3 DISCUSSION
Although Scedosporium infection is more common in
immunocompromised patients, it can also cause infection in
immunocompetent hosts8,17,18. And the lung is one of
the most common sites of Scedosporium infections. Patients with
underlying lung diseases are more likely to develop infections.
According to present knowledge of Scedosporium lung infection in
immunocompetent adult patients3,19, the infection rate
of males and females is similar, and their age ranges from 26 to
84-year-old (mean 56.4 years). The most common underlying lung disease
is the cavitary lesion caused by pulmonary tuberculosis, followed by
bronchiectasis. Asthma, pleural tuberculosis, and chronic restrictive or
obstructive pulmonary disease have also been reported. Here we reported
a case series including a 43-year-old female, a 36-year-old female and a
45-year-old male, all of them were non-Transplant, non-HIV-infected
hosts, and without a history of long-term high-dose glucocorticoid use,
so they were considered the immunocompetent adult hosts. Among them, 2
female patients had a history of bronchiectasis. The left pulmonary
bullectomy was also performed for the first female. And another was
infected with pulmonary nontuberculous mycobacteria for many years. Both
of them were mixed infection cases. Until now, only three mixed
pulmonary infection cases of Scedosporium and nontuberculous
mycobacteria was reported15,20,21. Two patients had a
history of pulmonary tuberculosis and one had a 15-year history of
nontuberculous mycobacteria (NTM) pneumonia. Although the reason for the
rareness of coinfection with NTM and Scedosporium is unclear,
some investigators considered it might be related to the lower frequency
of cavitations in individuals with NTM than in those with
tuberculosis15. Another male patient in our case had a
history of emphysema. He was in good health before this thick and had no
habit of smoking. However, he had been working on a construction site
for a long time and had a history of exposure to second-hand smoke,
which may be the important incentive caused him to developSedosporium infection.
There are many similarities between the clinical and imaging features ofSedosporium and Aspergillus infection. But their antifungal drug
resistance is much different. The susceptibility to antifungal drugs
among different species for Sedosporium is also quite different.
Therefore, the differential diagnosis of microorganisms timely and
accurately is crucial for conducting precise
treatment13. In the reported
cases3,22, etiological culture of sputum,
bronchoalveolar lavage fluid and lung biopsy specimens, NGS and
polymerase chain reaction are the main methods to diagnoseSedosporium infection. Among them, the positive rate of biopsy
tissue samples are higher than that of bronchoalveolar lavage fluid and
sputum samples, and even multiple tests may be required to obtain
positive results for bronchoalveolar lavage fluid and sputum samples. In
our case, the first patient used NGS of bronchoalveolar lavage fluid to
assist in the diagnosis of Sedosporium . The second patient was
diagnosed the Sedosporium infection by continuous sputum
cultures. The NGS and cultures of sputum and bronchoalveolar lavage
fluid were all performed in the third patient to diagnose theSedosporium . And NGS combined with traditional microbial culture
could make diagnosis more accurate and efficient.
Sedosporium species are highly resistant to many available
antifungals, including amphotericin B, echinocandins, flucytosine and
the first-generation azoles. Currently, voriconazole is still preferred
for the first-line drug therapy, and the recommend adult dosage was 6
mg·kg-1, q12h on
the first day, followed by 4 mg·kg-1, bid with
intravenous administration, or 200 mg bid with oral
administration13, but its duration of therapy is
uncertain. In 10 cases of Sedosporium pulmonary infections in
immunocompetent hosts treated with voriconazole3,19,
the treatment dosage was adjusted according to a combination of
recommended dosage and TDM results, and the therapy duration ranged from
1 to 10 months. Among them, one was recovered, eight was improved in
clinical symptoms or images, and one was died. The maximum follow-up
time of them was 18 months. And there was no recurrence case reported.
The cured case was a 51-year-old female with no underlying lung
diseases, but with surgery history. And she was continuously treated
with voriconazole for 3 months. All three patients in this case received
no operation but voriconazole alone with a recommended dose or above.
The TDM results of their voriconazole were all reached the standard
between 0.5-5mg·L-1. There was no Sedosporiumdetected in the first patient with 2-month treatment. The third patient
was treated for 3-month with complete improvement in symptoms and
imaging. The second patient responded poorly to the recommended dose of
voriconazole and failed to achieve pathogenic clearance even after
12-month of continuous treatment, but her symptoms improved slightly.
Research23 found voriconazole therapy may have a
better effect when MIC was below 2 g·mL-1, but a
limited effect to treatment at MIC of 4 g·mL-1 and may
lead to treatment failure. No guideline recommendation could be given
because no antifungal susceptibility testing results were available for
the second patient. In the cases of pulmonary nontuberculous
mycobacterial and Sedosporiumcoinfection15,20,21, only one patient who had no
indication for surgery was treated with voriconazole alone for 6-month
with initial dose of 400 mg daily, then increased to 500 mg daily based
on TDM results. The symptoms and imaging improved after 6 months, but no
follow-up records were reported. Another patient was followed up for 2
years after discontinuation of methylprednisolone and no deterioration
was found with pulmonary imaging. Therefore, patients without
indications for surgery could be treated with voriconazole alone with
the recommended dose or above and treatment outcomes such as pathogens
clearance or clinical and imaging improvement in most patients could be
received. TDM would be required for dose adjustment and continuous
treatment for at least 2 months also would be required. To patients with
long duration of pulmonary nontuberculous mycobacterial infection and
mixed infection with Sedosporium with no indication for surgery,
voriconazole monotherapy could be less effective in clearing the
pathogenic, and real-time drug sensitivity may be an important option to
guide treatment. Current treatment experience needs to be confirmed with
more clinical practices. Besides, posaconazole has been shown effective
against Sedosporium in animal models, but was less active than
voriconazole24-26. In this case, patient 2 failed to
achieve clearance of pathogenic even after switching to posaconazole
treatment for more than 1 month. It suggests that posaconazole only have
limited effect to those patients Sedosporium is not cleared with
voriconazole.
Considering the experience of Sedosporium clearance from patients
with cystic fibrosis, combination therapy may be a good option, such as
voriconazole or posaconazole was synergistic with echinocandins in a
double combination27, and a combination of
voriconazole, caspofungin and amphotericin B aerosol was recommended in
a triple combination28. Besides, novel drug studies
found that Manogepix (APX001A), Olorofim (F901318), and fosmanogepix
(APX001) showed good antifungal activity, and vitro activity of the
first two kinds were higher than voriconazole againstSedosporium 29-31. The antirheumatic drug
Auranofin32 was also found effective against a variety
of fungus, including Sedosporium . And the Sedosporiumevading host immunity is associated with thioredoxin
reductase33. The appearance of the above new drugs,
new applications and new targets will provide new basis and options for
the treatment of Sedosporium infections.