Pulmonary Fungal Infection*

Emphasis on Microbiological Spectra, Patient

Outcome, and Prognostic Factors
Kuan-Yu Chen, MD; Shiann-Chin Ko, MD; Po-Ren Hsueh, MD;
Kwen-Tay Luh, MD, FCCP; and Pan-Chyr Yang, MD, PhD, FCCP

Study objectives: To investigate the microbiological spectra, patient outcome, and prognostic
factors of pulmonary fungal infection.
Design: The medical and microbiological records of patients with pulmonary fungal infection
were retrospectively analyzed.
Setting: A university-affiliated tertiary medical center.
Patients and methods: From January 1988 to December 1997, all cases of pulmonary fungal
infection were reviewed. The criteria for inclusion were obvious lung lesion shown on chest
radiographs and one of the following: (1) the presence of fungi in or isolation of fungi from the
biopsy specimen of open thoracotomy, thoracoscopy, transbronchial lung biopsy, or ultrasound-
guided percutaneous needle aspiration/biopsy; or (2) isolation of fungi from pleural effusion or
blood, with no evidence of extrapulmonary infection.
Results: A total of 140 patients were included. Ninety-four cases of pulmonary fungal infection
(67%) were community acquired. The most frequently encountered fungi were Aspergillus
species (57%), followed by Cryptococcus species (21%) and Candida species (14%). There were 72
patients with acute invasive fungal infection, with a mortality rate of 67%. Multivariate logistic
regression analysis showed that nosocomial infection (p 0.014) and respiratory failure
(p 0.001) were significantly and independently associated with death of acute invasive fungal
infection.
Conclusions: Pulmonary fungal infection of community-acquired origins is becoming a serious
problem. It should be taken into consideration for differential diagnosis of community-acquired
pneumonia. Furthermore, acute invasive fungal infection is associated with a much higher
mortality rate for patients with nosocomial infection or complicating respiratory failure. Early
diagnosis with prompt antifungal therapy, or even with surgical intervention, might be warranted
to save patients lives. (CHEST 2001; 120:177184)

Key words: community-acquired; fungal pneumonia; nosocomial pneumonia

Abbreviation: RR relative risk

F ungal infection has emerged as a worldwide

health-care problem in the last decade. The 1 4
infection has been difficult to evaluate since diag-
noses were seldom confirmed. Fungi isolated from
increasing incidence of fungal infection has also sputum may represent either pathogens or sapro-
become a serious problem in Taiwan. From 1980 phytes. A previous report demonstrated that Can-
to 1994, a 27-fold increase in bloodstream infec- dida colonization could be found in respiratory
tions due to Candida species was observed at samples obtained by BAL, endotracheal aspirate,
National Taiwan University Hospital.5 However, or protected specimen brushing in critically ill
the prevalence and prognosis of pulmonary fungal patients.6 Therefore, identification of fungi in
biopsy specimens obtained by invasive diagnostic
*From the Departments of Internal Medicine (Drs. Chen, Ko, procedures such as bronchoscopy, thoracoscopy,
Hsueh, and Yang) and Laboratory Medicine (Dr. Luh), National or thoracotomy was usually necessary to confirm
Taiwan University Hospital, Taipei, Taiwan.
Manusript received August 1, 2000; revision accepted February the diagnosis. In this study, we reviewed the
14, 2001. clinical features of patients with pulmonary fungal
Correspondence to: Pan-Chyr Yang, MD, PhD, FCCP, Depart- infection using strict criteria to analyze the micro-
ment of Internal Medicine, National Taiwan University Hospital,
No. 7 Chung-Shan South Rd, Taipei 100, Taiwan; e-mail: biological spectra, patient outcome, and prognos-
pcyang@ha.mc.ntu.edu.tw tic factors of this disease.

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 Materials and Methods Results
The medical records of consecutive patients with diagnoses of Clinical Characteristics
pulmonary fungal infection treated at National Taiwan University
Hospital during the period of January 1988 through December
From January 1988 to December 1997, medical
1997 were reviewed. The inclusion of a patient required that the and microbiological records of 187 patients with
following criteria were met: obvious lung lesion shown on chest pulmonary fungal infection were reviewed. Of these,
radiography and at least one of the following: (1) identification of 140 patients fulfilled the inclusion criteria by various
fungi in biopsy specimens obtained from open thoracotomy, diagnostic methods (Table 1). There were 74 pa-
thoracoscopy, transbronchial lung biopsy, or ultrasound-guided tients included by pathologic examinations of biopsy
percutaneous needle biopsy; (2) isolation of fungi species from specimens. Fifty-eight patients had fungi isolated
specimens of open thoracotomy biopsy, thoracoscopic biopsy,
transbronchial lung biopsy, or ultrasound-guided percutaneous
from biopsy specimens, aspirated fluids, pleural ef-
needle aspiration/biopsy; (3) isolation of fungal species from fusions, or blood. Three patients had cryptococci
pleural effusion or blood, with no evidence of extrapulmonary confirmed by microscopic examinations of aspirated
infection. Pulmonary cryptococcal infection was also defined as fluids, and five patients had positive cryptococcal
cryptococci identified by microscopic examination of percutane- antigen detected in the aspirated fluids. Of the 140
ous needle aspiration fluid or positive cryptococcal antigen (an cases included in the analysis, there were 5 cases in
antigen titer equal to or 1:8) in percutaneous needle aspiration 1988, 8 in 1989, and 6 in 1990. There were 10, 11, and
fluid,7 with resolution of pulmonary lung lesion after antifungal
therapy.
8 cases annually in 1991, 1992, and 1993, respectively.
Acute invasive fungal infection was defined as patients with However, there were 15 cases annually from 1994
rapid progression of disease clinically or radiographically, and at through 1997 (16 in 1994, 26 in 1995, 20 in 1996, and
least one of the followings: (1) fungal invasion of lung paren- 30 in 1997), with increases in both nosocomial and
chyma noted by pathologic examination or (2) fungal isolation community-acquired infections (Fig 1).
from sterile site such as blood or pleural effusion. Pulmonary The demographic features of the 140 patients are
fungal infection developing after 48 h of hospital admission summarized in Table 2, including 72 patients with
was regarded as nosocomial; otherwise, the fungal infection
was considered community acquired. Previous use of antibi-
acute invasive fungal infection and 68 with myce-
otics was defined as receiving antibiotic therapy before hospi- toma. The majority of patients were male in both
tal admission or for 48 h during hospital admission before a patient groups. No significant difference in age and
clinical diagnosis of fungal pneumonia was made. Antecedent gender ratio was demonstrated between both
chemotherapy was defined as receiving anticancer chemother- groups. There were more nosocomial infections in
apy 1 month before clinical diagnosis of fungal pneumonia. patients with acute invasive fungal infection than in
Long-term steroid use was defined as receiving steroid therapy those with mycetoma (54% vs 10%; p 0.001). One
for 1 month before clinical diagnosis of fungal pneumonia.
Fever was defined as body temperature 37.5C. Neutrope-
hundred nineteen patients (85%) had underlying
nia was defined as absolute neutrophil count 1,000/L in diseases or associated medical conditions. Eighty-
peripheral blood. Complicating fungemia was defined as the
same fungal species were identified both in the lung and
blood. Respiratory failure was defined as Pao2 60 mm Hg Table 1Diagnostic Methods for the 140 Patients
and/or Paco2 50 mm Hg while breathing room air. With Pulmonary Fungal Infection
For isolation of fungi, specimens were inoculated onto Sab-
ouraud dextrose agar plates (BBL Microbiology Systems; Cock- Methods Data
eysville, MD). Identification of molds was based on gross colony
Pathologic 74 (53)
morphologies and microscopic pictures. Cornmeal agar (BBL
Thoracotomy or thoracoscopy 50 (36)
Microbiology Systems) slide cultures were used to identify molds.
Percutaneous ultrasound-guided biopsy 9 (6)
Yeasts were identified to species level by standard method, and Transbronchial lung biopsy 10 (7)
their identity was confirmed by the API ID 32C (bioMerieux; Necropsy 5 (4)
Marcy-IEtoile, France).8 Microbiological 58 (41)
The following data were collected for each patient: age and Thoracotomy or thoracoscopy 8 (6)
gender; predisposing factors, including underlying diseases and Percutaneous ultrasound-guided biopsy 26 (19)
associated medical conditions; antimicrobial agents administered; Transbronchial lung biopsy 3 (2)
clinical symptoms; peripheral WBC and differential cell counts; Pleural effusion 16 (11)
findings in chest radiographs; strains of pathogens isolated or Blood 5 (4)
found in biopsy specimens; regimens and durations of antifungal Microscopic 3 (2)
therapy; invasive or surgical procedures; durations of hospitaliza- Percutaneous ultrasound-guided aspiration 3 (2)
tion; and patient outcome. Serologic 5 (4)
Differences in survival among subgroups of variables were Percutaneous ultrasound-guided aspiration 5 (4)
analyzed by 2 test, or Fishers exact test when necessary. A *Data are presented as No. (%).
multivariate logistic regression model was applied (SPSS 8.0 for Including one patient who coughed up a piece of necrotic lung
Windows; SPSS; Chicago, IL) with only variables that were tissue that proved to be aspergillosis by pathologic examination.
significantly associated with survival in the univariate analysis. A Diseases diagnosed by microscopy or serology were all cryptococ-
p value of 0.05 was considered significant. cosis.

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 with mycetoma, mostly aspergilloma (53% vs 11%;
p 0.001). The most common presentations among
the 140 patients were cough (63%), fever (54%), and
dyspnea (47%). Peripheral WBC counts were
20,000/L in 17 patients (12%). Pulmonary fungal
infection developed in 28 patients (20%) during
granulocytopenia after chemotherapy.
The most frequent radiographic manifestations
were single nodular lesions (n 74; 53%), followed
by consolidations (n 45; 32%), multiple nodular
Figure 1. Annual incidence of pulmonary fungal infection during lesions (n 14; 10%), and interstitial pattern (n 7;
the 10-year period in National Taiwan University Hospital. 5%). Seventy-two patients (51%) had cavitary le-
sions, including 6 patients with abscess formation
confirmed by percutaneous aspiration. Thirty-four
five patients had compromised immunity due to (in patients (24%) had pleural effusions. There were 99
order of decreasing frequency) malignancy, diabetes patients with unilateral lesions and 41 with bilateral
mellitus, long-term steroid use, cirrhosis of the liver, lesions. For patients with unilateral involvement of
organ transplantation, uremia, alcoholism, and pulmonary fungal infection, upper lobes (right upper
AIDS. The rate of immunocompromised status was lobe, 21%; left upper lobe, 12%) were the most
higher in patients with acute invasive fungal infec- common lobes of distribution, followed by lower
tion (89% vs 31%; p 0.001). However, previous lobes (right lower lobe, 15%; left lower lobe, 9%).
tuberculous infection was more frequent in patients The most common radiologic manifestation in pa-

Table 2Demographic Data, Clinical Courses, Treatments, and Outcomes of Different Patient Groups With
Pulmonary Fungal Infection*

Acute Invasive Fungal

Total Infection Mycetoma
Variables (n 140) (n 72) (n 68)

Mean age, yr 45 41 49
Male/female gender, No. 82/58 44/28 38/30
Male patients, % 59 60 56
Hospital acquired 46 (33) 39 (54) 7 (10)
ICU acquired 38 (27) 33 (46) 5 (7)
Underlying conditions
Immunocompromised 85 (61) 64 (89) 21 (31)
Malignancy 38 (27) 33 (46) 5 (7)
Hematologic (leukemia and lymphoma) 29 (21) 27 (38) 2 (3)
Lung cancer 3 (2) 1 (1) 2 (3)
Others 6 (4) 4 (6) 2 (3)
Diabetes mellitus 27 (19) 11 (15) 16 (24)
Chemotherapy 23 (16) 21 (29) 2 (3)
Long-term steroid use 22 (15) 19 (26) 3 (4)
Organ transplantation 8 (6) 8 (11) 0 (0)
AIDS 7 (5) 7 (10) 0 (0)
Uremia 5 (3) 5 (7) 0 (0)
Cirrhosis of the liver 1 (1) 1 (1) 0 (0)
COPD 7 (5) 5 (7) 2 (3)
Previous TB infection 44 (31) 8 (11) 36 (53)
None 21 (15) 2 (3) 19 (28)
Mean ( SD) hospital stay, d 47 57 69 67 24 29
Antifungal therapy 98 (70) 68 (94) 30 (44)
Amphotericin B 65 (46) 57 (79) 8 (12)
Fluconazole 61 (44) 37 (51) 24 (35)
Itraconazole 10 (7) 8 (11) 2 (3)
Operation 63 (45) 12 (17) 51 (75)
ICU admission 38 (27) 33 (46) 5 (7)
Death 51 (36) 48 (67) 3 (4)
*Data are presented as No. (%) unless otherwise indicated. TB tuberculosis.
Other malignancies included breast (n 2), urinary bladder (n 1), nasopharyngeal (n 1), hepatocellular (n 1), and esophageal (n 1).

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 tients with Aspergillus infection was nodular type interstitial pattern of chest radiographs. Nodular
(n 60; 74.1%; Fig 2, top, left), followed by consol- pattern was most commonly found in chest radiog-
idation (n 21; 25.9%; Fig 2, top, right). One raphy of patients with cryptococcal infection
patient with invasive aspergillosis had concurrent (n 23; 76.7%; Fig 2, middle, left), followed by

Figure 2. Top, left: Aspergilloma. A 22-year-old man with diabetes mellitus presented with
hemoptysis. Chest radiography shows a cavitary nodular lesion with air-crescent in the right lower lung.
He underwent wedge resection and Aspergillus species was found. Top, right: Invasive aspergillosis. A
26-year-old woman with acute lymphoblastic leukemia status post bone marrow transplantation
presented with fever. Chest radiography shows a consolidation in the left upper lung field. Aspergillus
niger was isolated from specimen by percutaneous fine-needle aspiration. Middle, left: Cryptococcoma.
A 53-year-old woman without any underlying diseases presented with cough. A posteroanterior chest
radiograph shows a well-defined nodule in lateral aspect of the right middle lung area. She underwent
thoracoscopic resection, and pathology findings revealed a cryptococcoma. Middle, right: Cryptococcal
pneumonia. A 34-year-old man without any underlying diseases presented with dry cough, fever, and
dyspnea. Chest radiography shows consolidations in the bilateral lower lung fields. The cryptococcal
antigen titer of the aspiration specimen was 1:2,560. Bottom, center: Candida pneumonia. A 45-year-old
woman with acute myeloblastic leukemia presented with fever. Chest radiography shows a lobar
consolidation in the right upper lung field. C albicans was isolated from specimen of percutaneous
fine-needle biopsy.

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 consolidation (n 5; 16.7%; Fig 2, middle, right) Table 4 Patients and Mortality Rate With Different
and interstitial pattern (n 2; 6.7%). As for patients Patterns of Pulmonary Fungal Infections*
with Candida infection, consolidation was the most Patients, No. Mortality, No. (%)
frequent pattern found (n 17; 87%; Fig 2, bottom,
Total 140 51 (36.4)
center), followed by nodular pattern (n 1; 5%) and Aspergillus spp 80 32 (40.0)
interstitial pattern (n 2; 10%). Aspergilloma 41 3 (7.3)
Invasive aspergillosis 33 24 (72.7)
Microbiology Systemic 6 5 (83.3)
Cryptococcus spp 30 2 (6.7)
The fungi identified from the 140 patients are Cryptococcoma 23 0 (0)
shown in Table 3. The major fungal species encoun- Pneumonia 5 0 (0)
tered were Aspergillus (n 80, 57%), Cryptococcus Systemic 2 2 (100)
Candida spp 20 14 (70.0)
(n 30, 20%), and Candida species (n 20; 14%). Pneumonia 12 9 (75.0)
Various types of pulmonary infection caused by Systemic 8 5 (62.5)
different fungal species are listed in Table 4. For Others 10 3 (30.0)
patients with nosocomial pulmonary infections, the Mycetoma 4 0 (0)
Pneumonia 4 2 (50.0)
most common pathogen isolated was Aspergillus
Systemic 2 1 (50.0)
species (n 27), followed by Candida species
(n 16) and Cryptococcus species (n 1). Eigh- *Systemic pneumonia plus concurrent fungemia.
Including two patients with lung abscess and two patients with
teen patients had complicating fungemia. The major endobronchial lesion.
fungi isolated from blood were Candida albicans, Candida pneumonia, including three patients with lung abscess.
Aspergillus fumigatus, and Aspergillus flavus (re-
spectively, n 3; 16%).
Aspergillus species were the leading pathogen in tion of biopsy specimens. Hemoptysis (n 32) was
both patient groups with acute invasive infection and the main symptom of patients with aspergilloma,
mycetoma. Among patients with Aspergillus infec- with nine patients having life-threatening episodes.
tion, there was no difference in the incidences of Five patients underwent transarterial embolization.
nosocomial and community-acquired infections Even after surgical intervention, four patients still
(p 0.722). Aspergilloma (n 41; 29%) was com- had episodes of hemoptysis.
monly encountered. For these patients, most Most patients (n 29; 97%) had cryptococcal
(n 34) had previous history of pulmonary tubercu- infection that was considered community acquired.
losis. Five patients had aspergilloma complicated by Only one patient acquired cryptococcal infection in
active tuberculosis, verified by microscopic examina- the hospital. Cryptococcoma (n 23; 76%) was the
most common presentation of cryptococcal infection.
No patients with cryptococcoma died. For Candida
Table 3Fungal Species Identified From 140 Patients infection, nosocomial infection was more prevalent
With Pulmonary Fungal Infections than community-acquired infection (n 16 vs
Fungal species No.
n 4; p 0.001). Primary Candida pneumonia was
the most frequent manifestation (pulmonary consol-
Aspergillus spp 80 idation as the initial radiographic presentation), fol-
Aspergillus fumigatus 12
Aspergillus flavus 9
lowed by disseminated infection (pneumonia plus
Aspergillus niger 2 candidemia). The mortality rate (70%) of patients
Aspergillus terreus 1 with pulmonary Candida infection was higher than
Cryptococcus spp 30 that of any other group of patients (Table 4).
Cryptococcus neoformans 30 During hospital admission, 39 bacterial isolates
Candida spp 20
Candida albicans 9
were concomitantly found in the blood of 24 pa-
Candida tropicalis 4 tients. The majority of bacterial isolates were Gram-
Candida glabrata 4 negative bacilli (24 isolates; 61%), of which the most
Candida parapsilosis 2 common isolates were Pseudomonas aeruginosa (5
Others isolates; 15%), Klebsiella pneumoniae (5 isolates;
Mycelium sterila 3
Penicillium marneffei 2
15%), and Enterobacter cloacae (5 isolates; 15%).
Coccidioides immitis 1 The most common Gram-positive isolates were me-
Mucor spp 1 thicillin-resistant Staphylococcus aureus (4 isolates;
Rhizopus spp 1 10%), followed by methicillin-resistant Staphylococ-
Histoplasma capsulatum 1 cus epidermidis (3 isolates; 8%), and Enterococcus
Rhodotorula glutinis 1
faecalis (3 isolates; 8%).

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 Treatment and Outcome as well as their relative influence on mortality (uni-
variate analysis). Patients with compromised immu-
The clinical courses, treatments and outcomes of nity (relative risk [RR], 7.67), absolute neutrophil
different patient groups with pulmonary fungal in- count 1,000/L (RR, 3.50), previous antibiotic use
fections were also demonstrated in Table 2. The (RR, 9.23), and nosocomial fungal infection (RR,
mean hospital stay is longer in patients with acute 9.23) had a higher risk of mortality. Patients who had
invasive fungal infection than those with mycetoma chest radiographic manifestations of bilateral in-
(69 67 days vs 24 29 days; p 0.001). A total of volvement (RR, 3.80) also had a higher risk of death.
98 patients received systemic antifungal therapy Patients who had complications of respiratory failure
(acute invasive fungal infection vs mycetoma, 94% vs (RR, 20.9) were more likely to die than those who
44%, respectively; p 0.001), with amphotericin B did not have these complications. Multivariate logis-
(79% vs 12%; mean duration, 33 days vs 27 days), tic regression analysis showed that hospital-acquired
fluconazole (51% vs 35%; mean duration, 47 days vs infection (p 0.014) and respiratory failure
55 days), or itraconazole (11% vs 3%; mean duration, (p 0.001) were significantly and independently
74 days vs 93 days). The use of antifungal agents did associated with death.
not influence the outcome (mortality rates, with vs
without antifungal agents, 66% vs 75%) of patients
with acute invasive fungal infection. Sixty-three pa- Discussion
tients underwent surgical resection of pulmonary
lesions (acute invasive fungal infection vs mycetoma, There has been an increasing incidence of pulmo-
19% vs 81%). Thirty-eight patients were admitted to nary fungal infection at our hospital in the past
the ICU (acute invasive fungal infection vs myce- decade. A large portion was acquired from sources
toma, 45.8% vs 7.4%). Fifty-one patients died, and other than the hospital. The most frequently encoun-
47 of these had compromised immunity. The mor- tered pathogens were Aspergillus species, followed
tality rate is much higher in patients with acute by Cryptococcus species and Candida species. The
invasive fungal infection than those with mycetoma major prognostic factors of acute invasive fungal
(67% vs 4%, respectively; p 0.001). infection were the source of fungal infection and the
Because of the relatively higher mortality rate occurrence of respiratory failure.
(67%), we studied the clinical characteristics and Previous literature was concerned mostly with
outcomes of patients with acute invasive fungal invasive and systemic fungal infections in patients
infection. Table 5 summarizes clinical, epidemio- with cancer,2 organ transplantation,9 11 and AIDS.12
logic, microbiological, and laboratory variables of To our knowledge, there has been no large-scale
patients with acute invasive fungal infection studied, study on the incidence, microbiological spectra, pa-

Table 5Prognostic Factors and RRs of Death in the 72 Patients With Active Invasive Fungal Infection*

Patients in Each Patients Who Died, Univariate analysis: RR of Death Multivariate Logistic
Variables Category, No. No. (%) Within Each Category (95% CI) Regression p Value

Underlying conditions
Immunocompetent 8 2 (25) 1.0
Immunocompromised 64 46 (72) 7.67 (1.41, 41.57) 0.053
ANC 1,000/L 44 25 (57) 1.0
ANC 1,000/L 28 23 (82) 3.50 (1.12, 10.89) 0.369
Previous antibiotic use
No 27 10 (37) 1.0
Yes 45 38 (84) 9.23 (3.00, 28.35) 0.343
Clinical features
Nosocomial
No 33 14 (42) 1.0
Yes 39 34 (87) 9.23 (2.88, 29.59) 0.014
Chest radiography
Unilateral 43 24 (56) 1.0
Bilateral 29 24 (83) 3.80 (1.22, 11.84) 0.232
Complication
Respiratory failure
No 22 5 (23) 1.0
Yes 50 43 (86) 20.89 (5.82, 74.94) 0.001
*ANC absolute neutrophil count; CI confidence interval.

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 tient outcome, and prognosis of pulmonary fungal States. Aspergillus species, however, accounted for
infection. Thus, we reviewed the patients with pul- only 1.1% of fungal infections.21 A population-based
monary fungal infection during a 10-year period and active laboratory surveillance for invasive fungal
found the incidence of the disease rising in the infection22 also reveals that Candida species (72.8
recent years. A number of factors may be associated per million per year) was the most common patho-
with an increasing incidence of pulmonary fungal gen, followed by Cryptococcus species (65.5), Coc-
infection. Impaired T-lymphocyte function due to cidioides species (15.3), Aspergillus species (12.4),
high-dose steroid therapy, chemotherapy, or AIDS, and Histoplasma species (7.1). For pulmonary fungal
as well as depressed neutrophil count or function infection, Aspergillus species was considered as a
due to hematologic malignancies, or anticancer che- leading cause of nosocomial fungal pneumonia.23
motherapy, may increase the risk of fungal infec- Our study demonstrated that Aspergillus species
tion.13 The use of broad-spectrum antibiotics in were the most common pathogen in patient groups
critically ill patients may change normal flora, espe- with acute invasive infections. Aspergillus species
cially overgrowth of Candida species in the GI tract, were also most frequently encountered in either
which may translocate into the bloodstream.14 Hy- nosocomial or community-acquired patient groups,
peralimentation and invasive devices, including cen- which indicates that Aspergillus species could be
tral vascular catheter, urinary catheter, and chest important pathogens of severe pulmonary fungal
tube, may also contribute to the development of infection acquired from sources other than hospitals.
fungal infection.15 Cryptococcus species was the second most com-
The main problem in dealing with pulmonary mon pathogen of pulmonary fungal infection in our
fungal infection is in distinguishing simple coloniza- study. In the majority of patients, cryptococcal infec-
tion from invasive or disseminated infection. A diag- tion was community acquired (97%). Only two pa-
nosis of invasive disease requires the presence of the tients died of pulmonary cryptococcal infection. In
fungus in normally sterile tissues, while dissemina- previous literature, pulmonary cryptococcosis may
tion is defined as invasion of noncontiguous organs occur mostly in immune-compromised hosts.24 26
secondary to hematogenous spread.16 In our study, The outcome of patients with cryptococcal infection
we used strict criteria to define pulmonary fungal in our study is relatively good. This may be due to the
infection and excluded patients who had fungi iso- low frequency of immune-compromised status
lated from airway secretion. Therefore, the preva- (38%). Candida infection accounted for the third
lence of fungal pneumonia may be underestimated. most common cause of fungal pneumonia. Similar to
A large portion (68%) of pulmonary fungal infection a previous report,27 the mortality rate of Candida
was community acquired in our study. This suggests pneumonia (70%) is higher than that of the patients
that, in addition to nosocomial infection,17 commu- with pulmonary infection caused by other fungal
nity-acquired fungal infections may also cause signif- species.
icant morbidity and mortality. Multivariate logistic regression analysis showed
We demonstrated that Aspergillus, Cryptococcus, that nosocomial fungal infection and respiratory
and Candida species, often responsible for opportu- failure were significantly and independently associ-
nistic infection in an immune-compromised host,18,19 ated with death of acute invasive pulmonary fungal
were the most common pathogens. However, among infection. Patients with nosocomial fungal infection
the patients included, there were 57 apparently had a higher frequency of immune-compromised
immune-competent patients with pulmonary fungal status (83%), which might be a contributory factor of
infections, including 23 patients with no underlying mortality. They had a higher proportion of Candida
disease. This implies that these fungi may be also an pneumonia than the community-acquired patient
important cause of pulmonary infection in relatively group (26.1% vs 8.2%). The high mortality rate of
healthy patients. Candida pneumonia (70%) might have also contrib-
Aspergillus species are found worldwide in the uted to the higher mortality risk of patients with
environment and are acquired primarily through the nosocomial fungal infection. The complication of
respiratory tract. Though known as a soil fungus, respiratory failure might reflect the severity of pul-
Asperillus spores have often been found in hospital monary fungal infection or deterioration of underly-
air, including inside the hospital operating rooms.20 ing pulmonary function, which might be associated
Thus, exposure to Aspergillus is almost universal. with mortality.
The National Nosocomial Infections Surveillance In conclusion, pulmonary fungal infection, partic-
study of the Centers for Disease Control and Pre- ularly community-acquired fungal infection, has be-
vention reveals that Candida species accounted for come an emerging problem that deserves more
19,621 infections (72%) and represented the sixth clinical attention. Aspergillus species was a major
most common nosocomial pathogens in the United pathogen of pulmonary fungal infection in Taiwan, in

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groups. Patients who had nosocomial fungal infec- fungal infections following renal transplantation in third-
world countries. Nephrol Dial Transplant 1993; 8:168 172
tion or complicating respiratory failure had a high 12 Minamoto GY, Rosenberg AS. Fungal infection in patients
risk of death. Acute invasive fungal infection in with acquired immunodeficiency syndrome. Med Clin North
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14 Samonis G, Gikas A, Toloudis P, et al. Prospective study of
sis and more aggressive treatment for infection the impact of broad-spectrum antibiotics on yeast flora of the
control, such as resection of the pulmonary lesion, human gut. Eur J Clin Microbiol 1994; 13:665 667
might be necessary to improve their outcome. 15 Anaissie E, Solomkin JS. Fungal infection. In: Meakins JL,
ed. Surgical infections: diagnosis and treatment (vol 1) New
York, NY: Scientific American, 1994; 411 425
16 Dean DA, Burchard KW. Fungal infection in surgical pa-
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