Review Articles
Update on the
Laboratory Diagnosis of Invasive Fungal InfectionsBrunella Posteraro1, Riccardo Torelli1, Elena De Carolis1, Patrizia Posteraro2 and Maurizio Sanguinetti1
1Institute of
Microbiology, Università Cattolica del Sacro Cuore, Largo F. Vito,
1-00168, Rome, Italy.
2Laboratory of Clinical Pathology and Microbiology, Ospedale San Carlo-IDI IRCSS, via Aurelia, 275-00165 Rome, Italy.
2Laboratory of Clinical Pathology and Microbiology, Ospedale San Carlo-IDI IRCSS, via Aurelia, 275-00165 Rome, Italy.
Correspondence
to:
Maurizio Sanguinetti, Institute of Microbiology, Università Cattolica
del Sacro Cuore. Largo F. Vito, 1-00168, Rome, Italy. Tel:
+39-06-3015-4964, Fax: +39-06-3015-152. E-mail: msanguinetti@rm.unicatt.it
Competing interests: The authors have declared that no competing interests exist.
Competing interests: The authors have declared that no competing interests exist.
Published: January 14, 2011
Received: December 30, 2010
Accepted: December 31, 2010
Medit J Hemat Infect 2011, 3: e2011002; DOI 10.4084/MJHID.2011.002
This article is available from: http://www.mjhid.org/article/view/7438
This is an Open Access article
distributed under the terms of
the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited
Abstract
Recent
advances in the management of patients with haematological malignancies
and transplant recipients have paralleled an increase in the incidence
of fungal diseases due to pathogenic genera such as Candida and
Aspergillus and the emergence of less common genera including Fusarium
and Zygomycetes. Despite availability of new antifungal agents these
opportunistic infections have high mortality. Rapid and reliable
species identification is essential for antifungal treatment, but
detection of the increasing diversity of fungal pathogens by
conventional phenotypic methods remains difficult and time-consuming,
and the results may sometimes be inconclusive, especially for unusual
species. New diagnostic techniques (e.g., 1,3-beta-d-glucan detection)
could improve this scenario, although further studies are necessary to
confirm their usefulness in clinical practice.
Introduction
Despite the development of new techniques and new antifungal agents, diagnosis of invasive fungal infection (IFI), which still relies upon a combination of clinical observation and laboratory investigation, remains a challenge especially for immunocompromised patients with haematological disease.[1] This has important clinical repercussions since delayed diagnosis and therapy contribute significantly to the high mortality rates associated with IFIs,[2] whereas early intervention with antifungal drugs may result in more effective management of high-risk patients.[3] While superficial and subcutaneous fungal infections often produce characteristic lesions that suggest the diagnosis, a thorough knowledge of potential causative organisms is yet required to aid the diagnostic process, mainly in situations where systemic fungal infection is suspected but the clinical presentation is nonspecific and then ascribable to a wide range of infections, underlying illnesses, or complication of treatments.[4]
The exact identification of the infecting organism is became essential in light of the increased use of prophylactic schedules that predispose the patient not just to fungal infection, but also to the selection of fungal species such as non-albicans Candida (e.g., C. glabrata and C. krusei), Aspergillus terreus, Scedosporium species, and Zygomycetes, many of which are intrinsically resistant to the available antifungal agents.[5,6]
Culture-based detection methods
Laboratory diagnosis of IFI remains based on conventional approaches, such as the direct microscopically detection of the etiologic agent in clinical specimen and the isolation and identification of the pathogen in culture, and non-culture based methods involving detection of a serologic response to the pathogen or other marker of its presence such as fungal antigens or metabolites.4 Visual examination of fungi in tissue samples allows presumptive identification based on cellular morphology and staining properties, but it should be appreciated that invasive procedures necessary to obtain biopsies may be precluded in haematological patients. It should be noted that microbiological cultures are often insensitive or of limited use, since even with modern blood cultures systems candidaemia can be transient and not detected, or Aspergillus cannot be cultured from a significant proportion of sputum or bronchoalveolar lavage samples from patients with invasive aspergillosis (IA).[7]
Although a variety of culture media and incubation conditions may be required for recovery of fungal agents, chromogenic primary isolation media (e.g., CHROMagar Candida medium) can be employed for the presumptive identification of the most medically important Candida species, including C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis. Most yeasts isolated from clinical samples can be identified using one of the numerous commercial identification systems, such as API 20C AUX, VITEK 2, and RapID Yeast Plus.[4,8] Although the kits are relatively easy to use, it should be remembered that additional morphologic-based tests are often required to avoid confusion between organisms with identical biochemical profiles.
Unlike pathogenic yeasts, filamentous fungi can be identified only by visualization of macroscopic (colonial form, surface colour, and pigmentation) or microscopic (spore-bearing structures) morphologic characteristics, following to sub-cultivation of a mould isolate to encourage sporulation,[4] a process that takes days to weeks. In addition to the use of genetic probes for the culture confirmation of dimorphic systemic fungal pathogens (e.g., Histoplasma capsulatum), an alternative and useful approach to the detection and identification of fungi in clinical specimens involves a broad-range polymerase chain reaction (PCR) followed by nucleic acid sequencing, after which the nucleic acid sequence is compared with known sequence database and identification is based on DNA homology.[9] However, these methods are expensive and time-consuming, and they are not currently suitable for routine identification.
By contrast, matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is becoming a reliable method for identification of microorganisms. The remarkable reproducibility of the methodology is based on the measurement of constantly expressed and highly abundant proteins such as ribosomal molecules.[10,11] Some recent studies have shown the potential of the MALDI-TOF technique to identify fungal clinical species such as Aspergillus and Fusarium. Recently, the MALDI-TOF technology provided a fast and accurate identification of common and unusual species of Aspergillus when tested on 124 clinical and 16 environmental isolates.[12] With regard to Fusarium species, a recent case report supported the usefulness of MALDI-TOF analysis in diagnosing an infection due to Fusarium proliferatum, which is a very infrequent pathogen within this genus.[13]
Antigen-based detection methods
To facilitate early diagnosis of IFI, important advances have been made in the development of laboratory markers (e.g., galactomannan [GM] and 1,3-beta-d-glucan [BG] assays), which have led to the potential for newer paradigms regarding prevention and early treatment of IFIs.[14] Among fungal markers, GM, a component of fungal cell wall that can be detected by a sandwich-type enzyme-linked immunosorbent assay (ELISA) in serum or plasma,[15] bronchoalveolar lavage (BAL) fluid,[16,17] and cerebrospinal fluid,[18] has recently been approved by the US Food and Drug Administration at a serum cut-off of 0.5, as a diagnostic adjunct for IA.[14] Together with clinical criteria, a positive serum or BAL fluid GM would strongly suggest probable IA, as defined by authoritative consensus criteria.[19] However, this technique has shown contradictory results, in terms of sensitivity and specificity, due to several factors, including the impact of prior antifungal therapy on the levels of circulating fungal components,[20] the occurrence of false-positive results in association with some antibiotic treatments,21,22 and the different cut-offs of positivity among studies.[14] Thus, a recently published meta-analysis of 27 studies showed an overall sensitivity of 71% and specificity of 89% for proven cases of IA when used for surveillance.[23] In addition, GM also correlates well with outcome.[24]
In contrast to GM, BG is a cell wall constituent of several fungi, including Aspergillus, Candida, and Fusarium, a spectrum of pathogens that encompasses the majority of those emerging in neutropenic patients with either prolonged neutropenia or chemotherapy-induced mucositis, with some notable exceptions such as Zygomycetes, a rare but emerging cause of invasive mycosis.[25,26] Measurement of serum BG has been shown to be an aid in the diagnosis of fungaemia and deep-seated mycoses, including IA.[27,28] Among commercially available assays, the Fungitell, which is also an ELISA technique, is widely used to detect serum BG concentrations as low as 1 pg/mL.[27] The cut-off for a positive result is >80 pg/ml. As with GM, variable results have been reported for BG assay, with a slightly higher sensitivity and specificity, ranging from 70% to 90%.[28,29] When performances of both GM and BD tests were compared to determine their diagnostic usefulness for high-risk haematological malignancy patients, GM assay was significantly better for detecting non-fumigatus Aspergillus species, whereas BG was shown to have a higher sensitivity in detecting IA and other mould infections.[30]
Non-culture based methods for diagnosis of candidiasis are of limited value because the levels of circulating antigens are low and the transient nature of the antigenaemia requires sensitive assays and frequent sampling of at-risk patients.[1,31] However, the use of Platelia Candida, an ELISA that combines the detection of mannan antigen and anti-mannan antibodies in serum, led to earlier diagnosis of Candida infection when compared with blood cultures.[31] In haematological patients with hepatosplenic lesions, assessing mannan/anti-mannan antibodies shortened significantly the median time of diagnosis of candidiasis when compared with imaging.[32]
Molecular-based detection methods
A range of polymerase chain reaction (PCR)-based methods have been developed with the prospect of give highly specific, highly sensitive, and rapid means for fungal detection and identification.[33] Most of them have focused on Aspergillus and Candida species, using different specimens types (e.g., serum, plasma, or BAL fluid), even though pan-fungal PCR amplification technology may be able to detect a broad range of fungal targets.[33] Although PCR has been studied for years, the lack of standardization and clinical validation has led to its exclusion from consensus criteria for defining IFI.[19] Nevertheless, a recent prospective evaluation of serial PCR assays against [34] or along with GM and computed tomography [35] was carried out in haematological patients, thus showing acceptable sensitivity and specificity. In such one study, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%.[35] Of note, in a systematic review and meta-analysis of Aspergillus PCR tests for diagnosis of IA,[36] the authors proposed that a single PCR-negative test is sufficient to exclude IA, whereas two PCR-positive results are required to confirm disease. Compared with Aspergillus PCR, only a few Candida PCR methods have received major clinical evaluation.[37] As confirmed by a national consensus evaluation,[38] performance of these tests is generally good, with sensitivities and specificities consistently >90%.[33] Although addressed to critically ill patients, a prospective clinical trial published in 2008 reported positive predictive values and negative predictive values of >90% for a PCR method that detects several species of Candida.[39]
Conclusion
Molecular detection methods, combined with additional microbiological and clinical information, has the potential not only to accurately and rapidly identify fungal pathogens, but also to indicate whether the pathogen is likely to respond to conventional antifungal treatment.[9] Inclusion of these methods in a diagnostic surveillance strategy to exclude IFI in high-risk patients with haematological malignancy [40] should result in improved clinical management, thus allowing more rational use of antifungal drugs.
Despite the development of new techniques and new antifungal agents, diagnosis of invasive fungal infection (IFI), which still relies upon a combination of clinical observation and laboratory investigation, remains a challenge especially for immunocompromised patients with haematological disease.[1] This has important clinical repercussions since delayed diagnosis and therapy contribute significantly to the high mortality rates associated with IFIs,[2] whereas early intervention with antifungal drugs may result in more effective management of high-risk patients.[3] While superficial and subcutaneous fungal infections often produce characteristic lesions that suggest the diagnosis, a thorough knowledge of potential causative organisms is yet required to aid the diagnostic process, mainly in situations where systemic fungal infection is suspected but the clinical presentation is nonspecific and then ascribable to a wide range of infections, underlying illnesses, or complication of treatments.[4]
The exact identification of the infecting organism is became essential in light of the increased use of prophylactic schedules that predispose the patient not just to fungal infection, but also to the selection of fungal species such as non-albicans Candida (e.g., C. glabrata and C. krusei), Aspergillus terreus, Scedosporium species, and Zygomycetes, many of which are intrinsically resistant to the available antifungal agents.[5,6]
Culture-based detection methods
Laboratory diagnosis of IFI remains based on conventional approaches, such as the direct microscopically detection of the etiologic agent in clinical specimen and the isolation and identification of the pathogen in culture, and non-culture based methods involving detection of a serologic response to the pathogen or other marker of its presence such as fungal antigens or metabolites.4 Visual examination of fungi in tissue samples allows presumptive identification based on cellular morphology and staining properties, but it should be appreciated that invasive procedures necessary to obtain biopsies may be precluded in haematological patients. It should be noted that microbiological cultures are often insensitive or of limited use, since even with modern blood cultures systems candidaemia can be transient and not detected, or Aspergillus cannot be cultured from a significant proportion of sputum or bronchoalveolar lavage samples from patients with invasive aspergillosis (IA).[7]
Although a variety of culture media and incubation conditions may be required for recovery of fungal agents, chromogenic primary isolation media (e.g., CHROMagar Candida medium) can be employed for the presumptive identification of the most medically important Candida species, including C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis. Most yeasts isolated from clinical samples can be identified using one of the numerous commercial identification systems, such as API 20C AUX, VITEK 2, and RapID Yeast Plus.[4,8] Although the kits are relatively easy to use, it should be remembered that additional morphologic-based tests are often required to avoid confusion between organisms with identical biochemical profiles.
Unlike pathogenic yeasts, filamentous fungi can be identified only by visualization of macroscopic (colonial form, surface colour, and pigmentation) or microscopic (spore-bearing structures) morphologic characteristics, following to sub-cultivation of a mould isolate to encourage sporulation,[4] a process that takes days to weeks. In addition to the use of genetic probes for the culture confirmation of dimorphic systemic fungal pathogens (e.g., Histoplasma capsulatum), an alternative and useful approach to the detection and identification of fungi in clinical specimens involves a broad-range polymerase chain reaction (PCR) followed by nucleic acid sequencing, after which the nucleic acid sequence is compared with known sequence database and identification is based on DNA homology.[9] However, these methods are expensive and time-consuming, and they are not currently suitable for routine identification.
By contrast, matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is becoming a reliable method for identification of microorganisms. The remarkable reproducibility of the methodology is based on the measurement of constantly expressed and highly abundant proteins such as ribosomal molecules.[10,11] Some recent studies have shown the potential of the MALDI-TOF technique to identify fungal clinical species such as Aspergillus and Fusarium. Recently, the MALDI-TOF technology provided a fast and accurate identification of common and unusual species of Aspergillus when tested on 124 clinical and 16 environmental isolates.[12] With regard to Fusarium species, a recent case report supported the usefulness of MALDI-TOF analysis in diagnosing an infection due to Fusarium proliferatum, which is a very infrequent pathogen within this genus.[13]
Antigen-based detection methods
To facilitate early diagnosis of IFI, important advances have been made in the development of laboratory markers (e.g., galactomannan [GM] and 1,3-beta-d-glucan [BG] assays), which have led to the potential for newer paradigms regarding prevention and early treatment of IFIs.[14] Among fungal markers, GM, a component of fungal cell wall that can be detected by a sandwich-type enzyme-linked immunosorbent assay (ELISA) in serum or plasma,[15] bronchoalveolar lavage (BAL) fluid,[16,17] and cerebrospinal fluid,[18] has recently been approved by the US Food and Drug Administration at a serum cut-off of 0.5, as a diagnostic adjunct for IA.[14] Together with clinical criteria, a positive serum or BAL fluid GM would strongly suggest probable IA, as defined by authoritative consensus criteria.[19] However, this technique has shown contradictory results, in terms of sensitivity and specificity, due to several factors, including the impact of prior antifungal therapy on the levels of circulating fungal components,[20] the occurrence of false-positive results in association with some antibiotic treatments,21,22 and the different cut-offs of positivity among studies.[14] Thus, a recently published meta-analysis of 27 studies showed an overall sensitivity of 71% and specificity of 89% for proven cases of IA when used for surveillance.[23] In addition, GM also correlates well with outcome.[24]
In contrast to GM, BG is a cell wall constituent of several fungi, including Aspergillus, Candida, and Fusarium, a spectrum of pathogens that encompasses the majority of those emerging in neutropenic patients with either prolonged neutropenia or chemotherapy-induced mucositis, with some notable exceptions such as Zygomycetes, a rare but emerging cause of invasive mycosis.[25,26] Measurement of serum BG has been shown to be an aid in the diagnosis of fungaemia and deep-seated mycoses, including IA.[27,28] Among commercially available assays, the Fungitell, which is also an ELISA technique, is widely used to detect serum BG concentrations as low as 1 pg/mL.[27] The cut-off for a positive result is >80 pg/ml. As with GM, variable results have been reported for BG assay, with a slightly higher sensitivity and specificity, ranging from 70% to 90%.[28,29] When performances of both GM and BD tests were compared to determine their diagnostic usefulness for high-risk haematological malignancy patients, GM assay was significantly better for detecting non-fumigatus Aspergillus species, whereas BG was shown to have a higher sensitivity in detecting IA and other mould infections.[30]
Non-culture based methods for diagnosis of candidiasis are of limited value because the levels of circulating antigens are low and the transient nature of the antigenaemia requires sensitive assays and frequent sampling of at-risk patients.[1,31] However, the use of Platelia Candida, an ELISA that combines the detection of mannan antigen and anti-mannan antibodies in serum, led to earlier diagnosis of Candida infection when compared with blood cultures.[31] In haematological patients with hepatosplenic lesions, assessing mannan/anti-mannan antibodies shortened significantly the median time of diagnosis of candidiasis when compared with imaging.[32]
Molecular-based detection methods
A range of polymerase chain reaction (PCR)-based methods have been developed with the prospect of give highly specific, highly sensitive, and rapid means for fungal detection and identification.[33] Most of them have focused on Aspergillus and Candida species, using different specimens types (e.g., serum, plasma, or BAL fluid), even though pan-fungal PCR amplification technology may be able to detect a broad range of fungal targets.[33] Although PCR has been studied for years, the lack of standardization and clinical validation has led to its exclusion from consensus criteria for defining IFI.[19] Nevertheless, a recent prospective evaluation of serial PCR assays against [34] or along with GM and computed tomography [35] was carried out in haematological patients, thus showing acceptable sensitivity and specificity. In such one study, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%.[35] Of note, in a systematic review and meta-analysis of Aspergillus PCR tests for diagnosis of IA,[36] the authors proposed that a single PCR-negative test is sufficient to exclude IA, whereas two PCR-positive results are required to confirm disease. Compared with Aspergillus PCR, only a few Candida PCR methods have received major clinical evaluation.[37] As confirmed by a national consensus evaluation,[38] performance of these tests is generally good, with sensitivities and specificities consistently >90%.[33] Although addressed to critically ill patients, a prospective clinical trial published in 2008 reported positive predictive values and negative predictive values of >90% for a PCR method that detects several species of Candida.[39]
Conclusion
Molecular detection methods, combined with additional microbiological and clinical information, has the potential not only to accurately and rapidly identify fungal pathogens, but also to indicate whether the pathogen is likely to respond to conventional antifungal treatment.[9] Inclusion of these methods in a diagnostic surveillance strategy to exclude IFI in high-risk patients with haematological malignancy [40] should result in improved clinical management, thus allowing more rational use of antifungal drugs.
References
- Cuenca-Estrella M, Bernal-Martinez L,
Buitrago MJ, Castelli MV, Gomez-Lopez A, Zaragoza O, Rodriguez-Tudela
JL. Update on the epidemiology and diagnosis of invasive fungal
infection. Int J Antimicrob Agents. 2008; 32:S143-147. doi:10.1016/S0924-8579(08)70016-5.
- Morrell M, Fraser VJ, Kollef MH. Delaying
the empiric treatment of Candida bloodstream infection until positive
blood culture results are obtained: a potential risk factor for
hospital mortality. Antimicrob Agents Chemother. 2005; 49:3640-3645. doi:10.1128/AAC.49.9.3640-3645.2005
- Murali S, Langston A. Advances in
antifungal prophylaxis and empiric therapy in patients with hematologic
malignancies. Transpl Infect Dis. 2009; 11:480-490.doi:10.1111/j.1399-3062.2009.00441.x
PMid:19725908.
- Dismukes WE, Pappas PG, Sobel JD. Clinical Mycology. New York, Oxford University Press. 2003.
- Perea S, Patterson TF. Antifungal
resistance in pathogenic fungi. Clin Infect Dis. 2002; 35:1073-1080.doi:10.1086/344058.
- Rodriguez-Tudela JL, Alcazar-Fuoli L,
Cuesta I, Alastruey-Izquierdo A, Monzon A, Mellado E, Cuenca-Estrella
M. Clinical relevance of resistance to antifungals. Int J Antimicrob
Agents. 2008; 32:S111-113. doi:10.1016/S0924-8579(08)70010-4.
- Singh N, Paterson DL. Aspergillus
infections in transplant recipients. Clin Microbiol Rev. 2005;
18:44-69. doi:10.1128/CMR.18.1.44-69.2005
PMid:15653818 PMCid:544171.
- Sanguinetti M, Porta R, Sali M, La Sorda M,
Pecorini G, Fadda G, Posteraro B. Evaluation of VITEK 2 and RapID yeast
plus systems for yeast species identification: experience at a large
clinical microbiology laboratory. J Clin Microbiol. 2007; 45:1343-1346.
doi:10.1128/JCM.02469-06
PMid:17287333 PMCid:1865843.
- Persing DH, Tenover FC, Versalovic J, Tang JW, Unger ER, Relman DA, White TJ. Molecular Microbiology. Washington, ASM Press. 2004.
- Fenselau C, Demirev PA. Characterization
of intact microorganisms by MALDI mass spectrometry. Mass Spectrom Rev.
2001; 20:157-171. doi:10.1002/mas.10004 PMid:11835304.
- Santos C, Paterson RR, Venâncio A, Lima N.
Filamentous fungal characterizations by matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry. J Appl
Microbiol. 2010; 108:375-385. doi:10.1111/j.1365-2672.2009.04448.xPMid:19659699.
- Alanio A, Beretti JL, Dauphin B, Mellado
E, Quesne G, Lacroix C, Amara A, Berche P, Nassif X, Bougnoux ME.
MALDI-TOF Mass Spectrometry for fast and accurate identification of
clinically relevant Aspergillus species. Clin Microbiol Infect. 2010,
Epub ahead of print.doi:10.1111/j.1469-0691.2010.03323.xPMid:20673266.
- Seyfarth F, Ziemer M, Sayer HG, Burmester
A, Erhard M, Welker M, Schliemann S, Straube E, Hipler UC. The use of
ITS DNA sequence analysis and MALDI-TOF mass spectrometry in diagnosing
an infection with Fusarium proliferatum. Exp Dermatol. 2008; 17:965-71.doi:10.1111/j.1600-0625.2008.00726.x
PMid:18547323.
- Almyroudis NG, Segal BH. Prevention and
treatment of invasive fungal diseases in neutropenic patients. Curr
Opin Infect Dis. 2009; 22:385-393.doi:10.1097/QCO.0b013e32832e074d
PMid:19506476.
- Maertens J, Verhaegen J, Lagrou K, Van
Eldere J, Boogaerts M. Screening for circulating galactomannan as a
noninvasive diagnostic tool for invasive aspergillosis in prolonged
neutropenic patients and stem cell transplantation recipients: a
prospective validation. Blood. 2001; 97:1604-1610. doi:10.1182/blood.V97.6.1604
PMid:11238098.
- Sanguinetti M, Posteraro B, Pagano L,
Pagliari G, Fianchi L, Mele L, La Sorda M, Franco A, Fadda G.
Comparison of real-time PCR, conventional PCR, and galactomannan
antigen detection by enzyme-linked immunosorbent assay using
bronchoalveolar lavage fluid samples from hematology patients for
diagnosis of invasive pulmonary aspergillosis. J Clin Microbiol. 2003;
41:3922-3925.doi:10.1128/JCM.41.8.3922-3925.2003
PMid:12904419 PMCid:179803.
- Clancy CJ, Jaber RA, Leather HL, Wingard
JR, Staley B, Wheat LJ, Cline CL, Rand KH, Schain D, Baz M, Nguyen MH.
Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary
aspergillosis among solid-organ transplant recipients. J Clin
Microbiol. 2007; 45:1759-1765.doi:10.1128/JCM.00077-07
PMid:17428933 PMCid:1933052.
- Viscoli C, Machetti M, Gazzola P, De Maria
A, Paola D, Van Lint MT, Gualandi F, Truini M, Bacigalupo A.
Aspergillus galactomannan antigen in the cerebrospinal fluid of bone
marrow transplant recipients with probable cerebral aspergillosis. J
Clin Microbiol. 2002; 40:1496-1499.doi:10.1128/JCM.40.4.1496-1499.2002
PMid:11923380 PMCid:140329.
- De Pauw B, Walsh TJ, Donnelly JP, Stevens
DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O,
Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes
WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P,
Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell
TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization
for Research and Treatment of Cancer/Invasive Fungal Infections
Cooperative Group; National Institute of Allergy and Infectious
Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised
definitions of invasive fungal disease from the European Organization
for Research and Treatment of Cancer/Invasive Fungal Infections
Cooperative Group and the National Institute of Allergy and Infectious
Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect
Dis. 2008; 46:1813-1821.doi:10.1086/588660
PMid:18462102 PMCid:2671227.
- Marr KA, Laverdiere M, Gugel A, Leisenring
W. Antifungal therapy decreases sensitivity of the Aspergillus
galactomannan enzyme immunoassay. Clin Infect Dis. 2005;
40:1762-1769. doi:10.1086/429921 PMid:15909264.
- Adam O, Aupérin A, Wilquin F, Bourhis JH,
Gachot B, Chachaty E. Treatment with piperacillin-tazobactam and
false-positive Aspergillus galactomannan antigen test results for
patients with hematological malignancies. Clin Infect Dis. 2004;
38:917-920. doi:10.1086/383148
PMid:14999641.
- Mattei D, Rapezzi D, Mordini N, Cuda F, Lo
Nigro C, Musso M, Arnelli A, Cagnassi S, Gallamini A. False-positive
Aspergillus galactomannan enzyme-linked immunosorbent assay results in
vivo during amoxicillin-clavulanic acid treatment. J Clin Microbiol.
2004; 42:5362-5363. doi:10.1128/JCM.42.11.5362-5363.2004
PMid:15528743 PMCid:525269.
- Pfeiffer CD, Fine JP, Safdar N. Diagnosis
of invasive aspergillosis using a galactomannan assay: a meta-analysis.
Clin Infect Dis. 2006; 42:1417-1427.doi:10.1086/503427
PMid:16619154.
- Miceli MH, Grazziutti ML, Woods G, Zhao W,
Kocoglu MH, Barlogie B, Anaissie E. Strong correlation between serum
aspergillus galactomannan index and outcome of aspergillosis in
patients with hematological cancer: clinical and research implications.
Clin Infect Dis. 2008; 46:1412-1422. doi:10.1086/528714
PMid:18419445.
- Chamilos G, Luna M, Lewis RE, Bodey GP,
Chemaly R, Tarrand JJ, Safdar A, Raad II, Kontoyiannis DP. Invasive
fungal infections in patients with hematologic malignancies in a
tertiary care cancer center: an autopsy study over a 15-year period
(1989-2003). Haematologica. 2006; 91:986-989.PMid:16757415.
- Pagano L, Caira M, Nosari A, Van Lint MT,
Candoni A, Offidani M, Aloisi T, Irrera G, Bonini A, Picardi M,
Caramatti C, Invernizzi R, Mattei D, Melillo L, de Waure C, Reddiconto
G, Fianchi L, Valentini CG, Girmenia C, Leone G, Aversa F. Fungal
infections in recipients of hematopoietic stem cell transplants:
results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica
Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007;
45:1161-1170. doi:10.1086/522189 PMid:17918077.
- Odabasi Z, Mattiuzzi G, Estey E,
Kantarjian H, Saeki F, Ridge RJ, Ketchum PA, Finkelman MA, Rex JH,
Ostrosky-Zeichner L. Beta-D-glucan as a diagnostic adjunct for invasive
fungal infections: validation, cutoff development, and performance in
patients with acute myelogenous leukemia and myelodysplastic syndrome.
Clin Infect Dis. 2004; 39:199-205. doi:10.1086/421944
PMid:15307029.
- Ostrosky-Zeichner L, Alexander BD, Kett
DH, Vazquez J, Pappas PG, Saeki F, Ketchum PA, Wingard J, Schiff R,
Tamura H, Finkelman MA, Rex JH. Multicenter clinical evaluation of the
(1→3) beta-D-glucan assay as an aid to diagnosis of fungal infections
in humans. Clin Infect Dis. 2005; 41:654-659. doi:10.1086/432470
PMid:16080087.
- Kami M, Tanaka Y, Kanda Y, Ogawa S,
Masumoto T, Ohtomo K, Matsumura T, Saito T, Machida U, Kashima T, Hirai
H. Computed tomographic scan of the chest, latex agglutination test and
plasma (1→3)-beta-D-glucan assay in early diagnosis of invasive
pulmonary aspergillosis: a prospective study of 215 patients.
Haematologica. 2000; 85:745-752. PMid:10897127.
- Hachem RY, Kontoyiannis DP, Chemaly RF,
Jiang Y, Reitzel R, Raad I. Utility of galactomannan enzyme immunoassay
and (1→3) beta-D-glucan in diagnosis of invasive fungal infections: low
sensitivity for Aspergillus fumigatus infection in hematologic
malignancy patients. J Clin Microbiol. 2009; 47:129-133. doi:10.1128/JCM.00506-08
PMid:19005145 PMCid:2620882.
- Sendid B, Poirot JL, Tabouret M, Bonnin A,
Caillot D, Camus D, Poulain D. Combined detection of mannanaemia and
antimannan antibodies as a strategy for the diagnosis of systemic
infection caused by pathogenic Candida species. J Med Microbiol. 2002;
51:433-442. PMid:11990496.
- Prella M, Bille J, Pugnale M, Duvoisin B,
Cavassini M, Calandra T, Marchetti O. Early diagnosis of invasive
candidiasis with mannan antigenemia and antimannan antibodies. Diagn
Microbiol Infect Dis. 2005; 51:95-101.doi:10.1016/j.diagmicrobio.2004.08.015.08.015
PMid:15698714.
- White PL, Perry MD, Barnes RA. An update
on the molecular diagnosis of invasive fungal disease. FEMS Microbiol
Lett. 2009; 296:1-10. doi:10.1111/j.1574-6968.2009.01575.x
PMid:19416355.
- Suarez F, Lortholary O, Buland S, Rubio
MT, Ghez D, Mahé V, Quesne G, Poirée S, Buzyn A, Varet B, Berche P,
Bougnoux ME. Detection of circulating Aspergillus fumigatus DNA by
real-time PCR assay of large serum volumes improves early diagnosis of
invasive aspergillosis in high-risk adult patients under hematologic
surveillance. J Clin Microbiol. 2008; 46:3772-3777. doi:10.1128/JCM.01086-08
PMid:18845828 PMCid:2576581.
- Cuenca-Estrella M, Meije Y, Diaz-Pedroche
C, Gomez-Lopez A, Buitrago MJ, Bernal-Martinez L, Grande C, Juan RS,
Lizasoain M, Rodriguez-Tudela JL, Aguado JM. Value of serial
quantification of fungal DNA by a real-time PCR-based technique for
early diagnosis of invasive aspergillosis in patients with febrile
neutropenia. J Clin Microbiol. 2009; 47:379-384. doi:10.1128/JCM.01716-08
PMid:19109479 PMCid:2643681.
- Mengoli C, Cruciani M, Barnes RA, Loeffler
J, Donnelly JP. Use of PCR for diagnosis of invasive aspergillosis:
systematic review and meta-analysis. Lancet Infect Dis. 2009; 9:89-96.
doi:10.1016/S1473-3099(09)70019-2.
- White PL, Archer AE, Barnes RA. Comparison
of non-culture-based methods for detection of systemic fungal
infections, with an emphasis on invasive Candida infections. J Clin
Microbiol. 2005; 43:2181-2187. doi:10.1128/JCM.43.5.2181-2187.2005
PMid:15872239 PMCid:1153728.
- White PL, Barton R, Guiver M, Linton CJ,
Wilson S, Smith M, Gomez BL, Carr MJ, Kimmitt PT, Seaton S, Rajakumar
K, Holyoake T, Kibbler CC, Johnson E, Hobson RP, Jones B, Barnes RA. A
consensus on fungal polymerase chain reaction diagnosis?: a United
Kingdom-Ireland evaluation of polymerase chain reaction methods for
detection of systemic fungal infections. J Mol Diagn. 2006; 8:376-384.
doi:10.2353/jmoldx.2006.050120 PMid:16825512 PMCid:1867606.
- McMullan R, Metwally L, Coyle PV,
Hedderwick S, McCloskey B, O'Neill HJ, Patterson CC, Thompson G, Webb
CH, Hay RJ. A prospective clinical trial of a real-time polymerase
chain reaction assay for the diagnosis of candidemia in nonneutropenic,
critically ill adults. Clin Infect Dis. 2008; 46:890-896.
doi:10.1086/528690 PMid:18260751.
- Barnes RA, White PL, Bygrave C, Evans N,
Healy B, Kell J. Clinical impact of enhanced diagnosis of invasive
fungal disease in high-risk haematology and stem cell transplant
patients. J Clin Pathol. 2009; 62:64-69. doi:10.1136/jcp.2008.058354
PMid:19103864.