Fungal Infections in Neutropenic Hematological Disorders 23
Dr Farah Jijina 24
Fungal Infections in Neutropenic Hematological Disorders 25
Dr Farah Jijina 26
Fungal Infections in Neutropenic Hematological Disorders 27
Dr Farah Jijina 28
Fungal Infections in Neutropenic Hematological Disorders 29
Dr Farah Jijina 30
Fungal Infections in Neutropenic Hematological Disorders 31
Dr Farah Jijina 32
Fungal Infections in Neutropenic Hematological Disorders 33
Dr Farah Jijina 34
Fungal Infections in Neutropenic Hematological Disorders 35
Dr Farah Jijina 36
Case 2 (contd..) Day + 25 (20/1/06) Afebrile except for fever spikes with Amphotericin B. Day + 29: Received 2300mg Amphotericin B. Unable to tolerate. Creatinine rising, hypokalemia Change to Voriconazole (Vfend) Day + 30: Neutrophil recovery (700/cu mm). Day + 37 (06 Feb 2006) On oral Voriconazole Rpt BM: In Remission Discharge on Voriconazole, Augmentin, Levofloxacin 37
10 Mar 2006: After 1 Consolidation 03 April 2006: After 2 Consolidation 38
Question 5: The following is a criteria for PROVEN Fungal Infection Candida cultured from catheterised Urine Galactomannan test in Plasma for Zygomycosis Tissue biopsy showing fungal hyphae with accompanying tissue damage 1-3 beta-d-glucan test in serum for Aspergillosis Question to Col J Kotwal How do we diagnose Systemic Fungal Infections in ICU settings or Immunocompromised Hosts? (Excluding Endemic Fungal Infections) 39
Associate Professor in Pathology and Senior Adviser in Pathology and Hematology Armed Forces Medical College, Pune Formerly at Army Hospital Research & Referral, New Delhi Graduate of Lady Hardinge Medical College, New Delhi. Post Graduate, AFMC, Pune. Post-Doctoral Fellowship in Hematopathology at All India Institute of Medical Sciences, New Delhi Gold Medal for Standing First in MD (Pathology examination), Pune University Col Jyoti Kotwal MBBS, MD (Pathology) Abstract Histological and cultural evidence from tissue biopsies or resected material is required for definitive diagnosis of systemic fungal infections. However it is not always possible to fulfil this criterion. The current methods of diagnosis of IFI include signs and symptoms, microscopy, culture, serology, imaging procedures and biopsy. All tissues from patients with suspected systemic fungal infections should be stained with special fungal stains (GMS and PAS) as grams stain and H&E stain may miss out the fungal infection or misinterpret it as fibrin filaments. As far as culture is concerned, reliable results can be obtained from normally sterile body fluids like blood, CSF, pleural effusion and biopsy material. These fungi should then be identified till the species level. Despite stringent repeated cultures only 50% of autopsy proven candidiasis have positive blood culture. Thus thre is an important role of serology. Several antigen and antibody test methods have been used for systemic fungal infections. Antibody tests have a sensitivity of 17-90%, but the tests show delayed or decreased reaction in immuno-supressed and thus have a limited role. The antigen detection tests like CandTec have more utility. The antibody test has no role in diagnosis of aspergillosis. However the FDA approved galactomannan antigen assay shows high sensitivity and specificity, especially now with the lowered cut-offs for the test. However there is a problem of false negative in paediatric patients and those on anti-mycotic therapies and of false positivity in patients on â-lactam antibiotics. The use of this test is in the nascent stage in India and has been tried at CMC, Vellore and SGRH, New Delhi. There may be a major role for PCR for the early detection of systemic fungal infections and in this context the use of rapid multiplex PCR techniques which take 6 hrs to give results need to be clinically evaluated. This is still used as a research toll and is not available for clinical use. For mucor mycosis, tissue diagnosis is the major diagnostic method as no reliable serological, PCR based or skin tests are available. Pan fungal PCR on serial serum samples might be useful for diagnosis of disseminated mucor mycosis and is under evaluation. To conclude, a combination of various methods with regular screening are necessary for early diagnosis of systemic fungal infections. 40
Laboratory Diagnosis of Systemic Fungal Infections 41
Col Jyoti Kotwal 42
Laboratory Diagnosis of Systemic Fungal Infections 43
Col Jyoti Kotwal 44
Laboratory Diagnosis of Systemic Fungal Infections 45
Col Jyoti Kotwal 46
Laboratory Diagnosis of Systemic Fungal Infections 47
Col Jyoti Kotwal 48
Question 6: If Resources are not a constraint, the Drug of Choice for Invasive Aspergillus is Itraconazole Amphotericin D Caspofungin Voriconazole Question to Dr Eric Bow What are the Guidelines for Systemic Fungal Infections and New Anti-Fungal Agents 49
Dr. Eric J. Bow MD, MSc, D. Bacteriol, FRCPC Professor and Head, Section of Haematology/Oncology Department of Internal Medicine, University of Manitoba. Head, Department of Medical Oncology and Haematology, and Director, Infection Control Services, CancerCare Manitoba, Canada. Professor of Medicine and Medical Microbiology at the University of Manitoba, Winnipeg. Graduated from the University of Calgary Trained in General Internal Medicine and Haematology at McMaster University, Clinical Microbiology at the University of Toronto, and in Infectious Diseases at the University of Manitoba. Member of the Manitoba Blood and Marrow Transplant (MBMT) Program. Research interests: o Prevention and management of bacterial and fungal infections in neutropaenic cancer patients o Cytotoxic therapy-induced intestinal epithelial damage o Management strategies in adult acute myeloid leukemia o Impact of cytotoxic therapy on quality of life in cancer patients. 50
Guidelines to Manage Systemic Fungal Infections 51
Dr. Eric J. Bow 52
Guidelines to Manage Systemic Fungal Infections 53
Dr. Eric J. Bow 54
Guidelines to Manage Systemic Fungal Infections 55
Dr. Eric J. Bow 56
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