Early Diagnosis Of Invasive Fungal Infections Research Articles

Role of (1-3)-Β-D-Glucan Test in the Diagnosis of Invasive Fungal Infections among High-Risk Patients in a Tertiary Care Hospital.

Background Invasive fungal infections (IFI) are associated with high mortality. Serum fungal biomarkers offer an advantage over the traditional methods in early diagnosis and better clinical outcomes. The aim of the study was to evaluate the role of (1–3)-β-D-glucan (BDG) assay in the patients suspected of IFI. Materials and Methods This prospective study was conducted in the Department of Microbiology, Dayanand Medical College and Hospital, Ludhiana, over a period of 1 year. A total of 862 serum samples were received from patients suspected of IFI, for the BDG test (Fungitell, Associates of Cape Cod Inc., USA). The test was performed as per kit protocol. Appropriate samples were processed for KOH fungal smear and fungal culture. Blood culture was done by Bactec (Biomerieux). Statistical Analysis Results were analyzed using descriptive statistical methods. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated at different cutoffs. In addition, the receiver operating characteristic (ROC) curve using SPSS 21.00 software was calculated and the diagnostic accuracy was shown by the area under the ROC curve (AUC). Results Among 862 patients, 546 (63.3%) were males. The predominant age group (25.6%) was between 61 and 70 years. The most common risk factor (54.8%) was prolonged intensive care unit stay. Out of the total samples, 455 (52.8%) samples were found positive for BDG. Fungal elements were seen in 48 (10.5%) KOH smears and fungal growth was obtained in 81 (17.8%) cultures. Comparison of BDG assay and culture at different cutoffs yielded AUC—0.823. Sensitivity (100%), specificity (51.3%), accuracy (55.6%), PPV (15.8%), and NPV (100%) were observed at the kit cutoff of 80 pg/mL. Optimum sensitivity and specificity of 79.2% and 70.3%, respectively, were observed at a cutoff of 142.4pg/mL. A significant correlation was observed between BDG positivity and piperacillin–tazobactam use and dialysis. Among BDG positive patients, 38(8.4%) succumbed to death. Conclusion Detection of BDG helps in the early diagnosis of IFI in critically ill patients. As the assay has a high NPV, a negative test can be used to stop the empirical antifungal drugs. The use of a higher cutoff can be useful to avoid false-positive results.

A Rapid, Visible, and Highly Sensitive Method for Recognizing and Distinguishing Invasive Fungal Infections via CCP-FRET Technology.

Invasive fungal infection (IFI) is one of the leading causes of death in the intensive care unit (ICU) due to its high morbidity and mortality among immunocompromised patients. Early diagnosis of IFI is typically infeasible because of the lack of clinical signs and symptoms. By virtue of the cationic conjugated polymer-based fluorescence resonance energy transfer (CCP-FRET) technology, we develop a rapid, visible, simple, and sensitive method for simultaneous detection and discrimination of three types of pathogens, including Candida albicans (C.albicans), Klebsiella pneumoniae (K.pneumoniae), and Cryptococcus neoformans (C.neoformans). The CCP-FRET system contains a CCP fluorescent probe and pathogen-specific DNA labeled with fluorescent dyes. These two components spontaneously self-assemble into the complex under electrostatic attraction, resulting in an efficient FRET from CCP to fluorescent dyes when irradiated with a 380 nm ultraviolet (UV) light. The CCP-FRET method can specifically identify the DNA molecules that are extracted from culture pathogen strains or blood samples via PCR and single base extension (SBE) reactions, without any cross-reactions on the DNA of nonspecific strains. In particular, the sensitivity of this method is down to 0.03125 ng, which is ten times higher than that of real-time PCR. We further evaluate its detection efficiency by testing 15 blood samples from neonatal patients who suffer from pathogen infections, in which some of them have undergone antipathogen treatments. Using the CCP-FRET method, 33.3% (5/15) of samples tested positive for C.albicans and/or K.pneumoniae infections, whereas no pathogen DNAs are recognized with real-time PCR, despite using the same primers. Interestingly, the CCP-FRET method can output unique fluorescent color as well as RGB patterns to different types of pathogen infections, by which the infection type can be conveniently determined. Collectively, the CCP-FRET method is a sensitive and reliable detection platform for rapid identification of fungal and bacterial multiple infections, holding great promise for uses in clinical testing.

Utility of Panfungal PCR in the diagnosis of invasive fungal infections in febrile neutropenia.

Background:The prevalence of invasive fungal infections (IFIs) is increasing due to the increasing population of immunocompromised patients. Fungal culture is the gold standard for diagnosis but not sensitive and the turnaround time is long. Samples for histopathology are difficult to obtain because of profound cytopenias. We conducted this study with the aim to evaluate panfungal PCR for the diagnosis of IFIs in patients of febrile neutropenia.Methods:This was a single-centre, cross-sectional observational study. Patients of febrile neutropenia suspected of having IFI were included in the study. Panfungal PCR was performed on the blood of included patients along with other investigations for diagnosis of IFI. The sensitivity, specificity, positive predictive value, and negative predictive value of panfungal PCR were calculated using EORTC/MSG 2008 criteria as the gold standard.Results:Fifty patients of febrile neutropenia were included in the study, of which 52% were diagnosed positive by panfungal PCR assay. The sensitivity, specificity, positive predictive value, and negative predictive value of panfungal PCR assay was found to be 82.76%, 90.48%, 92.31% and 79.17% respectively.Conclusion:Panfungal PCR is a promising and highly sensitive diagnostic test for screening at-risk patients suspected to have IFIs. The use of panfungal PCR assay in combination with other diagnostic modalities and clinical judgment can be very helpful in the early diagnosis of IFI.

Biomarker-guided antifungal stewardship policies for patients with invasive candidiasis.

Invasive fungal infections (IFIs) are among the life-threatening issues in patients with impaired immune system. High administration of antifungals in these patients imposes a heavy economic burden on the national health system. In addition, despite the usually expensive antifungal regimens, the mortality rate due to fungal infections is still high, resulting in the loss of hundreds of lives per year. Survival rate is an indicator of the success of national healthcare policies. Early diagnosis of IFI is critical because any delays may be fatal. The weakness of the old-fashioned culture-based diagnostic methods lies in their time-consuming laboratory procedures. To overcome this problem, several diagnostic approaches have been developed to facilitate the early diagnosis of invasive candidiasis as the most prevalent IFI. These methods are based on the detection of serologic and molecular footprints. However, nowadays, antibiotic resistance and proper and cost-effective use of antibiotics are given special attention in national healthcare policies. The instructions for controlling these indices have been collected under the name of antibiotic stewardship. The present review study was targeted toward providing insight into novel diagnostic biomarkers and antifungal stewardship programs. The simultaneous investigation of these two issues facilitates the achievement of a novel health policy for the treatment of systemic candidiasis in immunocompromised patients.

Invasive fungal infection following chemotherapy for acute myeloid leukaemia-Experience from a developing country.

The incidence of invasive fungal infections (IFI) is believed to be higher in patients with acute myeloid leukaemia (AML) undergoing chemotherapy in non-HEPA-filtered rooms. The aim of this study is to review the incidence of IFI in a large cohort of patients with AML treated at a single centre in India. Two hundred and twenty-two patients with AML treated with either induction chemotherapy or salvage chemotherapy between 2008 and 2013 were studied retrospectively. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy, prophylactic strategies, engraftment (ANC>500), the presence of IFI and survival were collected. IFI was diagnosed in 86 patients (38.7%) with proven IFI in 12 (5.4%). Use of posaconazole prophylaxis (P=.001) was the only factor associated with reduced incidence of IFI. Survival in patients with proven IFI was lower than those without proven IFI, but not statistically significant (59.4% vs 78.5%; P=.139). There is a high incidence of IFI during induction chemotherapy for acute myeloid leukaemia in developing countries. Posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal yet cost-effective strategies for prevention and early diagnosis of IFI are required to improve survival in patients undergoing chemotherapy for AML.

Infección fúngica invasiva en pacientes inmunosuprimidos atendidos en un hospital de tercer nivel

Antecedentes: las infecciones fúngicas invasivas son una causa importante de morbimortalidad mundial. El aumento en la incidencia de estas micosis se relaciona con el incremento de las condiciones de inmunosupresión.Objetivo: Describir las características demográficas y clínicas de pacientes inmunosuprimidos tratados con antifúngicos por sospecha de infecciones fúngicas invasivas en una institución de tercer nivel.Materiales y métodos: estudio descriptivo de corte transversal, en el que se incluyeron pacientes que recibieron tratamiento antifúngico durante 2012 y 2013, por sospecha de infecciones fúngicas invasivas (aspergilosis, criptococosis, histoplasmosis y mucormicosis) y condición de inmunosupresión.Resultados: se analizaron 81 pacientes, con predominio masculino (66,5%) y una media de edad de 44 años. El diagnóstico de base más frecuente fue neoplasia hematolinfoide seguido de infección por el virus de la inmunodeficiencia humana (VIH). La aspergilosis angioinvasiva (52%) y la criptococosis (28%) fueron las sospechas clínicas más frecuentes. El 43 y 85% de los pacientes tuvieron hallazgos anormales en radiografía y tomografía axial computarizada de tórax respectivamente. De aquellos con sospecha de aspergilosis, el 23% tuvo prueba de galactomanano positiva, en tanto que en aquellos con sospecha de criptococosis pulmonar, el 75% fue positivo para el antígeno capsular. El 22% de los pacientes fallecieron y el 17% requirieron estancia en UCI y soporte hemodinámico.Conclusión: es importante sospechar de forma temprana la infecciones fúngicas invasivas, así como establecer un algoritmo diagnóstico e instaurar el tratamiento antifúngico de manera anticipada para disminuir los desenlaces fatales. La dificultad en la confirmación microbiológica de las infecciones fúngicas invasivas continúa siendo una problemática local, similar a lo reportado en la literatura mundial.

Clinical value of plasma (1, 3)-β-D-glucan in the detection of invasive fungal infections

Objective To discuss the clinical value of plasma (1, 3)-β-D-glucan detection (G test) for early diagnosis of invasive fungal infections (IFI). Methods A total of 180 cases of IFI were divided into suspected group (84 cases), diagnosed group (49 cases) and clinical diagnosis group (47 cases). At the same period, the other 44 hospitalization patients with bacterial infection and 53 healthy persons were selected.All personnel were participated in the experiment using the MB-80 system for rapid detection of microbial dynamic detection, simultaneous plasma G test was evaluated using ROC curve analysis G optimal threshold test. Results Candida albicans was a common respiratory infections of IFI.Compared with bacterial group (9.4pg/mL) and normal group (7.8pg/mL) plasma glucan content median, IFI group plasma G test (29.3pg/mL) was significantly higher, and the differences were statistically significant(Z=-2.41, P=0.015; Z=-2.19, P=0.028), Compared with the median plasma glucan content of the diagnosis group (105.8pg/mL) and clinical diagnosis group (46.3pg/mL), to be diagnosed group (8.1pg/mL) was significantly lower, and the differences were statistically significant(Z=-2.99, P=0.003; Z=-2.19, P=0.027). ROC curve analysis showed that when the cutoff value was 9.35pg/mL, its specificity (67.2%), sensitivity (70.3%) and negative/positive predictive value (69.3% / 65.8%) were the best, and more consistent with the culture method, the Kappa value was 0.603, the difference was statistically significant (P=0.036). Conclusion In the early diagnosis of IFI, plasma G test has good results and can be widely used. Key words: Mycoses; Infection; Diagnosis

Meeting the Challenge of Invasive Fungal Infections: Part 2

The 23rd European Congress of Clinical Microbiology and Infectious Diseases 2013 Berlin, Germany, 27-30 April 2013. This second and final installment of the report on the 23rd European Congress of Clinical Microbiology and Infectious Diseases follows on from Part 1, published in the September 2013 (volume 8, issue 9) issue of Future Microbiology. Invasive fungal infections (IFIs) are a well-recognized complication in immunocompromised patients, with neutropenic patients with leukemia and hematopoietic stem cell transplant recipients at especially high risk. Early diagnosis of IFIs is essential, since delaying the initiation of adequate antifungal therapy increases the risk of death. The rapid diagnosis, and effective treatment and prophylaxis of IFIs were among the topics discussed during the 2013 conference of the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2013).

Diagnostic Strategies for Invasive Fungal Infections in Patients With Hematologic Malignancies and Hematopoietic Stem Cell Transplant Recipients

Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

1–3 β-D-glucan: From Diagnosis to Prognosis

There are increasing numbers of patients at risk for invasive fungal infections (IFI). The early diagnosis of IFI’s is limited by the lack of sensitivity and delayed turn-around time of routine cultures. Delays in diagnosis are associated with poor outcomes, especially with immunocompromised hosts and patients within the intensive care unit (ICU). Over the last decade, fungal biomarkers such as galactomannan and 1,3-β-D-glucan (BDG) have been increasingly utilized for the early and accurate diagnosis of these infections. This review will evaluate the recent clinical data on the BDG assay, focusing on its ability to assist in the diagnosis of invasive candidiasis in the ICU, and also whether BDG kinetics can predict the prognosis of the patient. Similarly, this review will evaluate BDG in invasive Aspergillus and Pneumocystis jiroveci diagnosis and prognosis, as well as the current limitations of the assay.

Itraconazole for invasive fungal infection with pediatric malignancies

Invasive fungal infection (IFI) is an increasingly common and often fatal infection in children with hematological malignancies and solid tumor. Prophylactic therapy with anti-fungal agents is very important for these patients, because the early diagnosis of IFI is very difficult. A total of 0.5 mL/kg per day of itraconazole oral solution (ITCZ-OS) was administered in twice-daily doses to 22 children with hematological malignancies who had received chemotherapy, and its usefulness and safety regarding the prevention of IFI were examined. Prophylactic therapy with ITCZ-OS was completed in 18 (81.8%) of the 22 children. Of these, IFI was not strongly suspected in any child. Side-effects included non-alcoholic steatohepatitis in two children, syndrome of inappropriate anti-diuretic hormone secretion in one, and liver dysfunction in one. The administration of ITCZ-OS was discontinued in these cases. These four children had received vincristine sulfate (VCR) or irinotecan hydrochloride, which were reported to interact with ITCZ. In most children the plasma levels of ITCZ were satisfactory. The plasma levels, however, were slightly increased in VCR-treated children; ITCZ should be carefully administered. Although the number of subjects was small in the present study, the plasma concentrations of ITCZ-OS favorably increased in the children with hematological malignancies, suggesting that this agent exhibits prophylactic effects on IFI. It must be considered, however, that some combined agents cause side-effects via their interactions with ITCZ.

Bronchoalveolar Lavage Fungal Antigen Detection in Critically Ill Children

Bronchoalveolar Lavage Fungal Antigen Detection in Critically Ill Children

Prevention and Early Treatment of Invasive Fungal Infection in Patients with Cancer and Neutropenia and in Stem Cell Transplant Recipients in the Era of Newer Broad-Spectrum Antifungal Agents and Diagnostic Adjuncts

Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies.

Monitoring of 1,3-Beta-D-Glucan (BGL) Antigenemia in Neutropenic Patients with Acute Leukemia at High Risk for Invasive Fungal Infections (IFI).

Invasive candidiasis (IC) and aspergillosis (IA), the most frequent IFI in leukemic patients, are associated with high morbidity and mortality. As early diagnosis of IFI is difficult, empirical antifungal therapy is recommended in persistently febrile neutropenic patients. This standard of care results in a broad use of antifungals. New non-invasive diagnostic tests such as circulating BGL, a fungal cell wall component, are thus needed to optimize management of patients with IFI. The objective of the current study was to evaluate the utility of monitoring BGL antigenemia in neutropenic patients at high risk for IFI. We conducted a prospective study of 189 episodes of neutropenia (median duration 22 days, range 7–113) following induction (n=107) or consolidation chemotherapy (n=82) in 99 consecutive patients with acute leukemia (85 AML, 14 ALL). Blood was collected 2× weekly before onset of fever and daily thereafter until resolution of fever. BGL was measured by colorimetric assay (Wako, Japan). Two cut-off values (5 or 11 pg/ml) were studied. A positive result was defined by 2 consecutive samples with BGL higher than the cut-off value. A median of 2 (0–4) febrile episodes occurred per neutropenic episode. Among 320 febrile episodes, 31 IFI were diagnosed according to EORTC-MSG criteria: 17 IC (4 proven, 13 probable) and 14 IA (5 proven, 9 probable). A median of 15 samples (4–47) per episode of neutropenia were analyzed over a median period of 34 days (19–121). The diagnostic performance of BGL was evaluated in patients with proven or probable IFI compared with febrile patients without IFI (Table). In patients with IC, the median time between onset of fever as first sign of IFI and BGL positivity (>= 5) was 0 (−3 to 17 days) as compared with 16 (0 to 51 days) until diagnosis of infection using conventional microbiological and imaging techniques (p=0.03). In IA patients, it was 3 (−9 to 14 days) vs. 7 (1 to 21 days) (p=0.07). In IC and IA, median peak BGL (21 [6–111] and 15 [7–51] pg/ml) occurred on day 13 (1 to 41) and on day 7 (3 to 20) after fever onset, respectively. Median time to initiation of antifungal therapy after fever onset was similar in IC (2.5, range: 1 to 10 days) and IA (5, range: 0 to 10 days). BGL antigenemia decreased or cleared in patients responding to therapy (n=19) and continued to increase (peak 111 and 66 pg/ml) in 2 cases of IC, in whom therapy failed. BGL was negative (< 5 pg/ml) in 100/102 episodes of bacteremia. In conclusion, monitoring of 1,3-beta-D-glucan antigenemia provides a new tool for early diagnosis and follow-up of IFI in neutropenic patients with acute leukemia.Diagnostic Performance of BGLBGL Cut-off (pg/ml)2 × 52 × 52 × 52 × 112 × 112 × 11Type of proven/probable IFIICIAAll IFIICIAAll IFISensitivity %659376354338Specificity %898989999999PPV %485265868692NPV %949993919386Positive Likelihood Ratio5.98.56.9354338Negative Likelihood Ratio0.40.10.30.70.60.6

Evaluation of pan-fungal PCR assay andAspergillusantigen detection in the diagnosis of invasive fungal infections in high risk paediatric cancer patients

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infection. As the early diagnosis of invasive fungal infection (IFI) is difficult, these infections are still associated with high morbidity and mortality. Recently, Pan-fungal polymerase chain reaction (PCR) has been a promising aid in rapid, early diagnosis of IFI. During the past few years, increasing numbers of suspected IFIs were encountered at our institution in patients with prolonged neutropenia after intensified immunosuppressive chemotherapy. The aim of this study was to investigate the diagnostic utility of both the aspergillus galactomannan (GM) antigen and the pan-fungal PCR assay in the diagnosis of IFI in high risk febrile neutropenic paediatric cancer patients. During one year period, 91 febrile neutropenic (FN) paediatric cases at high risk for developing IFI while receiving chemotherapy were investigated at National Cancer Institute, Egypt. These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing pan-fungal primers. Of the 91 FN episodes, 15 were proven IFI; whereas 27 cases were either probable (n=13) or possible IFI (n=14), and 49 were unlikely to be IFI episodes. Based on positive results for proven/probable IFI and compared to culture results, Pan-fungal PCR showed sensitivity, specificity, positive and negative predictive values of 75%, 92%, 84% and 87%; respectively. Aspergillus antigen test showed a sensitivity of 79%, specificity of 61%, positive and negative predictive values of 54% and 83%; respectively. A negative PCR in the proven and probable cases was closely related to previous antifungal therapy for a prior history of IFI. In patients at high risk for IFI, neither the sensitivity, nor specificity of the GM test was sufficient. The results of PCR assay was reasonably specific but not very sensitive and had a chance of missing the diagnosis of IFI. The PCR assay seems a promising test for objectively defining IFI, but is not recommended as the only tool for diagnosing IFI. Combining microscopy, culture, and PCR may improve the diagnostic outcome.

Voriconazole and Liposomal Amphotericin B (Ambisome) Effectively Prevent Mold Infections in Patients (pts) with Acute Myelogenous Leukemia (AML) Following Remission Induction Chemotherapy (RIC).

Invasive fungal infections (IFI) are a frequent cause of morbidity and death in pts with AML and high-risk myelodysplastic syndrome (HR-MDS). Because early diagnosis of IFI is difficult, antifungal prophylaxis (AFP) including mold-active agents has become an important strategy to reduce morbidity and mortality in this patient population and is routinely used at MDACC for AML and HR-MDS pts undergoing RIC. We retrospectively compared the efficacy and safety of 6 AFP regimens (Sept 97- July 04) among 659 evaluable pts with newly diagnosed AML and HR-MDS who received RIC and had been enrolled in our prospective AFP trials. See regimens listed in Table below. There were no significant differences among the 6 regimens with regard to key baseline characteristics (age, gender, diagnosis, cytogenetics, type of RIC, Zubrod PS, WBC count, non-fungal infection and protected environment) and median days of AFP. 37 pts (5.6%) developed IFI (yeast 3 %; mold 2.6%). No mold infections were observed among pts randomized to AMBI or VORI. With the exception of VORI, which was significantly more effective than IV ITRA (p =0.03), all comparisons of efficacy among the AFP regimens were not significant. Drug discontinuation was the highest with IV VORI (21%) and ABLC (18%). VORI was more toxic than IV ITRA, Caspo, and F+I (p=0.023, 0.001 and 0.031 respectively). VORI toxicity was reversible and consisted of visual and/or auditory hallucinations and elevation in serum bilirubin. There was a trend toward developing VORI toxicity if baseline bilirubin levels were elevated (OR=4.9; p=0.10).We conclude that the rate of IFI in AML and HR-MDS pts undergoing RIC given mold-active AFP is 5.6 %. VORI and AMBI effectively prevented mold infections. VORI was more effective that IV ITRA but was associated with a high rate of reversible drug-related adverse events.ABLC (n=131)AMBI (n=69)F+I (n=67)IV ITRA (n=225)CASPO (n=106)VORI (n=61)Median age, years (range)65(21–87)63(36–83)57(19–84)62(17–89)65(22–82)59(23–79)Zubrod ≤ 2 (%)127(97)69(100)65(97)214(95)101(95)61(100)Median days AFP (range)17(3–32)14(3–28)16(3–44)20(3–41)21(3–38)21(3–34)Breakthrough IFI (%)7(5)3(4)3(5)17(8)7(7)0 Yeast (%)2(2)3(4)1(1)11(5)3(3)0 Mold (%)5(4)02(3)6(3)4(4)0Drug-related AFP DC (%)24(18)10(14)5(7)23(10)4(4)13(21)ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week;AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week;F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d;IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d;CASPO: Caspofungin: 50 mg IV/d;VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID.

Advances in the molecular and serological diagnosis of invasive fungal infection in haemato-oncology patients.

Current laboratory diagnostic methods for invasive fungal infection (IFI) in haemato-oncology patients are insensitive, resulting in late diagnosis and contributing to high mortality. In recent years, progress has been made in the development and evaluation of sensitive sero-diagnostic assays, including detection of genomic DNA sequences and fungal antigens, which aid in a rapid, early diagnosis of IFI. The sensitivity and specificity of the assays vary considerably between studies, highlighting the need to correlate serological results with conventional laboratory tests and clinical or radiological findings. As part of management protocols, these assays may help to confirm the diagnosis of suspected IFI; however, the impact on mortality from IFI may be greatest when they are used to screen high-risk patients. Persistently positive screening results could direct early aggressive antifungal therapy, guided further by radiological and microbiological findings combined with regular clinical review, while the excellent negative predictive value may allow treatment to be withheld in patients with antibiotic resistant neutropenic fever but no other signs of IFI. However, this pre-emptive approach requires evaluation in prospective randomized trials.