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Shin DW, Cho J, Choi KS, Lee J, Choi Y, Choi SJ, Kim SA, Moon SM, Kim ES, Kim HB, Park KU, Hong YJ, Song KH. False-positive results of galactomannan assays in patients administered glucose-containing solutions. Sci Rep 2024; 14:2552. [PMID: 38291146 PMCID: PMC10827775 DOI: 10.1038/s41598-024-53116-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 01/28/2024] [Indexed: 02/01/2024] Open
Abstract
Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.
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Affiliation(s)
- Dong Woo Shin
- Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jungwon Cho
- Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Kyung Suk Choi
- Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jungwha Lee
- Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yunsang Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Seong Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sang-A Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Song Mi Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Eu Suk Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Hong Bin Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Kyoung Un Park
- Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yun Ji Hong
- Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Kyoung-Ho Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
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Acet-Öztürk NA, Ömer-Topçu D, Vurat Acar K, Aydın-Güçlü Ö, Pınar İE, Demirdöğen E, Görek-Dilektaşlı A, Kazak E, Özkocaman V, Ursavas A, Özkalemkaş F, Ener B, Ali R, Akalın H. Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience. Eur J Clin Microbiol Infect Dis 2024; 43:33-43. [PMID: 37910269 DOI: 10.1007/s10096-023-04686-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 10/16/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.
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Affiliation(s)
| | - Dilara Ömer-Topçu
- Department of Pulmonology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Kübra Vurat Acar
- Department of Internal Medicine, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Özge Aydın-Güçlü
- Department of Pulmonology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - İbrahim Ethem Pınar
- Department of Hematology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Ezgi Demirdöğen
- Department of Pulmonology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | | | - Esra Kazak
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Vildan Özkocaman
- Department of Hematology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Ahmet Ursavas
- Department of Pulmonology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Fahir Özkalemkaş
- Department of Hematology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Beyza Ener
- Department of Microbiology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Rıdvan Ali
- Department of Hematology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Halis Akalın
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Uludağ University, Bursa, Turkey
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Chong E, Ko JH, Kim DR, Lee YH, Yang J, Kim H, Huh K, Kang CI, Chung DR, Peck KR, Jeong IH, Kim TY, Huh HJ, Lee NY, Shin A, Kim YJ, Sohn YM, Cho SY, Kang ES. False-positive Aspergillus galactomannan immunoassay in the glucose component of total parenteral nutrition products. Microbiol Spectr 2023; 11:e0167323. [PMID: 37800931 PMCID: PMC10715174 DOI: 10.1128/spectrum.01673-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 07/26/2023] [Indexed: 10/07/2023] Open
Abstract
IMPORTANCE This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.
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Affiliation(s)
- Eunbin Chong
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Doo Ri Kim
- Division of Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Young Ho Lee
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jinyoung Yang
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Haein Kim
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Cheol-In Kang
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Doo Ryeon Chung
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyong Ran Peck
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Hwa Jeong
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Tae Yeul Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hee Jae Huh
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Nam Yong Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Areum Shin
- Division of Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Yae-Jean Kim
- Division of Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - You Min Sohn
- Department of Pharmaceutical Services, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sun Young Cho
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eun-Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Chang E, Kang SW, Huh JW, Kim MN, Bae S, Jung J, Kim MJ, Kim SH, Choi SH, Lee SO, Kim YS, Sung H, Chong YP. False positive Aspergillus galactomannan assay results caused by specific parenteral nutrition. Med Mycol 2023; 61:myad094. [PMID: 37656877 DOI: 10.1093/mmy/myad094] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/04/2023] [Accepted: 08/29/2023] [Indexed: 09/03/2023] Open
Abstract
In September 2022, the proportion of clinically false positive results with high index values for the galactomannan (GM) assay increased dramatically in our hospital and remained high until November 2022. We aimed to identify the possible causative agent that led to the dramatic increase in false positivity in GM assay. A case-control-control study was conducted, and patients admitted to two intensive care units between September and November 2022 were included. We defined each time point at which the GM assay was conducted in a patient as an episode and classified episodes into strong-positive (≥10.0 index; case), positive (control), and negative (<0.5 index; control) groups. We compared the medications administered in three groups and measured GM levels in relevant medications, including parenteral nutrition (PN). In total, 118 episodes in 33 patients were classified into three groups. There were 46 negative, 23 positive, and 49 strong-positive episodes, and there was a significant difference in the use of Winuf® PNs (P < .001) between the three groups. Forty episodes (82%) in the strong-positive group received Winuf®, compared with three (6.5%) in the negative group and one (4.3%) in the positive group (P < .001). All samples of Winuf® PNs used in the five patients whose GM results were repeatedly strong-positive were strongly positive for GM. False positivity in GM assay can be caused by the administration of specific PNs. A thorough investigation of prescribed medications should be considered when there is an abrupt increase in the proportion of strong-positive or positive GM results.
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Affiliation(s)
- Euijin Chang
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Sung-Woon Kang
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Jin-Won Huh
- Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Mi-Na Kim
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seongman Bae
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
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The Alteration of Serum Galactomannan Levels in Surgically Treated Patients with Aspergilloma: a Prospective Observational Study. Indian J Surg 2021. [DOI: 10.1007/s12262-021-03150-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Yang L, Song J, Wang Y, Feng J. Metagenomic Next-Generation Sequencing for Pulmonary Fungal Infection Diagnosis: Lung Biopsy versus Bronchoalveolar Lavage Fluid. Infect Drug Resist 2021; 14:4333-4359. [PMID: 34707378 PMCID: PMC8542593 DOI: 10.2147/idr.s333818] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 09/30/2021] [Indexed: 12/18/2022] Open
Abstract
Purpose Metagenomic next-generation sequencing (mNGS) is widely used for pulmonary infection; nonetheless, the experience from its clinical use in diagnosing pulmonary fungal infections is sparse. This study aimed to compare mNGS results from lung biopsy and bronchoalveolar lavage fluid (BALF) and determine their clinical diagnostic efficacy. Patients and Methods A total of 106 patients with suspected pulmonary fungal infection from May 2018 to January 2020 were included in this retrospective study. All patients' lung biopsy and BALF specimens were collected through bronchoscopy. Overall, 45 (42.5%) patients had pulmonary fungal infection. The performance of lung biopsy and BALF used for mNGS in diagnosing pulmonary fungal infections and identifying pathogens was compared. Additionally, mNGS was compared with conventional tests (pathology, galactomannan test, and cultures) with respect to the diagnosis of pulmonary fungal infections. Results Lung biopsy-mNGS and BALF-mNGS exhibited no difference in terms of sensitivity (80.0% vs 84.4%, P=0.754) and specificity (91.8% vs 85.3%, P=0.39). Additionally, there was no difference in specificity between mNGS and conventional tests; however, the sensitivity of mNGS (lung biopsy, BALF) in diagnosing pulmonary fungal infections was significantly higher than that of conventional tests (conventional tests vs biopsy-mNGS: 44.4% vs 80.0%, P<0.05; conventional tests vs BALF-mNGS: 44.4% vs 84.4%, P<0.05). Among 32 patients with positive mNGS results for both biopsy and BALF specimens, 23 (71.9%) cases of consistency between the two tests for the detected fungi and nine (28.1%) cases of a partial match were identified. Receiver operating curve analysis revealed that the area under the curve for the combination of biopsy and BALF was significantly higher than that for BALF-mNGS (P=0.018). Conclusion We recommend biopsy-based or BALF-based mNGS for diagnosing pulmonary fungal infections because of their diagnostic advantages over conventional tests. The combination of biopsy and BALF for mNGS can be considered when higher diagnostic efficacy is required.
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Affiliation(s)
- Lei Yang
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Junxiu Song
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Yubao Wang
- Institute of Infectious Diseases, The Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China
| | - Jing Feng
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
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Challenges with Utilizing the 1,3-Beta-d-Glucan and Galactomannan Assays To Diagnose Invasive Mold Infections in Immunocompromised Children. J Clin Microbiol 2021; 59:e0327620. [PMID: 33883182 DOI: 10.1128/jcm.03276-20] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Establishing the diagnosis of invasive mold infections (IMI) in immunocompromised children is challenging due to nonspecific clinical presentations and the limited sensitivity of traditional culture-based methods. Rapid non-culture-based diagnostics such as the 1,3-beta-d-glucan and galactomannan assays have emerged as promising adjuncts to conventional diagnostic tests in adults. Available data suggest that 1,3-beta-d-glucan has limited accuracy in the pediatric population and is not recommended to be used for the diagnosis of IMI in children. On the other hand, the diagnostic performance of the serum and bronchoalveolar lavage galactomannan in immunocompromised children is comparable to results observed in adults and can be used as a screening tool in children at high risk of developing invasive aspergillosis (IA) who are not receiving mold-active antifungal prophylaxis and as a diagnostic tool in symptomatic children suspected of having IA. Herein, we summarize the available evidence for the use of these rapid non-culture-based diagnostics in immunocompromised children. We also summarize potential causes of false positivity for the 1,3-beta-d-glucan and galactomannan assays.
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Mercier T, Castagnola E, Marr KA, Wheat LJ, Verweij PE, Maertens JA. Defining Galactomannan Positivity in the Updated EORTC/MSGERC Consensus Definitions of Invasive Fungal Diseases. Clin Infect Dis 2021; 72:S89-S94. [PMID: 33709125 DOI: 10.1093/cid/ciaa1786] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The consensus definitions of invasive fungal diseases from the EORTC/MSGERC were recently revised and updated. They now include consensus cutoff values for the galactomannan test that support the diagnosis of probable invasive aspergillosis. In this supplement article, we provide a rationale for these proposed thresholds based on the test's characteristics and performance in different patient populations and in different specimen types.
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Affiliation(s)
- Toine Mercier
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Hematology, University Hospitals Leuven, Leuven, Belgium
| | - Elio Castagnola
- Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Kieren A Marr
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Paul E Verweij
- Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Johan A Maertens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Hematology, University Hospitals Leuven, Leuven, Belgium
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Rudloff E, Hopper K. Crystalloid and Colloid Compositions and Their Impact. Front Vet Sci 2021; 8:639848. [PMID: 33869319 PMCID: PMC8044465 DOI: 10.3389/fvets.2021.639848] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/01/2021] [Indexed: 12/18/2022] Open
Abstract
This manuscript will review crystalloid (hypo-, iso-, and hyper-tonic) and colloid (synthetic and natural) fluids that are available for intravenous administration with a focus on their electrolyte, acid-base, colligative, and rheological effects as they relate to each solution's efficacy and safety. The goal is for the reader to better understand the differences between each fluid and the influence on plasma composition, key organ systems, and their implications when used therapeutically in animals with critical illness.
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Affiliation(s)
- Elke Rudloff
- BluePearl Specialty + Pet Emergency, Glendale, WI, United States
| | - Kate Hopper
- Department of Veterinary Surgical & Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
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Reagan KL, Wheat LJ, Sykes JE. Effect of an oral probiotic nutraceutical containing Aspergillus-derived ingredients on a serum and urine galactomannan antigen assay in dogs. Vet J 2020; 265:105551. [PMID: 33129555 DOI: 10.1016/j.tvjl.2020.105551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 09/15/2020] [Accepted: 09/23/2020] [Indexed: 10/23/2022]
Abstract
A commercial Aspergillus galactomannan antigen (GMA) enzyme linked immunosorbent assay (ELISA) is used to support a diagnosis of systemic aspergillosis in dogs. In human patients, false positive results have been associated with administration of medications derived from molds. We sought to determine the effect of administration of a commercially available oral probiotic nutraceutical that contained Aspergillus-derived ingredients on serum and urine Aspergillus GMA levels in dogs by conducting a prospective, cross-over study. Galactomannan index (GMI) was measured on the solubilized probiotic nutraceutical and was positive (GMI ≥ 0.5) with a mean of 7.91. Serum and urine galactomannan indices were measured in 10 healthy dogs before (day 0) and after 1 week (day 7) of probiotic nutraceutical administration, then again 2 weeks after the probiotic nutraceutical was discontinued (day 21). Median (range) serum GMI were 0.19 (0.08-0.62), 0.22 (0.07-1.15) and 0.17 (0.14-0.63) at day 0, 7 and 21, respectively. Two of 10 dogs developed positive GMI (≥0.5) results after probiotic nutraceutical administration; however, no significant changes were noted over the study period. Median (range) urine GMI results were 0.06 (0.04-0.22), 0.07 (0.05-0.41) and 0.06 (0.03-0.16) at day 0, 7 and 21, respectively. A trend towards an increase urine GMI was noted between day 0 and 7 (P = 0.18), and decrease was noted between day 7 and 21 (P = 0.09). Administration of probiotics containing Aspergillus-derived ingredients to dogs did not reliably result in elevated Aspergillus GMA levels.
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Affiliation(s)
- K L Reagan
- Department of Medicine and Epidemiology, University of California Davis, Davis, CA 95616, USA.
| | - L J Wheat
- Mira Vista Diagnostics, Indianapolis, IN 46214, USA
| | - J E Sykes
- Department of Medicine and Epidemiology, University of California Davis, Davis, CA 95616, USA
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Hage CA, Carmona EM, Epelbaum O, Evans SE, Gabe LM, Haydour Q, Knox KS, Kolls JK, Murad MH, Wengenack NL, Limper AH. Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2019; 200:535-550. [PMID: 31469325 PMCID: PMC6727169 DOI: 10.1164/rccm.201906-1185st] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background: Fungal infections are of increasing incidence and importance in immunocompromised and immunocompetent patients. Timely diagnosis relies on appropriate use of laboratory testing in susceptible patients.Methods: The relevant literature related to diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses was systematically reviewed. Meta-analysis was performed when appropriate. Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation approach.Results: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and for the diagnosis of invasive pulmonary aspergillosis, the role of PCR in the diagnosis of invasive pulmonary aspergillosis, the role of β-d-glucan assays in the diagnosis of invasive candidiasis, and the application of serology and antigen testing in the diagnosis of the endemic mycoses.Conclusions: Rapid, accurate diagnosis of fungal infections relies on appropriate application of laboratory testing, including antigen testing, serological testing, and PCR-based assays.
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de Heer K, Gerritsen MG, Visser CE, Leeflang MMG. Galactomannan detection in broncho-alveolar lavage fluid for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev 2019; 5:CD012399. [PMID: 31107543 PMCID: PMC6526785 DOI: 10.1002/14651858.cd012399.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test. OBJECTIVES To assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook. SEARCH METHODS We searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies. SELECTION CRITERIA We included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used 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) classification as reference standard. DATA COLLECTION AND ANALYSIS Two review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment. MAIN RESULTS We included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%. AUTHORS' CONCLUSIONS The optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.
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Affiliation(s)
- Koen de Heer
- FlevoziekenhuisDepartment of Internal MedicineAlmereNetherlands
- Academic Medical CenterDepartment of HematologyAmsterdamNetherlands
| | | | - Caroline E Visser
- Academic Medical CentreDepartment of Medical MicrobiologyAmsterdamNetherlands
| | - Mariska MG Leeflang
- Amsterdam University Medical Centers, University of AmsterdamDepartment of Clinical Epidemiology, Biostatistics and BioinformaticsP.O. Box 22700AmsterdamNetherlands1100 DE
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Safdar A, Pouch SM, Scully B. Infections in Allogeneic Stem Cell Transplantation. PRINCIPLES AND PRACTICE OF TRANSPLANT INFECTIOUS DISEASES 2018. [PMCID: PMC7121717 DOI: 10.1007/978-1-4939-9034-4_11] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a widely used modality of therapy for a variety of malignant and nonmalignant diseases. Despite advances in pharmacotherapy and transplantation techniques, infection remains one of the most severe and frequently encountered complications of allo-HSCT. This chapter will address the risk factors for development of infection following allo-HSCT, including those related to the host, the conditioning regimen, and the graft, as well as the timing of opportunistic infections after allo-HSCT. The most common bacterial, viral, fungal, and parasitic infections, as well as issues surrounding their diagnostics and treatment, will be discussed. Finally, this chapter will address vaccination and other preventative strategies to be utilized when caring for patients undergoing allo-HSCT.
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Affiliation(s)
- Amar Safdar
- grid.416992.10000 0001 2179 3554Clinical Associate Professor of Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX USA
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Walter W, Bornhäuser M, Stölzel F, Zeidler A, Knoth H. In vitro detection of Candida and Aspergillus antigen in parenteral nutrition and fixed combinations of piperacillin‐tazobactam. Mycoses 2018; 61:931-937. [DOI: 10.1111/myc.12841] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2018] [Indexed: 01/05/2023]
Affiliation(s)
- Wencke Walter
- Klinik‐ApothekeUniversitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden Germany
| | - Martin Bornhäuser
- Medizinische Klinik und Poliklinik IUniversitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden Germany
| | - Friedrich Stölzel
- Medizinische Klinik und Poliklinik IUniversitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden Germany
| | - Anne Zeidler
- Klinik‐ApothekeUniversitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden Germany
| | - Holger Knoth
- Klinik‐ApothekeUniversitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden Germany
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Lheureux O, Montesinos I, Taton O, Antoine M, Preiser JC, Nortier J, Creteur J, Jacobs F, Grimaldi D. False-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report. JMM Case Rep 2017; 4:e005116. [PMID: 29114397 PMCID: PMC5643004 DOI: 10.1099/jmmcr.0.005116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 09/05/2017] [Indexed: 11/18/2022] Open
Abstract
Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent. Case presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Conclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.
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Affiliation(s)
- Olivier Lheureux
- Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
| | - Isabel Montesinos
- Department of Microbiology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Olivier Taton
- Department of Pulmonary Medicine, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Martine Antoine
- Department of Cardiac Surgery, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Jean-Charles Preiser
- Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
| | - Joelle Nortier
- Department of Nephrology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Jacques Creteur
- Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
| | - Frederique Jacobs
- Department of Infectious Diseases, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - David Grimaldi
- Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
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Detection and Management of Fungal Respiratory Infection by Using Molecular Markers. Fungal Biol 2017. [DOI: 10.1007/978-3-319-34106-4_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Weinberg L, Collins N, Van Mourik K, Tan C, Bellomo R. Plasma-Lyte 148: A clinical review. World J Crit Care Med 2016; 5:235-250. [PMID: 27896148 PMCID: PMC5109922 DOI: 10.5492/wjccm.v5.i4.235] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 07/06/2016] [Accepted: 10/09/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To outline the physiochemical properties and specific clinical uses of Plasma-Lyte 148 as choice of solution for fluid intervention in critical illness, surgery and perioperative medicine.
METHODS We performed an electronic literature search from Medline and PubMed (via Ovid), anesthesia and pharmacology textbooks, and online sources including studies that compared Plasma-Lyte 148 to other crystalloid solutions. The following keywords were used: “surgery”, “anaesthesia”, “anesthesia”, “anesthesiology”, “anaesthesiology”, “fluids”, “fluid therapy”, “crystalloid”, “saline”, “plasma-Lyte”, “plasmalyte”, “hartmann’s”, “ringers”“acetate”, “gluconate”, “malate”, “lactate”. All relevant articles were accessed in full. We summarized the data and reported the data in tables and text.
RESULTS We retrieved 104 articles relevant to the choice of Plasma-Lyte 148 for fluid intervention in critical illness, surgery and perioperative medicine. We analyzed the data and reported the results in tables and text.
CONCLUSION Plasma-Lyte 148 is an isotonic, buffered intravenous crystalloid solution with a physiochemical composition that closely reflects human plasma. Emerging data supports the use of buffered crystalloid solutions in preference to saline in improving physicochemical outcomes. Further large randomized controlled trials assessing the comparative effectiveness of Plasma-Lyte 148 and other crystalloid solutions in measuring clinically important outcomes such as morbidity and mortality are needed.
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Savio J, Menon NR, Sudharma AR, Jairaj V, Mathew J. Galactomannan Assay and Invasive Pulmonary Aspergillosis - Comparison of the Test Performance at an in-house and the Kit Cut-off. J Clin Diagn Res 2016; 10:DC01-4. [PMID: 27656435 PMCID: PMC5028428 DOI: 10.7860/jcdr/2016/19175.8310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 06/21/2016] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Invasive Pulmonary Aspergillosis (IPA) is an important opportunistic infection with a high degree of mortality and morbidity. Galactomannan assay (GM assay) is found to be useful for diagnosis of IPA in patients with neutropenia. However the utility of this assay has not been evaluated in a mixed patient population with other co-morbid conditions. Though a kit cut-off of 0.5 has been recommended for the diagnosis of IPA, studies have reported a higher sensitivity with cut-offs more than 0.5. AIM To establish an in-house cut-off and compare its utility with the kit cut-off to diagnose and categorize IPA as proven, probable and possible in patients with varied underlying risk factors. MATERIALS AND METHODS This observational study was done in St John's Medical College, Bangalore, Karnataka, India from January 2013-December 2014. GM assay was performed on 25 each of healthy controls and clinically diagnosed cases of IPA. The in-house cut-off was calculated by plotting the Receiver Operating Characteristic Curve (ROC). RESULTS The in-house cut-off was calculated to be 0.52. Using this and the kit cut-off (0.5), the Sensitivity, Specificity, Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) were found to be 75%, 79%, 76%, 82% and 79%, 71%, 77%, 82% respectively. Diabetes mellitus was found to be associated with more than 50% of the patients. CONCLUSION The established in house cut-off using healthy controls and patients with clinical diagnosis of IPA was not significantly different from that of the kit cut-off. Using either of these cut-offs, we could re-categorize two of the possible IPA cases in the probable group. This study helped to understand the clinical utility of this assay even in a mixed patient population with multiple co-morbidities.
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Affiliation(s)
- Jayanthi Savio
- Associate Professor, Department Microbiology, St John’s Medical College, Bangalore, Karnataka, India
| | | | - Arun Ramachandran Sudharma
- Junior Research Fellow, Department Microbiology, St. Johns Research Institute, Bangalore, Karnataka, India
| | - Vinutha Jairaj
- PG Resident, Department Microbiology, St John’s Medical College, Bangalore, Karnataka, India
| | - Joshila Mathew
- Senior Laboratory Technician, St John’s Medical College, Bangalore, Karnataka, India
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Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JAH, Bennett JE. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1-e60. [PMID: 27365388 DOI: 10.1093/cid/ciw326] [Citation(s) in RCA: 1789] [Impact Index Per Article: 198.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 05/11/2016] [Indexed: 12/12/2022] Open
Abstract
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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Affiliation(s)
- Thomas F Patterson
- University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System
| | | | - David W Denning
- National Aspergillosis Centre, University Hospital of South Manchester, University of Manchester, United Kingdom
| | - Jay A Fishman
- Massachusetts General Hospital and Harvard Medical School
| | | | | | | | - Kieren A Marr
- Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland
| | - Vicki A Morrison
- Hennepin County Medical Center and University of Minnesota, Minneapolis
| | | | - Brahm H Segal
- University at Buffalo Jacobs School of Medicine and Biomedical Sciences, and Roswell Park Cancer Institute, New York
| | | | | | - Thomas J Walsh
- New York-Presbyterian Hospital/Weill Cornell Medical Center, New York
| | | | | | - John E Bennett
- Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland
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Maschmeyer G, Donnelly JP. How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation. Br J Haematol 2016; 173:179-89. [PMID: 26729577 PMCID: PMC7161791 DOI: 10.1111/bjh.13934] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 12/13/2015] [Indexed: 12/20/2022]
Abstract
Pulmonary complications affect up to 40% of patients with severe neutropenia lasting for more than 10 d. As they are frequently associated with fever and elevation of C‐reactive protein or other signs of inflammation, they are mostly handled as pneumonia. However, the differential diagnosis is broad, and a causative microbial agent remains undetected in the majority of cases. Pulmonary side effects from cytotoxic treatment or pulmonary involvement by the underlying malignancy must always be taken into account and may provide grounds for invasive diagnostic procedures in selected patients. Pneumocystis jirovecii (in patients not receiving co‐trimoxazole as prophylaxis), multi‐resistant gram‐negative bacilli, mycobacteria or respiratory viruses may be involved. High‐risk patients may be infected by filamentous fungi, such as Aspergillus spp., but these infections are seldom proven when treatment is initiated. Microorganisms isolated from cultures of blood, bronchoalveolar lavage or respiratory secretions need careful interpretation as they may be irrelevant for determining the aetiology of pulmonary infiltrates, particularly when cultures yield coagulase‐negative staphylococci, enterococci or Candida species. Non‐culture based diagnostics for detecting Aspergillus galactomannan, beta‐D‐glucan or DNA from blood, bronchoalveolar lavage or tissue samples can facilitate the diagnosis, but must always be interpreted in the context of clinical and imaging findings. Systemic antifungal treatment with mould‐active agents, given in combination with broad‐spectrum antibiotics, improves clinical outcome when given pre‐emptively. Co‐trimoxazole remains the first‐line treatment for Pneumocystis pneumonia, while cytomegalovirus pneumonia will respond to ganciclovir or foscarnet in most cases. The clinical outcome of acute respiratory failure can also be successful with proper intensive care, when indicated.
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Affiliation(s)
- Georg Maschmeyer
- Department of Haematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany
| | - J Peter Donnelly
- Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands
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Microbiologic Diagnosis of Lung Infection. MURRAY AND NADEL'S TEXTBOOK OF RESPIRATORY MEDICINE 2016. [PMCID: PMC7152380 DOI: 10.1016/b978-1-4557-3383-5.00017-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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Plasmalyte: No Longer a Culprit in Causing False-Positive Galactomannan Test Results. J Clin Microbiol 2015; 54:795-7. [PMID: 26719444 DOI: 10.1128/jcm.02813-15] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 12/22/2015] [Indexed: 12/18/2022] Open
Abstract
False-positive galactomannan (GM) results have been reported in patients treated with gluconate-containing solutions, such as Plasmalyte. The GM optical density index was tested on 33 distinct batches of Plasmalyte and was found to be negative in all of the batches, confirming that Plasmalyte is no longer a cause of false-positive GM results.
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Maschmeyer G, Carratalà J, Buchheidt D, Hamprecht A, Heussel CP, Kahl C, Lorenz J, Neumann S, Rieger C, Ruhnke M, Salwender H, Schmidt-Hieber M, Azoulay E. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 2015; 26:21-33. [PMID: 24833776 PMCID: PMC4269340 DOI: 10.1093/annonc/mdu192] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Revised: 04/29/2014] [Accepted: 05/02/2014] [Indexed: 12/13/2022] Open
Abstract
Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.
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Affiliation(s)
- G Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany.
| | - J Carratalà
- Department of Infectious Diseases, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain
| | - D Buchheidt
- Department of Hematology and Oncology, Mannheim University Hospital, Mannheim
| | - A Hamprecht
- Institution for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne
| | - C P Heussel
- Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, University Hospital, Heidelberg
| | - C Kahl
- Department of Hematology and Oncology, Klinikum Magdeburg, Magdeburg
| | - J Lorenz
- Department of Pneumology, Infectious Diseases, Sleep Medicine and Intensive Care, Klinikum Lüdenscheid, Lüdenscheid
| | - S Neumann
- Medical Oncology, AMO MVZ, Wolfsburg
| | - C Rieger
- Department of Medicine III, University Hospital Großhadern, München
| | - M Ruhnke
- Department of Medical Oncology and Hematology, Charité University Medicine Campus Mitte, Berlin
| | - H Salwender
- Department of Hematology, Oncology, Stem Cell Transplantation, Asklepios Klinik Altona, Hamburg
| | - M Schmidt-Hieber
- Department of Hematology, Oncology and Tumor Immunology, Helios-Klinikum Berlin-Buch, Berlin, Germany
| | - E Azoulay
- AP-HP, Hopital Saint-Louis, Service de Réanimation Médicale, Université Paris-Diderot, Sorbonne Paris-Cité, Faculté de Médecine, Paris, France
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Current challenges in the microbiological diagnosis of invasive aspergillosis. Mycopathologia 2014; 178:403-16. [PMID: 24947167 DOI: 10.1007/s11046-014-9763-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 05/28/2014] [Indexed: 12/18/2022]
Abstract
The diagnosis of invasive aspergillosis is challenging because no sufficiently sensitive or specific tests have been developed to date. Infection can only be confirmed using histology, although this approach is unavailable in many patients. Therefore, diagnosis of invasive aspergillosis is based on a combination of the presence of host factors, radiological and clinical findings, and mycological criteria. In clinical practice, lack of optimal diagnostics often leads to empirical therapy and great cost and toxicity. Mycological criteria include the isolation of Aspergillus from clinical samples or the detection of biomarkers in fluids. Culture is cheap and easy and enables the identification of fungi and performance of antifungal susceptibility testing; however, it has low sensitivity and specificity. Non-culture-based diagnosis is based on the detection of fungal biomarkers such as galactomannan or (1 → 3)-β-D-glucan in normally sterile body fluids. These procedures enable faster and more sensitive and specific detection of Aspergillus; however, diagnostic accuracy is affected by the patient's underlying condition. Finally, while detection of Aspergillus DNA is promising, the lack of standardization limits its inclusion as a mycological criterion for the definition of probable invasive aspergillosis. New diagnostic procedures based on lateral flow technology are also promising but need further evaluation. In the present review, we discuss current culture-based and non-culture-based procedures for the microbiological diagnosis of invasive aspergillosis.
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Lamoth F, Alexander BD. Nonmolecular methods for the diagnosis of respiratory fungal infections. Clin Lab Med 2014; 34:315-36. [PMID: 24856530 DOI: 10.1016/j.cll.2014.02.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diagnosis of invasive fungal pneumonias by conventional culture methods is difficult to assess and often delayed. Nonmolecular fungal markers have emerged as an important adjunctive tool to support their diagnosis in combination with other clinical, radiologic, and microbiological criteria of invasive fungal diseases. Concerns about the sensitivity and specificity of some tests in different patient populations should lead to warnings about their widespread use. None can identify the emerging and particularly deadly fungal pathogens responsible for mucormycosis. The role of nonmolecular fungal markers should be better defined in combination with other microbiological and radiologic tools in preemptive antifungal strategies.
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Affiliation(s)
- Frédéric Lamoth
- Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Box 102359, Durham, NC 27710, USA; Clinical Microbiology Laboratory, Department of Pathology, Duke University Medical Center, 108 Carl building, Durham, NC 27710, USA; Infectious Diseases Service and Institute of Microbiology, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
| | - Barbara D Alexander
- Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Box 102359, Durham, NC 27710, USA; Clinical Microbiology Laboratory, Department of Pathology, Duke University Medical Center, 108 Carl building, Durham, NC 27710, USA.
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Ng TY, Kang ML, Tan BH, Ngan CCL. Case report: Enteral nutritional supplement as a likely cause of false-positive galactomannan testing. Med Mycol Case Rep 2013; 3:11-3. [PMID: 24567893 PMCID: PMC3930958 DOI: 10.1016/j.mmcr.2013.11.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 11/17/2013] [Indexed: 11/29/2022] Open
Abstract
The detection of galactomannan (GM) in the serum of in immunocompromised patients is widely used for the early diagnosis of invasive aspergillosis. We report a case of a false-positive GM test presumably caused by the enteral nutritional supplement given to a non-neutropenic patient with intestinal graft-versus-host disease after a hematopoietic stem cell transplant. Clinicians should be alert to the possibility of false-positive GM results in patients on nutritional supplements.
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Affiliation(s)
- Tong-Yong Ng
- Department of Pathology, Singapore General Hospital, Singapore
| | - Mei-Ling Kang
- Department of Infectious Diseases, Singapore General Hospital, Singapore
| | - Ban-Hock Tan
- Department of Infectious Diseases, Singapore General Hospital, Singapore
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Ben-Ami R, Halaburda K, Klyasova G, Metan G, Torosian T, Akova M. A multidisciplinary team approach to the management of patients with suspected or diagnosed invasive fungal disease. J Antimicrob Chemother 2013; 68 Suppl 3:iii25-33. [DOI: 10.1093/jac/dkt390] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
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Riwes MM, Wingard JR. Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies. Expert Rev Hematol 2013; 5:661-9. [PMID: 23216596 DOI: 10.1586/ehm.12.53] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Invasive fungal disease is associated with increased morbidity and mortality in hematologic malignancy patients and hematopoietic stem cell transplant recipients. Timely recognition and treatment of invasive fungal diseases in these patients are essential and decrease mortality. However, conventional definitive diagnostic methods are difficult and time consuming. While conventional microbiological and histopathological methods are still needed for a definitive diagnosis of invasive fungal disease, new noninvasive diagnostic methods including serologic and molecular biomarkers are now available. These new diagnostic methods facilitate an early diagnosis of invasive fungal disease and allow for utilization of a pre-emptive treatment approach, which may ultimately lead to improved treatment outcomes and reduced toxicity.
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Affiliation(s)
- Mary Mansour Riwes
- University of Florida, College of Medicine, Division of Hematology/Oncology 1600 W Archer Road, Gainesville, FL 32610-0278, USA
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31
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Zhang XB, Chen GP, Lin QC, Lin X, Zhang HY, Wang JH. Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease. Med Mycol 2013; 51:688-95. [PMID: 23527739 DOI: 10.3109/13693786.2013.777162] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Invasive pulmonary aspergillosis (IPA) is difficult to diagnose in chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate whether detection of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) might be a useful means of making the diagnosis. Patients with COPD and new pulmonary infiltrates were enrolled. BALF was collected for culture and detection of GM. Venous blood was also sampled for GM detection. Biopsy samples were obtained whenever possible. Eleven cases of IPA were diagnosed (three proven and eight probable); 80 controls without IPA diagnosed were recruited. At a GM cut-off of 0.5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing IPA were 90.9, 66.3, 27.0 and 98.1% in serum, and 90.9, 62.5, 25.0 and 98.0% in BALF, respectively. At a cut-off of 1.0, the specificity, PPV and NPV in BALF increased to 95.0, 71.4 and 98.7%; the sensitivity remained 90.9%. The sensitivity in serum was substantially lower than BALF (45.5% versus 90.9%). Receiver operating characteristic curve analysis identified an optimal BALF GM cut-off value of 1.25, with a sensitivity of 90.9% and a specificity of 96.3% for diagnosing IPA. At a relatively high cut-off value, BALF GM detection is a useful tool for the diagnosis of IPA in COPD. Besides piperacillin-tazobactam and amoxicillin-clavulanate, many other factors may also cause false-positive of GM detection in patients without IPA. Further work is needed to identify factors that might lead to false-positive or false-negative results.
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Affiliation(s)
- Xiao-Bin Zhang
- * Department of Respiratory Medicine, the First Affiliated Hospital of Fujian Medical University, Laboratory of respiratory diseases in Fujian Medical University
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Barton RC. Laboratory diagnosis of invasive aspergillosis: from diagnosis to prediction of outcome. SCIENTIFICA 2013; 2013:459405. [PMID: 24278780 PMCID: PMC3820361 DOI: 10.1155/2013/459405] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Accepted: 11/14/2012] [Indexed: 06/02/2023]
Abstract
Invasive aspergillosis (IA), an infection caused by fungi in the genus Aspergillus, is seen in patients with immunological deficits, particularly acute leukaemia and stem cell transplantation, and has been associated with high rates of mortality in previous years. Diagnosing IA has long been problematic owing to the inability to culture the main causal agent A. fumigatus from blood. Microscopic examination and culture of respiratory tract specimens have lacked sensitivity, and biopsy tissue for histopathological examination is rarely obtainable. Thus, for many years there has been a great interest in nonculture-based techniques such as the detection of galactomannan, β -D-glucan, and DNA by PCR-based methods. Recent meta-analyses suggest that these approaches have broadly similar performance parameters in terms of sensitivity and specificity to diagnose IA. Improvements have been made in our understanding of the limitations of antigen assays and the standardisation of PCR-based DNA detection. Thus, in more recent years, the debate has focussed on how these assays can be incorporated into diagnostic strategies to maximise improvements in outcome whilst limiting unnecessary use of antifungal therapy. Furthermore, there is a current interest in applying these tests to monitor the effectiveness of therapy after diagnosis and predict clinical outcomes. The search for improved markers for the early and sensitive diagnosis of IA continues to be a challenge.
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Affiliation(s)
- Richard C. Barton
- Mycology Reference Centre, Department of Microbiology, Leeds Teaching Hospitals Trust, Leeds LS1 3EX, UK
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D'Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L, Meersseman P, Meersseman W, Lagrou K, Maertens J. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol 2012; 50:1258-63. [PMID: 22301025 PMCID: PMC3318563 DOI: 10.1128/jcm.06423-11] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Accepted: 01/26/2012] [Indexed: 12/26/2022] Open
Abstract
Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in immunosuppressed patients. Timely diagnosis of IPA improves survival but is difficult to make. We examined the analytical and clinical validity of galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in diagnosing IPA in a mixed population by retrospectively reviewing records of 251 consecutive at-risk patients for whom BAL fluid GM testing was ordered. The performance of the enzyme immunoassay was evaluated by using a range of index cutoffs to define positivity. Three samples were associated with proven IPA, 56 were associated with probable IPA, 63 were associated with possible invasive fungal disease (IFD), and 129 were associated with no IFD. Using a BAL fluid GM index of ≥0.8 (optimal optical density [OD] index cutoff identified by a receiver operating characteristic curve), the sensitivity in diagnosing proven and probable IPA was 86.4%, and the specificity was 90.7%. At this cutoff, positive and negative predictive values were 81% and 93.6%, respectively. However, an OD index value of ≥3.0 corresponded to a 100% specificity, thus ruling the disease in, irrespective of the pretest probability. Conversely, an OD index cutoff of <0.5 corresponded to a high sensitivity, virtually always ruling the disease out. For all values in between, the posttest probability of IPA depends largely on the prevalence of disease in the at-risk population and the likelihood ratio of the OD index value. Detection of GM in BAL fluid samples of patients at risk of IPA has an excellent diagnostic accuracy provided results are interpreted in parallel with clinico-radiological findings and pretest probabilities.
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Affiliation(s)
- Jorien D'Haese
- Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit
| | - Koen Theunissen
- Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit
| | | | - Hélène Schoemans
- Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit
| | - Greet De Vlieger
- Department of General Internal Medicine, Medical Intensive Care Unit, Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - Liesbet Lammertijn
- Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit
| | - Philippe Meersseman
- Department of General Internal Medicine, Medical Intensive Care Unit, Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - Wouter Meersseman
- Department of General Internal Medicine, Medical Intensive Care Unit, Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | | | - Johan Maertens
- Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit
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Abstract
Fungal pneumonia is increasingly common, particularly in highly immunosuppressed patients, such as solid organ or hematopoietic stem cell transplant recipients, and the diagnosis is evolving. Although standard techniques such as microscopy and culture remain the mainstays of diagnosis, relatively recent advances in serological and molecular testing are important additions to the field. This article reviews the laboratory tools used to diagnose fungal respiratory disease.
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Affiliation(s)
- Erika D Lease
- Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina 27710, USA
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Galactomannan antigenemia after infusion of gluconate-containing Plasma-Lyte. J Clin Microbiol 2011; 49:4330-2. [PMID: 21976760 DOI: 10.1128/jcm.05031-11] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
We demonstrated that sodium gluconate was the factor causing false-positive galactomannan (GM) antigenemia of Plasma-Lyte hydration solution. Infusion of sodium gluconate-containing solution but not gluconate-free Plasma-Lyte resulted in positive serum GM antigenemia. Serum GM concentrations also correlated with the volume and in vitro concentrations of GM within gluconate-containing solutions of infused Plasma-Lyte.
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Abstract
PURPOSE OF REVIEW The purpose of this review is to describe important findings published during the past 18 months using bronchoalveolar lavage (BAL) for diagnosis of pulmonary mycoses. RECENT FINDINGS Clinical studies and meta-analysis have established a high sensitivity and specificity for Aspergillus galactomannan testing of BAL specimens for diagnosis of invasive aspergillosis, superior to that observed with other diagnostic methods. Similar findings have been reported in histoplasmosis and blastomycosis. SUMMARY Fungal antigen testing of BAL specimens is recommended if bronchoscopy is performed for diagnosis of pulmonary infiltrates in patient groups at risk for aspergillosis or the endemic mycoses if the diagnosis cannot be established by evaluation of sputum specimens or detection of antigen in the urine or serum.
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Patterson TF. Clinical utility and development of biomarkers in invasive aspergillosis. TRANSACTIONS OF THE AMERICAN CLINICAL AND CLIMATOLOGICAL ASSOCIATION 2011; 122:174-183. [PMID: 21686223 PMCID: PMC3116344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
The diagnosis of invasive aspergillosis remains very difficult, and there are limited treatment options for the disease. Pre-clinical models have been used to evaluate the diagnosis and treatment of Aspergillus infection and to assess the pathogenicity and virulence of the organism. Extensive efforts in Aspergillus research have significantly expanded the genomic information about this microorganism. The standardization of animal models of invasive aspergillosis can be used to enhance the evaluation of genomic information about the organism to improve the diagnosis and treatment of invasive aspergillosis. One approach to this process has been the award of a contract by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to establish and standardize animal models of invasive aspergillosis for the development of new diagnostic technologies for both pulmonary and disseminated Aspergillus infection. This work utilizes molecular approaches for the genetic manipulation of Aspergillus strains that can be tested in animal-model systems to establish new diagnostic targets and tools. Studies have evaluated the performance characteristics of assays for cell-wall antigens of Aspergillus including galactomannan and beta-D-glucan, as well as for DNA targets in the organism, through PCR. New targets, such as proteomic and genomic approaches, and novel detection methods, such as point-of-care lateral-flow devices, have also been evaluated. The goal of this paper is to provide a framework for evaluating genomic targets in animal models to improve the diagnosis and treatment of invasive aspergillosis toward ultimately improving the outcomes for patients with this frequently fatal infection.
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Affiliation(s)
- Thomas F Patterson
- The University of Texas Health Science Center at San Antonio, Department of Medicine-Division of Infectious Diseases, 7703 Floyd Curl Drive, MSC 7881, San Antonio, TX 78229-3900, USA.
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Nguyen MH, Leather H, Clancy CJ, Cline C, Jantz MA, Kulkarni V, Wheat LJ, Wingard JR. Galactomannan testing in bronchoalveolar lavage fluid facilitates the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies and stem cell transplant recipients. Biol Blood Marrow Transplant 2010; 17:1043-50. [PMID: 21087680 DOI: 10.1016/j.bbmt.2010.11.013] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2010] [Accepted: 11/09/2010] [Indexed: 10/18/2022]
Abstract
Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.
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Affiliation(s)
- M Hong Nguyen
- University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
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Lopes da Silva R, Ribeiro P, Abreu N, Ferreira T, Fernandes T, Monteiro A, Costa F, Caldas J, Silva M, Carande L, Ferreira G, Conduto A, Cruz E, Sousa MH, Rodrigues AS, Costa I, Veiga J, de Sousa AB. Early Diagnosis of Invasive Aspergillosis in Neutropenic Patients. Comparison between Serum Galactomannan and Polymerase Chain Reaction. CLINICAL MEDICINE INSIGHTS-ONCOLOGY 2010; 4:81-8. [PMID: 20703324 PMCID: PMC2918359 DOI: 10.4137/cmo.s5228] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Background: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients, so early diagnosis is mandatory. Aim: Consecutive patients with hematological malignancies undergoing intensive chemotherapy were screened for IA with two different methods which were compared. Methods: From October 2000 to August 2003 we tested 1311 serum samples from 172 consecutive patients with a polymerase chain reaction assay and between April 2005 and April 2008 we tested 806 serum samples from 169 consecutive patients with a Galactomannan (GM) test. Bronchoalveolar (BAL) samples were obtained whenever the patient’s condition allowed and tested with either method. Results: The serum PCR assay had a sensitivity of 75.0% and a specificity of 91.9% and the serum GM assay had a sensitivity of 87.5% and a specificity of 93.1%, (P > 0.05). The presence of two or more consecutive positive serum samples was predictive of IA for both assays. BAL GM/PCR was positive in some patients without serum positivity and in patients with 2 or more positive serum GM/PCR. Conclusions: No significant differences between the 2 serum tests were found. The GM assay has the advantage of being standardized among several laboratories and is incorporated in the criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), however is much more expensive. BAL GM and PCR sampling aids in IA diagnosis but needs further validation studies to differentiate between colonization and true infection in cases where serum GM or PCR are negative.
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41
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[Diagnosis of invasive pulmonary aspergillosis: value of bronchoalveolar lavage galactomannan for immunocompromised patients]. ACTA ACUST UNITED AC 2009; 58:100-3. [PMID: 19892488 DOI: 10.1016/j.patbio.2009.07.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2009] [Accepted: 07/12/2009] [Indexed: 11/22/2022]
Abstract
Invasive pulmonary aspergillosis (IPA) is an emerging disease associated with high mortality. The diagnosis is difficult, based on a combination of elements that are clinical, radiological and biological. For early detection of cases of IPA, during 25 months, we have systematically carried out on the LBA (N=355) of immunocompromised patients (N=313) a determination of Aspergillus galactomannan (GM) by ELISA (PlateliaAspergillus, BioRad). We observed 14 cases of probable API. The sensitivity of GM compared to direct examination (DE) and culture is, respectively, 64% versus 29% and 57%. The determination of GM is definitely more sensitive than the ED. Excellent specificity (98%) allows its implementation as a screening test in patients at risk.
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Wheat LJ. Approach to the Diagnosis of Invasive Aspergillosis and Candidiasis. Clin Chest Med 2009; 30:367-77, viii. [DOI: 10.1016/j.ccm.2009.02.012] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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The role of bronchoalveolar lavage galactomannan in the diagnosis of pediatric invasive aspergillosis. Pediatr Infect Dis J 2009; 28:283-6. [PMID: 19238113 DOI: 10.1097/inf.0b013e31818f0934] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND : Molecular biomarkers such as the galactomannan assay are of increasing interest in clinical settings for diagnosis of invasive aspergillosis (IA). The use of bronchoalveolar lavage galactomannan (BAL GM) is being validated in adult populations, but has not been systematically evaluated in pediatric patients. METHODS : A retrospective analysis was performed of patients for whom GM assays from BAL were submitted between November 1, 2006 and November14, 2007 at Childrens Hospital Los Angeles. Medical charts were reviewed and patients were categorized as having no, possible, probable, and proven IA, per established definitions. RESULTS : Of 85 pediatric patients who had a BAL GM submitted during the study, 59 were immunocompromised. Three patients were identified as having proven IA, 6 had probable IA, 37 had possible IA, and 39 had no evidence of IA; 38 had a concurrent serum GM performed. A positive, linear correlation was established between BAL and serum GM, using OD index values (rho = 0.48, P = 0.002). Among immunocompromised patients, receiver operating characteristic curves demonstrated an optimal BAL GM OD cut-off value of 0.87, that yielded a sensitivity for probable/proven IA of 78% and a specificity of 100%. At 0.87, the positive and negative predictive values among immunocompromised patients were 58% and 96%, respectively. CONCLUSIONS : We found a correlation between BAL GM values and a diagnosis of IA. We also noted a linear relationship between serum and BAL GM values. Receiver operating characteristic curves obtained from our pediatric data validate the current cut off for serum and suggest a possible cut off for BAL specimens.
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Abstract
PURPOSE OF REVIEW Invasive aspergillosis is a common cause of morbidity and mortality in hematopoietic stem cells transplant recipients. Owing to its intrinsic high mortality rate, early diagnosis and treatment are critical. This review will therefore address the most important recent advances in diagnosing, preventing and treating invasive aspergillosis in hematopoietic stem cells transplant. RECENT FINDINGS The present review will focus on therapeutic and prophylactic aspects, with particular regard to clinical use of drugs other than voriconazole (which has a well known and consolidated role for first-line therapy), combination therapy and prophylactic regimens, particularly with posaconazole. This review will also briefly deal with the clinical role of diagnostic tests such as the detection of galactomannan in body fluids other than blood, beta-D-glucan in serum and fungal DNA by PCR in body fluids. SUMMARY Galactomannan antigen detection is a rather reliable diagnostic test for invasive aspergillosis, particularly when a lower threshold of sensitivity is used. PCR is still to be validated. Liposomal amphotericin B at 3 mg/kg per day showed a similar efficacy in invasive aspergillosis as reported for voriconazole. Therapeutic drug monitoring of Aspergillus-active azoles should be implemented whenever possible in order to maximize the antifungal effect and minimize toxicity. Posaconazole showed to be active in prophylaxis, though its effectiveness in the global patient population is still controversial.
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False-Positive Results of Aspergillus Galactomannan Antigenemia in Liver Transplant Recipients. Transplantation 2009; 87:256-60. [DOI: 10.1097/tp.0b013e31819288d5] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Performance characteristics of the platelia Aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in bronchoalveolar lavage fluid. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2008; 15:1760-3. [PMID: 18845830 DOI: 10.1128/cvi.00226-08] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
We have evaluated the Platelia Aspergillus enzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.
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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; 46:3772-7. [PMID: 18845828 DOI: 10.1128/jcm.01086-08] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Detection of galactomannan antigen (GMA) in serum is the standard assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematological disorders. Detection of Aspergillus DNA in serum has been proposed, but its sensitivity is lower than that of GMA when small serum volumes (SSV) are used. In this study, we investigated whether extraction of DNA from large serum volumes (LSV) improves diagnostic yield. In a 13-month prospective study, we compared the performances of twice-weekly screening of serum for GMA by an enzyme immunoassay and weekly screening for Aspergillus fumigatus DNA by a real-time PCR (RT-PCR) assay of 1.0 ml (LSV) or 100 mul (SSV) of serum. We included 124 patients (138 treatment episodes), with 17 episodes of EORTC (European Organization for Research and Treatment of Cancer)/MSG (Mycoses Study Group)-documented IA. In all, 1,870 samples were screened for GMA. The sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV and NPV, respectively) of GMA for IA were 88.2%, 95.8%, 75%, and 98.3%, respectively. We screened 938 samples for Aspergillus DNA by using LSV; 404 of these samples were also tested with SSV. The Se, Sp, PPV, and NPV of RT-PCR were 100%, 96.7%, 81%, and 100%, respectively, with LSV and 76.5%, 96.7%, 81.3%, and 95.6%, respectively, with SSV. DNA detection gave a positive result when performed on LSV in two cases of IA where the GMA assay result remained negative. Furthermore, in four IA cases, DNA was detected earlier than GMA. The use of LSV for extraction improved the performance of the RT-PCR, which appears highly sensitive and specific for the early diagnosis of IA in high-risk patients with hematological disorders.
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