What should be the optimal cut-off of serum 1,3-ß-D-glucan for the detection of invasive pulmonary aspergillosis in patients with haematological malignancies?

BACKGROUND: The detection of 1,3-ß-d-glucan (BDG), a cell wall component of several medically important fungi, is a promising tool for the diagnosis of invasive pulmonary aspergillosis. The aim of this study was to evaluate the diagnostic accuracy of the BDG test in invasive pulmonary aspergillosis (IPA) by focusing on the optimal cut-off value. METHODS: The records of the Infection Control Committee were reviewed to identify patients with haematological malignancies and stem cell transplantation who had at least 1 BDG (Fungitell kit) measurement during the period January 2008 through April 2011. The European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria (independent of BDG results) were used to categorize the patients with IPA. Patients with possible IPA were not included in the study. RESULTS: A total of 128 patients (50 with proven or probable IPA) were included in the study. At the manufacturer's recommended cut-off value of 80 pg/ml, the sensitivity of BDG was 66% (95% CI 51.2-78.7), specificity 75.6% (95% CI 64.6-84.5), positive predictive value (PPV) 63.4%, and negative predictive value (NPV) 77.6%. A receiver operating characteristic (ROC) curve was constructed to define the optimum serum BDG cut-off for the diagnosis of IPA. At a cut-off value of 181 pg/ml, the sensitivity was 52% (95% CI 37.4-66.3), specificity 94.8% (95% CI 87.4-98.6), PPV 86.7%, and NPV 75.5%. CONCLUSIONS: Although higher cut-off levels increased the specificity of the BDG test, sensitivity decreased to an unacceptable level; the commercially recommended cut-off value appears to be appropriate for screening purposes.

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of large-scale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2). METHODS: A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH. RESULTS: A-HIT1 evaluated 88 patients (27 ±â€¯11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 ±â€¯7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 ±â€¯13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 ±â€¯13 (7-90) days. Only 2 centers were aware of the target LDL levels. A-HIT2 enrolled 1071 FH patients (53 ±â€¯8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population. CONCLUSIONS: The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed.

Usefulness of (1→3)ß-D glucan in early diagnosing Pneumocystis jirovecii pneumonia: a case report.

Pneumocystis jirovecii pneumoniae (PJP) may be difficult to diagnose. Since pneumocystis cannot be cultured, the diagnosis of PJP requires microscopic examination to identify pneumocystis from induced sputum or bronchoalveolar lavage (BAL) fluid. In order to evaluate the usefulness of (1→3) beta-D-glucan (BDG) levels in the early diagnosis of PJP, we describe the case of PJP in a 25-year-old male with acute lymphoblastic leukaemia (ALL) admitted to hospital with progressive dyspnea and fever with chills. The patient was not infected with human immunodeficiency virus (HIV). Sputum, blood, and urine cultures were negative; smears for acid-fast bacilli and tests for viral antibodies were both negative. The microbiology study of the BAL with Giemsa and immunofluorescence staining, seven days after admission showed the existence of P. jiroveci in the lungs. Further, one day and five days after admission, (1→3) beta-D-glucan (BDG) levels were very high. The high serum level of BDG considerably decreased after treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and the clinical condition of the patient increasingly improved.

Factors influencing the early mortality in haematological malignancy patients with nosocomial Gram negative bacilli bacteraemia: a retrospective analysis of 154 cases.

BACKGROUND: The aim of this study is to assess the factors influencing the early mortality (7-day after index blood culture) in haematological malignancy patients with Gram negative bacilli (GNB) bacteraemia. METHODS: Infection control committee records were reviewed to identify the cases between March 2006 and June 2011. Only one bacteraemic episode per patient was included in the study. RESULTS: A total of 154 patients with GNB bacteraemia were identified. The early mortality rate was 19.5% (30 out of 154). Blood cultures revealed Enterobacteriacea in 120 patients (Escherichia coli; 86, Klebsiella spp.; 28, Enterobacter cloacea; 6) and glucose non-fermenting GNB in 34 patients (Pseudomonas aeruginosa; 15, Acinetobacter baumannii; 11, Stenotrophomonas maltophilia; 7, Burkholderia cepacia; 1). Forty (33.3%) out of 120 Enterobacteriaceae were extended spectrum beta-lactamase (ESBL) producers and 18 (52.9%) out of 34 glucose non-fermenting GNB were multidrug resistant. Carbapenems were administered as first line therapy in 139 out of 154 patients. In univariate analysis Pitt's bacteraemia score, presence of aplastic anaemia, bacteraemia caused by glucose non-fermentating GNB, inappropriate empirical antibacterial treatment, presence of severe sepsis or septic shock, unable to achieve microbiological cure, and intensive care unit (ICU) acquired bacteraemia were associated with mortality. Multivariate analysis showed ICU acquired bacteraemia (OR, 12.55; 95% CI, 2.34-67.38, p=0.003) as an independent factor associated with early mortality. CONCLUSION: Haematological malignancy patients who require ICU care are at high risk for early mortality related to GNB bacteraemia. Based on the local findings pointing out high rate of multidrug resistance, carbapenems combined with colistin seems to be a reasonable approach as empirical treatment of these patients. However, increasing carbapenem resistance rate is of concern.

Can bacteraemia lead to false positive results in 1,3-beta-D-glucan test? Analysis of 83 bacteraemia episodes in high-risk patients for invasive fungal infections.

BACKGROUND: Although bacteraemia has been reported to be related to false positive results in the 1,3-beta-D-glucan (BDG) test, the evidence for this interaction is limited. AIMS: To investigate the association between bacteraemia and the BDG test. METHODS: Records of the Infection Control Committee were reviewed to identify bacteraemia in patients who were hospitalized in the haematology ward and stem cell transplantation unit. Patients who had undergone the BDG test at least once within 5 days of a positive blood culture were included in the study. BDG levels in the sera were assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA) according to the manufacturer's specifications. The cutoff for BDG positivity was 80 pg/mL. RESULTS: Eighty-three bacteraemic episodes were identified in 71 patients. BDG positivity was detected in 14 patients with bacteraemia, and only 1 patient with Escherichia coli bacteraemia had high BDG levels (over 80 pg/mL) despite having no evidence of invasive fungal infection (IFI). CONCLUSIONS: Our study suggests that the cross-reactivity of the BDG test with a concomitant or recent bacteraemia is a very rare condition. Patients with risk factors for IFI should be evaluated cautiously when a positive BDG test is reported.

Factors influencing the early mortality in haematological malignancy patients with nosocomial Gram negative bacilli bacteraemia: a retrospective analysis of 154 cases

BACKGROUND: The aim of this study is to assess the factors influencing the early mortality (7- day after index blood culture) in haematological malignancy patients with Gram negative bacilli (GNB) bacteraemia. METHODS: Infection control committee records were reviewed to identify the cases between March 2006 and June 2011. Only one bacteraemic episode per patient was included in the study. RESULTS: A total of 154 patients with GNB bacteraemia were identified. The early mortality rate was 19.5% (30 out of 154). Blood cultures revealed Enterobacteriacea in 120 patients (Escherichia coli; 86, Klebsiella spp.; 28, Enterobacter cloacea; 6) and glucose non-fermenting GNB in 34 patients (Pseudomonas aeruginosa; 15, Acinetobacter baumannii; 11, Stenotrophomonas maltophilia; 7, Burkholderia cepacia; 1). Forty (33.3%) out of 120 Enterobacteriaceae were extended spectrum beta-lactamase (ESBL) producers and 18 (52.9%) out of 34 glucose non-fermenting GNB were multidrug resistant. Carbapenems were administered as first line therapy in 139 out of 154 patients. In univariate analysis Pitt's bacteraemia score, presence of aplastic anaemia, bacteraemia caused by glucose non-fermentating GNB, inappropriate empirical antibacterial treatment, presence of severe sepsis or septic shock, unable to achieve microbiological cure, and intensive care unit (ICU) acquired bacteraemia were associated with mortality. Multivariate analysis showed ICU acquired bacteraemia (OR, 12.55; 95% CI, 2.34-67.38, p = 0.003) as an independent factor associated with early mortality. CONCLUSION: Haematological malignancy patients who require ICU care are at high risk for early mortality related to GNB bacteraemia. Based on the local findings pointing out high rate of multidrug resistance, carbapenems combined with colistin seems to be a reasonable approach as empirical treatment of these patients. However, increasing carbapenem resistance rate is of concern.

La bacteriemia, ¿puede inducir resultados falsos positivos en la determinación de 1,3-beta- d -glucano? Análisis de 83 episodios de bacteriemia en pacientes en alto riesgo de infecciones micóticas invasivas / Can bacteraemia lead to false positive results in 1, 3-beta- d -glucan test? Analysis of 83 bacteraemia episodes in high-risk patients for invasive fungal infections

Antecedentes. Aunque se ha descrito que la bacteriemia se relaciona con resultados falsos positivos en la determinación de 1,3-beta- d -glucano (BDG), las pruebas de esta interacción son limitadas. Objetivo. El objetivo de este estudio fue investigar la asociación entre la bacteriemia y la determinación de BDG. Métodos. Para identificar a los pacientes con bacteriemia hospitalizados en la sala de hematología y la unidad de trasplante de células progenitoras, se revisaron los archivos de historias clínicas del comité de control de infecciones. En el estudio se incluyeron a los pacientes sometidos como mínimo a una determinación de BDG al cabo de 5 días de un resultado positivo del hemocultivo. La determinación de los valores séricos de BDG se analizó con el test Fungitell (Associates of Cape Cod, East Falmouth, MA, EE. UU.), de acuerdo con las especificaciones del fabricante. El punto de corte para la determinación de un resultado positivo se estableció en 80pg/mL. Resultados. Se identificó un total de 83 episodios de bacteriemia en 71 pacientes. En 14 de ellos, la determinación de BDG fue positiva, pero sólo se identificaron valores elevados en un paciente con bacteriemia por Escherichia coli (>80pg/mL), a pesar de que no se detectaron pruebas de infección fúngica invasora (IFI). Conclusiones. Los resultados del presente estudio sugieren que la reactividad cruzada entre la determinación de BDG y con una bacteriemia concomitante o reciente es excepcional. Cuando se documenten resultados positivos de la determinación de BDG, es preciso valorar con precaución a los pacientes con factores de riesgo de IFI(AU)

Background. Although bacteraemia has been reported to be related to false positive results in the 1,3-beta- d -glucan (BDG) test, the evidence for this interaction is limited. Aims. To investigate the association between bacteraemia and the BDG test. Methods. Records of the Infection Control Committee were reviewed to identify bacteraemia in patients who were hospitalized in the haematology ward and stem cell transplantation unit. Patients who had undergone the BDG test at least once within 5 days of a positive blood culture were included in the study. BDG levels in the sera were assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA) according to the manufacturer's specifications. The cutoff for BDG positivity was 80pg/mL. Results. Eighty-three bacteraemic episodes were identified in 71 patients. BDG positivity was detected in 14 patients with bacteraemia, and only 1 patient with Escherichia coli bacteraemia had high BDG levels (over 80pg/mL) despite having no evidence of invasive fungal infection (IFI). Conclusions. Our study suggests that the cross-reactivity of the BDG test with a concomitant or recent bacteraemia is a very rare condition. Patients with risk factors for IFI should be evaluated cautiously when a positive BDG test is reported(AU)