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Penicillium species : Is it a contaminant or pathogen ? Delayed diagnosis in a

case of pneumonia caused by Penicillium chrysogenum in a systemic lupus
erythematosis patient.

Article  in  International Journal of Tropical Medicine and Public Health · January 2016

DOI: 10.5455/214966/ijtmph.

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 International Journal of Tropical Medicine and Public Health

Volume 6, Issue 1, 2016 Case Report

Crosshouse books DOI: 10.5455/214966/ijtmph
ISSN No. 2049-1964

PENICILLIUM SPECIES: IS IT A CONTAMINANT OR PATHOGEN? DELAYED DIAGNOSIS IN

A CASE OF PNEUMONIA CAUSED BY PENICILLIUM CHRYSOGENUM IN A SYSTEMIC LUPUS
ERYTHEMATOSUS PATIENT
Sharana Mahomed1,2, Prinita Baijnath3, Koleka Mlisana1,2
1
Department of Medical Microbiology, National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-
Natal, South Africa, 2Department of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-
Natal, Durban, South Africa, 3Department of Pulmonology, University of KwaZulu-Natal, Durban, South Africa
Email: sharana.mahomed@gmail.com
Received: Date Jan 11, 2016 Revised and Accepted: Date Feb 23, 2016

ABSTRACT

We report a case of pneumonia caused by Penicillium species in an 18-year-old female patient with systemic lupus erythematosus. This patient
had an intermittent chronic cough of one-year duration. She was previously treated with antibiotics but showed no improvement. Microbiological
investigation of sputum samples cultured a pure growth of Penicillium species. This organism was repeatedly cultured on subsequent samples. In
lieu of her clinical presentation, she was commenced on antifungal therapy. After 2 weeks of intravenous amphotericin B and an additional 10 weeks
of itraconazole treatment, the patient had complete resolution of symptoms. In addition, subsequent sputum cultures revealed no growth. She was
discharged for follow-up. This case highlights the importance of the correlation between the organisms isolated in the microbiology laboratory with
the clinical presentation of the patient.

Keywords: Fungal disease, Penicillium species, systemic lupus erythematosus.

INTRODUCTION
Infections caused by fungal pathogens are rapidly becoming more
common in immunocompromised patients.[1] It is well documented
that Candida species and Aspergillus species are common etiological
agents of opportunistic infections in these patients.[2] In recent years,
however, other uncommon fungal pathogens have also been reported.[3]
Penicillium species are common environmental commensals that are
usually considered non-pathogenic. Apart from Penicillium marneffei,
members of the genus Penicillium have rarely been reported as infective
agents.[4]
We report a case of pneumonia caused by Penicillium species in a young
female patient with systemic lupus erythematosus (SLE).
CASE REPORT
chest showed infective changes with bilateral infiltrates. Sputum was
sent for microscopy, culture, and susceptibility including acid fast
bacilli detection to exclude TB. GeneXpert MTB/RIF (Cepheid) assay
was negative for TB. Due to the presentation and history of the patient,
she was treated for a chest infection with amoxicillin/clavulanate and
discharged.
About 1 month later, she was reviewed and complained of a worsening
cough, productive of yellow sputum. On examination, she was in
respiratory distress. Bilateral crepitations were audible on auscultation,
and a chest X-ray showed increased infiltrates and lung involvement.
Laboratory investigations revealed a leukocyte count of 19,000/mm,
and renal and liver function tests were unremarkable. The erythrocyte
sedimentation rate was 62 mm/h, and urine analysis was normal. Beta-
D-Glucan enzyme immunoassay was negative for Aspergillus. Blood
cultures did not grow any organisms.

An 18-year-old female patient with known SLE and was seen at the
rheumatology follow-up clinic due to an intermittent chronic cough of
1-year duration. The cough was productive of whitish colored sputum
with no hemoptysis. She had previously been treated with different
antibiotics by her primary general practitioner, with no improvement.
There were no other constitutional symptoms, and the patient was HIV
non-infected. In addition, she had no history of previous tuberculosis
(TB) infection or any TB contact. She had no other medical, occupational,
or surgical history of note and was on chloroquine, mycophenolate
mofetil, and high dose steroids for SLE.
On examination, she was clinically stable and not in respiratory distress.
However, on chest auscultation, bilateral crepitations at the lung bases
were present. All other systems were unremarkable. An X-ray of the
Microbiology investigations were repeated and due to her unresolved
symptoms, a high-resolution computed tomography (HRCT) scan was
performed to aid in the diagnosis and management. The HRCT showed
scattered fibrotic bands and nodular opacities in the right anterior
segment of the upper lobe as well as the posterior segments of the lower
lobe. Similar findings were noted in the left lower lobe. The presence
of “tree in bud opacities” (highly suggestive of active infection) was
present. Significant axillary lymph nodes were seen bilaterally, and
mediastinal lymph nodes were also noted (Figure 1).
All sputum samples were inoculated onto sabouraud glucose agar
without cycloheximide and processed according to standard operating
procedures in the mycology laboratory. After 3 days velvety, greenish-
blue colonies that were highly suggestive of the mold Penicillium
Mahomed, et al.
Figure 1: HRCT showing axillary and mediastinal lymph nodes
species grew on all plates at room temperature. No other organisms
were isolated. Macroscopically, the reverse side of the mold was
uncolored. Microscopic examination using lactophenol blue revealed
conidial heads with smooth-walled stripes and divergent branches.
Metulae were cylindrical and smooth walled. Bore phialides were flask
shaped. Conidia were globose with smooth walls. On further incubation
of subcultures, the fungus grew at 25°C and 37°C after an incubation
of 2 weeks. There was no growth at 42°C. Although we did not have
access to mycological speciation, the isolate matched with a Penicillium
chrysogenum control strain in all essential characteristics. This method
of speciation has previously been described.[5]
The clinical significance of the Penicillium species isolated was
questioned and, therefore, repeat sputum samples were requested. The
repeat sputum samples cultured Penicillium species again. In light of the
repeat cultures, clinical and radiological presentation of the patient, as
well as the immunocompromised nature of the patient’s disease (SLE),
she was diagnosed with fungal pneumonia and initiated on liposomal
amphotericin B.
A marked clinical improvement was seen after 2 weeks of amphotericin B.
In light of the possible side effects of prolonged amphotericin B, the
patient was initiated on oral itraconazole 200 mg/day twice a day
(to maintain serum drug levels at approximately 800 ng/ml). After
2 weeks of itraconazole, a repeat HRCT still showed active infection,
and thus the duration of itraconazole use was extended. After 10 weeks
of itraconazole treatment, the patient was clinically stable and with
complete resolution of symptoms. In addition, subsequent sputum
cultures revealed no growth. She was discharged for follow-up.
DISCUSSION
We report a case of pneumonia caused by Penicillium species in an
18-year-old female patient with SLE. Microbiological investigation of
sputum samples cultured a pure growth of Penicillium species. Ordinarily,
the clinical significance of this organism would have been questioned,
and it would have been regarded as a laboratory contaminant. However,
in this case, the patient showed no improvement clinically, and the
organism was repeatedly cultured on subsequent samples.
Penicillium species is a rare cause of disease. Before the use of
antiretroviral therapy, P. marneffei was a major cause of mycosis in
HIV-infected individuals.[4] Other species of Penicillium are rare causes
of human infections. In recent years, however, reports of opportunistic
infections caused by emerging fungal pathogens have been described.[1]
P. chrysogenum, in particular, has been cited as an emerging pathogen.[6]
These organisms are ubiquitous in nature and found in soil, decaying
matter, sewage plantations, and construction sites. The isolation of
P. chrysogenum from a Russian space station has also highlighted
15 Inter J Trop Med Pub Health Vol 6, Issue 1, 2016; 14-16
the organism’s survival capabilities, contributing to its unique
characteristics.[7]
Other infections caused by this organism have been reported.
P. chrysogenum has been implicated in cases of Types 1 and 3 allergy
such as asthma and hypersensitivity pneumonitis. Both non-invasive
and invasive infections have been reported. Rare infections reported
include a case of keratitis resulting from a super-imposed infection
of a vernal shield ulcer; and an interesting case of cutaneous infection
in an immunocompetent patient.[8,9] In a comprehensive review of
otomycosis, Yassin et al., reported on P. chrysogenum as being one of the
causative pathogens.[10]
Invasive infections caused by P. chrysogenum are predominantly seen in
patients with impaired cellular immunity. Cases of endocarditis, central
nervous system (CNS) infection, and systemic infection have been
described.[11-13] In this case report, the patient was HIV non-infected
with SLE. A decrease in both relative and absolute T-cell counts has
been demonstrated in SLE patients, predisposing them to infection.[14]
In addition, this patient was on high dose steroids, contributing to her
immunocompromised state.
In this case, the patient completed 2 weeks of amphotericin B and
10 weeks of itraconazole before the HRCT had shown complete
resolution of infection. Due to the rarity of infections, antifungal
susceptibility profiles of Penicillium species have not yet been
determined. The appropriate drug for treatment of Penicillium species-
related infections has not been determined.
Treatment with amphotericin B, flucytosine, and azoles such as
itraconazole and fluconazole has been described in the literature.
Lopez-Martinez et al., reported on a rare case of cutaneous infection
caused by P. chrysogenum in an immunocompetent patient.[9] The
patient was successfully treated with itraconazole and subsequently
had no recurrence of infection. The use of amphotericin B and topical
natamycin in a patient with post-traumatic endophthalmitis resulted in
the complete eradication of the organism.[15]
P. chrysogenum has also been reported as the cause of CNS infection in
a 73-year-old immunocompetent patient. The organism was isolated
thrice on subsequent cerebrospinal fluid specimens. The patient was
successfully treated with fluconazole.[12] A case of systemic infection in a
cotton farmer with acute myeloid leukemia has also been described.[13]
The patient was treated with amphotericin B and itraconazole. Fungal
blood cultures positive for P. chrysogenum in an African American female
with severe sepsis syndrome was reported by Barcus et al. The patient
presented with an acute abdomen and an exploratory laparotomy
revealed an incarcerated hernia. The patient was successfully treated
with 6 weeks of amphotericin B lipid complex, followed by an extended
course of oral itraconazole.[16]
Despite the use of appropriate antifungals, cases associated with
mortality have also been described. A case of CNS infection was reported
by Lyratzopoulos et al. Despite the use of a combination treatment with
amphotericin B and 5-flurouracil, the patient died.[17] Upshaw et al.,
reported on a fatal case of endocarditis in a 31-year-old female patient
with an aortic prosthesis treated with amphotericin B.[11] A 30-year-old
HIV-infected male with necrotizing esophagitis died despite treatment
with amphotericin B and infarction.[18]
In this patient, the source of infection was pneumonia. P. chrysogenum,
as a cause of pneumonia, has very rarely been reported on. A case of
necrotizing pneumonia due to P. chrysogenum in a cancer patient has
been cited in the literature.[5] The right lower pulmonary lobe was
infiltrated by the organism and resolution of disease was successfully
achieved with a combination of surgery (lobectomy) and itraconazole.
A case of invasive pulmonary mycosis in a lung transplant recipient
patient has also been reported.[6] In this case, however, zygomycosis was
 Mahomed, et al.
the initial diagnosis, followed by isolation of P. chrysogenum from tissue
biopsy samples. The patient had courses of posaconazole empirically,
followed by voriconazole, caspofungin, and liposomal amphotericin B.
This is, therefore, the third case report of pneumonia caused by
P. chrysogenum. In light of the repeat sputum samples that cultured pure
growths of the organism, clinical and radiological presentation of the
patient and ultimately the favorable response to antifungal treatment,
we can strongly postulate that the Penicillium species was the causative
agent of infection in this patient.
An important aspect highlighted in this case was the significant delay
in the clinical diagnosis. A differential diagnosis usually includes
common infections that are of local importance. South Africa has a high
prevalence of TB and in this case, the patient was repeatedly screened
for TB. In addition, radiographic features may mimic other opportunistic
infections such as TB, cryptococcosis, and histoplasmosis. Infection
can also concurrently occur with other common infections such as
pneumocystis pneumonia and pulmonary TB. Thus, infections caused
by uncommon pathogens can easily be missed. In this patient, an HRCT
was needed to diagnose active disease. In addition, as highlighted
previously, Penicillium species is ubiquitous in nature and is frequently
regarded as a contaminant when isolated. Thus, clinical significance
was queried and repeat sputum samples were requested, resulting in
further delay.
CONCLUSION
This case highlights the importance of the correlation between the
organisms isolated in the microbiology laboratory with the clinical
presentation of the patient. The isolation of organisms commonly
regarded as contaminants should not always be ignored, especially in an
immunocompromised individual. Liaison between the microbiologists
and clinicians cannot be over emphasized.
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