penetration C on v e n t i o n a l A m B h a v e b e tt er r e n a l p e n e t r a t i o n and L AmB May have better tissue penetration Fluconazole have good Urinary and CNS penetration 5 Flucytosine have good CNS as well as Urinary penetration but develops resistance quickly when used as monotherapy 9/18/2024 Candida infections in ICU 8

9. Candidiasis - Introduction Part of GI flora. Difficult to distinguish infection from colonization. Range from Benign cutaneous infection to deep seated invasive. Hematogenous seeding in deep infections 10% of ICU infections 9/18/2024 Candida infections in ICU 9

10. Species distribution C. Albicans most common (> 80%) C. Glabrata & C. Tropicalis are found largely in adults. C. Parapsilosis - found predominantly in nenonatal group, Form Biofilm less susceptible to Echinochandin C.Krussei – Gi surgery, Hematological malignanacy , Neutropenia and recent TAZACT , VANCOMYCIN , FLUCONAZOLE use. C. Guiillermondi - CVC infection In many tertiary centres in western country, C. Glabrata has over taken the C. Albicans as major infection. 9/18/2024 Candida infections in ICU 10

11. All nonneutropenic patients with candidemia should have a dilated ophthalmological examination, within the first week after diagnosis Follow-up blood cultures should be performed every day or every other day to establish the time point at which candidemia has been cleared Central venous catheters (CVCs) should be removed as early as possible in the course of candidemia 9/18/2024 Candida infections in ICU 11

12. Predisposing Factors 1/3 of ICU infections attributable to nosocomial clusters . Diabetes Prolong Antibacterial agent ( Overgrowth of Candida on mucosal surfaces ) Indwelling IV catheter Hyper-alimentation fluids, TPN Indwelling Urinary catheter Steroids Severe burns (> 50%) Abdominal and Thoracic surgery( Breaches in mucosa ) Respirators Neutropenia Immunosuppressive drugs Pr o l on g ed I CU s t ay Advanced age Pancreatitis Chemotherapy High disease severity score (APACHE II > 20) Re n al re pl ace m e n t th era p y Malnutrition M u lt i p l e s i t e c o l on i s a t io n Major trauma Hands of health care workers. Contaminated solutions. 9/18/2024 Candida infections in ICU 12

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15. Diagnosis Blood culture is gold standard. Takes upto 7 days. CVC induced candidiasis, the culture has high sensitivity. But for translocation from GI tract, blood culture is less sensitive. Insitu hybridization & MALDI TOF MS has shown promising results. 9/18/2024 Candida infections in ICU 15

16. Nonculture diagnostics PCR technique – Sensitivity of 95% & specificity of 92%. Mean time to positivity is 4.4 hours. Can identify species of Candida and identify poly Candida Fungemia . Advantage of non culture diagnostic test- Helps in diagnosis of deep seated culture negative Candidiasis. 9/18/2024 Candida infections in ICU 16

17. Non-culture diagnostics Beta Glucan assay – Pan fungal diagnostic test Detect cell wall component of most of fungas - Aspergillus , candida, Pneumocystitis . Mucorales & Cryptococcus not detected. >80 pg/ml positive, <60 pg/ml negative. 61-79 pg /ml indeterminate Early then blood culture, sensitive but no specific. For invasive candidiasis -75% sensitivit y& 80% specificity. False positive test in patients of Bacteremia & ICU residents. fungal contaminated immunoglobulin , ,beta lactum antibiotics , cellulose filter on HD 9/18/2024 Candida infections in ICU 17

18. Treatment definitions Prophylaxis therapies In high risk Patients as immunosuppression Pre-emptive therapies are antifungal treatments administered to patients at risk of IC, with a diagnosis based on fungal biomarkers or Scoring system. Empirical therapy I n patients with signs and symptoms of infection along with specific risk factors for IC, irrespective of biomarkers Directed/targeted therapies B ased on microbiological confirmation of an infection 9/18/2024 Candida infections in ICU 18

19. What is the preferred first-line empirical therapy in a non- neutropenic critically ill patient with invasive candidiasis? Echinocandins - in patients with septic shock and MOF Fluconazole for patients with low severity of disease in low fluconazole resistance LF- AmB (liposomal amphotericin B) - when previous treatment with echinocandins and azoles has already failed C. parapsilosis need a higher caspofungin dose (100 mg q24 h) 9/18/2024 Candida infections in ICU 19

20. Transition from an echinocandin to fluconazole (within 5– 7 days) –in Stable patients and isolates susceptible to fluconazole C. glabrata, transition to higher-dose fluconazole 800 mg (12 mg/kg) daily or voriconazole 200–300 (3–4 mg/kg) twice daily in fluconazole or voriconazole-susceptible isolates Lipid AmB (3–5 mg/kg daily) is alternative if intolerance or resistance to other antifungal agents Voriconazole - as step-down therapy for selected cases of candidemia due to C. krusei 9/18/2024 Candida infections in ICU 20

21. What Is the Treatment for Candidemia in Neutropenic Patients ? Echinocandin is recommended as initial therapy Lipid AmB , alternative because of the potential toxicity C. krusei, an echinocandin, lipid formulation AmB, or voriconazole is recommended M inimum duration for candidemia without metastatic complications is 2 weeks after documented clearance of Candida from the bloodstream, provided neutropenia and S/S resolved Catheter removal should be considered on an individual basis 9/18/2024 Candida infections in ICU 21

22. MIC for Candidiasis C.glabrata has high degree of Azole and Echinocandin resistance . C.glabrata is responsive to amphotericin B Candida lusitaniae : high MIC to amphotericin Parapsillosis may have higher MICS for echnocandins 9/18/2024 Candida infections in ICU 22

23. Candida in Urine Common organism recovered in urine in ICU. Asymptomatic candiduria in low risk patient should not be treated. Treatment indicated in symptomatic and neutropenic patients. Removal of folleys , Starting AmB or Fluconazole . Echinocandins , voriconazole , Isavuconazole dont concetrate well in urine Cystitis due to fluconazole resistant Candida, dAmB bladder irrigation done for 5 days. 9/18/2024 Candida infections in ICU 23

24. Candida in sputum Candida pneumonia is rare despite isolation from sputum, BAL Parenchymal invasion needs to be documented for diagnosis of Pneumonia. Rather, Don’t trace Candida in sputum to reduces ICU stay. 9/18/2024 Candida infections in ICU 24

25. Take away points Prolonged ICU stay & Non specific fever- High suspicion. Immunosuppression – Most likely fungal infection. Transplants – High probability. Limited armatorium of drugs. Excessive financial burden, interventions, Mortality with morbidity. Descalation of antibiotics, steroids, maintenance of sterility, early removal of invasive lines takes us through. 9/18/2024 Candida infections in ICU 25

26. Thank you 9/18/2024 Candida infections in ICU 26