23rd eccmid, 27-30 apr 2013 - berlin

Prof. Sevtap Arikan-Akdagli, MD Hacettepe University Medical School

Department of Medical Microbiology Ankara Turkey

www.flickr.com

23rd ECCMID, 27-30 Apr 2013 - Berlin

ESCMID Online Lecture Library

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Background information & moulds as causative agents of infections Diversity of epidemiology per the risk factor HSCT & hematological malignancies Organ tx ICU Mould infections : (Changing ?) epidemiology, reported outbreaks,

and in vitro susceptibility Aspergillosis Mucormycosis Fusariosis Scedosporiosis Other emerging mould infections in high risk patients Conclusions

Agenda


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Dermatophytes & dermatophytosis


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Epidemiology of dermatophytosis

• Among the most frequent human infections • Affects > 20-25% of world’s population • Increase in incidence • Geographical variations- Homogeneous

distribution vs. geographical restriction for some species

• Changes in epidemiology overtime (migrations, life style, socioeconomics, comorbidities)

Havlickova et al. Mycoses 2008; 51(Suppl. 4): 2; Ameen et al. Clin Dermatol 2010; 28: 197


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Italy

Gradual decrease in frequency:

Tinea cruris

Italy

Tinea corporis

Tinea capitis

Progressive increase in frequency:

Tinea unguium

Tinea pedis

Increase in isolation:

T. rubrum

Progressive decrease in isolation :

T. violaceum M. canis

E. floccosum


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Epidemiology of IFIs: General Perspective

• Geographical and temporal variability • Local epidemiological trends

• Changes in incidence and the infecting species in the last two decades

• Changes in antifungal susceptibility profiles • Poor outcome

Montagna et al. Infection 2013; March 6 Epub


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Median excess cost of 15 509 US $, Prolonged length of stay of 13 days,

All-cause inpatient mortality 38x higher

for the scedosporiosis cases as compared to control patients with comparable underlying hematologic disorders


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Transplantation Cancer

Opportunistic IFIs: THE HOST and the associated risk factors

Immunosupressed Debilitated, postoperative

Severely-ill

Bille et al. Curr Opin Infect Dis 2005; 18: 314

ICU


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Major changes in IFIs in the last decades

- More mucosal and invasive fungal infections - Infections due to more resistant species and strains - Infections due to uncommon genera and species - More antifungal drugs in clinical practice

Groll et al. J Infect 1996;33:23 Marr et al. Clin Infect Dis 2002;34:909

Fridkin and Jarvis. Clin Microbiol Rev 1996;9:499 Montagna et al. Infection 2013; March 6 Epub


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Emerged and/or Newly recognized

Altered hosts Fungi

Selective antifungal pressure

Changes in environmental

conditions

Emerging fungal infection

Walsh TJ, Groll AH. Transpl Infect Dis 1999;1:247

More isolates belonging to "uncommon" genera & species


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Opportunistic IFI: Causative agents

CANDIDA

ASPERGILLUS

OTHERS Mucormycetes C. neoformans

Fusarium Scedosporium Dematiaceous moulds............... ESCMID Online Lectu

re Library

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1985

1990

1995

2000s

Trichosporon

Fusarium Mucormycetes P. marneffei

C. immitis

Azole-R C. albicans

Non-albicans Candida

Acremonium Paecilomyces

Trichoderma

Scopulariopsis

Malassezia

B. capitatus

Hansenula

Walsh & Groll . Transpl Infect Dis 1999;1:247; Walsh et al. Clin Microbiol Infect 2004;10:48; Alastruey-Izquierdo et al. ICAAC 2012; abst. No. M-321

Emerging fungal pathogens in immunocompromised patients

Emergence and awareness of resistant Aspergillus

………


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Search of:

Worldwide Database for

nosocomial outbreaks

&

PubMed-Medline

Reports: 16 (Yeasts) 7 (Mucormycosis) 2 (Hyalohyphomycosis – Acremonium –Fusarium) 2 (Phaeohyphomycosis - Curvularia-Exophiala) 2 Dermatophytosis (Microsporum) 5 (pneumocystosis) Common genera (Candida, Aspergillus) excluded

OUTBREAK: >2 more nosocomial unusual fungal inf.s diagnosed in a short period ESCMID Online Lectu

re Library

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Supported by unrestricted grants from Astellas Pharma, Merck/MSD, Gilead Sciences, Pfizer

Culture Banking: G. Fischer, A. Hamprecht Molecular Biology: S. De Hoog Pharmacokinetics: C. Mueller, F. Farowski

Chair: O.A. Cornely Coordination: M.J.G.T. Vehreschild, K. Wahlers Clinicalsurveys.net: J.J. Vehreschild Documentation: S. Proske

ISHAM and ECMM Working Group www.fungiscope.net

GOALS: Collect epidemiological & clinical data

Develop an evidence-based approach for diagnosis

and treatment of IFIs due to emerging fungi

Courtesy of Prof. Oliver Cornely

Vehreschild et al. ICAAC 2012, abst. no. M-338


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Web-based electronic case form for registry Collection of clinical data & infecting strains



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March 2013: 328 valid cases



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LIFE- Leading International Fungal Education) “LIFE is a growing organisation. Leading International Fungal Infection (LIFE) has grown from the 20 year old charity the Fungal Research Trust and is dedicated to improving health in those with fungal disease (infection and allergy). The overall goal is to greatly improve fungal infection outcomes in patients through awareness, improved diagnosis and access to appropriate antifungal therapies, worldwide.” Leaded by: Prof. David Denning

www.life-worldwide.org

27 April 2013 15:30-16:30 - -POSTER SESSION “Globe trotting: The burden of serious fungal infections”

P1034 – P1045 (in association with the LIFE program)

23rd ECCMID 2013-Berlin

PUBLICATION ONLY “Fungal Infections”

R2855, R2873 (in association with the LIFE program) ESCMID Online Lectu

re Library

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Agenda


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Fig. 2. Timing of invasive fungal infections in allogeneic stem-cell transplant recipients. Reprinted with permission (Warnock David, 2003, personalcommunication).

Maschmeyer G. Int J Antimicrob Agents 27S (2006): S3

Allogeneic HSCT - - Timing of IFI with respect to the infecting mould

HSCT


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Marr et al. CID 2002; 34: 909

Timing of IFI for non-Aspergillus moulds HSCT


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Cohort-retrospective study

Years: 1999-2003

3228 cases of HSCT

(1249 allo, 1979 oto) General IFI incidence: 3.7%

Infecting fungi: Aspergillus (86 episodes)

Candida (30 episodes)

7.8% of the episodes in cases of allo HSCT

1.2% o f the episodes in cases of auto HSCT

Pagano et al. CID 2007: 45: 1161

Incidence of IA

SEIFEMB-2004 Study

HSCT

Italy

11 Transplantation Units


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983 IFIs among 875 HSCT recipients

HSCT

IA: 43 % IC: 28% Mucormycosis: 8%

One-year cumulative incidences based on the first IFI: 7.7 cases / 100 tx (matched unrelated allogeneic) 8.1 cases / 100 tx (mismatched-related allogeneic) 5.8 cases / 100 tx (matched-related allogeneic) 1.2 cases / 100 tx (autologous HSCT)


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TRANSNET: Cumulative incidence for each IFI

HSCT

Highest for aspergillosis Followed by candidiasis

Non-Asp Non-Muc


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Neofytos et al. Transplant Infect Dis 2010

SOT Which fungus for which SOT?


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SOT

1208 IFIs among 1063 organ tx recipients IC: 53 % IA: 19% Cryptococcosis: 8% Non-Asp moulds: 8%

Endemic fungi: 5% Mucormycosis: 2%

One-year cumulative incidences per each tx type and based on the first IFI:

11.6% (Small bowel tx) 8.6% (Lung tx) 4.7% (Liver tx) 4% (Heart tx) 3.4% (Pancreas tx) 1.3% (Kidney tx)

March 2001-March 2006


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TRANSNET: Cumulative incidence for each IFI

SOT

6 and 12 months after tx.

Non-ASP


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SOT

Slight increase in cumulative incidence of IFI in general from 2002 to 2005 Incidence of IA remains unchanged

TRANSNET


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Shoham et al. J Intensive Care Med Dec 1, 2009

Risk factors and infecting fungi ICU


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IA

17-26% in lung tx recipients

5-24% in acute leukemia patients

5-15 % in allogenic bone marrow tx patients

2-13 % in heart tx recipients

1-3 % in lymphoma patients

Patterson et al. Transpl Infect Dis 2000; 2: 22; Kontoyiannis & Bodey. Eur J Clin Microbiol Infect Dis 2002; 21: 161; Meersseman et al. CID 2007; 45: 205

(Leuven,Belgium-Univ. Hosp.)

5.8% in Medical ICU

(COPD, liver failure)

Incidence of IA in ICU ICU


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AURORA Project Southern Italy 18 ICUs

(observational study) Febr 2007-Aug 2008

Montagna et al. Infection 2013; March 6 Epub

12.4%

12 Asp 1 Scedo

2.3 cases / 1000 admissions Mortality: 61.5%

ICU


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Agenda


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ICAAC 2012, San Francisco Abst. no. M-321 Population-Based Program of Aspergillus spp. Antifungal Resistance in Spain (FILPOP STUDY)

Seven

Spanish Hospitals Freq. of antifungal resistance in two different periods:

Oct 2010 May 2011

Aspergillus strains isolated

from resp. samples,

paranasal sinus aspirates, blood

cultures, and biopsies

277 strains isolated:

EUCAST method and

brkpt.s

% Species

56% A. fumigatus sensu stricto

9% A. flavus

9% A. terreus

8% A. tubingensis

7.5% A. niger

3% A. nidulans

7.5% Other species

Alastruey-Izquierdo et al.


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Lass-Flörl et al. Mycoses 2009; 52: 197

Incidence of aspergillosis in Europe


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3228 cases of HSCT

(1249 allo, 1979 oto)

Italy

11 Transplantation Units General IFI incidence: 3.7%

Infecting fungi: Aspergillus (86 episodes)

Candida (30 episodes)

7.8% of the episodes in cases of allo HSCT

1.2% o f the episodes in cases of auto HSCT

Pagano et al. CID 2007: 45: 1161

Incidence of IA

SEIFEMB-2004 Study

HSCT


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• July 2005 • Five previously

healthy women • Asp meningitis

following anesthesia for C/S

……..

Possibly due to suboptimal storage conditions during the 6-month period after the tsunami disaster

Sri Lanka


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Outbreak of fungal infection due to contaminated methylprednisolone injection

Multistate Outbreak of Fungal Infection Associated with Injection of Methylprednisolone Acetate Solution from a Single Compounding Pharmacy — United States, 2012 Weekly October 19, 2012 / 61(41);839-842

CDC

USA

14,000 persons potentially exposed to medications from at least one of the contaminated lots

Four categories of cases

following injection: 1. Fungal

meningitis 2. Basilar stroke

3. Spinal osteomyelitis or epidural abscess

at the site of injection

4. Septic arthritis or osteomyelitis

following injection of that

joint

Evidence of a fungal inf. in 26 (37%) cases (Culture, histopath. or PCR)

Fungal identification in 14 cases: Exserohilum spp. n=13 Aspergillus fumigatus n=1


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Nonimmunocompromised postoperative patients High A. fumigatus airborne conidia levels

Spain

Seven patients


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0

0,5

1

1,5

2

2,5

3

AMB Itra Vori Caspo

fumigatusflavusnidulansterreusustusniger

CLSI, 24 h Geo mean MIC (μg/ml) (MEC for Caspo)

Arikan et al. Antimicrob Agents Chemother 2001, 45: 327; Arikan et al. Antimicrob Agents Chemother 2002, 46: 3084; Arikan et al. J Clin Microbiol 1999, 37: 3946; Meletiadis et al. J Clin Microbiol 2002, 40: 2876; Kanj et al. Medicine 1996, 75: 142; Iwen et al. J Clin Microbiol 1998, 36: 3713; Denning et al. Antimicrob Agents

Chemother 1997, 41: 1364; Cuenca-Estrella et al. ICAAC 2012 San Francisco; M-321

Antifungal Susceptibility


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ICAAC 2012, San Francisco Abst. no. M-321 Population-Based Program of Aspergillus spp. Antifungal Resistance in Spain (FILPOP STUDY)

Seven

Spanish Hospitals Freq. of antifungal resistance in two different periods:

Oct 2010 May 2011

Resistance reported for: EUCAST

method and brkpt.s

Alastruey-Izquierdo et al.

Average prevalence of R: < 8%

Resistance rate in cryptic/sibling species: >50%

AMB resistance:

A. alliaceus A. fumigatiaffinis

A. insuetus A. westerdijikiae A. lentulus (66%) A. flavus (22%)

A. terreus (27%)

Azole resistance: Section Usti (all azoles)

A. lentulus (Itra, all isolates) A. fumigatiaffinis (Itra, all isolates)

A. tubingensis (Itra, one isolate) A. fumigatus (Posa, one isolate)


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Agenda


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Soil, decaying vegetation, manure, foodstuff..

INHALATION of the

aerosolized spores

Entry of spores through the

disrupted SKIN following

trauma/burn

INGESTION of contaminated

foodstuff

Renovation

Routes of entry –Order Mucorales


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Figure 2. Frequency of non-Aspergillus mould infections at Fred Hutchinson Cancer Research Center (Seattle). The number of patients who developed proven or probable infection with Fusarium species (), Zygomycetes (), and Scedosporium species () from 1985 through 1999 are shown.

Fusarium Zygomycetes

Scedosporium

Marr et al. CID 2002; 34: 909

Any increase in non-Aspergillus moulds?


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02468

101214161820

1989-1993 1994-1998

cases/100 000 admissions

Kontoyiannis et al. Clin Infect Dis 2000; 30:851

M.D. Anderson Cancer Center, Houston, TX

Underlying reason?

Any increase in incidence of mucormycosis?


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Imhof et al. Clin Infect Dis 2004,39:743

Chronic GVHD Prophylactic vori Histopathologic evidence

Vori for IA Histopathologic evidence

Chronic GVHD

Prophylactic vori Rhizopus microsporus

Vori for IA

Cunninghamella spp.

Acute GVHD

Vori for IA

Rhizopus arrhizus

Vori for inv fusariosis

Histopathologic evidence

Invasive Mucormycosis in HSCT Recipients Receiving Voriconazole

Siwek GT et al. Clin Infect Dis 2004;39:584

• Four cases of invasive mucormycosis (HSCT recipients)

• Receiving immunosuppressive therapy for presumed GVHD

• Receiving voriconazole prophylaxis

Marty FM et al. New Engl J Med 2004;350:950

• Four cases of invasive mucormycosis (HSCT recipients)

• Receiving immunosuppressive therapy for presumed GVHD

• Three receiving voriconazole prophylaxis

• One receiving empirical voriconazole therapy ESCMID Online Lectu

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13 European countries


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Maravi-Poma et al. Intensive Care Med. 2004;30:724; Linder et al. Am J Perinatol 1998;15:35; Mathews et al. J Med Vet Mycol. 1997;35:61; Mitchell et al. Lancet. 1996; 17:348:441; Patterson et al. Yale J Biol Med 1986; 59:453; Boyce et al. South

Med J 1981;74:1132; Mead et al. JAMA; 1979; 20: 242:272

o Contaminated wooden tongue depressors o Contaminated elastic bandages o Nonsterile wound dressings o Postsurgical

Gastric mucormycosis

Primary cutaneous mucormycosis

Necrotizing fasciitis

Nosocomial mucormycosis


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CONCLUSIONS: Wooden tongue depressors contaminated by R. microsporus var. rhizopodiformis used to prepare oral medications (to be given through a NG catheter) caused an outbreak of fungal gastritis with an attributable mortality of 40%.

12-bed ICU Gastric mucormycosis-an outbreak of 5 patients

(4 pneumonia, 1 polytrauma)


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May-September 2004 Burns Unit

Admission: 27 patients Burn wounds:

Infected with Absidia: 5 Colonized with Absidia: 2

(attack rate: 25.9/100)

Christiaens et al. J Hosp Infect 2005; 61: 88

Absidia corymbifera was cultured from a new brand of nonsterile elastoplast bandages which were in use for burns patients. ESCMID Online Lectu

re Library

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“Cutaneous zygomycosis following attempted radial artery cannulation” Kapadia & Polenakovik. Skinmed 2004; 3: 336

A 70-year-old man was seen in a hospital consultation for evaluation of cellulitis of the left arm. The patient had multiple medical problems, including advanced liver disease due to alcohol, diabetes mellitus, congestive heart failure, atrial fibrillation, chronic renal in sufficiency, and hypopituitarism requiring steroid replacement. Most recently, he was admitted to the intensive care unit, where he required intubation and mechanical ventilation support following respiratory failure secondary to pneumonia. At that time, an attempt was also made to place an arterial line in the left radial artery. A large bulla was found on the lateral aspect of the left wrist several days after the attempted arterial line placement. Subsequently, the lesion drained serosanguineous fluid, and, during the next 2 days, it ulcerated with necrosis extending around the wrist and to the elbow......Small tissue clippings were taken from the edge of the lesion and placed on culture plates. By the next morning, the patient's tissue culture grew a mold, later identified as Rhizopus.


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0

5

10

15

20

25

30

35

40

Rhizopus Mucor Absidia Rhizomucor Cunninghamella Apophysomyces

Itra

Posa

Vori

Terbi

AMB

Dannaoui et al. J Antimicrob Chemother 2003, 51: 45; Sun et al. Antimicrob Agents Chemother 2002, 46: 1581; Tawara et al. Antimicrob Agents Chemother 2000, 44: 57; Sun et al. Antimicrob Agents Chemother 2002, 46: 2310, Sancak et al. 3rd National Congress of Fungal Diseases and

Clinical Mycology, S-13, 378

CLSI 24 h, Geo mean MIC

Antifungal susceptibility


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AFST

Routine testing Not indicated Clinical relevance unknown In vitro-in vivo correlation?

R. oryzae & R. microsporus Posaconazole more effective in inf.s due to strains with MICs of 0.25 µg/ml as compared to those with MICs of 2 µg/ml

MIC

MFC High posaconazole MFC Clinical failure (R. oryzae , single strain)

CLSI M38-A2, EUCAST Def. Doc. E.Def 9.1, Rodriguez et al. AAC 2009; 53: 5022; Rodriguez et al. AAC 2010; 54: 1665, Spreghini et al. JAC 2010; 65: 2158

Mucorales


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Epidemiologic knowledge: Genus-, species-, & strain-based variations

AFST

Mucor Relatively high posaconazole

MICs

Rhizopus & Mucor Species-based

differences in azole susceptibility

Rhizopus oryzae Strain-based variations in posaconazole susceptibility

Sun et al. AAC 2002; 46: 1581; Dannaoui et al. JAC 2003; 51: 45; Almyroudis et al. AAC 2007; 51: 2587; Arikan et al. Med Mycol 2008; 46: 567; Rodriguez et al. AAC 2009; 53: 5022; Alastruey-Izuierdo et al. AAC 2009; 53: 1686; Pastor et al. AAC 2010; 54: 4550; Rodriguez et al. AAC 2010; 54: 1665; Vitale et al. JCM 2012; 50: 66;

Drogari-Apiranthitou et al. JAC 2012; 67: 1937

Cunninghamella Relatively high posaconazole

MICs (spec. for C. echinulata)

C. bertholletiae Posaconazole

MICs lower than AMB MICs

Mucorales


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Background information & moulds as causative agents of infections Diversity of epidemiology per the risk factor HSCT & hematological malignancies Organ tx ICU Mould infections : (Changing ?) epidemiology, reported outbreaks ,


Agenda


© by author

Italy Multicenter SEIFEM-2004 project

Hematological malignancy

Pagano et al. Hematologica 2006; 91: 1068

Fusarium infections - Incidence

234 HSCT rec.s 250 IFIs


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Fusarium infections - Incidence North America Multicenter PATH Project

HSCT

Neofytos et al. CID 2009; 48 (1 Febr): 265


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Girmenia et al.

Trends in epidemiology of fusariosis


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Risk factors for fusariosis


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Assessment of airborne mycoflora in critical areas of the Principal Hospital of Cumaná, state of Sucre, Venezuela [Article in Spanish] Centeno S, Machado S. Invest Clin. 2004 Jun;45(2):137-44.

Surveillance of nosocomial fungal infections in a burn care unit. Infection.

1992 May-Jun;20(3):132-5. India. Chakrabarti A, Nayak N, Kumar PS, Talwar P, Chari PS, Panigrahi D.

(Portugal)

Fusarium is isolated during monitorization of airborne fungi in ICUs


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283 hospital water system samples

(water tanks, water, showers, sinks, and swabs from sink, shower heads, and wall)

57%

43%

Fusarium spp. (+)Fusarium spp. (-)

Anaissie et al. CID 2001, 33: 1871; Anaissie et al. Blood 2003, 101: 2542

Molecular match of strains of 8 fusariosis patients (F. solani) with an environmental or another patient’s isolate

Hospital water system as the reservoir for Fusarium


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Inhalation of spores: primarily from air secondarily by aerosolization from water

Nosocomial fusariosis Possible routes of acquisition


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In vitro susceptibility

CLSI M38 microdilution24h

F. solani F. oxysporum

AMB 1.85-10.4 (1>16) 2.38-19 (2->16)

Itra >16 (>16) 0.11 (0.03-0.25)

Vori 1.92-3.4 (0.25-8) 0.5-1.6 (0.25-2)

Posa 19.3 (1->16) 1 (1)

Ravu 27.4 (4->16) 5.6 (4-8)

Caspo (16->16) (16->16)

Arikan et al. J Clin Microbiol 1999, 37: 3946; Arikan et al. Antimicrob Agents Chemother 2002, 46: 245; Paphitou et al. Antimicrob Agents Chemother 2002, 46: 3298; Pfaller et al. Antimicrob Agents Chemother 2002, 46: 1032; Clancy et al. EJ Clin Microbiol ID 1998, 17: 573

Macro/microdil. adapted from CLSI method

F. proliferatum F. verticilloides

AMB 1–2 1

Vori 1–2 0.5–2

Ravu 0.5–>16

MIC range (µg/ml)

GM MIC (range) (µg/ml)

Clancy CJ, Nguyen MH. Eur J Clin Microbiol Infect Dis 1998;17:573–5; Minassian B et al. Clin Microbiol Infect 2003;9:1250–2; Lionakis MS et al. Antimicrob Agents Chemother 2003,47:3252–9


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BAL from 4 ICU patients grew F. solani.

The bronchoscope was in use only in ICU.

The origin of the contamination of the bronchoscope could not be established.

Fusarium was isolated from the water supply of the endoscopy department. However, water entering the endoscope washer-disinfector is passed through a 0.2 µm filter and rinse water cultures from the washer-disinfector were negative.

J Hosp Infec 2008; 1

Ireland


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Khor et al.

Chang et al.

Donnio et al. Am J Ophthalmol; 2007: 143: 356

Gorscak et al.

Asia North America France Switzerland

Contact lens-associated fusarium keratitis in Switzerland Kaufmann et al. Klin Monbl Augenheilkd. 2008;225:418

Cornea 2007; 26: 1187

Gaujoux et al.


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Background information & moulds as causative agents of infections Diversity of epidemiology per the risk factor HSCT & hematological malignancies Organ tx ICU Mould infections : (Changing ?) epidemiology, reported outbreaks ,


Agenda


© by author

Inhalation

Trauma

Air-borne outbreak of nosocomial S. prolificans infection has been reported.

(leukemic patients in the same ward, in rooms without HEPA filters/laminar airflows)

Guerrero et al. Lancet 2001; 357: 1267

Scedosporium: Routes of Entry – Airborne outbreaks


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Two fatal infections in immunocompromised patients caused by Scedosporium inflatum (prolificans)

Two fatal infections caused by Scedosporium inflatum in immunocompromised patients are described. One patient developed peritonitis with this fungus 3 mths post renal transplantation. After a stormy course in the intensive care unit he eventually died. The other patient was suffering from non-Hodgkin's lymphoma and showed persistent neutropenia. Progressive deterioration occurred, and disseminated fungal infection was found at post mortem. Both isolates were resistant to all commonly available antifungal agents.

Wise et al. Pathology 1993; 25: 187


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2007; 13: 1170 Cooley et al.

renovation

No significant change in the incidence of S. apiospermum infections in time

renovation


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0

10

20

30

40

50

60

70

miconazole voriconazole albaconazole nystatin

apiospermumprolificans

MIC90 (µg/ml)

Meletiadis et al. Antimicrob Agents Chemother 2002; 46: 62; Meletiadis et al Antimicrob Agents Chemother 2003; 47: 106

Scedosporium: In vitro antifungal susceptibility


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AAC 2012; 56: 2635

N=332 CLSI M38-A2

Lowest MICs (MIC90 < 2 µg/ml) of voriconazole as compared to to other drugs against P. apiosperma and P. boydii

AMB, Itra, Vori, Posa, Isavu, Caspo, Mica, Anidula

Voriconazole being the only drug with meaningful activity against S. aurantiacum (MIC90 = 1 µg/ml)

Bimodal distribution of MICs in general (except for voriconazole), rendering species-based susceptibility predictions difficult

Moderate activity of posaconazole and micafungin against a number of Scedosporium strains ESCMID Online Lectu

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Resistance noted for AMB (some cases)

Azoles (Fluconazole) Flucytosine

Strabelli et al. Rev Soc Bras Med Trop 1990, 23: 233; Fung-Tomc et al. Antimicrob Agents Chemother 1998; 42: 313; Ioakimidou et al. DMID 2013; 75: 313;

Acremonium


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An unusual cluster of Acremonium kiliense fungaemias in a haematopoietic cell transplantation unit Ioakimidou et al. DMID 2013; 75: 313 Greece

Acremonium skin and soft tissue infection in a kidney transplant recipient Israel et al. Transplantation 2013; 95: e20 USA

Phoma and Acremonium invasive fungal rhinosinusitis in congenital acute lymphocytic leukemia and literature review Roehm et al. Int J Pediatr Otorhinolaryngol 2012 ;76:1387 USA

Acremonium kiliense: reappraisal of its clinical significance (- peritonitis - CAPD) Khan et al. JCM 2011; 49: 2342 Kuwait Catheter-Related Acremonium kiliense Fungemia in a Patient with Ulcerative Colitis under Treatment with Infliximab Díaz-Couselo & Zylberman Case Rep Infect Dis 2011;2011:710740 Argentina


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Resistance noted for

AMB (P. lilanicus) Fluconazole, itraconazole, flucytosine (P. lilanicus)

Aguilar et al. Antimicrob Agents Chemother 1998, 42: 1601; Fung-Tonc et al. Antimicrob Agents Chemother 1998; 42: 313

Paecilomyces Paecilomyces


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Use of Voriconazole for the Treatment of Paecilomyces lilacinus Cutaneous Infections: Case Presentation and Review of Published Literature Rimawi et al. Mycopathologia 2013; 175: 3459 (-Imm.compromised host) USA

Simultaneous cutaneous infection due to Paecilomyces lilacinus and Alternaria in a heart transplant patient Lavergne et al. Transpl Infect Dis 2012;14:E156 France

Paecilomyces lilacinus peritonitis in a peritoneal dialysis patient Wolley et al. Perit Dial Int 2012;32:364

A Rare Case of Fungal Maxillary Sinusitis due to Paecilomyces lilacinus in an Immunocompetent Host, Presenting as a Subcutaneous Swelling Permi et al. J Lab Physicians 2011;3:46 India

Paecilomyces lilacinus in transplant patients: an emerging infection Rosmaninho et al. Eur J Dermatol 2010; 20: 643 Portugal


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Fluconazole Flucytosine Itraconazole

Munoz et al. J Clin Microbiol 1997, 35: 499; Richter et al. J Clin Microbiol 1999, 37: 1154; Chouaki et al. Clin Infect Dis 2002, 35: 1360

Cases of invasive infections; hematologic malignancy / organ transplant rec.

MIC (μg/ml)

AMB 1-2

Itra 16

Vori 2

Trichoderma


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Fatal post-operative Trichoderma longibrachiatum mediastinitis and peritonitis in a paediatric patient with complex congenital cardiac disease on peritoneal dialysis Santillan Salas et al. J Med Microbiol 2011 60(Pt 12):1869 USA

First case of Trichoderma longibrachiatum infection in a renal transplant recipient in Tunisia and review of the literature Trabelsi et al. Tunis Med 2010 ;88: 52 Tunisia

Fatal Trichoderma harzianum infection in a leukemic pediatric patient Kantarcıoğlu et al. Med Mycol 2009; 47: 207 Turkey

Trichoderma fungaemia in a neutropenic patient with pulmonary cancer and HIV infection Lagrange-Xelot et al. CMI 2008; 14: 1190 France Invasive pulmonary infection due to Trichoderma longibrachiatum mimicking invasive Aspergillosis in a neutropenic patient successfully treated with voriconazole combined with caspofungin Alanio et al. CID 2008; 46:e116 France


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Fluconazole Flucytosine

Alternaria

Bipolaris Cladosporium

Husain et al. Clin Infect Dis 2003, 37: 221; Mc Ginnis et al. J Clin Microbiol 1998, 36: 2353; Sharkey et al. J Am Acad Dermatol 1990; 23: 577; Mc Ginnis et al. Med Mycol 1998, 36: 243

Dematiaceous moulds other than S. prolificans


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…….. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. …..Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity….


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Background information & moulds as causative agents of infections Diversity of epidemiology per the risk factor HSCT & hematological malignancies Organ tx ICU Mould infections : (Changing ?) epidemiology, reported outbreaks

, and in vitro susceptibility Aspergillosis Mucormycosis Fusariosis Scedosporiosis Other emerging mould infections in high risk patients Conclusions

Agenda


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Epidemiology of mould infections displays a variable trend.

Increase in incidence of some of these infections is

reported in some centers. Among these, genera that are less-susceptible or resistant to antifungal drugs do exist.

Surveillance of local epidemiological trends remains of

major significance in rational direction of antifungal therapy.

Conclusions


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23rd eccmid, 27-30 apr 2013 - berlin

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