In vivo response in a mixed infection model of azole susceptible and resistant Aspergillus spp. strains Laura Alcazar-Fuoli, CNM, ISCIII
|
|
- Ernest Hamilton
- 5 years ago
- Views:
Transcription
1 In vivo response in a mixed infection model of azole susceptible and resistant Aspergillus spp. strains Laura Alcazar-Fuoli, CNM, ISCIII Pre-Advances Against Aspergillosis Workshop: Aspergillus Speciation in the 21st Century - Implications for Laboratory and Clinical Practice Meliá Castilla Hotel and Conference Centre Madrid, Spain
2 Genetic relatedness Introduction: Mixed infections Definition: Denotes diseases involving several microorganisms. Kingdom A + Kingdom B Genus A+ Genus B Species A + Species B Strain A + Strain B Substrain A + Substrain B
3 Types and sites of polymicrobial diseases Medically important bacterial fungal interactions. Anton Y. Peleg, Deborah A. Hogan & Eleftherios Mylonakis Nature Reviews Microbiology 8,
4 Relations required for development of human disease William Costerton and Mark E. Shirtliff Brian M. Peters, Mary Ann Jabra-Rizk, Graeme A. O'May, J. Polymicrobial Interactions: Impact on Pathogenesis and Human Disease. Clin. Microbiol. Rev. 2012, 25(1):193.
5 Relations required for development of human disease William Costerton and Mark E. Shirtliff Brian M. Peters, Mary Ann Jabra-Rizk, Graeme A. O'May, J. Polymicrobial Interactions: Impact on Pathogenesis and Human Disease. Clin. Microbiol. Rev. 2012, 25(1):193.
6 Clinical challenges of mixed infections by fungi: How the host responds to polymicrobial infection compared to monomicrobial infection?. Composition of microbial populations will modify the clinical course and severity of the disease. Diagnostic tools. Impact on the selection of antimicrobial therapy and response to treatment, especially when it involves pathogens exhibiting antimicrobial resistance.
7 Cases of mixed infections by fungi Case 1: A 29-year-old female with acute nonlymphoblastic leukemia who received a bone marrow transplant in Surveillance of yeast colonization and drug regimen. AMB resistant D R Soll, M Staebell, C Langtimm, M Pfaller, J Hicks, and T V Rao. J Clin Microbiol August; 26(8): Multiple Candida strains in the course of a single systemic infection.
8 Cases of mixed infections by fungi Case 2: A 33 year-old man that had a right lung transplantation procedure in Treated with azathioprine, cyclosporine and prednisone. Four months after transplantation, the patient was diagnosed with cytomegalovirus pneumonia. Six weeks later he presented with productive cough and hyaline septate branched hyphae were seen in the BAL. AMB and Aspergillus flavus was recovered. The patient died 15 days later and deep pulmonary nodule, and culture showed growth of both A. flavus and Aspergillus fumigatus.
9 Case 3: A 48-year-old caucasian woman with leukaemia. Infection by several Aspergillus species. Cases of mixed infections by fungi MCF CPF +AMB
10 Cases of mixed infections by fungi Infection by several cryptic species of A. fumigatus complex Case 4: A 68-year-old male smoker with COPD and long term inhaled and systemic corticosteroids. ICU Day 13: BA pure A. fumigatus VRZ Day 16: BA pure A. fumigatus. Day 17: A. fumigatus and white colonies of a mycelial fungus of slow sporulation identified as A. lentulus. Died
11 Cases of mixed infections by fungi Infection by several cryptic species of A. fumigatus complex Case 5: A 43-year-old Argentine woman that underwent kidney transplantation in May Immunosuppressive regimen comprised a combination of mycophenolate mofetil hydrochloride, cyclosporine and prednisolone. Three graft rejection episodes. AMB Characteristic morphological and phylogenetic analyses demonstrated the presence of A. fumigatus and A. lentulus. Died
12 Infection by several cryptic species of A. fumigatus complex It is important to study several isolates per patient in order to reveal the presence of cases of co-infection by cryptic species
13 Mix infections are complex Bad response High mortality rates Diagnosis is difficult Even more complicated when cryptic species are involved
14 Mix infections are complex Bad response High mortality rates Diagnosis is difficult Even more complicated when cryptic species are involved Model of mix infection with A. fumigatus and A. lentulus
15 Aspergillus fumigatus and Aspergillus lentulus
16 Design of a Multiplex Real Time PCR (MN- PCR) for simultaneous detection of A. fumigatus and A. lentulus
17 Design of One-step Nested Multiplex Real Time PCR (MN-PCR) for the simultaneous detection of A. fumigatus and A. lentulus
18 Molecular identification of Aspergillus section Fumigati β-tubulina: Clustal V CM3538Tub.seq CM4330_T ub.seq CM3599Tub.seq CM3134Tub.seq CM3583Tub.seq AY SEQ CM1290TuB.seq AY SEQ AY SEQ CM3537Tub.seq AY SEQ CM4370_T ub(sens).seq CM3364TUB.SEQ CM4428Tub2.seq CM4426TUB.s eq CM4420TUB.s eq CM4387Tub.seq CM4415_T UB.seq CM4428Tub.SEQ AB248076_ As pergillus fumis ynnematus.seq CM4063bT ub.s eq AB248077_ As pergillus fumis ynnematus.seq AB248078_ As pergillus fumis ynnematus.seq CM4063bT ub(sens).seq CBS109890bT ub(sens).s eq CM237T ub.s eq A. fumigatus CBS525Btub.seq CBS544T ub.s eq Nlaciniosa(AY870748).SEQ N. fischeri Nspinosa(AF057329).s eq Nspinosa(AY870765).seq Nspinosa(AY870761).seq Nspinosa(AY870759).seq Nspinosa(AY870762).seq Nspinosa(AY870760).seq CBS111_55T ub.seq AY870757_ Nc oreana_ibt s eq AY870758_ Nc oreana_kacc41659.s eq CM2280Tub.seq CM3227Tub.SEQ DQ094884_ Afumigatiaffinis _ IBT seq DQ094885_ Afumigatiaffinis _ IBT seq DQ094886Anovofumigatus _IBT s eq DQ094887Anovofumigatus _IBT s eq CBS208T ub.s eq CM3914Tub.seq CM4060bT ub.s eq CBS404T ub.s eq CM3769Tub.seq Npseudofisc heri(af057325).seq CM2270TuB.seq Npseudofisc heri(ay870742)cbs208_ 92.SEQ AY590130_ Aviridinutans _MK284.seq CM3147Tub.seq AY590129_ Aviridinutans _MK246.seq CM4518Tub.seq A. AF134780_Aviridinutans_ IMI s eq CBS114218T ub.seq CM3740Tub.seq Nhirats ukae(af057324).seq CM3305Tub.seq CM3764Tub.seq CM4328_tub.seq CBS117067T ub.seq N. hiratsukae CM3303Tub.seq CBS109356T ub.seq Nglabra(AY870734).seq Nglabra(AY870735).SEQ Nglabra(AY870736).SEQ CBS165_63T ub.seq CBS113_64T ub.seq Naurata(AF057318)CBS466_65.SEQ Nspinosa(AY870763).SEQ AfumigatusXM s eq A. lentulus A. fumisynnematus A. fumigatiaffinis N. pseudofischeri viridinutans N. glabra
19 Molecular identification of Aspergillus section Fumigati RodletA: Clustal V 22.6 CM4387_NRodA.s eq CM4420RodA.s eq CM4426RodA.s eq CM4415_RODA.s eq CM4370_Rod.seq CM4428RodA.s eq CM4415RodA.s eq CM4426RodA3_049.seq AY738519AL.seq DQ Alentulus_FH220.s eq AY738525AL.seq AY738514AL.seq CM3537Rod.seq CM3538Rod.seq CM1290Rod.seq AY738522AL.seq CM3583Rod.seq CM4330_RodA.seq CM3364ROD.s eq CM3599Rod.seq CM3134Rod.seq AB249898_Afumisynnematus.seq AB249899_Afumisynnematus.seq CM4063Rod.seq AB249897_Afumisynnematus.seq AB249897_Afumisynnematus.seq CM237rod.s eq N.udagawae(DQ439767).SEQ M0742_RODA.seq CBS109890Rod.seq CM3622ROD.s eq CM3663ROD.s eq CM3550ROD.s eq N.fischeri(DQ439770).SEQ CM3587ROD.s eq A.neoliptic us(dq439771).seq CBS525RodCON.seq CBS544_65Rod.seq CM2280Rod.seq CM3227ROD.s eq CBS111_55Rod.seq AB250103Aviridinutans.seq CM4518_RODA.s eq A. CM3147Rod.seq N.udagawae(DQ058375).SEQ N.udagawae(DQ439769).SEQ CBS114218Rod.seq AF057344_Neosartorya hirats ukae.s eq CM3740Rod.seq CM3764Rod.seq CM4328Rod.seq CBS117067Rod.seq CM3305Rod.seq CM3303Rod.seq CBS109356Rod.seq CBS113Rod.seq CBS165_63Rod.seq N. CBS208ROD.seq CBS404_67RODA.s eq CM2270Rod.seq CM3769Rod.seq CM4060Rod.seq CM3914Rod.seq RodEmericelaNidulans.seq A. lentulus A. fumisynnematu A. fumigatus N. fischeri A. fumigatiaffinis viridinutans N. hiratsukae glabra N. pseudofischeri
20 Design of a Nested Multiplex Real Time PCR (MN-PCR) for the simultaneous detection of A. fumigatus and A. lentulus cyp51a A. fumigatus A. lentulus A. fumigatiaffinis N. fischeri A. viridinutans N. pseudofischeri 1.2 > 97% Nucleotide Substitutions (x100) 0 CM 3673 CM 3764 CM 5280 CM 4387 CM 4063 CM 4909 CM 5441 CM 4635 CM 3147 CM 3914 CM 4060 A. lentulus A. fumisynnematus N. udagawae N. hiratsukae A. fumigatiaffinis A. viridinutans N. pseudofischeri
21 Design of a Nested Multiplex Real Time PCR (MN-PCR) for the simultaneous detection of A. fumigatus and A. lentulus A. fumigatus CYP51A A. lentuluscyp51a A. fumigatus CYP51A A. lentuluscyp51a A. fumigatus A. fumigatus CYP51A A. lentuluscyp51a A. fumigatus CYP51A A. lentuluscyp51a A. fumigatus CYP51A A. lentuluscyp51a A. lentulus Samson et al. Studies in Mycology 59: A. fumigatus CYP51A A. lentuluscyp51a 71 bp
22 Design of One-step Nested Multiplex Real Time PCR (MN-PCR) for the simultaneous detection of A. fumigatus and A. lentulus Fungal species and strains Aspergillus flavus (CM-2669) Aspergillus terreus (CM-2013) Fusarium verticillioides (CM-2975 Fusarium oxysporum (CM-2914) Scedosporium prolificans (CM-1627) Scedosporium apiospermum (CM-3169) Cryptococcus neoformans (CL-2132) Rhizopus oryzae (CM-3020) Rhizomucor variabilis (CM-2437) Candida albicans (ATCC64551) Candida glabrata (CL-5533) Human Mice Fungal species and strains section fumigati A. fumigatiaffinis (CM-2280) N. hirasukae (CM-5817) N. pseudofischeri (CM-5593) A. novofumigatus (CM-6098) A.viridinutans (CM-3147) N. udagawe (CM-5416) A. fumisynnematus (CM-4063) A. fumigatus (20 strains) A. lentulus (20 strains)
23 Design of One-step Nested Multiplex Real Time PCR (MN-PCR) for the simultaneous detection of A. fumigatus and A. lentulus FAM HEX A. fumigatus strains A. lentulus strains Sensitivity Reproducibility Specificity A. fumigatus 100 fg/ul 96,3 % 100 % A. lentulus 100 fg/ul 97,6 % 100 %
24 Validation of the MN-PCR in a murine model of aspergillosis Cyclophosphamide model 10 5 conidia spores in 30 µl of saline solution Hydrocortisone acetate 10 5 conidia spores in 30 µl of saline solution A. lentulus A. fumigatus A. lentulus A. fumigatus
25 ng of fungal DNA / l ng of fungal DNA / l Validation of the MN-PCR in a murine model of aspergillosis Cyclophosphamide model 10 5 conidia spores in 30 µl of saline solution Hydrocortisone acetate 10 5 conidia spores in 30 µl of saline solution % (8/8) 92 % (12/13) % (10/10) 100 % (10/10) A. fumigatus A. lentulus 0 A. fumigatus A. lentulus
26 ng of fungal DNA/ mg of murine DNA Validation of the MN-PCR in a murine model of aspergillosis Cyclophosphamide model 10 5 conidia spores in 30 µl of saline solution % (3/5) % (3/5) 5 BALs 72h post infection 0.1 Control not infected 0.0 Control NI A. fumigatus A.lentulus
27 In vivo model of mixed infection with azole susceptible and resistant Aspergillus spp. (A. fumigatus and A. lentulus) Antifungal response
28 Mixed infection model of R. oryzae-a. fumigatus. Corticosteroid-immunosuppressed mice to explore whether in vivo exposure with other antifungals used in the treatment of invasive aspergillosis provoke selection pressure for breakthrough mucormycosis during infection.
29 Voriconazole pre-exposure in vitro accelerates breakthrough infection in vivo with R. oryzae Lewis RE, Liao G, Wang W, Prince RA, Kontoyiannis DP. Voriconazole pre-exposure selects for breakthrough mucormycosis in a mixed model of Aspergillus fumigatus-rhizopus oryzae pulmonary infection. Virulence Jul-Aug;2(4): Epub 2011 Jul 1.
30 Voriconazole accelerates mortality due to R. oryzae in a mixed infection model of pulmonary aspergillosis and mucormycoses Lewis RE, Liao G, Wang W, Prince RA, Kontoyiannis DP. Voriconazole pre-exposure selects for breakthrough mucormycosis in a mixed model of Aspergillus fumigatus-rhizopus oryzae pulmonary infection. Virulence Jul-Aug;2(4): Epub 2011 Jul 1.
31 Alternative host model to study fungal infections Galleria mellonela Greater wax moth Insect model, although we use the larval phase Lepidoptera
32 Alternative host model to study fungal infections Galleria mellonela structure (Larval stage)
33 Galleria mellonela Immunity Haemocytes Antimicrobial Peptides ROS Melanization
34 Alternative host model to study fungal infections Role of virulence factors (mutant screening) Host-pathogen interations Antifungal efficacy and resistance detection Host response
35 Alternative host model to study fungal infections
36 Alternative host model to study fungal infections Galleria mellonela Disadvantages Lacks adaptative immunity Genome not known Expertise required to breed in the laboratory Advantages Allows different temperatures incubations Controlled inocula Easy to monitor survival Easy to implement in the laboratory Suitable for antimicrobial efficacy testing
37 Aspergillus fumigatus Aspergillus lentulus Aspergillus fumigatus and Aspergillus lentulus A
38 Radial growth (cm) Model of A. fumigatus and A. lentulus; in vitro assays Microscopic morphology (RPMI) Macroscopic morphology (MM) AkuB KU80 AkuB KU A.lentulus CM1290 A.fumigatus akub KU80 CM1290 CM akub CM hr 24 hr h 48h 72h 4d 5d Time
39 Correlation between virulence of A. lentulus and A. fumigatus in mice and G. mellonella Cyclophosphamide model A. lentulus A. fumigatus A. fumigatus A. lentulus
40 Histopathology of infected G. mellonella Aspergillus fumigatus Aspergillus lentulus 20 x magnification, PAS stain
41 % Hemocites relative to PBS Haemocyte density by obtaining the hemolymph from infected larvae A. fumigatus A. lentulus Time (minutes)
42 Survival rate of G. mellonella infected with A. fumigatus and A. lentulus Untreated Treated with voriconazole
43 Histopathology of infected G. mellonella treated with voriconazol A. fumigatus A. lentulus 20 x magnification, PAS stain
44 Fungal burden by qpcr of infected G. mellonella treated with voriconazol Aspergillus fumigatus Aspergillus lentulus
45 Fungal burden by qpcr of infected G. mellonella treated with voriconazol Aspergillus fumigatus 15 X p < 0,5 Aspergillus lentulus 3,5 X
46 Correlation between virulence of a mixed infection in mice and G. mellonella Cyclophosphamide model Inoculum: 10 5 Mixed infection: A. fumigatus + A. lentulus: 5 x 10 4 each A. fumigatus A. lentulus Mixed
47 Survival rate of G. mellonella infected with a mixed infection of A. fumigatus and A. lentulus A Untreated B Treated with voriconazole
48 Survival rate of G. mellonella infected with a mixed infection of A. fumigatus and A. lentulus A Untreated B Treated with voriconazole
49 Fungal burden of G. mellonella infected with a mixed infection of A. fumigatus and A. lentulus Untreated Treated with voriconazole A. fumigatus A. lentulus A. fumigatus A. lentulus
50 Fungal burden of G. mellonella infected with a mixed infection of A. fumigatus and A. lentulus A. lentulus is selected by voriconazole in a mixed infection A. fumigatus A. lentulus
51 Fungal burden of G. mellonella at 4 day post- infection p < 0,05 Fungal burden of infected larvae with A. fumigatus is reduced in the mixed infection but not for A. lentulus Single infection Mix infection
52 Conclusions Mixed infections are complex and challenge fungal diagnosis and treatment. We were able to simultaneously detect two species closely related such as A. fumigatus and A. lentulus by qpcr showing a promising target for clinical detection of Aspergillus section Fumigati in single or mixed infections. Microbial virulence and correlation between antifungal susceptibility data in vitro/in vivo can be explored in the Galleria mellonella model of Aspergillus spp infection. Aspergillus infected larvae did not respond to VCZ treatment when they were infected with A. lentulus only or in combination with A. fumigatus. The presence of antifungal resistant species would likely complicate the management of fungal infections.
53 Knowledgments Members of the Mycology Reference Laboratory Spanish National Center for Microbiology Manuel Cuenca Estrella Alicia Gomez Lopez Oscar Zaragoza and Rocio Garcia Emilia Mellado Maria Jose Buitrago Gema del Rio
AUSTRALIAN ANTIFUNGAL SUSCEPTIBILITY DATA : PART 2 THE MOULDS ASPERGILLUS, SCEDOSPORIUM AND FUSARIUM.
AUSTRALIAN ANTIFUNGAL SUSCEPTIBILITY DATA 00-0: PART THE MOULDS ASPERGILLUS, SCEDOSPORIUM AND FUSARIUM. AUSTRALIAN Sarah Kidd, Rose Handke and ANTIFUNGAL David Ellis SUSCEPTIBILITY DATA 00-00 David SA
More informationIntroduction. Study of fungi called mycology.
Fungi Introduction Study of fungi called mycology. Some fungi are beneficial: ex a) Important in production of some foods, ex: cheeses, bread. b) Important in production of some antibiotics, ex: penicillin
More informationResistance epidemiology
ECMM/EFISG symposium: Multidrug resistance in fungi? A formidable foe Resistance epidemiology Ana Alastruey Izquierdo Mycology Reference Lab Spain Instituto de Salud Carlos III Disclousure I have received
More informationVoriconazole. Voriconazole VRCZ ITCZ
7 7 8 7 8 fluconazole itraconazole in vitro in vivo Candida spp. C. glabrata C. krusei Cryptococcus neoformans in vitro Aspergillus spp. in vitro in vivo Aspergillus fumigatus Candida albicans C. krusei
More informationUse of Antifungal Drugs in the Year 2006"
Use of Antifungal Drugs in the Year 2006" Jose G. Montoya, MD Associate Professor of Medicine Associate Chief for Clinical Affairs Division of Infectious Diseases Stanford University School of Medicine
More informationDiagnosis of Invasive Septate Mold Infections A Correlation of Microbiological Culture and Histologic or Cytologic Examination
Microbiology and Infectious Disease / DIAGNOSIS OF SEPTATE MOLD INFECTIONS Diagnosis of Invasive Septate Mold Infections A Correlation of Microbiological Culture and Histologic or Cytologic Examination
More informationAPX001 A novel broad spectrum antifungal agent in development for the treatment of invasive fungal infections
APX001 A novel broad spectrum antifungal agent in development for the treatment of invasive fungal infections TIMM, Belgrade, Serbia October, 2017 New antifungal drugs in the pipeline S15 Dr. Michael Hodges
More informationMycological Profile of Bronchial Wash Specimens in Patients with Lower Respiratory Tract Infections
International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 11 (2017) pp. 176-182 Journal homepage: http://www.ijcmas.com Original Research Article https://doi.org/10.20546/ijcmas.2017.611.022
More informationEMERGING FUNGAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
EMERGING FUNGAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS DR LOW CHIAN YONG MBBS, MRCP(UK), MMed(Int Med), FAMS Consultant, Dept of Infectious Diseases, SGH Introduction The incidence of invasive fungal
More informationNewer Combination Therapies
Newer Combination Therapies William J. Steinbach, MD Associate Professor of Pediatrics, Molecular Genetics & Microbiology Pediatric Infectious Diseases Duke University Medical Center Combination Therapy
More informationReceived 22 November 2007/Returned for modification 29 December 2007/Accepted 12 January 2008
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2008, p. 1396 1400 Vol. 52, No. 4 0066-4804/08/$08.00 0 doi:10.1128/aac.01512-07 Copyright 2008, American Society for Microbiology. All Rights Reserved. In Vitro
More informationUpdate zu EUCAST 2012 Cornelia Lass-Flörl
Update zu EUCAST 2012 Cornelia Lass-Flörl Frühjahrstagung 2012 Paul-Ehrlich-Gesellschaft Sektion Antimykotische Chemotherapie Bonn, 4./5. Mai 2012 Agenda 1. Breakpoints 2. Rationale documents and technical
More information2046: Fungal Infection Pre-Infusion Data
2046: Fungal Infection Pre-Infusion Data Fungal infections are significant opportunistic infections affecting transplant patients. Because these infections are quite serious, it is important to collect
More informationAntifungal Pharmacodynamics A Strategy to Optimize Efficacy
Antifungal Pharmacodynamics A Strategy to Optimize Efficacy David Andes, MD Associate Professor, Department of Medicine Division of Infectious Diseases Medical Microbiology and Immunology University of
More informationConventional or molecular measurement of Aspergillus load. Dr Karl Clemons California Institute for Medical Research
Conventional or molecular measurement of Aspergillus load Dr Karl Clemons California Institute for Medical Research Everyone quantifies burdens or numbers of organisms, so what s the big deal?? Why does
More informationClinical relevance of resistance in Aspergillus. David W. Denning University Hospital of South Manchester [Wythenshawe Hospital]
Clinical relevance of resistance in Aspergillus David W. Denning University Hospital of South Manchester [Wythenshawe Hospital] The University of Manchester Steps to establishing clinical validity of resistance/susceptibility
More informationUse of Antifungals in the Year 2008
Use of Antifungals in the Year 2008 Jose G. Montoya, MD Associate Professor of Medicine Associate Chief for Clinical Affairs Division of Infectious Diseases Stanford University School of Medicine Diagnosis
More informationAspergillosis in the critically ill patient
Aspergillosis in the critically ill patient José Artur Paiva Director of Emergency and Intensive Care Department Centro Hospitalar São João Porto Associate Professor of Medicine University of Porto Infection
More informationFungal Infection Pre-Infusion Data
Fungal Infection Pre-Infusion Data Registry Use Only Sequence Number: Date Received: CIBMTR Center Number: Event date: / / CIBMTR Form 2046 revision 5 (page 1 of 5). Last Updated May, 2018. Infection Episode
More informationAn Evaluation of Galleria mellonella as a Model for Aspergillus ustus Infections
An Evaluation of Galleria mellonella as a Model for Aspergillus ustus Infections Isak Jatoi Spring Valley High School Invasive aspergillosis is a serious cause of mortality and morbidity in immunocompromised
More informationAntifungal Susceptibility Testing
Infect Dis Clin N Am 20 (2006) 699 709 Antifungal Susceptibility Testing Annette W. Fothergill, MA, MBA, MT(ASCP), CLS(NCA) a, Michael G. Rinaldi, PhD a,b, Deanna A. Sutton, PhD, MT, SM(ASCP), SM, RM(NRM)
More informationCommon Fungi. Catherine Diamond MD MPH
Common Fungi Catherine Diamond MD MPH Birth Month and Day & Last Four Digits of Your Cell Phone # BEFORE: http://tinyurl.com/kvfy3ts AFTER: http://tinyurl.com/lc4dzwr Clinically Common Fungi Yeast Mold
More informationFungi GUIDE TO INFECTION CONTROL IN THE HOSPITAL CHAPTER NUMBER 53: Author Moi Lin Ling, MBBS, FRCPA, CPHQ, MBA
GUIDE TO INFECTION CONTROL IN THE HOSPITAL CHAPTER NUMBER 53: Fungi Author Moi Lin Ling, MBBS, FRCPA, CPHQ, MBA Chapter Editor Ziad A. Memish, MD, FRCPC, FACP Cover heading - Topic Outline Topic outline
More informationBiomarkers for the diagnosis of emerging invasive fungal infections :
Biomarkers for the diagnosis of emerging invasive fungal infections : Challenges, Perspectives Example of Mucorales infections Laurence Millon Parasitologie-Mycologie, CHU Besançon UMR CNRS 3249 Chrono
More informationEpidemiology and Resistance in Aspergillus and other Moulds
Epidemiology and Resistance in Aspergillus and other Moulds Nathan Wiederhold, PharmD Associate Professor Director, Fungus Testing Laboratory Invasive Mould Infections Often opportunistic Associated with
More informationECMM Excellence Centers Quality Audit
ECMM Excellence Centers Quality Audit Person in charge: Department: Head of Department: Laboratory is accredited according to ISO 15189 (Medical Laboratories Requirements for quality and competence) Inspected
More informationManagement Strategies For Invasive Mycoses: An MD Anderson Perspective
Management Strategies For Invasive Mycoses: An MD Anderson Perspective Dimitrios P. Kontoyiannis, MD, ScD, FACP, FIDSA Professor of Medicine Director of Mycology Research Program M. D. Anderson Cancer
More informationHow Can We Prevent Invasive Fungal Disease?
How Can We Prevent Invasive Fungal Disease? Chris Kibbler Professor of Medical Microbiology University College London And Royal Free Hospital, London, UK Invasive Aspergillosis 2 - Acquisition Preventive
More informationMANAGEMENT OF HOSPITAL-ACQUIRED FUNGAL INFECTIONS
MANAGEMENT OF HOSPITAL-ACQUIRED FUNGAL INFECTIONS Paul D. Holtom, MD Associate Professor of Medicine and Orthopaedics USC Keck School of Medicine Numbers of Cases of Sepsis in the United States, According
More informationResearch priorities in medical mycology
Research priorities in medical mycology David W. Denning National Aspergillosis Centre University Hospital of South Manchester The University of Manchester Agenda How many patients are there with serious
More informationProphylaxis versus Diagnostics-driven approaches to treatment of Invasive fungal diseases. Y.L. Kwong Department of Medicine University of Hong Kong
Prophylaxis versus Diagnostics-driven approaches to treatment of Invasive fungal diseases Y.L. Kwong Department of Medicine University of Hong Kong Pathogenic yeast Candida Cryptococcus Trichosporon Pathogenic
More informationAntifungal Agents - Cresemba (isavuconazonium), Vfend. Prior Authorization Program Summary
Antifungal Agents - Cresemba (isavuconazonium), Noxafil (posaconazole), Vfend (voriconazole) Prior Authorization Program Summary FDA APPROVED INDICATIONS DOSAGE 1,2,14 Drug FDA Indication(s) Dosing Cresemba
More informationHistopathology Description:
2013-2-1 CANINE HEART Ahmed M. Abubakar BOVINE PATHOLOGY CONTRIBUTING INSTITUTION : The Royal Veterinary college, Dept. of Pathology and Biology Signalment: 11-month-old male Border Collie dog (Canis familiaris)
More informationWHICH ANTIFUNGAL AGENT IS THE CHOICE FOR SUSPECTED FUNGAL INFECTIONS?
WHICH ANTIFUNGAL AGENT IS THE CHOICE FOR SUSPECTED FUNGAL INFECTIONS? Assoc. Prof. Dr. Serkan SENER Acibadem University Medical School Department of Emergency Medicine, Istanbul Acibadem Ankara Hospital,
More informationInvasive Fungal Infections in Solid Organ Transplant Recipients
Outlines Epidemiology Candidiasis Aspergillosis Invasive Fungal Infections in Solid Organ Transplant Recipients Hsin-Yun Sun, M.D. Division of Infectious Diseases Department of Internal Medicine National
More informationIn Vitro Interactions of Antifungal agents and Tacrolimus against Aspergillus Biofilms
AAC Accepted Manuscript Posted Online 24 August 2015 Antimicrob. Agents Chemother. doi:10.1128/aac.01510-15 Copyright 2015, American Society for Microbiology. All Rights Reserved. 1 In Vitro Interactions
More informationSummary of the risk management plan (RMP) for Cresemba (isavuconazole)
EMA/576866/2015 Summary of the risk management plan (RMP) for Cresemba (isavuconazole) This is a summary of the risk management plan (RMP) for Cresemba, which details the measures to be taken in order
More informationTEPZZ Z9Z74_A_T EP A1 (19) (11) EP A1 (12) EUROPEAN PATENT APPLICATION
(19) TEPZZ Z9Z74_A_T (11) EP 3 090 741 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: 09.11.2016 Bulletin 2016/4 (21) Application number: 1642039.1 (1) Int Cl.: A61K 31/203 (2006.01) A61K
More informationUpdate from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance 13
Fungal Infections Preface: Fungal Infections Luis Ostrosky-Zeichner and Jack D. Sobel xiii The Global Burden of Fungal Diseases 1 Snigdha Vallabhaneni, Rajal K. Mody, Tiffany Walker, and Tom Chiller Fungal
More informationAntifungal Susceptibility of Aspergillus Isolates from the Respiratory Tract of Patients in Canadian Hospitals: Results of the CANWARD 2016 Study.
1 Antifungal Susceptibility of Aspergillus Isolates from the Respiratory Tract of Patients in Canadian Hospitals: Results of the CANWARD 2016 Study. J. FULLER 1,3, A. BULL 2, S. SHOKOPLES 2, T.C. DINGLE
More informationHistory of Aspergillus. History of Aspergillus. Biology of Aspergillus flavus Fungus Saphrophyte Haploid filamentous fungi Mycelium secrets enzymes
Anthony Fossaceca Anthony Nuzzi Swati Vasireddy History of Aspergillus Pier Antonio Micheli Italian priest and Biologist Discovered the fungi in 1729 Structure Aspergillum (holy water sprinkler) Hence
More informationPathogenesis of ocular fungal Infections. Dr Lalitha Prajna. MD. Department of Ocular Microbiology, Aravind Eye Hospital, Madurai. Tamil Nadu.
Pathogenesis of ocular fungal Infections Dr Lalitha Prajna. MD. Department of Ocular Microbiology, Aravind Eye Hospital, Madurai. Tamil Nadu. Introduction Fungal infections of the eye are rare ( exception:
More informationEUCAST-AFST Available breakpoints 2012
EUCAST-AFST Available breakpoints th NSMM meeting Göteborg, Sweden October th EUCAST-AFST documents Reference Methods Yeast E.DEF. () TN- E.DEF. (CMI epub July) E.DEF. () TN- E.DEF. () Breakpoints Compound
More informationIn vitro cross-resistance between azoles in Aspergillus fumigatus: a reason for concern in the clinic?
4 th Congress on Trends in Medical Mycology (TIMM) In vitro cross-resistance between azoles in Aspergillus fumigatus: a reason for concern in the clinic? Emilia Mellado Mycolgy Reference Laboratory Centro
More informationFungal Infection Post-Infusion Data
Fungal Infection Post-Infusion Data Registry Use Only Sequence Number: Date Received: CIBMTR Center Number: Event date: / / Visit: 100 day 6 months 1 year 2 years >2 years. Specify: CIBMTR Form 2146 revision
More informationStaphylococci. Gram stain: gram positive cocci arranged in clusters.
Microbiology lab Respiratory system Third medical year Lab contents: Gram positive bacteria (Staphylococcus and Streptococcus spp), two types of filamentous fungi (Aspergillus and Penicillium spp), and
More informationCorrelation of culture with histopathology in fungal burn wound colonization and infection
burns 33 (2007) 341 346 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/burns Correlation of culture with histopathology in fungal burn wound colonization and infection Christina
More informationFungal infection in the immunocompromised patient. Dr Kirsty Dodgson
Fungal infection in the immunocompromised patient Dr Kirsty Dodgson Aims Discuss different types of fungi Overview of types of clinical infections Clinical Manifestations Fungus Includes Moulds Aspergillus
More informationTailored Antifungal Modification in Breakthrough Mold Infections. Russell E. Lewis University of Bologna
Tailored Antifungal Modification in Breakthrough Mold Infections Russell E. Lewis University of Bologna 45 year-old patient with AML and documented pulmonary aspergillosis during remissioninduction chemotherapy
More informationOral Candida biofilm model and Candida Staph interactions
Oral Candida biofilm model and Candida Staph interactions Mark Shirtliff, PhD Associate Professor Department of Microbial Pathogenesis, School of Dentistry Department of Microbiology and Immunology, School
More informationEpidemiology and ecology of fungal diseases
Epidemiology and ecology of fungal diseases Healthcare Focus on: - individual - diagnosis - treatment Public Health Focus on: - population - prevention The nature of fungi Kingdom Fungi (lat. fungus, -i)
More informationThe incidence of invasive fungal infections
AN EPIDEMIOLOGIC UPDATE ON INVASIVE FUNGAL INFECTIONS * Michael A. Pfaller, MD ABSTRACT *Based on a presentation given by Dr Pfaller at a symposium held in conjunction with the 43rd Interscience Conference
More informationISHAM Symposium: S33: Ocular aspects of Fungal Infections Friday, 8 May 2015, ; MR101/102 Level 1
ISHAM Symposium: S33: Ocular aspects of Fungal Infections Friday, 8 May 2015, 14.15 15.45; MR101/102 Level 1 Chairs: Ariya Chindamporn, TH and Phillip A Thomas, IN 14:15-14:35 AGENDA Clinical overview
More informationTOWARDS PRE-EMPTIVE? TRADITIONAL DIAGNOSIS. GALACTOMANNAN Sensitivity 61% Specificity 93% Neg Predict Value >95% β-d-glucan Neg Predict Value 100% PCR
TOWARDS PRE-EMPTIVE? GALACTOMANNAN Sensitivity 61% Specificity 93% Neg Predict Value >95% TRADITIONAL DIAGNOSIS β-d-glucan Neg Predict Value 100% PCR diagnostics FUNGAL BURDEN FIRST TEST POSITIVE FOR ASPERGILLOSIS
More informationPROGRESSI NELLA TERAPIA ANTIFUNGINA. A tribute to Piero Martino
PROGRESSI NELLA TERAPIA ANTIFUNGINA A tribute to Piero Martino 1946-2007 ITALIAN ICONS IERI, OGGI, E DOMANI IERI, OGGI, E DOMANI IERI, OGGI, E DOMANI 1961 CAUSES OF DEATH IN PATIENTS WITH MALIGNANCIES
More informationWelcome to the 8 th Advances Against Aspergillosis international conference
Welcome to the 8 th Advances Against Aspergillosis international conference Introduction and summary of global disease burden David W. Denning National Aspergillosis Centre Wythenshawe Hospital The University
More informationChallenges and controversies of Invasive fungal Infections
Challenges and controversies of Invasive fungal Infections Mona Al-Dabbagh, MD, MHSc Assistant Professor of Pediatrics, COM-KSAU-HS Consultant Pediatric Infectious Diseases and Transplant Infectious Diseases
More informationFactors influencing the Aspergillus fumigatus survival into the host mediated by the calcineurin pathway
Factors influencing the Aspergillus fumigatus survival into the host mediated by the calcineurin pathway Gustavo H. Goldman Universidade de São Paulo, Brazil Calcineurin is a calmodulin/ca +2 dependent
More informationNijmegen Institute for Infection, Inflammation and Immunity (N4i) 2, Nijmegen, the. and Hematology 4, University Medical Center
JCM Accepts, published online ahead of print on January 0 J. Clin. Microbiol. doi:./jcm.01-0 Copyright 0, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
More informationAntifungal Pharmacotherapy
Interpreting Antifungal Susceptibility Testing: Science or Smoke and Mirrors A. W. F O T H E R G I L L, M A, M B A U N I V E R S I T Y O F T E X A S H E A L T H S C I E N C E C E N T E R S A N A N T O
More informationInvasive Pulmonary Aspergillosis in
Infection & Sepsis Symposium Porto, April 1-3, 2009 Invasive Pulmonary Aspergillosis in Non-Immunocompromised Patients Stijn BLOT, PhD General Internal Medicine & Infectious Diseases Ghent University Hospital,
More informationHow to make a fast diagnosis
How to make a fast diagnosis 8 th Advances Against Aspergillosis 1 3 February 2018 Lisbon, Portugal Cornelia Lass-Flörl Division of Hygiene and Medical Microbiology Innsbruck Medical University Division
More informationRole of iron in invasive fungal infections
Role of iron in invasive fungal infections Günter Weiss Department of Internal Medicine Clinical Immunology and Infectious Diseases Medical University of Innsbruck, Austria Iron at the host-pathogen-interface
More informationInvasive Aspergillosis in Steroid-Treated Patients
Invasive Aspergillosis in Steroid-Treated Patients Dimitrios P. Kontoyiannis, MD, ScD Professor of Medicine Department of Infectious Diseases Infection Control and Employee Health PMN damaging Aspergillus
More informationTable 1. Antifungal Breakpoints for Candida. 2,3. Agent S SDD or I R. Fluconazole < 8.0 mg/ml mg/ml. > 64 mg/ml.
AUSTRALIAN ANTIFUNGAL SUSCEPTIBILITY DATA 2008-2011 Part 1: The Yeasts In this article, an update of recent changes to the CLSI antifungal standards for susceptibility testing of yeasts is presented. We
More informationMonitorization, Separation and Quantification of Antifungals used for Invasive Aspergillosis Treatment by High Performance Thin Layer Chromatography
Monitorization, Separation and Quantification of Antifungals used for Invasive Aspergillosis Treatment by High Performance Thin Layer Chromatography M. P. Domingo, M. Vidal, J. Pardo, A. Rezusta, L. Roc,
More informationInvasive Aspergillosis in India: Unique Challenges. Dr Rajeev Soman Consultant Physician PD Hinduja Hospital Mumbai
Invasive Aspergillosis in India: Unique Challenges Dr Rajeev Soman Consultant Physician PD Hinduja Hospital Mumbai Aspergillus Challenges Capable of surviving & thriving in all the diverse environmental
More informationVoriconazole Rationale for the EUCAST clinical breakpoints, version March 2010
Voriconazole Rationale for the EUCAST clinical breakpoints, version 2.0 20 March 2010 Foreword EUCAST The European Committee on Antimicrobial Susceptibility Testing (EUCAST) is organised by the European
More informationInvasive aspergillosis (IA) has emerged as a major cause of morbidity. Aspergillus terreus
1594 Aspergillus terreus An Emerging Amphotericin B Resistant Opportunistic Mold in Patients with Hematologic Malignancies Ray Y. Hachem, M.D. 1 Dimitrios P. Kontoyiannis, M.D., Sc.D. 1 Maha R. Boktour,
More informationInvasive sino-orbital mycosis in an aplastic anemia patient caused by Neosartorya laciniosa
JCM Accepts, published online ahead of print on 23 January 2013 J. Clin. Microbiol. doi:10.1128/jcm.02919-12 Copyright 2013, American Society for Microbiology. All Rights Reserved. 1 1 Invasive sino-orbital
More informationStudy of systemic fungal infections in renal transplant recipients
Original Research Article Study of systemic fungal infections in renal transplant recipients N.D. Srinivasaprasad 1*, G. Chandramohan 1, M. Edwin Fernando 2 1 DM (Nephrology), Assistant Professor, 2 DM
More informationArchives of Infect Diseases & Therapy, 2017
Research Article Archives of Infectious Diseases & Therapy Antifungal sensitivity profile of Fusarium spp. resulting keratitits LSM Sigera 1, PI Jayasekera 1, ULF Shabry 1 and MAI Malkanthi 1 1 Dept. of
More informationAspergillus species. The clinical spectrum of pulmonary aspergillosis
Pentalfa 3 maart 2016 The clinical spectrum of pulmonary aspergillosis Pascal Van Bleyenbergh, Pneumologie UZ Leuven Aspergillus species First described in 1729 * >250 species * ubiquitous Inhalation of
More informationCURRENT AND NEWER ANTI-FUNGAL THERAPIES- MECHANISMS, INDICATIONS, LIMITATIONS AND PROBLEMS. Dr AMIT RAODEO DM SEMINAR
CURRENT AND NEWER ANTI-FUNGAL THERAPIES- MECHANISMS, INDICATIONS, LIMITATIONS AND PROBLEMS Dr AMIT RAODEO DM SEMINAR Introduction The incidence of invasive fungal infections in critically ill intensive
More informationNon-commercial use only
Italian Journal of Medicine 2017; volume 11:52-56 Assessment of indoor and outdoor airborne fungi in an Educational, Research and Treatment Center Nasrin Rostami, 1 Hossien Alidadi, 2 Hossein Zarrinfar,
More informationESCMID Online Lecture Library. by author. Salvage Therapy of Invasive Aspergillosis Refractory to Primary Treatment with Voriconazole
Salvage Therapy of Invasive Aspergillosis Refractory to Primary Treatment with Voriconazole J.A. Maertens, hematologist, MD, PhD University Hospital Gasthuisberg Leuven, Belgium Current guidelines: first-line
More informationon November 3, 2018 by guest
JOURNAL OF CLINICAL MICROBIOLOGY, June 2007, p. 1811 1820 Vol. 45, No. 6 0095-1137/07/$08.00 0 doi:10.1128/jcm.00134-07 Copyright 2007, American Society for Microbiology. All Rights Reserved. Multicenter
More informationnumber Done by Corrected by Doctor د.حامد الزعبي
number Fungi#1 Done by نرجس الس ماك Corrected by مهدي الشعراوي Doctor د.حامد الزعبي Introduction to Mycology -Terms: -Medical Mycology: The study of mycosis and their etiological agents -Mycosis: Disease
More informationVoriconazole October 2015 Risk Management Plan. Voriconazole
Voriconazole October 2015 VI.2 VI.2.1 Elements for a Public Summary Overview of disease epidemiology Invasive aspergillosis (IA) is the most devastating of Aspergillus related diseases, targeting severely
More information, Aspergillus A. terreus. 4 Candida albicans. 2 Otomycosis. , Histoplasmosis Paracoccidiomycosis
Jpn. J. Med. Mycol. Vol. 44, 277 283, 2003 ISSN 0916 4804 1 2 2 1 2, Aspergillus A. terreus, A. flavus, A. niger, Candida,. A. terreus,, CT, fungus ball, drainage,, Key words: otolaryngologic mycosis,
More informationOPPORTUNISTIC MYCOSES
OPPORTUNISTIC MYCOSES Candida yeasts that is, fungi that exist predominantly in a unicellular form. small (4-6 µm), thin-walled, ovoid cells (blastospores) that reproduce by budding. do not require special
More informationManagement of fungal infection
Management of fungal infection HKDU symposium 17 th May 2015 Speaker: Dr. Thomas Chan MBBS (Hons), MRCP, FHKCP, FHKAM Synopsis Infection caused by fungus mycoses Skin infection by fungus is common in general
More informationDiagnosis,Therapy and Prophylaxis of Fungal Diseases
mycoses Diagnosis,Therapy and Prophylaxis of Fungal Diseases Original article Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year
More informationAbout the Editor Gerri S. Hall, Ph.D.
About the Editor Gerri S. Hall, Ph.D. Dr. Hall s professional career has been focused on clinical microbiology: direct clinical activities of various areas such as bacteriology, mycobacteria, STD testing,
More informationTrends in Invasive Fungal Infection (IFI) in Haematology-Oncology Patients. Saturday, April 18, 2015 Charlottetown, P.E.I.
Trends in Invasive Fungal Infection (IFI) in Haematology-Oncology Patients Saturday, April 18, 2015 Charlottetown, P.E.I. Moderator & Speaker: Shariq Haider MD, FRCPC, FACP, CCST(UK), DTMH(UK) Professor
More informationDimitrios P. Kontoyiannis, MD, ScD. Frances King Black Endowed Professor
Dimitrios P. Kontoyiannis, MD, ScD Frances King Black Endowed Professor Disclosures Research support from Merck, Pfizer and Astellas and has served as speaker for Gilead/Merck, Mylan, Inc and as consultant
More informationActivity of Posaconazole Combined with Amphotericin B against Aspergillus flavus Infection in Mice: Comparative Studies in Two Laboratories
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2004, p. 758 764 Vol. 48, No. 3 0066-4804/04/$08.00 0 DOI: 10.1128/AAC.48.3.758 764.2004 Copyright 2004, American Society for Microbiology. All Rights Reserved.
More informationCandida auris - an update on a globally emerging pathogen
Candida auris - an update on a globally emerging pathogen Dr Elizabeth M. Johnson Public Health England Mycology Reference Laboratory Bristol Scottish Microbiology and Virology Network Meeting 2017 Disclosures
More informationSelecting an Invertebrate Model Host for the Study of Fungal Pathogenesis
Selecting an Invertebrate Model Host for the Study of Fungal Pathogenesis The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation
More informationWertigkeit der Diagnostik von Pilzinfektionen an der Intensivstation
Wertigkeit der Diagnostik von Pilzinfektionen an der Intensivstation Cornelia Lass-Flörl Division für Hygiene und medizinische Mikrobiologie MUI Innsbruck Key message... 1. Surveillance-Kulturen spielen
More informationFungal infections in ICU. Tang Swee Fong Department of Paediatrics Universiti Kebangsaan Malaysia
Fungal infections in ICU Tang Swee Fong Department of Paediatrics Universiti Kebangsaan Malaysia Epidemiology of invasive fungal infections - US +300% Martin GS, et al. N Engl J Med 2003;348:1546-1554
More informationAntifungal susceptibility testing: Which method and when?
Antifungal susceptibility testing: Which method and when? Maiken Cavling Arendrup mad@ssi.dk SSI & Juan Luis Rodriguez Tudela jlrtudela@isciii.es ISCIII Agenda Summary of current standards and selected
More informationDepartment of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
ORIGINAL ARTICLE 10.1111/j.1469-0691.2006.01471.x Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review P. R. Kumashi, A. Safdar, G. Chamilos,
More informationTherapy of Hematologic Malignancies Period at high risk of IFI
Therapy of Hematologic Malignancies Period at high risk of IFI Neutrophils (/mm 3 ) 5 Chemotherapy Conditioning Regimen HSCT Engraftment GVHD + Immunosuppressive Treatment Cutaneous and mucositis : - Direct
More informationAntifungal Resistance in Asia: Mechanisms, Epidemiology, and Consequences
5th MMTN Conference 5-6 November 2016 Bangkok, Thailand 10:20-10:45, 6 Nov, 2016 Antifungal Resistance in Asia: Mechanisms, Epidemiology, and Consequences Yee-Chun Chen, M.D., PhD. Department of Medicine,
More information1. Pre-emptive therapy. colonization, colonization, pre-emptive therapy. , ICU colonization. colonization. 2, C. albicans
Jpn. J. Med. Mycol. Vol. 45, 217 221, 2004 ISSN 0916 4804,.,, colonization, pre-emptive therapy. 2, non-albicans Candida., fluconazole.,. Key words: postoperative infection, non-albicans Candida, pre-emptive
More informationSCY-078 ECMM Symposium Cologne, Germany October 2017
A New Path for Antifungal Treatments SCY-078 ECMM Symposium Cologne, Germany October 2017 David Angulo, M.D. Chief Medical Officer SCYNEXIS at a Glance Company created in 2000 Spin-off of Sanofi, initially
More informationAspergillosis in Pediatric Patients
Aspergillosis in Pediatric Patients Emmanuel Roilides, MD, PhD, FIDSA, FAAM 3rd Department of Pediatrics Aristotle University School of Medicine Thessaloniki, Greece 1 Transparency disclosures Independent
More informationReceived 18 December 2008/Returned for modification 9 February 2009/Accepted 9 April 2009
JOURNAL OF CLINICAL MICROBIOLOGY, June 2009, p. 1942 1946 Vol. 47, No. 6 0095-1137/09/$08.00 0 doi:10.1128/jcm.02434-08 Copyright 2009, American Society for Microbiology. All Rights Reserved. Activity
More information