Prevention of Fungal Infections

Slideshow transcript

Slide 1: PREVENTION OF FUNGAL INFECTIONS Gamini Kumarasinghe Division of Microbiology National University Hospital, Singapore 1

Slide 2: Fungi range in size C. albicans Amanita muscaria Polyporus sulphureus chlamydospores Mycelia inside potato Black bread mold 2 Mycelia on various foods

Slide 3: Fungal Habitats Found in virtually every habitat on the earth where organic materials exist, including the Antartica • salt, sugar etc • leather, wax, jet fuel, plastics etc • thermal pools, volcanic craters 3

Slide 4: Prevention Of Fungal Infections • Advancements in modern medicine has left many individuals with impaired immune systems • These individuals are the most vulnerable to the fungal diseases 4

Slide 5: Prevention Of Fungal Infections The usual reservoir - not an infected human or animal - a site in nature where the fungus is growing as a saprophyte Chung & Bennett, 1992 5

Slide 6: Prevention Of Fungal Infections Because human mycoses are poorly communicable from person to person, mycoses are often endemic but rarely epidemic. Chung & Bennett, 1992 6

Slide 7: Prevention Of Fungal Infections mopping the floor e.g. diving boards & floor mats periodically with a fungicidal solution 7

Slide 8: ISOLATION PRECAUTIONS ? 8

Slide 9: Isolation Precautions Respiratory isolation - not indicated even when the patient in the adjacent bed is immunosuppressed Outside of neonatal candidiasis, transmission of a deep mycosis has been extraordinarily rare (C & B; Garner, 1996) 9

Slide 10: INFECTION IN THE HOSPITAL Immuno-compromised patients 10

Slide 11: Infection In The Hospital Aspergillosis 11

Slide 12: Infection In The Hospital Aspergillosis Patients susceptible to invasive aspergillosis are particularly congregated in • oncology • transplantation • intensive care units 12

Slide 13: Nosocomial Aspergillosis “safety levels” for bio-aerosols ? • Rural outdoor air – 10,000 CFU/cm • Threshold limit in indoor environment unknown Positive correlation – increased spore count & IA (Iwen et al, 1994; Hay et al, 1995) 13

Slide 14: Protective Isolation Positive Pressure Ventilation (PPV) • sealed room • with an anteroom • air-floor at least 12 ACH • HEPA filter (99.97% efficient at 0.3 µg particles) (ASHRAE, 1998; Humphreys, 2003) 14

Slide 15: Protective Isolation Laminar air-flow (LAF) • much greater ACH • expensive • noise • drafts Uncomfortable to the patient (ASHRAE, 1998; Humphreys, 2003) 15

Slide 16: Positive Pressure Ventilation Room Anteroom Patient’s Room Exhaust Bed Adapted from HPAC, 2000 PPV : 12 ACH LAF : 400 ACH 16

Slide 17: Infection In The Hospital Aspergillosis Keeping patients in such special rooms - considerable cost - nursing care, medical attention - emotional stress on the patient 17

Slide 18: Nosocomial Aspergillosis Most institutions rely on PPV filtration & not on LAF Important risk factor • immunosuppressive condition High risk patients may develop IA even with low spore count (Hay et al, 1995) 18

Slide 19: Protective Isolation HEPA filters Haematological malignancies - protective for highly IC patients - effective at controlling outbreaks due to Aspergillus conidia (Hahn et al., 2002) 19

Slide 20: Protective Isolation HEPA filters Bone marrow transplant recipients - tenfold greater incidence than other IC patients - risk could be eliminated by using HEPA with LAF (Sheretz et al., 1987) 20

Slide 21: Protective Isolation Portable HEPA filters ? 21

Slide 22: Protective Isolation Portable HEPA filters - costly preventive strategy of questionable value1 - under field conditions portable units not recommended2 1. Mantadakis & Samonis, 2006 2. Engelhart et al., 2003 22

Slide 23: Nosocomial infections: other moulds Fusarium, Trichosporon spp., dematiaceous moulds, Zygomycetes etc may affect immunocompromised patients (Walter EA, 1995) 23

Slide 24: Fungal Infections “other moulds” IC individuals risk infections by more than 270 species • contaminated skin lotions, twigs, medications etc • gain access: through GI tract • normally a sign of contamination (but in neutropaenic might indicate disseminated disease) 24 Perfect JR, 2005

Slide 25: Fungal Infections IC individuals risk infections by more than 270 species Good housekeeping 25 Perfect JR, 2005

Slide 26: Infection In The Hospital Candidiasis 26

Slide 27: Infection In The Hospital Candidiasis The usual reservoir is the patient's own body 27

Slide 28: Infection In The Hospital Candidiasis Patients with severe and prolonged neutropenia Prone to develop disseminated candidiasis from numerous small ulcers caused by Candida species in the stomach, oesophagus, and intestine 28

Slide 29: Infection In The Hospital Prevention of candidiasis Despite massive oral doses of nystatin, to reduce Candida in stools prevention of disseminated candidiasis has not been convincingly demonstrated 29

Slide 30: Infection In The Hospital Topical / Non-absorbable antifungal agents • clotrimazole • nystatin • amphotericin B - decrease colonizing burden - mucosal manifestations However, does not reduce invasive candidiasis or mould infection (Tollemar, 1997; Boeckh & Marr, 2001) 30

Slide 31: Infection In The Hospital Candidiasis in Neonatal Units • Low birth weight more susceptible • blood stream infection following IV catheters 31

Slide 32: Prophylaxis Candidiasis in Neonatal Units • candidaemia in low birth weight – high mortality • preliminary data – fluconazole reduces infections • this practice is not used widely • criteria for initiation prophylaxis is unknown Aseptic techniques, care of umbilical catheters Burwell, 2006 32

Slide 33: INFECTION IN THE LABORATORY 33

Slide 34: Infection In The Laboratory • Ubiquitous fungi, such as Candida and Aspergillus, can be handled with BSL 1 precautions • Standard microbiologic technique is all that is required 34

Slide 35: Infection In The Laboratory H. capsulatum or C. immitis • for opening culture dishes • pipetting, vortexing, • any other activity that might generate an aerosol • handling ‘mould forms’ Class 1 or class 2 biologic safety cabinet 35

Slide 36: Infection In The Laboratory • Most other procedures with pathogenic fungi can be done at biosafety level 2 • This includes processing clinical specimens and working with the ‘yeast form’ of H. capsulatum or spherules of C. immitis 36

Slide 37: Classification of Microorganisms • Risk group 1 ubiquitous • Risk group 2 hepatitis B, HIV • Risk group 3 TB, Fungi* • Risk group 4 African h’gic fevers – aerosol generating procedures* – ‘mould forms’ 37

Slide 38: PRECAUTIONS WITH INFECTED LABORATORY ANIMALS 38

Slide 39: Precautions With Infected Laboratory Animals • Biosafety level 2 precautions are adequate for all mycoses • Urine of animals may contain C neoformans, H capsulatum & C immitis & contaminate cage bedding • Animal bedding contaminated with the tissue forms might convert and grow the mould during prolonged storage 39

Slide 40: Environmental control 40

Slide 41: Environmental control Yeasts • Candida is present in the subject's endogenous reservoir (Odds, 1998) • However, exogenous sources such as another person, food, intravenous catheters, and parenteral fluids—have also been reported (Meunier, 1987) • Reduction in risk factors, aseptic practices & reducing Candida colonization 41

Slide 42: Environmental control Aspergillus spp. & other molds Outbreaks of infections after construction work in hospitals (Bodey & Vartivarian, 1989) 42

Slide 43: • Construction & renovation associated with IA (Weems et al, 1987) • HEPA significantly reduces the incidence of lA (Humphreys, 2004) • Enhanced cleaning & the sealing of windows • the use of prophylactic anti-fungal agents ??? 43

Slide 44: Prevention Of Fungal Infections Endemic areas of histoplasmosis / coccidiomycosis Preventing inhalation of infected dust - more difficult - control measures appear prudent around desert military training areas, airports and helicopter landing areas, construction sites etc e.g. water sprays, disinfectants (DHHS, 1997) 44

Slide 45: Environmental control • Cryptococcosis is an exogenous infection • usually acquired prior to hospitalization by inhalation of fungal spores found in soil, vegetable matter, and bird excrement. 45

Slide 46: Environmental control • proper cooking of food • avoidance of raw vegetables & pepper • no potted plants or flowers should be allowed on the ward (Tollemar, 1997) 46

Slide 47: Fungi in the environment One year old study in a major tertiary care hospital About 200 bone marrow and organ transplants / yr Dept of Environmental and Occupational Health Science, University of Illinois at Chicago Curtis et al, 2005 47

Slide 48: Fungi in the environment One year old study: monitor fungi in the hospital • extensive indoor renovations • several large demolition & building projects within 1 km Curtis et al, 2005 48

Slide 49: Fungi in the environment One year old study • Aspergillus propagules in all parts of the hospital • Aspergillus concentrations higher indoors cf to outside • Total fungi were significantly higher outside Therefore, infiltration of outside air cannot be the primary mechanism for producing airborne aspergillus levels Curtis et al, 2005 49

Slide 50: Fungi in the environment One year old study Aspergillus sources in the hospital • dust from duct cleaning • renovation • sites of water damage • moisture condensation Curtis et al, 2005 50

Slide 51: Fungi in the environment One year old study Approaches to controlling aspergillus infections in hospitals • moisture / water control • HEPA filters • sealed positive pressure rooms • environmental monitoring of aspergillus Curtis et al, 2005 51

Slide 52: Potted plants & Flowers • differences in opinion • current guidance, in favour of their removal from clinical areas • not in the vicinity of IC patients CDC, MMWR 2000;49(RR10):1-128 52

Slide 53: Fungal Infection Prevention Routine measures – not the ideal solution 53

Slide 54: Fungal Infection Prevention • Environmental fungi - preventing exposure, not effective • Endogenous flora - difficult • Improving host defences - not always possible 54

Slide 55: Prevention Resort to Antifungal Agents • Prophylactic • Empirical & • Pre-emptive therapy 55

Slide 56: Prophylaxis Antimicrobials administered to patients at high risk of developing the disease, who are not infected and not manifesting symptomatic disease. Goodman et al., 1992 56

Slide 57: Empiric therapy • commencement of Rx at the first clinical suspicion • still results in about 10% break through infections De Pauw, 2005 57

Slide 58: Emperic therapy Toxicity & cost are major shortcomings of such therapy Hence, “preemptive” approach Maertens clin inf dis 2005 Nov 1 58

Slide 59: Preemptive Therapy 59

Slide 60: Preemptive Therapy The administration of antimicrobials to patients already infected, but who do not yet manifest symptomatic disease in whom there are markers of pathogen invasion Synonymous with secondary prophylaxis or preventive therapy Singh N., 2001 60

Slide 61: Diagnosis of fungal infections • conventional microbiological • histological • radiological techniques were the cornerstone of diagnosis 61

Slide 62: Diagnosis of fungal infections Limited impact on clinical decision making • too insensitive • time consuming • lacked general accessibility So P-E therapy depends on microbiological markers i.e. non-culture techniques Hope et al., 2005 62

Slide 63: Microbiologic markers Non culture based assays 63

Slide 64: Preemptive therapy Non culture based assays • galactomannan • beta-D-glucon (accuracy, role in diagnosis remains unclear, Wheat 2006) • fungal DNA by PCR (validation & standardization needed) Maertens et al, 2006 64

Slide 65: Preemptive therapy Galactomannan • multicentre study; 61% sensitivity & 93% specificity (Pfeiffer et al., 2005) • clinical issues unanswered does the assay correlates with fungal burden ? impact of antifungals on test performance ? cut-off value ? false-positives and false-negative values etc etc ? In conjunction with imaging techniques Maertens et al., December 2006 65

Slide 66: preemptive therapy Galactomannan and computed tomography • Galactomannan • thoraxic computed tomography scanning • bronchoscopy with lavage Conclusion: Reduce the exposure to expensive and potentially toxic drugs & offer effective antifungal control Failed to detect non-Aspergillus IFI Maertens et al., 2005 66

Slide 67: Candida markers Mannan is a major component of the Candida cell wall Platelia Ag/Ab; Bio-Rad Lab 93% specificity & 80% sensitivity (Sendid et al., 1999 & 2002, Year et al., 2001) 67

Slide 68: PROPHYLAXIS 68

Slide 69: Antifungal prophylaxis Invasive Yeast Infection Oral fluconazole At a dose of 400 mg/day • provides protection against invasive yeasts • if infection occurs despite fluconazole - assume the isolate is resistant - moulds universally resistant Emergence of non-albicans resistant strains C krusei, C glabrata – naturally resistant (MMWR, 2000; Goodman et al, 1992) 69

Slide 70: Antifungal prophylaxis Invasive Mould Infection • regimens studied - moderate dose amphotericin B - low dose amphotericin B - aerosolized amphotericin B - intranasal amphotericin B - lipid formulations of amphotericin B - itraconazole • no regimen shown to be effective Hence, environmental protection strategies Boeckh & Marr, 2001; MMWR 2000; 49:1-125 70

Slide 71: Prophylaxis Solid Organ Transplant (SOT) A more controversial issue - primary antifungal chemoprophylaxis, because only a few trials have been done (Tollemar et al, 1995; Lumbreras, 1996) 71

Slide 72: Pneumocystis jirovecii • Autologous and allogenic transplantation • Prophylaxis with TMP-SMX – negligible rates • Dapsone, atovaquone or inhaled pentamidine 72 (Espinel-Ingroff et al., 1997, 2000)

Slide 73: Pneumocystis jirovecii Adults - ALL - CNS tumours receiving high-dose corticosteroid therapy - patients receiving combination corticosteroid therapy with either myelotoxic agents or fludarabine prophylaxis should be considered (Sullivan et al, 2001) 73

Slide 74: Pneumocystis jirovecii Children acute lymphoblastic leukemia allogeneic BMT SCT recipients - are known high-risk groups that should be offered prophylaxis. Momin & Chandrasekar, 1995: Link et al, 1993 74

Slide 75: New antifungal agents 75

Slide 76: New antifungal agents • Less toxic formulations of amp B • Improved azoles: Itraconazole, Voriconazole Posaconazole • Echinocandin: micafungin Despite these advances, mortality rates for IFI is about 90% Denning et al., 1998 76

Slide 77: Summary and Conclusions 77

Slide 78: Summary of major recommendation for prevention of invasive fungal infection (Sullivan et al, 2001) Rating Type of Prevention Handwashing to prevent spread of exogenous Alll Candida species Fungal surveillance cultures are not indicated in Dll asymptomatic patients Topical antifungal agents are not recommended Dll for prevention of invasive fungal infection Fluconazole (400 mg/day) is recommended to All prevent invasive yeast Patients are to avoid hospital construction or Alll renovation areas 78

Slide 79: Future • Pre-emptive approach for the prevention • Methods to monitor aspergillus in hospitals & other environments - use of ELISA* - DNA hybridization** - PCR** * Arruda et al., 1992 ** Rath & Ansorg, 2000 79

Slide 80: Conclusions • The prevention an important goal of IC patients • Non-culture microbiologic assays • Prophylactic fluconazole at a dose of 400 mg/day decrease both the rate of invasive yeast infection and mortality • Thus far, no prophylactic strategy has been shown to decrease the incidence of invasive mould infection • Enhanced cleaning of the environment 80