|
|
||||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Departments of Internal Medicine (Drs. Chen, Ko, Hsueh, and Yang) and Laboratory Medicine (Dr. Luh), National Taiwan University Hospital, Taipei, Taiwan.
Correspondence to: Pan-Chyr Yang, MD, PhD, FCCP, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Taipei 100, Taiwan; e-mail: pcyang{at}ha.mc.ntu.edu.tw
| Abstract |
|---|
|
|
|---|
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.
Key Words: community-acquired fungal pneumonia nosocomial pneumonia
| Introduction |
|---|
|
|
|---|
| Materials and Methods |
|---|
|
|
|---|
Acute invasive fungal infection was defined as patients with rapid
progression of disease clinically or radiographically, and at least one
of the followings: (1) fungal invasion of lung parenchyma noted by
pathologic examination or (2) fungal isolation from sterile site
such as blood or pleural effusion. Pulmonary fungal infection
developing after 48 h of hospital admission was regarded as
nosocomial; otherwise, the fungal infection was considered community
acquired. Previous use of antibiotics was defined as receiving
antibiotic therapy before hospital admission or for > 48 h during
hospital admission before a clinical diagnosis of fungal pneumonia was
made. Antecedent chemotherapy was defined as receiving anticancer
chemotherapy < 1 month before clinical diagnosis of fungal pneumonia.
Long-term steroid use was defined as receiving steroid therapy for
> 1 month before clinical diagnosis of fungal pneumonia. Fever was
defined as body temperature > 37.5°C. Neutropenia was defined as
absolute neutrophil count < 1,000/µL in 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 and/or
PaCO2
50 mm Hg while breathing
room air.
For isolation of fungi, specimens were inoculated onto Sabouraud dextrose agar plates (BBL Microbiology Systems; Cockeysville, MD). Identification of molds was based on gross colony morphologies and microscopic pictures. Cornmeal agar (BBL Microbiology Systems) slide cultures were used to identify molds. Yeasts were identified to species level by standard method, and their identity was confirmed by the API ID 32C (bioMerieux; Marcy-IEtoile, France).8
The following data were collected for each patient: age and gender; predisposing factors, including underlying diseases and associated medical conditions; antimicrobial agents administered; clinical symptoms; peripheral WBC and differential cell counts; findings in chest radiographs; strains of pathogens isolated or found in biopsy specimens; regimens and durations of antifungal therapy; invasive or surgical procedures; durations of hospitalization; and patient outcome.
Differences in survival among subgroups of variables were analyzed by
2 test, or Fishers exact test when
necessary. A multivariate logistic regression model was applied (SPSS
8.0 for Windows; SPSS; Chicago, IL) with only variables that were
significantly associated with survival in the univariate analysis. A p
value of
0.05 was considered significant.
| Results |
|---|
|
|
|---|
|
|
|
|
|
|
Most patients (n = 29; 97%) had cryptococcal infection that was considered community acquired. Only one patient acquired cryptococcal infection in the hospital. Cryptococcoma (n = 23; 76%) was the most common presentation of cryptococcal infection. No patients with cryptococcoma died. For Candida infection, nosocomial infection was more prevalent than community-acquired infection (n = 16 vs n = 4; p < 0.001). Primary Candida pneumonia was the most frequent manifestation (pulmonary consolidation as the initial radiographic presentation), followed by disseminated infection (pneumonia plus candidemia). The mortality rate (70%) of patients with pulmonary Candida infection was higher than that of any other group of patients (Table 4) .
During hospital admission, 39 bacterial isolates were concomitantly found in the blood of 24 patients. The majority of bacterial isolates were Gram-negative bacilli (24 isolates; 61%), of which the most common isolates were Pseudomonas aeruginosa (5 isolates; 15%), Klebsiella pneumoniae (5 isolates; 15%), and Enterobacter cloacae (5 isolates; 15%). The most common Gram-positive isolates were methicillin-resistant Staphylococcus aureus (4 isolates; 10%), followed by methicillin-resistant Staphylococcus epidermidis (3 isolates; 8%), and Enterococcus faecalis (3 isolates; 8%).
Treatment and Outcome
The clinical courses, treatments and outcomes of different patient
groups with pulmonary fungal infections were also demonstrated in Table 2 . The mean hospital stay is longer in patients with acute invasive
fungal infection than those with mycetoma (69 ± 67 days vs
24 ± 29 days; p < 0.001). A total of 98 patients received
systemic antifungal therapy (acute invasive fungal infection vs
mycetoma, 94% vs 44%, respectively; p < 0.001), with amphotericin
B (79% vs 12%; mean duration, 33 days vs 27 days), fluconazole (51%
vs 35%; mean duration, 47 days vs 55 days), or itraconazole (11% vs
3%; mean duration, 74 days vs 93 days). The use of antifungal agents
did not influence the outcome (mortality rates, with vs without
antifungal agents, 66% vs 75%) of patients with acute invasive fungal
infection. Sixty-three patients underwent surgical resection of
pulmonary lesions (acute invasive fungal infection vs mycetoma, 19% vs
81%). Thirty-eight patients were admitted to the ICU (acute invasive
fungal infection vs mycetoma, 45.8% vs 7.4%). Fifty-one patients
died, and 47 of these had compromised immunity. The mortality rate is
much higher in patients with acute invasive fungal infection than those
with mycetoma (67% vs 4%, respectively; p < 0.001).
Because of the relatively higher mortality rate (67%), we studied the clinical characteristics and outcomes of patients with acute invasive fungal infection. Table 5 summarizes clinical, epidemiologic, microbiological, and laboratory variables of patients with acute invasive fungal infection studied, as well as their relative influence on mortality (univariate analysis). Patients with compromised immunity (relative risk [RR], 7.67), absolute neutrophil count < 1,000/µL (RR, 3.50), previous antibiotic use (RR, 9.23), and nosocomial fungal infection (RR, 9.23) had a higher risk of mortality. Patients who had chest radiographic manifestations of bilateral involvement (RR, 3.80) also had a higher risk of death. Patients who had complications of respiratory failure (RR, 20.9) were more likely to die than those who did not have these complications. Multivariate logistic regression analysis showed that hospital-acquired infection (p = 0.014) and respiratory failure (p = 0.001) were significantly and independently associated with death.
|
| Discussion |
|---|
|
|
|---|
Previous literature was concerned mostly with invasive and systemic fungal infections in patients with cancer,2 organ transplantation,9 10 11 and AIDS.12 To our knowledge, there has been no large-scale study on the incidence, microbiological spectra, patient outcome, and prognosis of pulmonary fungal infection. Thus, we reviewed the patients with pulmonary fungal infection during a 10-year period and found the incidence of the disease rising in the recent years. A number of factors may be associated with an increasing incidence of pulmonary fungal infection. Impaired T-lymphocyte function due to high-dose steroid therapy, chemotherapy, or AIDS, as well as depressed neutrophil count or function due to hematologic malignancies, or anticancer chemotherapy, may increase the risk of fungal infection.13 The use of broad-spectrum antibiotics in critically ill patients may change normal flora, especially overgrowth of Candida species in the GI tract, which may translocate into the bloodstream.14 Hyperalimentation and invasive devices, including central vascular catheter, urinary catheter, and chest tube, may also contribute to the development of fungal infection.15
The main problem in dealing with pulmonary fungal infection is in distinguishing simple colonization from invasive or disseminated infection. A diagnosis of invasive disease requires the presence of the fungus in normally sterile tissues, while dissemination is defined as invasion of noncontiguous organs secondary to hematogenous spread.16 In our study, we used strict criteria to define pulmonary fungal infection and excluded patients who had fungi isolated from airway secretion. Therefore, the prevalence of fungal pneumonia may be underestimated. A large portion (68%) of pulmonary fungal infection was community acquired in our study. This suggests that, in addition to nosocomial infection,17 community-acquired fungal infections may also cause significant morbidity and mortality.
We demonstrated that Aspergillus, Cryptococcus, and Candida species, often responsible for opportunistic infection in an immune-compromised host,18 19 were the most common pathogens. However, among the patients included, there were 57 apparently immune-competent patients with pulmonary fungal infections, including 23 patients with no underlying disease. This implies that these fungi may be also an important cause of pulmonary infection in relatively healthy patients.
Aspergillus species are found worldwide in the environment and are acquired primarily through the respiratory tract. Though known as a soil fungus, Asperillus spores have often been found in hospital air, including inside the hospital operating rooms.20 Thus, exposure to Aspergillus is almost universal. The National Nosocomial Infections Surveillance study of the Centers for Disease Control and Prevention reveals that Candida species accounted for 19,621 infections (72%) and represented the sixth most common nosocomial pathogens in the United States. Aspergillus species, however, accounted for only 1.1% of fungal infections.21 A population-based active laboratory surveillance for invasive fungal infection22 also reveals that Candida species (72.8 per million per year) was the most common pathogen, followed by Cryptococcus species (65.5), Coccidioides species (15.3), Aspergillus species (12.4), and Histoplasma species (7.1). For pulmonary fungal infection, Aspergillus species was considered as a leading cause of nosocomial fungal pneumonia.23 Our study demonstrated that Aspergillus species were the most common pathogen in patient groups with acute invasive infections. Aspergillus species were also most frequently encountered in either nosocomial or community-acquired patient groups, which indicates that Aspergillus species could be important pathogens of severe pulmonary fungal infection acquired from sources other than hospitals.
Cryptococcus species was the second most common pathogen of pulmonary fungal infection in our study. In the majority of patients, cryptococcal infection was community acquired (97%). Only two patients died of pulmonary cryptococcal infection. In previous literature, pulmonary cryptococcosis may occur mostly in immune-compromised hosts.24 25 26 The outcome of patients with cryptococcal infection in our study is relatively good. This may be due to the low frequency of immune-compromised status (38%). Candida infection accounted for the third most common cause of fungal pneumonia. Similar to a previous report,27 the mortality rate of Candida pneumonia (70%) is higher than that of the patients with pulmonary infection caused by other fungal species.
Multivariate logistic regression analysis showed that nosocomial fungal infection and respiratory failure were significantly and independently associated with death of acute invasive pulmonary fungal infection. Patients with nosocomial fungal infection had a higher frequency of immune-compromised status (83%), which might be a contributory factor of mortality. They had a higher proportion of Candida pneumonia than the community-acquired patient group (26.1% vs 8.2%). The high mortality rate of Candida pneumonia (70%) might have also contributed to the higher mortality risk of patients with nosocomial fungal infection. The complication of respiratory failure might reflect the severity of pulmonary fungal infection or deterioration of underlying pulmonary function, which might be associated with mortality.
In conclusion, pulmonary fungal infection, particularly community-acquired fungal infection, has become an emerging problem that deserves more clinical attention. Aspergillus species was a major pathogen of pulmonary fungal infection in Taiwan, in either nosocomial or community-acquired patient groups. Patients who had nosocomial fungal infection or complicating respiratory failure had a high risk of death. Acute invasive fungal infection in almost all patients was treated as bacterial pneumonia initially, with poor outcome even with later antifungal therapy. For these patients, early diagnosis and more aggressive treatment for infection control, such as resection of the pulmonary lesion, might be necessary to improve their outcome.
| Footnotes |
|---|
Manusript received August 1, 2000; revision accepted February 14, 2001.
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
H. Brodoefel, M. Vogel, H. Hebart, H. Einsele, R. Vonthein, C. Claussen, and M. Horger Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. Am. J. Roentgenol., August 1, 2006; 187(2): 404 - 413. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Yamamoto, E. Ueta, T. Kamatani, and T. Osaki DNA identification of the pathogen of candidal aspiration pneumonia induced in the course of oral cancer therapy J. Med. Microbiol., May 1, 2005; 54(5): 493 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
P.-R. Hsueh, Y.-J. Lau, Y.-C. Chuang, J.-H. Wan, W.-K. Huang, J.-M. Shyr, J.-J. Yan, K.-W. Yu, J.-J. Wu, W.-C. Ko, et al. Antifungal Susceptibilities of Clinical Isolates of Candida Species, Cryptococcus neoformans, and Aspergillus Species from Taiwan: Surveillance of Multicenter Antimicrobial Resistance in Taiwan Program Data from 2003 Antimicrob. Agents Chemother., February 1, 2005; 49(2): 512 - 517. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Tan, X. Sun, X. Zhu, Z. Zhang, J. Li, and Q. Shu Epidemiology of Nosocomial Pneumonia in Infants After Cardiac Surgery Chest, February 1, 2004; 125(2): 410 - 417. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |