Fatal breakthrough infection with Fusarium andiyazi: New multi-resistant aetiological agent cross-reacting with Aspergillus galactomannan enzyme immunoassay

Abstract

Disseminated infections caused by members of the Fusarium fujikuroi species complex (FFSC) occur regularly in immunocompromised patients. Here, we present the first human case caused by FFSC-member Fusarium andiyazi. Fever, respiratory symptoms and abnormal computerised tomography findings developed in a 65-year-old man with acute myelogenous leukaemia who was under posaconazole prophylaxis during his remission-induction chemotherapy. During the course of infection, two consecutive blood galactomannan values were found to be positive, and two blood cultures yielded strains resembling Fusarium species, according to morphological appearance. The aetiological agent proved to be F. andiyazi based on multilocus sequence typing. The sequencing of the internal transcribed spacer region did not resolve the closely related members of the FFSC, but additional data on partial sequence of transcription elongation factor 1 alpha subunit did. A detailed morphological study confirmed the identification of F. andiyazi, which had previously only been reported as a plant pathogen affecting various food crops.

Full text

Case report
Fatal breakthrough infection with Fusarium andiyazi: new
multi-resistant aetiological agent cross-reacting with Aspergillus
galactomannan enzyme immunoassay
Nesrin Kebabcı,
1
Anne D. van Diepeningen,
2
Beyza Ener,
3
Tuba Ersal,
4
Martin Meijer,
2
Abdullah M.S. Al-Hatmi,
2
Vildan
€
Ozkocaman,
4
Ahmet Ursavas
ß,
5
Ezgi D. C
ßetino
glu
5
and
Halis Akalın
1
1
Faculty of Medicine, Department of Clinical Microbiology and Infectious Diseases, Uluda 
g University, Bursa, Turkey,
2
CBS-KNAW Fungal Biodiversity
Centre, Utrecht, The Netherlands,
3
Faculty of Medicine, Department of Medical Microbiology, Uluda 
g University, Bursa, Turkey,
4
Faculty of Medicine,
Department of Heamatology, Uluda
g University, Bursa, Turkey and
5
Faculty of Medicine, Department of Chest Diseases, Uluda 
g University, Bursa, Turkey
Summary Disseminated infections caused by members of the Fusarium fujikuroi species complex
(FFSC) occur regularly in immunocompromised patients. Here, we present the first
human case caused by FFSC-member Fusarium andiyazi.Fever, respiratory symp-
toms and abnormal computerised tomography findings developed in a 65-year-old
man with acute myelogenous leukaemia who was under posaconazole prophylaxis
during his remission–induction chemotherapy. During the course of infection, two
consecutive blood galactomannan values were found to be positive, and two blood
cultures yielded strains resembling Fusarium species, according to morphological
appearance. The aetiological agent proved to be F. andiyazi based on multilocus
sequence typing. The sequencing of the internal transcribed spacer region did not
resolve the closely related members of the FFSC, but additional data on partial
sequence of transcription elongation factor 1 alpha subunit did. A detailed morpho-
logical study confirmed the identification of F. andiyazi, which had previously only
been reported as a plant pathogen affecting various food crops.
Key words: Acute leukaemia, posaconazole prophylaxis, Fusarium andiyazi,Fusarium fujikuroi species complex,
galactomannan, breakthrough infections.
Introduction
Fusarium species are ubiquitous in soil and plant deb-
ris. They are also important plant pathogens and in
recent years have emerged as pathogens affecting both
immunocompetent and immunocompromised human
hosts. In the first patient group Fusarium infections
tend to be superficial or locally invasive, and present
themselves as for example, onychomycosis, paronychia
and keratitis. In the group of the immunocompromised
patients, the infections like sinusitis, pulmonary and
haematogenously disseminated infections tend to be
uncommonly severe. The most frequent Fusarium spe-
cies isolated from clinical specimens are F. solani,F.
oxysporum, and F. verticillioides.
1–3
Patients with acute myelogenous leukaemia (AML)
or myelodysplastic syndrome (MDS) and neutropenia
after remission–induction chemotherapy have a high
risk of fatal invasive fungal infections (IFI).
4,5
Mortal-
ity rates resulting from candidiasis or aspergillosis are
reported to reach 40%–50%, while those from fusari-
osis or zygomycosis can reach 70% or higher.
6–9
In a
randomised clinical trial, posaconazole (POS) has been
shown to prevent IFIs more effectively than either
fluconazole (FLU) or itraconazole (ITR) and to
improve overall survival in patients undergoing
Correspondence: Beyza Ener, Uluda
g University, Faculty of Medicine,
Department of Medical Microbiology, 16059 G€
or€
ukle Bursa Turkey.
Tel.: +90 224 442 9156. Fax: +90 224 295 4149.
E-mail: bener@uludag.edu.tr
Submitted for publication 14 June 2013
Revised 2 September 2013
Accepted for publication 3 September 2013
©2013 Blackwell Verlag GmbH doi:10.1111/myc.12142
mycoses
Diagnosis, Therapy and Prophylaxis of Fungal Diseases

chemotherapy for AML or MDS.
4
The prophylactic
use of POS (600 mg day
1
) during remission–induc-
tion chemotherapy in AML patients is widely accepted
in most countries.
Detection of Aspergillus galactomannan (GM) using
the Platelia Aspergillus antigen immunoassay (BioRad
Laboratories, Marnes-la-Coquette, France) is one of the
microbiological criteria for the diagnosis of invasive
aspergillosis.
10,11
Although GM tests are considered
highly sensitive and specific for Aspergilli in patients,
cross-reactivity with other moulds like Fusarium spp.
have been reported.
12–14
However, this cross-reactivity
of Fusarium spp. in the GM assay is controversial.
15,16
We describe the case of a 65-year-old man with
AML who was under POS prophylaxis during his
remission–induction chemotherapy. He developed a
disseminated fusariosis with GM antigenemia caused
by a plant pathogen belonging to the Fusarium fujiku-
roi species complex (FFSC). Although disseminated
infections caused by members of the FFSC–especially
F. proliferatum and F. verticillioides–are not unheard,
17
here, we present the first proven case
10
caused by
Fusarium andiyazi.
Case presentation
A 65-year-old male patient with AML-M2 was hospita-
lised with the diagnosis of community-acquired pneu-
monia. The patient received remission–induction
chemotherapy, anti-biotherapy (piperacillin-tazobac-
tam; 3 94.5 g day
1
i.v. and clarithromycin;
29500 mg day
1
i.v.) for pneumonia and prophylac-
tic POS (3 9200 mg day
1
oral suspension) treatment
simultaneously. A computerised tomograph (CT) of his
thorax showed non-specific infection and calcificated
thickening (asbestos exposure) in both pleura (Fig. 1).
On the fourth day of treatment, because of persis-
tent fever and Stenotrophomonas maltophila growth in
his sputum culture, his anti-biotherapy was rear-
ranged (cefoperazone sulbactam; 2 92 g day
1
i.v.
and trimethoprim-sulphamethoxazole; 3 92 pharma-
ceutical vial day
1
i.v.). Although S. maltophila growth
was found in his BAL samples, there was no fungal
growth. No growth was obtained from his stool, urine,
or blood cultures. During the 26 days remission–
induction therapy, no positive GM values in his twice
weekly blood samples were observed. Refractory leu-
kaemia was considered because of blastic infiltration
in his control peripheral smear, and a second round of
chemotherapy was begun. Steroid therapy was given
because of presumably allergic petechial and ecchy-
motic lesions.
On the 12th day of second chemotherapy, the
patient ran a fever again and CT showed new ground-
glass areas and cavitations in some consolidation areas
(Fig. 2). Two consecutive blood GM antigen tests came
back positive (indices values: 2.98 on the 12th day of
chemotherapy and 3.6 on the 16th day of chemother-
apy), and he was started on a classic amphotericin B
(AMB) (1 mg kg
1
day
1
i.v.) treatment. Because the
patient rejected a second bronchoscopy, it was not
performed. He developed side effects of classic AMB, so
his therapy was switched to liposomal AMB
(3 mg kg
1
day
1
i.v.). However, his clinical condi-
tion deteriorated, and the patient died on the 20th day
of second chemotherapy. At the time of deterioration,
in two blood samples, fungal growth morphologically
Figure 1 Non-specific infection and calcificated thickening of
pleura (asbestos exposure).
Figure 2 New infiltration areas and cavitations in some
consolidations.
©2013 Blackwell Verlag GmbH2
N. Kebabcı et al.

similar to Fusarium species was observed. The isolate
was then sent to the CBS-KNAW Fungal Biodiversity
Centre for further characterisation and identified as
FFSC-member F. andiyazi.
Macroscopic and microscopic morphological
study
The clinical isolate has been deposited in the reference
collection of CBS-KNAW, Utrecht, Netherlands, under
accession number CBS 134430. The strain was cul-
tured on malt extract agar (MEA), oatmeal agar (OA),
synthetic nutrient agar, Dichloran 18% glycerol agar,
and carnation leaf agar.
18,19
Culture plates were incu-
bated at 25 °C. Strain CBS 134430 grew fast on OA
and formed a white-to-lilac colony (Fig. 3A obverse;
3B reverse). The microconidia proved one-celled
(Fig. 3H), but rather than being formed in chainswere
mostly in false heads (Fig. 3E). These microconidia
were formed on branching conidiophores of average
length (Fig. 3D and G). The macroconidia were long
and thin (Macroconidia from the aerial hyphae sur-
rounded by some microconidia are shown in Fig. 3F),
and can be formed in sporodochia (Fig. 3C). In this
isolate after 2 weeks pseudochlamydospores were seen
as thickening cells within the mycelium that lacked
the darker colouration of a cell wall (Fig. 3I).
DNA isolation and sequencing:
DNA was extracted from the fungus grown on MEA
after an incubation period of 5–7 days in the dark at
25 °C by using the MoBio-UltraClean
TM
Microbial DNA
Isolation Kit (MO BIO Laboratories, Inc., Carlsbad, CA,
USA). Multilocus sequence typing (MLST) was per-
formed based on the internal transcribed spacer region
(ITS), and partial transcription elongation factor 1
alpha (TEF1a). Fragments of rpb2 sequences were not
informative as no reference data are available and
these data are not shown. Fragments containing the
ITS region were amplified using the universal primers
LS266 (GCATTC CCAAACAACTCGACTC) and V9G
(TTACGTCCCTGCCC TTTGTA).
20
For the partial
sequence of TEF1a, primers EF1 (ATGGGTAAGGARG-
ACAAGAC) and EF2 (GG ARGTACCAGTSATCATGTT)
were used.
21
The PCR fragments were sequenced with the ABI
Prism
â
Big DyeTM Terminator v. 3.0 ready reaction
cycle sequencing kit (Applied Biosystems, Foster City,
CA, USA). Samples were analysed on an ABI PRISM
3700 Genetic Analyzer (Applied Biosystems), and con-
tigs were assembled using the forward and reverse
sequences by using the SeqMan program from the
Lasergene software program (DNASTAR, Madison, WI,
USA). The sequences were compared via BLAST to
sequences in GenBank (http://www.ncbi.nlm.nih.gov/
genbank/), the Fusarium-ID database (http://isolate.
fusariumdb.org/), the Fusarium MLST database (http://
www.cbs. knaw.nl/fusarium/), and the internal CBS
database.
22–24
Sequences of F. andiyazi strain CBS
134430 have been deposited in the GenBank database
with accession numbers KC954400 (ITS) and
KC954401 (TEF1a).
Phylogenetic analysis
Sequences of species of the FFSC, with Fusarium solani
species complex (FSSC) as an out-group, were col-
lected from GenBank and the CBS database. Where
possible, we used ITS and TEF1asequences from the
same isolate for both analyses. For the phylogenetic
analyses shown in this article, we used 23 aligned EF
sequences with a total length of 660 nucleotides and
14 aligned ITS sequences with a total length of 463
nucleotides.
Bayesian phylogenetic analyses were performed
using MrBayes 3.2.
25
The Metropolis-coupled Markov
chain Monte Carlo sampling approach was used to cal-
culate posterior probabilities. Four simultaneous Mar-
kov chains, three heated and one cold, were run
under a mixed model of sequence evolution and
gamma approximation for rate variation among sites.
Chains were analysed with random starting trees for
10
7
generations, sampling from trees every 1000th
generation. The burn-in period was set at 25%.
The ITS sequence of strain CBS 134430 indicates
that the species falls within the FFSC, but it does not
give a clear identification as to what species it belongs
to (Fig. 4). The analyses of the EF sequences confirm
the morphological finding that it actually is a F. andiy-
azi strain (Fig. 5)
Antifungal susceptibility testing
In vitro antifungal susceptibility testing was performed
for AMB (Bristol-Myers-Squib, Woerden, Netherlands),
FLU (Pfizer Central Research Sandwich, Tadworth,
Surrey, UK), ITR (Janssen Research Foundation,
Beerse, Belgium), voriconazole (VOR; Pfizer Central
Research Sandwich), POS (Schering-Plough, Kenil-
worth, NJ), isavuconazole (ISA; Basilea Pharmaceuti-
cals, Basel, Switzerland), caspofungin (CAS; Merck
Sharp & Dohme BV, Haarlem, the Netherlands) and
micafungin (MICA; Astellas, Tohoku, Japan). All
©2013 Blackwell Verlag GmbH 3
Fatal infection with Fusarium andiyazi

antifungal compounds were obtained from their man-
ufacturers as pure powders, and broth microdilution
was performed as described by the CLSI, in accordance
with the guidelines in document M38-A2.
26
Minimal
inhibitory concentrations (MICs) were the following:
AMB (8 lg ml), FLU (16 lg/ml
1
), ITR (8 lgml
1
),
(a) (b) (c)
(d) (e) (f)
(g) (h) (i)
Figure 3 Macroscopic and microscopic morphological study of Fusarium andiyazi strain CBS 134430. A. 10-day-old culture on Oatmeal
Agar (OA) (Obverse); B. same (Reverse); C. Sporodochia on carnation leaf agar; D. Branched conidiophore on OA; E. microconidia in
false heads in situ on OA; F. macroconidia from the aerial hyphae on OA; G. branched conidiophore on OAG; H. clavate to ovoid 0-sep-
tate microconidia on OA; I. pseudochlamydospores.
©2013 Blackwell Verlag GmbH4
N. Kebabcı et al.

VOR (2 lgml
1
), POS (1 lgml
1
), ISA (4 lgml
1
),
Minimum effective concentrations (MECs) were the fol-
lowing: CAS (8 lgml
1
) and MICA (>8lgml
1
).
Discussion
Although there are more than 100 Fusarium species,
the species of the FSSC (~50%) and the Fusarium oxy-
sporum species complex (~20%) are the most common
ones that cause infections in humans.
17
Disseminated
infections caused by members of the FFSC are not
unheard, and in this case, the cause is FFSC-member
F. andiyazi. It was described as new species from sor-
ghum in 2001
27
and this case reports the first isola-
tion from humans. Morphological characteristics are
often similar for Fusarium species. For this particular
species, the formation of pseudochlamydospores may
distinguish it from the other members of the FFSC.
However, this characteristic was relatively rare and
late in development, making it unsuitable for rapid
diagnostics. Based on MLST, the aetiological agent
was proven to be F. andiyazi. The sequencing of the
Figure 4 A Bayesian phylogenetic tree of
the internal transcribed spacer (ITS)
region illustrates that ITS sequences are
not useful for identification of members
of the Fusarium fujikuroi species complex.
Fusarium solani strains was used as out-
group. The numbers at the nodes are
Bayesian posterior probabilities. The scale
bar represents the number of estimated
changes per position for a unit of branch
length.
Figure 5 This Bayesian phylogenetic tree of a partial sequence of transcripion elongation factor 1-alpha shows that the different species
of the Fusarium fujikuroi species complex can all be recognised to species level. Fusarium solani strains was used as outgroup. The Fusari-
um andiyazi strain CBS 134430 that caused the fatal disseminated infection described in this report falls in a well-supported clade with
the environmental F. andiyazi strains. Numbers at the nodes are Bayesian posterior probabilities. The scale bar represents the number
of estimated changes per position for a unit of branch length.
©2013 Blackwell Verlag GmbH 5
Fatal infection with Fusarium andiyazi

ITS region did not resolve the closely related members
of the FFSC, but additional data on the partial TEF1a
sequence did. Although, sequencing ITS region is ideal
for most fungi, this is not the case for the members of
the genus Fusarium, for which it would be better to
rely on multiple sequences in a MLST for identifica-
tion.
21
F. andiyazi is a relatively new species that was
first found in sorghum in the US and Africa and has
since been identified on several other food crops
around the world.
27–29
A serum GM antigen test specific for Aspergillus may
cross-react with some other fungi species. Blastomyces
dermatitidis,Nigrospora oryzae,Paecilomyces lilacinus,
Penicillium chrysogenum and Trichothecium roseum are
among them.
16
It has been reported that also some
Fusarium species have a GM antigen, and indeed, in
some cases, the test became positive.
13,14,16
In our case,
it is also shown that the new human aetiological agent,
F. andiyazi, causes GM antigen test positivity. Although,
approximately 85% of Fusarium-infected patients
develop skin lesions, often as one of the earliest manifes-
tations, there were no skin lesions on our patient, and
GM positivity was the first clue to the diagnosis.
Although decreasing in numbers, Candida and Asper-
gillus species are the most common types of fungal
infections seen in patients with haematological malig-
nant diseases. In patients under prophylactic treat-
ment, breakthrough infections caused by rarely seen
species are important.
30
Although the breakpoints of
antifungal agents have not been established for most
moulds, the MICs/MECs of our Fusarium strain were
high for most of the antifungals used in this study.
The MIC for POS was 1 lgml
1
and it appears that
the strain is most susceptible to this drug. Considering
that almost all fungal pathogens isolated during POS
prophylaxis were susceptible in vitro to the triazole,
the possibility of reduced absorption in our patient
must be considered. Many factors, such as the devel-
opment of mucositis, impaired dietary intake and the
use of proton pump inhibitors may cause pharmacoki-
netic variability in AML patients, and therapeutic drug
monitoring may be required.
31,32
There are several described breakthrough fungal
cases that developed during VOR prophylaxis and
treatment.
33,34
POS is a next-generation oral azole
with in vitro activity against a wide spectrum of medi-
cally important fungi. A breakthrough case of Alterna-
ria alternata in a patient with Fanconi’s anaemia who
received antifungal prophylaxis with POS was
described recently. However, in that patient finally a
combined treatment with liposomal AMB and again
POS seemed to result in a synergistic positive
interaction.
35
We present this case to attract attention
to the potential of POS breakthrough infections and to
a new human opportunistic Fusarium pathogen that
can cause GM positivity.
Acknowledgments
None of the authors has a potential conflict of interest.
References
1 Reiss E, Shadomy HJ, Lyon GM (eds). Fundamental Medical Mycology .
Hoboken, NJ: Wiley-Blackwell, 2012: 397–411.
2 Campo M, Lewis RE, Kontoyiannis DP. Invasive fusariosis in patients
with hematologic malignancies at a cancer center. J Infect 2010; 60:
331–7.
3 Dignani MC, Anaissie E. Human fusariosis. Clin Microbiol Infect
2004; 10(Suppl. 1): S67–75.
4 Cornely OA, Maertens J, Winston DJ et al. Posaconazole vs. fluconaz-
ole or itraconazole prophylaxis in patients with neutropenia. N Engl
J Med 2007; 356: 348–59.
5 Egerer G, Geist MJP. Posaconazole prophylaxis in patients with acute
myelogenous leukaemia –results from an observational study.
Mycoses 2011; 54(Suppl. 1): S7–11.
6 Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in
patients with hematologic malignancy: ten years-experience at a
cancer center and implications for management. Blood 1997; 90:
999–1008.
7 Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: sys-
tematic review of the literature. Clin Infect Dis 2001; 32: 358–66.
8 Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and out-
come of zygomycosis: a review of 929 reported cases. Clin Infect Dis
2005; 41: 634–53.
9 Viscoli C, Girmenia C, Marinus A et al. Candidemia in cancer
patients: a prospective, multicenter surveillance study by the Inva-
sive Fungal Infection Group (IFIG) of the European Organization for
Research and Treatment of Cancer (EORTC). Clin Infect Dis 1999;
28: 1071–9.
10 de Pauw B, Walsh TJ, Donnell JP et al. Revised definitions of invasive
fungal disease from the European Organization for Research and
treatment of Cancer/invasive fungal infections cooperative group and
the national institute of allergy and infectious diseases mycoses study
group (EORTC/MSG) consensus group. Clin Infect Dis 2008; 46:
1813–21.
11 Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosi s using
a galactomannan assay: a meta analysis. Clin Infect Dis 2006; 42:
1417–27.
12 Kappe R, Schulze-Berge A. New cause of false positive results with
the Pastorex Aspergillus antigen latex agglutination test. J Clin Micro-
biol 1993; 31: 2489–90.
13 Tortorano AM, Esposto MC, Prigitano A et al. Cross reactivity of
Fusarium spp. in the Aspergillus Galactomannan enzyme-linked
immunosorbent assay. J Clin Microbiol 2012; 50: 1051–3.
14 Mikulska M, Furfaro E, Bono VD et al. Galactomannan testing might
be useful for early diagnosis of fusariosis. Diag Microbiol Infect Dis
2012; 72: 367–9.
15 Swanink CM, Meis JF, Rijs AJ, Donnelly JP, Verweij PE. Specificity of
a sandwich enzyme-linked immunosorbent assay for detecting Asper-
gillus galactomannan. J Clin Microbiol 1997; 35: 257–60.
16 Cummings JR, Jamison GR, Boudreaux JW, Howles MJ, Walsh TJ,
Hayden RT. Cross-reactivity of non-Aspergillus fungal species in the
Aspergillus galactomannan enzyme immunoassay. Diag Microbiol
Infect Dis 2007; 59: 113–5.
17 de Hoog GS, Guarro J, Gen
e J, Figueras MJ. Atlas of Clinical Fungi 3rd
Ed., CD-ROM. Utrecht: CBS-KNAW Fungal Biodiversity Centre, 2011.
©2013 Blackwell Verlag GmbH
6
N. Kebabcı et al.

18 Nirenberg HI. Untersuchungen €
uber die morphologische und biologi-
sche differenzierung in der Fusarium Sektion Liseola.Mitteilungen aus
der Biologischen Bundesanstalt f€
ur Land- und Forstwirtschaft (Berlin –
Dahlem) 1976; 169:1–117.
19 Leslie JF, Summerell BA (eds). The Fusarium Laboratory Manual.
Oxford: Blackwell Publishing Ltd, 2006.
20 Gerrits van den Ende AHG, de Hoog GS. Variability and molecular
diagnostics of the neurotropic species Cladophialophora bantiana.Stud
Mycol 1999; 43: 151–62.
21 O’Donnell K, Kistler HC, Cigelnik E, Ploetz RC. Multiple evolution ary
origins of the fungus causing Panama disease of banana: concor dant
evidence from nuclear and mitochondrial gene genealogies. Proc Natl
Acad Sci USA 1998; 95: 2044–9.
22 Benson DA, Cavanaugh M, Clark K et al. GenBank. Nucleic Acid Res
2013; 41: D36–42.
23 Geiser DM, Jim
enez-Gasco M, Kang S et al. FUSARIUM-ID v. 1.0, A
DNA sequence database for identifying Fusarium. Eur J Plant Pathol
2004; 110: 473–9.
24 O’Donnell K, Sutton DA, Rinaldi MG et al. Internet-accessible DNA
sequence database for identifying fusaria from human and animal
infections. J Clin Microbiol 2010; 48: 3708–18.
25 Ronquist FM, Teslenko P, van der Mark D et al. MrBayes 3.2: effi-
cient Bayesian phylogenetic inference and model choice across a
large model space. Syst Biol 2011; 61: 539–42.
26 Clinical and Laboratory Standards Institute. Reference Method for
Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi.
Approved standard, 2nd edn. Document M38-A2. Wayne, PA: Clini-
cal and Laboratory Standards Institute, 2008.
27 Marasas WFO, Rheeder JP, Lamprecht SC, Zeller KA, Leslie JF. Fusari-
um andiyazi sp. nov., a new species from sorghum. Mycologia 2001;
93: 1203–10.
28 dal Pr
a M, Tonti S, Pancaldi D, Nipoti P, Alberti I. First report of
Fusarium andiyazi associated with rice Bakanae in Italy. Plant Dis
2010; 94:1070.
29 Hsuan HM, Salleh B, Zakaria L. Molecular identification of Fusarium
species in Gibberella fujikuroi species complex from rice, sugarcane
and maize from Peninsular Malaysia. Int J Mol Sci 2011; 12: 6722–
32.
30 Girmenia C, Frustaci AM, Gentile G et al. Posac onazole prophylaxis
during front-line chemotherapy of acute myeloid leukemia: a single-
center, real-life experience. Haemotologica 2012; 97: 560–7.
31 Lebeaux D, Lanternier F, Elie C et al. Therapeutic drug monitoring of
posaconazole: a monocentric study with 54 adults. Antimicrob Agents
Chemother 2009; 53: 5224–9.
32 Thompson GR, Rinaldi MG, Pennick G, Dorsey SA, Patterson TF,
Lewis JS. Posaconazole therapeutic drug monitoring: a reference lab-
oratory experience. Antimicrob Agents Chemother 2009; 53: 2223–4.
33 Cudillo L, Girmenia C, Santilli S et al. Breakthrough fusariosis in a
patient with acute lymphoblastic leukemia receiving voriconazole
prophylaxis. Clin Infect Dis 2005; 40: 1212–3.
34 Kim MS, Sung HS, Won CH. Breakthrough disseminated fusariosis in
an immunocompromised patient on voriconazole therapy. Int J Der-
matol 2012; 51: 621–2.
35 Ferreira de Sousa I, Teixeira G, Abecasis M. Alternaria alternata infec-
tion in a patient with Fanconi’s anemia after an unrelated bone mar-
row transplant. Clin Drug Invest 2013; 33(Suppl. 1):S33–S36.
©2013 Blackwell Verlag GmbH 7
Fatal infection with Fusarium andiyazi