INVASIVE FUNGAL INFECTIONS IN THE INTENSIVE CARE UNIT.pptx

This ppt involves fungal infections in icu

1. INVASIVE FUNGAL INFECTIONS IN THE INTENSIVE CARE UNIT DR SAKSHI KULKARNI

2. INTRODUCTION The advances in critical care have, on one hand, managed to add to the survival of critically ill patients; however, on the other hand, they have also increased the incidence of opportunistic infections, especially fungal

3. RISK FACTORS Invasive procedures Central venous catheters Ventilators Prolonged antibiotics disrupting the normal flora Breach in the natural protective barriers The underlying medical or surgical conditions responsible for the prolonged stay in the intensive care unit

4. EPIDEMIOLOGY Most common - Invasive Candidiasis. This could be either candidemia or disseminated tissue candidiasis resulting from hematogenous dissemination or the direct inoculation of Candida into a sterile site during an invasive procedure. While earlier, most of the cases of invasive candidiasis were because of Candida albicans , Nonalbicans group has also emerged as a causative agent for it, namely C. parapsilosis , C. glabrata, C. tropicalis, and C. krusei .

5. The second most common –Aspergillosis Common in neutropenic patients or post-transplant patients, now it is being seen in non-neutropenic patients as well, particularly those with chronic pulmonary and liver conditions. It predominantly affects the lungs and sinuses in an immunocompetent patient In immunocompromised, it can results in cavitation and in aggressive angioinvasive disease. The species most commonly isolated are Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus terrus

6. Third most common- Mucormycosis The pathogens implicate here are Rhizopus, Mucor, Rhizomucor , Absidia , and Apophysomyces . Seen in patients with - Prolonged acidosis, Diabetic patients with uncontrolled sugars Patients suffering massive injuries due to road traffic accidents, disasters, or complex combat trauma

7. DEFINITION The The European Organization for Research and Treatment of Cancer (EORTC)/Invasive Fungal Infections Cooperative Group and the National Institute of allergy and infectious diseases mycosis study group (MSG) published the first standardized definitions for invasive fungal diseases (IFDs) came up with the latest definition in 2020. As per these definitions, IFD can either be a " proven " IFD or a " probable " IFD.

8. PROVEN IFD , the fungus needs to be detected either by blood culture or by histopathology/ culture of the tissue specimen. PROBABLE IFD , three components are taken into consideration: ( i ) Risk factor (ii) clinical characteristics of the disease entity (iii) mycological evidence [cultures, polymerase chain reaction (PCR), and antigen detection, microscopy).

9. CLINICAL FEATURES In neutropenic patients, patients with malignancies, or post-transplant patients, suspecting an IFD is relatively easier as compared to suspecting it in an immunocompetent patient. The physician needs to have a high index of suspicion to be able to make an early diagnosis and initiate antifungal treatment at earlier stages

10. Persistent fever despite ongoing antibiotic therapy Cough, hemoptysis, pleuritic chest pain, dyspnea Sinus tenderness and congestion Skin ulceration, nodules, and abscesses Abdominal pain, diarrhea, gastrointestinal bleeding, and hepatosplenomegaly Headache, altered sensorium, seizures, focal neurological deficits, visual disturbances, and redness of the eyes.

11. DIAGNOSIS The diagnostic approach involves first and foremost having a high index of suspicion, evaluating the risk factors, taking into consideration the clinical and radiological signs, and prescribing the appropriate laboratory investigations including specialized assays. Though blood C/S is an important part, but Sensitivity is suboptimal. Additionally, cultures may be negative in deep-seated tissue candidiasis or in patients already taking azole prophylaxis.

12. Apart from cultures, the serological markers, namely beta-D-glucan, mannan, and anti-mannan antibodies, can be used Nucleic acid-based detection, have been sensitive comparable to blood cultures, have been developed for Candida. They have an advantage of being able to deter deep-seated tissue candidiasis and remain unaffected by azole prophylaxis

13. Latest diagnostic tools include: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) Commercial assays based on fluorescence in situ hybridization (FISH) and the ones that allow molecular detection of fungi in blood

14. In order to guide the initiation of antifungal treatment, the " Candida Score " is used in non-neutropenic patients which takes into consideration the presence of total parenteral nutrition, severe sepsis, initial surgery, and multifocal Candida colonization. A score of <3 suggests a 2.3% risk of developing invasive candidiasis without treatment.

15. In cases of invasive aspergillosis, An important thing to keep in mind is that chest radiographs might be normal or might show some nonspecific findings in the early and at times even in the late stages of aspergillosis. CT chest might show diffuse infiltrates or the classical " halo " sign (zone of low attenuation with a translucent ground glass halo around).

16. The gold standard for diagnosis remains histopathological identification of the species in specimens obtained by invasive procedures. Cultures of bronchial secretions or secretions obtained by bronchoalveolar lavage (BAL) can be used for the detection of Aspergillus. Nonculture based tests include the detection of two fungal wall components-galactomannan in serum and BAL. samples and beta-D-glucan

17. Diagnosing Mucor requires careful and meticulous examination of the skin, sinuses, and palate to look for black eschar followed by debridement and then staining of the tissue sample with hematoxylin and eosin, periodic acid-Schiff (PAS), and visualization of broad non-septate irregularly branched hyphae.

18. TREATMENT Following classes are used Polyenes Azoles Echinocandins Pyrimidine analogs

19. The key factor determining the outcome in invasive candidiasis is time of treatment initiation. A delay of even 24/48 hrs can have negative impact An empirical antifungal in chosen the patient, prior use once patterns, the clinical status of patients, prior use of fluconazole, associated comorbidities, risk factors The antifungals that are usually preferred for invasive candidiasis include fluconazole and echinocandins.

20. In cases of documented Candida infection, a fundoscopic examination is warranted and treatment is immediately started. Echinocandins ( caspofungin 70 mg loading dose followed by 50 mg/day, micafungin 100 mg/ day, and anidulafungin 200 mg loading dose followed by 100 mg/day) are preferred in patients with hemodynamic instability In hemodynamically stable patients, fluconazole (3-6 mg/kg/day) can be used, provided there is no prior history of fluconazole usage and infection with nonalbicans species is not suspected.

21. Because the mortality of invasive pulmonary aspergillosis is high, treatment should be initiated the moment a clinical suspicion arises. The drug of choice is voriconazole , the recommended dosage is 6 mg/kg BD on day 1 and thereafter 4 mg/kg TDS, the duration of treatment can be months Salvage therapy options for refractory cases include echinocandins( caspofungin ), posaconazole (200 mg) and liposomal amphotericin B (3-5 mg/kg/day)

22. The treatment of mucormycosis is challenging because, in addition to antifungal therapy, it requires aggressive surgical intervention and management of the underlying predisposing conditions. The drug of choice remains liposomal amphotericin B at a dose of 5-10 mg/ kg/day with the maximal dose being used in case of cerebral involvement. The second-line agent that can be used is posaconazole at a dose of 400 mg BD. It can either be added to liposomal amphotericin B or used as a long- term monotherapy.

23. THE NEWER DRUGS Ravuconazole Albaconazole Monoclonal antibody: Mycograb NeuTec Pharma that is being considered in combination with amphotericin B.