3 Why bother with identification & susceptibility testing? Significant number of invasive fungal infectionsIncrease in ‘at-risk’ patient population
4 Why bother with identification & susceptibility testing? Significant number of invasive fungal infectionsIncrease in ‘at-risk’ patient populationIncrease in non-C. albicans speciesIncrease in ‘rarer’ speciesThe literature provides many examples of an increase in species other than Candida albicans.
5 Proportion of nosocomial Candida infections caused by different species in a teaching hospital Berrouane et al. J Clin Micro 1999; 37:531
6 Why bother with identification & susceptibility testing? Significant number of invasive fungal infectionsIncrease in ‘at-risk’ patient populationIncrease in non-C. albicans speciesIncrease in ‘rarer’ speciesIncrease in drug resistance
7 Increasing fluconazole resistance in Intensive Care Unit Moore et al. ECMM 1998
8 Why bother with identification & susceptibility testing? Significant number of invasive fungal infectionsIncrease in ‘at-risk’ patient populationIncrease in non-C. albicans speciesIncrease in ‘rarer’ speciesIncrease in drug resistanceMore drug choices availableInformed therapeutic choice
9 How do we identify yeasts? Culture morphologyChromagar
10 How do we identify yeasts? Germ tube testMicroscopic morphologyTerminal chlamydosporesArthrosporesOther tests
11 How do we identify yeasts? Traditional methodsWickerham testsAuxacolorCommercial kitsnumerous!Vitek-2API ID 32CMolecular methods
12 MICs He uses statistics like a drunken man uses lamp-posts ... For support rather than illumination
13 Do we have a good test of susceptibility for yeasts? CLSI (NCCLS) M27-A3 methodUSA standardEUCAST Document E-Def 7.1 methodEuropean standardExtensive clinical correlation work
14 Do we have a good test of susceptibility for yeasts? Disc diffusionno MIC obtainedscreening methodE-test stripsMIC value obtainedproblematic endpoints
15 Some are more equal than others! Do we have a good test of susceptibility for yeasts?An array of commercial formatsVitek-2YeastOneFungitestOthers…Some are more equal than others!Molecular methods
16 Candida albicans Most common cause of candidosis (50-70%) Can cause a wide range of diseasesMay cause vaginal and oral/oesophageal thrushProduces germ tubesAttributable mortality (18-25%)differences in patient age and underlying illness
17 Candida albicans - + ++ + ++ ++ ++ Azole susceptibility can depend on HIV statusFLU ITR VOR POS AMB 5FC CASPC.albicansC.albicans -FLU-resistantRates of resistance seen in our laboratoryflucytosine 6%fluconazole 1.2%5% of C. albicans with reduced susceptibility
18 Candida parapsilosis complex Candida parapsilosis, Candida orthopsilosis, Candida metapsilosis2nd most common species in blood, related to catheters and glucose solutions including TPNOften seen in neonatesGenerally do not cause thrushLess pathogenic than C. albicans
19 Candida parapsilosis complex FLU ITR VOR POS AMB 5FC CASPC.parapsilosisRates of resistance seen in our laboratoryfluconazole 0.4%
20 Candida glabrata 3rd or 4th most common species in blood Increasing in many institutionsCommon cause of thrush, particularly vaginalGenerally thought as unable to produce pseudohyphae in vitroEvidence of ability to grow as filamentous organism
21 Rates of resistance seen in our laboratory 1992-2006 Candida glabrataUsually reduced susceptibility to fluconazoleResponds poorly to amphotericin BFLU ITR VOR POS AMB 5FC CASPC.glabrataRates of resistance seen in our laboratoryfluconazole 53%
22 Candida tropicalisUsually 4th most common species in blood, much commoner in some institutionsGenerally does not cause thrushMore invasive than other Candida speciesHigh attributable mortality (33-50%)High frequency (~80-100%) of infection if coloniser during neutropenia
23 Rates of resistance seen in our laboratory 1992-2006 Candida tropicalisUsually fluconazole susceptible, but may develop resistance quicklyFLU ITR VOR POS AMB 5FC CASPC.tropicalisRates of resistance seen in our laboratoryflucytosine 20%fluconazole 46%
24 Candida krusei 5th most common species in blood Does not cause thrush, except in late-stage AIDSHigh mortality in leukaemic patients
25 Candida krusei May be a breakthrough species Always fluconazole resistant and amphotericin intermediateFLU ITR VOR POS AMB 5FC CASPC.krusei
26 Cryptococcus neoformans Neurotropic fungusMost common predisposing factor is AIDSAlso organ transplant recipients or cancer patients receiving chemotherapeuticsProduces a polysaccharide capsule - major virulence factor
27 Cryptococcus neoformans Combination therapy generally usedFLU ITR VOR POS AMB 5FC CASPCrypto.neoformansCryptococcus would generally be susceptible to some degree to most of the drugs – the exception is caspofungin which is intrinsically resistant.The most commonly used agents for treatment of cryptococcal infections are amphotericin B and flucytosine in combination.
28 High degree of mortality Rhodotorula mucilaginosaImage Courtesy of Carsten KettnerSaccharomyces speciesMalassezia speciesHigh degree of mortality
29 Can be intrinsically resistant to some antifungal drugs Species of…. Trichosporon Geotrichum BlastoschizomycesCan be intrinsically resistant to some antifungal drugs
31 Increasing incidence of invasive aspergillosis in hematopoietic stem cell transplant recipients Marr et al. Clin Infect Dis 2002; 34:909
32 What tests do we have to identify moulds? morphologymicroscopyadditional testsmolecular methodsExperience!
33 Can be a secondary pathogen in cases of carcinoma or TB AspergillusWide spectrum of disease – dependent on immune statusAllergic bronchopulmonary aspergillosisPulmonary aspergillomaInvasive aspergillosisCan be a secondary pathogen in cases of carcinoma or TB
34 Aspergillus fumigatus complex most common cause of aspergillosis ~90% of cases
35 Aspergillus niger complex Common cause of ear infections
36 Aspergillus terreus complex Cause of superficial, eye, ear and systemic infections
37 Aspergillus flavus complex Cause of pulmonary and sinus infections
38 In vitro susceptibility of filamentous fungi ITR VOR POS AMB 5FC CASP FLUAsp. fumigatus /Asp. nigerAsp. terreusAsp. flavus
39 Azole resistance in A. fumigatus complex Itraconazolerecent literature 0 - 5%7% RMLM 1992 – 2007 (n = 519)significant increase in resistance since 2004 – now 13%Itraconazole resistant isolates58% cross-resistant to voriconazole66% cross-resistant to posaconazoleData from Dr Susan Howard
40 Azole cross resistance of Asp. fumigatus complex MIC mg/LMosquera & Denning.Antimicrob Agents Chemother2002; 46:556
41 Other AspergilliKlich MA. Identification of common Aspergillus species (2002). CBS.
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