Download Pulmonary infection caused by Talaromyces purpurogenus in a

Le Infezioni in Medicina, n. 2, 153-157, 2016
case report
153
Pulmonary infection caused by
Talaromyces purpurogenus in a
patient with multiple myeloma
Altay Atalay1, Ayse Nedret Koc1, Gulsah Akyol2, Nuri Cakır1, Leylagul Kaynar2, Aysegul Ulu-Kilic3
Department of Medical Microbiology, University of Erciyes, Kayseri, Turkey;
Department of Haematology, University of Erciyes, Kayseri, Turkey;
3
Department of Infectious Disease and Clinical Microbiology, University of Erciyes, Kayseri, Turkey
1
2
SummaRY
A 66-year-old female patient with multiple myeloma (MM) was admitted to the emergency service on
29.09.2014 with an inability to walk, and urinary and
faecal incontinence. She had previously undergone autologous bone marrow transplantation (ABMT) twice.
The patient was hospitalized at the Department of
Haematology. Further investigations showed findings
suggestive of a spinal mass at the T5-T6-T7 level, and
a mass lesion in the iliac fossa. The mass lesion was
resected and needle biopsy was performed during a
colonoscopy. Examination of the specimens revealed
plasmacytoma. The patient also had chronic obstructive pulmonary disease (COPD) and was suffering
from respiratory distress. After consultation with an
infectious diseases specialist the patient was placed
on an intravenous antibiotherapy with piperacillin/
tazobactam (4.5 g x 3) on 17.10.2014. During piperacillin/tazobactam treatment, the patient suffered from
drowsiness, her general condition deteriorated, and
she had rales on auscultation of the lungs. The patient
underwent thoracic computerized tomography (CT)
which showed areas of focal consolidation in the lower lobes of the two lungs (more prominent on the left),
and increased medullary density. The radiology report
suggested that fungal infection could not be ruled out
nINTRODUCTION
Penicillium species are common and generally
non-pathogenic laboratory contaminants that
are widely found in nature [1]. Among Penicillium species, Penicillium marneffei (P. marneffei) is
Corresponding author
Altay Atalay
E-mail: [email protected]
based on the CT images. The sputum sample was sent
to the mycology laboratory and direct microscopic examination performed with Gram and Giemsa’s staining showed the presence of septate hyphae; therefore voriconazole was added to the treatment. Slow
growing (at day 10), grey-greenish colonies and red
pigment formation were observed in all culture media
except cycloheximide-containing Sabouraud dextrose
agar (SDA) medium. The isolate was initially considered to be Talaromyces marneffei. However, it was subsequently identified by DNA sequencing analysis as
Talaromyces purpurogenus. The patient was discharged
at her own wish, as she was willing to continue treatment in her hometown. Unfortunately, the patient
died on December 8, 2014. In conclusion, apart from T.
marneffei, less common strains such as T. purpurogenus
should be considered when clinical samples obtained
from patients with haematologic/oncologic disorders
show fungal colonies that form red pigments on the
culture media and when microscopic examination
suggests a morphological appearance similar to Penicillium species.
Keywords: multiple myeloma, Penicillium, Talaromyces
purpurogenus.
the only dimorphic and pathogenic species. This
pathogen can cause infections in both healthy individuals and immunosuppressed patients, particularly in those infected with HIV in Southeast
Asia [2]. This species was recently transferred to
the Talaromyces genus along with other Penicillium
species belonging to the Biverticillium sub-genus
[3]. Aside from Talaromyces marneffei (previously
named P. marneffei), rare cases of infections related
to species such as Penicillium chrysogenum, Penicillium oxalicum, Penicillium piceum and Penicillium
154 A. Atalay, et al.
purpurogenum have also been reported [4-7]. According to current taxonomic approaches, the last
two Penicillium species have also been transferred
to the Talaromyces genus, with their names being
changed to Talaromyces piceus and Talaromyces purpurogenus [3].
In this case report, we discuss the diagnosis and
clinical significance of a T. purpurogenus strain isolated from the sputum culture of a patient with
multiple myeloma (MM) who previously underwent autologous bone marrow transplantation
(ABMT) twice and later developed plasmocytoma. The strain in question was initially presumed
to be T. marneffei due to red pigments scattered in
the sputum culture, but it was later identified correctly as T. purpurogenus using DNA sequencing
analysis.
n CASE REPORT
A 66 year-old female patient, who was diagnosed
with MM at another healthcare center in 2010,
had previously received vincristine, adriamycin and dexamethasone (VAD) chemotherapy.
The patient subsequently underwent ABMT at
the Hematology Unit of our hospital in 2011 and
2013. Then the patient was followed at 3-monthly
intervals in remission. However, the patient was
admitted to the emergency service of our hospital
on September 29, 2014, with the complaints of urinary and fecal incontinence and inability to walk.
The patient was hospitalized at the department
of hematology and further investigations showed
findings suggestive of a spinal mass at the T5-
T6-T7 level and a mass lesion in the iliac fossa.
The mass lesion was resected and needle biopsy
was performed during a colonoscopy. The examination of the two specimens revealed plasmacytoma. The patient also had chronic obstructive
pulmonary disease (COPD) and she was suffering
from respiratory distress. A consultation with an
infectious diseases specialist was performed after
which the patient was placed on an intravenous
antibiotic therapy with piperacillin/tazobactam
(4.5 g x 3) on 17.10.2014. During piperacillin/tazobactam therapy, the patient developed suffered
from drowsiness, her general condition deteriorated, and there were rales on auscultation of the
lungs. Thoracic computerized tomography (CT)
scan was then performed. Lymph nodes with
short axes smaller than 1 cm were observed in the
mediastinum, and there was minimal free fluid in
the left hemithorax. Focal consolidated areas and
increases in medullary density were observed bilaterally in the lower lobes of the lungs that were
more prominent in the left lung. It was noted that
these findings could not rule out a possible fungal infection (Figure 1). In laboratory tests, white
blood cell count was 7.63 x 103/ µL (68.9% neutrophils), hemoglobin was 9.0 g/dL, and platelets was 208 x 103 µL. The sputum culture sent to
the bacteriology laboratory on October 30, 2014,
showed growth of Acinetobacter baumannii, and
the patient was placed on a therapy with colistin
and sultamicillin based on the antibiotic susceptibility tests. Direct microscopic examination was
performed on the sputum culture sent to the mycology laboratory in the same day, and the samples were inoculated onto Sabouraud dextrose
Figure 1 - Computerized tomography
scan shows pulmonary fungal lesions.
Pulmonary infection caused by Talaromyces purpurogenus in a patient with multiple myeloma 155
agar (SDA; Oxoid, United Kingdom) with and
without antibiotics (containing cycloheximide
and chloramphenicol) after Gram and Giemsa’s
staining, and then incubated at 37ºC and 25ºC.
Direct microscopic examination performed with
Gram and Giemsa’s staining showed presence of
septate hyphae. The voriconazole (4 mg/kg x 2)
was added to the treatment. Slow growing (at day
10), gray-greenish colonies were observed at both
37ºC and 25ºC in all culture media except cycloheximide-containing SDA and red pigment was
diffusely scattered on the culture medium (Figure
2). The isolate was initially considered to be T.
marneffei; however, this possibility was ruled out
when it was observed that the isolate did not form
circular white colonies similar to those of yeast on
sheep blood agar at the suitable temperature. In
corn meal-Tween 80 agar slide culture; non-specific septate, hyaline hyphae, conidiophores, and
bottle shaped phyllitis on some metulae branching from conidiophores, and circular conidium
chains branching from each phyllitis were observed (Figure 3). DNA analysis of the clinical
species was performed at a private laboratory
Figure 2 - Colony of Talaromyces purpurogenus and red pigment formation.
Figure 3 - Talaromyces purpurogenus
in slide culture.
(RefGen) by using PCR products and primers
and the ABI 3100 Genetic Analyzer device. The
data of sequence analysis was analyzed using the
“National Center for Biotechnology Information
(Bethesda, ABD)” BLAST system (http://www.
ncbi.nlm.nih.gov/BLAST/), and DNA of the isolate was found to be 100% consistent with Talaromyces purpurogenus. Antifungal susceptibility test
was not performed routinely. The isolated strain
could not be reproduced when an antifungal susceptibility test was attempted for the purpose of
this case report. There was no bacterial or fungal
growth in blood and subsequent sputum cultures.
The patient tested negative for human immunodeficiency virus antibodies (anti-HIV) and galactomannan antigen. The patient was administered
IVIG due to low IgG levels. Blood gas analysis was performed as the patient had persistent
tachypnea and tachycardia. The results of blood
gas analysis were found to be consistent with respiratory alkalosis; a repeat thoracic CT was then
performed on November 16, 2014, which revealed
healing and newly formed nodules, and a newly
formed consolidation in the left upper lobe. The
156 A. Atalay, et al.
patient was then placed on meropenem therapy.
The patient was discharged from the hospital on
her own wish, willing to continue treatment in
her hometown. We were soon informed that the
patient died on December 8, 2014.
nDISCUSSION
P. marneffei has been reported as the fourth most
common infectious agent among opportunistic
infections observed in patients with AIDS in endemic regions [2]. Although P. marneffei is the best
known primary pathogen in humans and animals
among Penicillium species, invasive fungal infections caused by species such as P. capsulatum, P.
chrysogenum, P. citrinum, P. decumbens, P. piceum, P.
commune and P. purpurogenum have also been reported on rare occasions [8-13]. Recently, species
such as P. piceum, P. purpurogenum and P. marneffei
have been transferred to Talaromyces genus, and
renamed as Talaromyces marneffei, T. piceus and T.
purpurogenus, respectively [3].
T. purpurogenus is a soil and herbal pathogen that
can grow at 37ºC [14]. According to the new taxonomy; T. purpurogenus, T. ruber and two new
species of T. amestolkiae and T. stollii are included
into the T. purpurogenus complex [15]. T. purpurogenus can be distinguished from other species in
the T. purpurogenus complex by its slow growth,
inability to grow under 18ºC, and production of
red pigment [15]. Talaromyces species such as T.
marneffei, T. purpurogenus, T. albobiverticillius and
T. minioluteus, as well as Penicillium species such
as P. citrinum, P. janthinellum and P. rubrum can
produce red pigments that spread in the medium
[2,16]. Due to red pigment that spread on the surface of the medium, we initially assumed that the
slowly-growing clinical isolate was T. marneffei,
before realizing that it was 100% consistent with
T. purpurogenus based on the DNA sequence analysis method.
To date, T. purpurogenus has been reported as the
causative agent of pulmonary infection only in
three cases [the underlying disorder was chronic
granulomatous disease (CGD) in one patient, and
acute myeloid leukemia (AML) in the other patient; the data on the third patient was obtained
from reference number 14, and the underlying
disease of this patient could not be identified]. It
was also the suspected etiologic agent in a new-
born with pulmonary hemorrhage and reported
as the causative agent of disseminated mycosis in
one German shepherd [8,14,17,18]. On the other
hand, it is still questionable whether the isolates
reported in these cases were accurately identified
according to the new taxonomy. Amphotericin
B was used in the two patients with underlying
CGD and AML. The first patient fully recovered
as evidenced by radiological and clinical assessment; however, the second patient remained stable for one month after achieving recovery but
died of septic shock after two months. The present patient died approximately one month after
initiation of voriconazole therapy.
In conclusion, it is important to bear in mind that
in case fungal colonies that produce red pigments
on the surface of the medium are observed, and in
case the microscopy findings of clinical samples
obtained from hematology-oncology patients indicate Penicillium-like morphology, there is a
possibility that the infection might be caused by
rarely encountered species other than T. marneffei,
such as T. purpurogenus.
Conflict of interest: The authors have no conflicts
of interest. They alone are responsible for the content and composition of the manuscript.
nREFERENCES
[1] Chowdhary A., Kathuria S., Agarwal K., et al.
Voriconazole-resistant Penicillium oxalicum: an emerging pathogen in immunocompromised hosts. Open. Forum. Infect. Dis. 16, 29, 2014.
[2] Arunmozhi Balajee S., Brandt M.E. Aspergillus and
Penicillium. In The Manual of Clinical Microbiology
(Versalovic J, Carroll K, Funke G, Jorgensen JH, Landry
ML, and Warnock D., Eds) 2011, 1836-1852. ASM Press,
Washington DC.
[3] Samson R.A., Yilmaz N., Houbraken J., et al. Phylogeny and nomenclature of the genus Talaromyces and
taxa accommodated in Penicillium subgenus Biverticillium. Stud. Mycol. 70, 159-183, 2011.
[4] Chowdhary A., Geltner C., Lass-Flörl C., Bonatti H.,
Muller L., Stelzmuller I. Invasive pulmonary mycosis
due to Penicillium chrysogenum: a new invasive pathogen. Transplantation 95, e21-e23, 2013.
[5] Barcus A.L., Burdette S.D., Herchline T.E. Intestinal
invasion and disseminated disease associated with Penicillium chrysogenum. Ann. Clin. Microbiol. Antimicrob. 4,
21, 2005.
[6] Santos P.E., Piontelli E., Shea Y.R., et al. Penicillium
Pulmonary infection caused by Talaromyces purpurogenus in a patient with multiple myeloma 157
piceum infection: diagnosis and successful treatment in
chronic granulomatous disease. Med. Mycol. 44, 749753, 2006.
[7] Weng C.H., Wang R.C., Hsieh T.Y., Tsai C.A., Lin
T.H. Penicillium pneumonia in a patient with newly diagnosed Franklin disease. Am. J. Med. Sci. 344, 69-71,
2012.
[8] Lyratzopoulos G., Ellis M., Nerringer R., Denning
D.W. Invasive infection due to Penicillium species other
than Penicillium marneffei. J. Infect. 45, 184-195, 2002.
[9] Chen M, Houbraken J, Pan W, et al. Pulmonary fungus ball caused by Penicillium capsulatum in a patient
with type 2 diabetes: a case report. BMC. Infect. Dis. 13,
496, 2013.
[10] Hoffman M., Bash E., Berger S.A., Burke M., Yust
I. Fatal necrotizing esophagitis due to Penicillium
chrysogenum in a patient with acquired immunodeficiency syndrome. Eur. J. Clin. Microbiol. Infect. Dis. 11,
1158-1160, 1992.
[11] Mok T., Koehler A.P., Yu M.Y., Ellis D.H., Johnson
P.J., Wickham N.W. Fatal Penicillium citrinum pneumonia with pericarditis in a patient with acute leukemia. J.
Clin. Microbiol. 35, 2654-2656, 1997.
[12] Alvarez S. Systemic infection caused by Penicillium
decumbens in a patient with acquired immunodeficiency syndrome. J. Infect. Dis. 162, 283, 1990.
[13] Santos P.E., Piontelli E., Shea Y.R., et al. Penicillium
piceum infection: diagnosis and successful treatment in
chronic granulomatous disease. Med. Mycol. 44, 749753, 2006.
[14] Zanatta R., Miniscalco B., Guarro J., et al. A case of
disseminated mycosis in a German shepherd dog due
to Penicillium purpurogenum. Med. Mycol. 44, 93-97, 2006.
[15] Yilmaz N., Houbraken J., Hoekstra E.S., Frisvad
J.C., Visagie C.M., Samson R.A. Delimitation and characterisation of Talaromyces purpurogenus and related
species. Persoonia 29, 39-54, 2012.
[16] Frisyad J.C., Yilmaz N., Thrane U., Rasmussen
K.B., Houbraken J., Samson R.A. Talaromyces atroroseus,
a new species efficiently producing industrially relevant red pigments. PloS One. 8, e84102, 2013.
[17] Breton P., Germand P., Morin O., Audouin A.F.,
Milpied N., Harousseau J.L. Rare pulmonary mycoses
in patients with hematologic diseases. Rev. Pneumo.
Clin. 54, 253-257, 1998.
[18] Novotny W.E., Dixit A. Pulmonary hemorrhage in
an infant following 2 weeks of fungal exposure. Arch.
Pediatr. Adolesc. Med. 154, 271-275, 2000.