Preemptive Treatment of Fungal Infection Based on Plasma (1 → 3)β-D-Glucan Levels after Liver Transplantation

Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kaneko, Junichi; Tamura, Sumihito; Makuuchi, Masatoshi

doi:10.1007/s15010-007-6240-7

Cited by 80 publications

(48 citation statements)

References 36 publications

(48 reference statements)

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“…Twenty-four (13%) patients were diagnosed with IFI. Consistent with our findings in the lung transplant population, albeit with an alternative test method, sensitivity (SN), specificity (SP), PPV, and NPV were 58%, 83%, 35%, and 93%, respectively (1).…”

Section: Discussionsupporting

confidence: 90%

The (1,3)β- d -Glucan Test as an Aid to Early Diagnosis of Invasive Fungal Infections following Lung Transplantation

Smith²,

et al. 2010

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The Fungitell assay for (1,3)␤-D-glucan (BG) detection in serum has been evaluated in patients with invasive fungal infections (IFIs) and healthy controls and for the early diagnosis of IFI in cancer patients. We evaluated the BG assay for the detection of IFI in lung transplant recipients. Serial serum samples were prospectively collected from patients undergoing lung transplants at Duke Hospital. Fungal infections were classified according to revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. A receiver operator characteristic (ROC) curve was generated; possible causes for false-positive and false-negative tests were investigated by linear regression analysis. Seven hundred fifty-six serum specimens from 59 subjects without IFI and 41 specimens from 14 patients with proven or probable IFI were tested. The area under the ROC curve was 0.69. Based on a 60-pg/ml positive cutoff, per-patient sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64%, 9%, 14%, and 50%, respectively; per-test estimates were 71%, 59%, 9%, and 97%, respectively. The majority (92%) of patients not diagnosed with an IFI had at least one BG level of >60 pg/ml, and 90% had at least one BG level of >80 pg/ml. Respiratory colonization with mold and hemodialysis significantly affected mean BG levels. In conclusion, the accuracy of the BG test is marginal and its utility as a tool for the early diagnosis of IFI is questionable in the lung transplant population. Although the NPV of the BG test is high, the low PPV limits its utility as a screening tool for early diagnosis of IFI.Lung transplant recipients are at relatively high risk for developing invasive fungal infections (IFIs). A recent national surveillance program reported the 1-year cumulative incidence of IFIs in lung transplant recipients to be 8.6%. The most common invasive fungal pathogen was Aspergillus species, responsible for 44% (109/248) of IFIs, followed by Candida (23%) and non-Aspergillus molds (20%) (11). Unfortunately, fungal infections are associated with high mortality, which is in part related to delayed or missed diagnoses owing to the lack of sensitive, noninvasive diagnostic tests.(1,3)␤-D-Glucan (BG) is a cell wall constituent of many pathogenic fungi, including Aspergillus, Candida, and Pneumocystis, and is detectable in patient serum during invasive disease caused by these fungi. It is also detectable in patients with infections caused by species of Fusarium, Trichosporon, Saccharomyces, and Acremonium (14). The BG assay (Fungitell; Associates of Cape Cod, Falmouth, MA) was approved by the U.S. Food and Drug Administration (FDA) for the qualitative detection of BG in the serum of patients with symptoms of or medical conditions predisposing to IFIs and as an aid in the diagnosis of deep-seated mycoses and fungemia. The assay has been evaluated in a multicenter study of patients with IFIs that included healthy controls (10) as well as for the early diagnosis of IFIs in patient...

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Section: Discussionsupporting

confidence: 90%

The (1,3)β- d -Glucan Test as an Aid to Early Diagnosis of Invasive Fungal Infections following Lung Transplantation

Smith²,

et al. 2010

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“…In 17 cohort studies (1,2,4,16,19,20,24,29,30,34,45,47,50,51,54,61,62), the pooled sensitivity, specificity, DOR, and AUC-SROC were 72% (95% CI, 67% to 77%), 78% (95% CI, 76% to 80%), 12.3 (95% CI, 6.0 to 25.1), and 0.79 (95% CI, 0.73 to 0.85), respectively. In 14 case-control studies (3, 14, 26, 27, 33, 38, 40, 43-46, 48, 49, 60), the pooled sensitivity, specificity, DOR, and AUC-SROC for IFI were 83% (95% CI, 80% to 86%), 86% (95% CI, 84% to 88%), 68.3 (95% CI, 30.7 to 151.8), and 0.95 (95% CI, 0.92 to 0.98), respectively.…”

Section: Resultsmentioning

confidence: 98%

“…The 36 studies included six assays: 17 used Fungitell (1,3,4,12,16,17,27,29,34,(45)(46)(47)(48)(49)(50)(51), 9 used the Fungitec G test (2,20,26,33,43,44,57,59,60), 6 used the Wako ␤-glucan test (14,19,24,40,54,56), 3 used the GKT-25 M set (32,61,62), and 1 used the fungal index (38). All studies but one were based in 1 of 13 countries, with the majority of assays in Japan (n ϭ 13), as well as in the United States (n ϭ 7), China (n ϭ 4), Spain (n ϭ 2), Austria (n ϭ 1), Belgium (n ϭ 1), Czech Republic (n ϭ 1), France (n ϭ 1), Germany (n ϭ 1), Kuwait (n ϭ 1), The Netherlands (n ϭ 1), Sweden (n ϭ 1), and Switzerland (n ϭ 1); one study that performed assays in multiple countries (Spain, Argentina, and France) was also included.…”

Section: Resultsmentioning

confidence: 99%

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Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

et al. 2012

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Serum 1,3-␤-D-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI).We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP. P neumocystis jiroveci pneumonia (PJP) continues to be a serious problem among immunocompromised patients despite the decreased number of cases among human immunodeficiency virus (HIV)-infected patients over the past decade with the widespread use of prophylaxis. The high mortality of patients requiring mechanical ventilation has remained unchanged, ranging from 50 to 60% (35). Although the gold standard for diagnosis is microscopic visualization of the organism, the methods are not sensitive, particularly in HIV-negative patients (31).The incidence of invasive fungal infection (IFI) has been increasing, especially among immunocompromised patients undergoing aggressive chemotherapy for cancer, bone marrow and organ transplantation, and advanced critical care. Despite advances in therapy, IFI is associated with considerable morbidity and a mortality rate of 30 to 70% for aspergillosis and 40 to 50% for candidiasis (15). Diagnosis of IFI is challenging because clinical and radiological signs and conventional microbiological and histological techniques are not sensitive enough (25). For these reasons, intensive research currently aims at the development of new diagnostic methods for PJP and IFI.One of these new diagnostic techniques is the assay for the serum 1,3-␤-D-glucan (BG) derived from major cell wall components of various medically important fungi. The Fungitell test (Associates of Cape Cod, Inc., East Falm...

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“…However, the BG assay has not been assessed extensively in populations with solid organ transplants. One study evaluated a preemptive strategy that involved the use of BG monitoring to enable the early detection of IFD in liver transplant recipients and found its sensitivity and specificity for fungal infections to be 58% and 83%, respectively (17). The same degree of sensitivity (64%) was observed in lung transplant patients using a cutoff point set at 60 pg/ml, but specificity was much lower (9%) (18).…”

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confidence: 99%

Contribution of (1,3)-Beta- d -Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation

et al. 2015

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bInvasive candidiasis (IC) causes high morbidity and mortality rates after liver transplantation, in part due to delayed diagnosis. The fungal cell wall component (1,3)-beta-D-glucan (BG) could be an early biomarker of IC. This preliminary prospective study was designed to evaluate the contribution of BG measurements to the diagnosis of IC after liver transplantation. All consecutive patients who underwent liver transplantation at Henri Mondor Hospital in France between January and June 2013 were enrolled prospectively in the study. They were monitored weekly for colonization by Candida, and colonization index values were calculated. Serum samples were tested for BG (Fungitell; Cape Cod Inc.) at least weekly between liver transplantation and discharge from the hospital. A total of 52 patients (including 39 male patients) were enrolled, with a median age of 55 years (range, 31 to 69 years). The median Model for End-Stage Liver Disease (MELD) score was 27 (range, 6 to 40). Cultures from 42 patients (81%) yielded Candida spp., with the most common Candida species isolated being Candida glabrata (47%). Six cases of documented IC were found for four of the 52 patients. On the day the clinical diagnosis of IC was made, analysis based on combining two sequential BG-positive samples (>146 pg/ml) and a colonization index of >0.5 revealed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) results of 83%, 89%, 50%, and 97.6%, respectively. The detection of BG associated with Candida colonization may be a promising tool based on a high NPV that can rule out IC among high-risk patients. Liver transplant recipients are at relatively high risk of developing invasive fungal disease (IFD) (1-4). The most common invasive fungal pathogens are Candida spp., followed by Aspergillus spp. (1, 5, 6). Such infections develop in 5% to 10% of transplant recipients and are a major cause of postoperative morbidity and death (4,(7)(8)(9). This is related in part to delayed or missed diagnoses because of the low sensitivity and specificity of the diagnostic tests currently available (1, 10, 11). A serological diagnostic method, i.e., quantification of (1,3)-beta-D-glucan (BG), was recently recommended in the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines on the detection of candidemia in adults (12). BG is a cell wall constituent found in many pathogenic fungi, including Candida, Aspergillus, and Pneumocystis, and it can be detected in patient sera during invasive disease caused by these fungi. In a meta-analysis, Karageorgopoulos et al. showed that BG detection displayed good sensitivity and specificity for the diagnosis of IFD in the general population (13). In the setting of invasive candidiasis (IC), the detection sensitivity of BG ranged from 64% to 100% (14-16). However, the BG assay has not been assessed extensively in populations with solid organ transplants. One study evaluated a preemptive strategy that involved the use of BG monitoring to enable the ...

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Preemptive Treatment of Fungal Infection Based on Plasma (1 → 3)β-D-Glucan Levels after Liver Transplantation

Abstract: Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation.

Cited by 80 publications

References 36 publications

The (1,3)β- d -Glucan Test as an Aid to Early Diagnosis of Invasive Fungal Infections following Lung Transplantation

The (1,3)β- d -Glucan Test as an Aid to Early Diagnosis of Invasive Fungal Infections following Lung Transplantation

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

Contribution of (1,3)-Beta- d -Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation

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