First Line Treatment of Probable and Proven Invasive Aspergillosis with Caspofungin in Oncohemopatic Patients. A Single Centre Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4836-4836
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Barbara Gamberi ◽  
Annalisa Imovilli ◽  
Cristiano Carbonelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Cyclosporin A ◽  
Ct Scan ◽  
Fungal Infections ◽  
Severe Neutropenia ◽  
Cell Transplant ◽  
First Line ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia. In particular fungal infections are the most difficult to treat and represent a major cause of mortality. Caspofungin (Caspo) is the first drug which is able to inhibit the growth of the fungal cell wall. Since January 2004 we have treated 64 consecutive adult neutropenic pts with Caspo as first line therapy. In the setting of persistent fever (3 days) despite broad spectrum antibiotic therapy and negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test were performed. In the setting of probable or proven fungal infection (according to the revised EORTC criteria and Cornely CID 2007) Caspo was administered at the dose of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. They were 35 males and 29 females; the mean age was 56 yrs (range 19–77 yrs). The diagnoses were: acute leukemia 46 (72%), myeloma 2 (3%), lymphoma 14 (22%) and chronic leukemia 2 (3%); the disease’s phases were: new onset 26 (41%), remission 16 (24%), relapse 22 (35%). Thirteen pts received an allogeneic and 5 an autologous hematopoietic stem cell transplant; the other pts received an induction or consolidation or rescue chemotherapy course. Fungal infections were proven in 13 cases (20% including 11 aspergillus spp, 1 aspergillus fumigatus, 1 G. capitatum) and probable in 51 cases (80%). The first site of infection was the lung in 63 pts (98%) and paranasal sinuses in 1 patient (2%). CT scan was positive (halo sign or air-crescent sign) in all the pts with a lung localization, while the chest X-ray was positive in 40% of them. BAL was performed in 31 pts. The mean time of treatment was 18 days (range 13–25 days). Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion of Caspo were seen, and it was not necessary to administer any drug before the infusion as premedication. The global (partial and complete) response was 55/64 (86%); 9 pts died for fungal infection. The efficacy responses were generally similar for probable and proven infections. No breakthrough fungal infections were found. All surviving patients, upon discharge from the hospital, received oral treatment with Voriconazole or Posaconazole. For all the cured pts, there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial factor for the resolution of the infection. Among the 55 responsive patients, 25 (45%) died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 cases there was the recurrence of the fungal infection. In conclusion the resolution rate of the infections is very high (86%); Caspo seems safe, it does not preclude any other treatment (such as Cyclosporin A), it is well tolerated and the cost is lower than other antifungal treatments.

First Line Antifungal Treatment with Caspofungin of Oncohemopatic Patients. A Single Centre Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5271-5271 ◽  
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Ct Scan ◽  
Mechanism Of Action ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Drugs ◽  
Severe Neutropenia ◽  
First Line ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia and among them fungal infections are the most difficult to treat and a major cause of mortality. The availability of a new class of antifungal drugs (echinocandins) could improve the chance of cure. Caspofungin (Caspo) is the first drug which is able to destroy the fungal cell wall. Since January 2004 we have treated 28 consecutive adult oncohemopatic and neutropenic pts with Caspo as first line therapy. In case of persistent fever (4 days) despite broad spectrum antibiotic therapy (association of Tazobactam/Piperacillin, Amikacin with or without Vancomycin) with negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test (this test is available at our Centre since February 2006) were performed. In the presence of any other sign or symptom we performed any other test according to the physicyan’s choice. In case of possible, probable or proven fungal infection (according to the EORTC criteria) Caspo was administered at the dosage of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. The pts were 15 males and 13 females; the mean age was 46 yrs (range 18–66 yrs). The diagnoses were: acute myeloid leukemia 13, acute lymphoblastic leukemia 5, multiple myeloma 2, lymphoma 8; the disease’s phases were: onset 9, complete remission 11, relapse 2, resistant 6. Six pts received an allogeneic and 4 an autologous BMT; the other pts received an induction or consolidation or rescue chemotherapy course. All the pts had severe neutropenia and the fungal infections were proven in 3 cases (2 aspergillus spp and 1 aspergillus fumigatus), probable in 3 cases and possible in 22 cases. The first site of infection was the lung in 27 pts and paranasal sinuses in 1 patient. CT scan was positive (halo sign, air-crescent sign or cavitation) in all the pts with a lung localization. The mean time of treatment was 18 days (range 6–21 days). The treatment was not discontinued for anyone because of adverse events and no modifications of the dosage were necessary. All the pts submitted to an allogeneic BMT received concomitant therapy with Cyclosporine A and we had not to change the dosage and we did not found any renal or liver alterations. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion as premedication. No breakthrough fungal infections were found. The infection was cured in 24/28 pts; 4 pts died for fungal infection progression (3 with a progression to the brain and in 1 case the infection remained in the lungs). For all the cured pts there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial fact for the resolution of the infection. Among the 24 cured patients 8 died later: 5 for hematologic disease and 3 for sepsis during malignant disease recurrence. In 2 cases there was the recurrence of the fungal infection despite the secondary prophylaxis with Caspo. In conclusion we can say we have a new treatment option for fungal infections in neutropenic pts with a new mechanism of action; this option seems safe, it does not preclude any other treatment (such as Cyclosporine), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost is lower than other antifungal treatments.

Successful Control of Preexistent Active Infection by Granulocyte Transfusions During Conditioning Induced Cytopenia In Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Stem Cell Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1329-1329 ◽  
Author(s):  
P. Dayand Borge ◽  
Narda Theobald ◽  
Rosamma DeCastro ◽  
Harry L. Malech ◽  
Susan Leitman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Granulomatous Disease ◽  
Hematopoietic Stem Cell ◽  
Fungal Infections ◽  
Host Cells ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Granulomatous Disease ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Abstract 1329 Chronic granulomatous disease (CGD) is a congenital disorder resulting from decreased or absent oxidase production by neutrophils. As a result, patients with CGD are prone to bacterial and fungal infections and have a shortened life expectancy. Hematopoietic stem cell transplantation (HSCT) can be curative, and patients are increasingly referred for transplant due to an ongoing infection not amenable to cure using standard treatments. The use of granulocyte transfusions has been described in patients undergoing transplant with an underlying infection at the time of conditioning, but reports are limited to single cases. We describe here the effects of granulocyte transfusions in four patients undergoing either an HLA matched sibling or unrelated donor HSCT, using an alemtuzumab containing regimen and sirolimus as GVHD prophylaxis. Age of the patients was 6 to 25 (mean 11.5) yrs, and weight was 15.3 to 54 (mean 27.5) kg. Three of the patients had persistent Aspergillus infection involving the spine, lung, and/or brain despite long term combination antifungal therapy including a triazole, echinocandin and/or amphotericin. The fourth patient had an Actinomyces pneumonia progressive on combination antibacterial treatment. None of the patients had detectable HLA antibodies prior to the transfusions, and none received G-CSF post-transplant. The granulocytes were started on the anticipated day of neutropenia after conditioning and graft infusion and continued until evidence of graft recovery. Volunteer community donors underwent mobilization with dexamethasone 8 mg PO plus G-CSF 480 mcg SC, followed the next day by a 7-liter leukapheresis procedure (Spectra) using Tricitrasol/Hetastarch (Hespan) as the anticoagulant/sedimenting solution. Patients received a mean of 4.5 transfusions each, with three patients receiving biweekly transfusions and one receiving transfusions three times a week. The mean number of granulocytes per component transfused was 6.17 × 10e10 (range 4.0–9.12). This resulted in a mean of 2.78 × 10e9 granulocytes transfused per kg recipient weight (range 0.76–4.48). All patients tolerated the infusions well, without respiratory symptoms. The mean increase in absolute neutrophil count posttransfusion was 1.95 × 10e3/uL (range 0.5–4.61), although the timing of collection of the blood count samples was variable for each transfusion. Using a dihydrorhodamine (DHR) fluorescence based assay we were able to track the presence of oxidase positive cells to help differentiate transfused donor from residual host cells. DHR assays were performed before and after every transfusion in one patient. The number of DHR positive cells prior to infusion was 0–1.4% with a rise to 68.2% 24 hours after transfusion. 24.5% oxidase positive cells were still detectable almost 72 hours after transfusion, just prior to the next transfusion. One product required sedimentation for ABO incompatibility. The mean time to engraftment was 22 days and did not differ in patients with CGD receiving the same transplant regimen with (n=4) or without (n=6) peri-transplant granulocyte transfusions (30 days). Although all four patients had infectious processes not responding to standard antimicrobial therapy prior to transplant, there was no evidence of progressive infection during the period of neutropenia. Imaging studies of the brain, lung and/or spine suggested improvement in the infectious process in all four patients, although the timing of the scans made assessments inconclusive. Our prior experience with granulocyte transfusions in patients with CGD not undergoing transplant is that the cells do not persist in the circulation longer than 24 hours. Higher cell doses per kg in our four patients may have contributed to the sustained detection of transfused circulating cells, particularly as three of the patients weighed less than 21 kg. Peri-transplant immune suppression may also have facilitated the longer circulation time of the cells. We conclude that community-donor granulocyte transfusions are well tolerated in non-alloimmunized CGD patients undergoing HSCT, do not impact engraftment, are logistically feasible, and may provide a therapeutic bridge for patients with an underlying infection during a prescribed period of neutropenia, thus decreasing transplantation risk for such patients. Disclosures: No relevant conflicts of interest to declare.

Outcomes of invasive fungal infections in hematopoietic stem cell transplant patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18008-e18008
Author(s):  
Shagufta Shaheen ◽  
Shivanck Upadhyay ◽  
Creticus Petrov Marak ◽  
Gagan Kumar ◽  
Achuta Kumar Guddati
Keyword(s):  
Stem Cell ◽  
Fungal Infection ◽  
Hospital Stay ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Fungal Infections ◽  
Length Of Hospital Stay ◽  
Invasive Fungal Infections ◽  
Cell Transplant ◽  
Hematopoietic Stem

e18008 Background: Invasive fungal infections are associated with higher mortality in hematopoietic stem cell transplant (HSCT) recipients despite the use of broad spectrum antifungal agents. With the increase in the number of patients undergoing HSCT and a newer array of immunosuppressants, it is necessary to examine the incidence and outcomes of fungal infection in this population. Methods: We used Nationwide Inpatient Sample from years 2000 to 2008 to examine the trends and outcomes of fungal infections in patients admitted for HSCT. We used ICD-9-CM codes to identify those with HSCT. Similarly we identified invasive fungal infection using ICD-9-CM codes. The engraftment period and subsequent admissions were examined separately. Outcomes studied were in-hospital mortality and length of hospital stay. Logistic regression analysis was used to identify independent association of fungal infection with mortality. The model was adjusted for demographic and hospital characteristics, Charlson's co-morbidity index and severity of sepsis using number of organ failures. Results: There were 291,182 admissions with HSCT from 2000 to 2008. Of these, 3.4% patients had invasive fungal infections. They were more frequent in allogenic transplant during the engraftment period (4.2%) and in those with graft versus host disease (GVHD) in subsequent admission (7.1%). The unadjusted in-hospital mortality was significantly higher in those with invasive fungal infection (28% vs. 7%, p<0.001). On adjusted analysis, the odds of mortality were highest for those with mucor (OR 4.3;95%CI 2.5-7.5) and aspergillus (OR 3.7; 95%CI 3.1-4.5) infections while the results did not reach significance for candidemia. The length of hospital stay was significantly longer in those with invasive fungal infections (median 19 days vs. 7 days, p<0.001). Conclusions: Fungal infections are common in HSCT recipients - especially in those with allografts and with GVHD. Mortality is high and is mostly associated with aspergillus and mucor. A higher index of suspicion for fungal infections in HSCT patients, strict isolation precautions and increased surveillance for aspergillus and mucor in HSCT patients may help decrease the length of hospital stay and mortality.

Antifungal Treatment with Caspofungin: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5386-5386
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Antibiotic Therapy ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
The Other ◽  
Broad Spectrum Antibiotic ◽  
Persistent Fever ◽  
Neutropenic Patients ◽  
The Mean

Abstract Infections are the main complication for patients with hematologic diseases and severe neutropenia and among them fungal infections are the most diffucult to treat and a major cause of mortality for these patients. Now we have a new antifungal class, Echinocandins which work with a new and different mechanism of action regarding azoles and amphotericin B, so we wanted to verify the tolerability and efficacy of Caspofungin (Caspo). From January 2004 until now we have treated 15 consecutive oncohemopatic and neutropenic patients admitted at our Institution. The schedule of treatment was: in case of persistent fever (at least 4 days) during broad spectrum antibiotic therapy a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum and blood cultures were performed. In case of positivity of one or more of these findings suggesting for invasive fungal disease, Caspofungin was administered at the dosage of 70 mg i.v. on the first day and 50 mg i.v. from the second day; the infusion time was 1 hour. The patients were 10 males and 5 females, the mean age was 46 yrs (range 19–60 yrs). The diagnoses were: acute myeloid leukemia 8, acute lymphoblastic leukemia 3, lymphoma 4; the disease’s phases were: onset 3, first remission 3, remission>I 2, partial remission 5, relapse 1, resistant 1. Two patients received an allogeneic BMT, 1 an autologous BMT, the other patients an induction or consolidation or rescue chemotherapy course. In four cases Caspo was administered as secondary prophylaxis of a previous invasive fungal infection while for the other patients Caspo was administered for persistent fever and at least one lesion of the lungs or other organs with no evidence of bacterial or viral infection. The mean time of treatment was 18 days (range 6–21 days); the treatment was not discontinued for anyone of them because of adverse events; the dosage of Caspo was not changed for anyone. For the 2 allogeneic BMT Cyclosporine A administration was not changed and we did not found any renal or liver alterations. All the patients received a concomitant broad spectrum antibiotic therapy (association of Tazobactam/Piperacilline, Amikacine and Vancomycin) and for none of them we registered any liver or renal disfunction. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion. We did not seen breakthrough fungal infections. In 2 patients a proven fungal infection (Aspergillus fumigatus and Aspergillus spp) was demonstrated so the other cases remained probable or possible infections. No progression of the infection was seen. All the infections, except one, resolved; one patient died after 6 days of antifungal treatment for leukemia progression. Five patients died: 4 for leukemia and 1 for bacterial infection (Pseudomonas aeruginosa) after the fungal infection. In conclusion now we have a new treatment option for fungal infections in neutropenic patients and this option is safe, it does not preclude any other treatment (such as CsA), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost of the drug is lower than other antifungal treatments. According to these preliminary data we have decided to continue this experience to verify them in a larger cohort of patients.

Fluconazole Treatment of Neonates and Infants with Severe Fungal Infections

1997 ◽  
Vol 25 (4) ◽  
pp. 214-218 ◽  
Author(s):  
AN Gürpinar ◽  
E Balkan ◽  
N Kiliç ◽  
İ Kiriştioǧlu ◽  
İ Avşar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Clinical Response ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Duration Of Therapy ◽  
Day Range ◽  
The Mean ◽  
Neonates And Infants

A total of 24 neonates and infants, aged from 2 days to 10 months, received treatment with intravenous fluconazole for microbiologically documented or presumed fungal infection. The mean fluconazole dosage was 6 mg/kg/day (range 2 –16 mg/kg/day) and the mean duration of therapy was 25 days (range 5–72 days). Efficacy was evaluated in neonates with proven fungal infections, as documented by the presence of pathogen at baseline. A positive clinical response was achieved in 23 of the 24 clinically evaluable patients (96%); eradication of the fungal organism was also achieved in 23 of the 24 evaluable patients (96%). Adverse events occurred in two patients (8%) but therapy was not discontinued in either patient. The present results confirm the efficacy and safety of fluconazole in the treatment of neonates and infants with severe fungal infections.

Caspofungin for invasive aspergillosis: A single-centre prospective study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20618-e20618 ◽  
Author(s):  
A. Bonini ◽  
A. Tieghi ◽  
B. Gamberi ◽  
A. Imovilli ◽  
C. Carbonelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Prospective Study ◽  
Fungal Infection ◽  
Ct Scan ◽  
Fungal Infections ◽  
Oral Treatment ◽  
Complete Response ◽  
Fungal Cell ◽  
First Line Therapy ◽  
A Prospective Study

e20618 Background: Infections are the main complication for neutropenic patients (pts).Fungal infections represent a frequent cause of death. Caspofungin (Caspo) is the first drug able to inhibit the growth of the fungal cell wall. Methods: Since 2004 we began a prospective study with the administration of Caspo as first line therapy in 63 consecutive adult neutropenic pts. With persistent fever despite antibiotics,a chest CT-scan and galactomannan test were performed. In case of probable or proven infection Caspo was administered at the dose of 70 mg on the first day followed by 50 mg daily. They were 35 males and 28 females; the mean age was 56 yrs. The diagnoses were: leukemia 44, myeloma 3, lymphoma 16; the disease's phases were: new onset 24, remission 16, relapse 23. 12 pts received an allogeneic and 6 an autologous transplant; the others received conventional chemotherapy. Results: Fungal infections were proven in 12 and probable in 51 cases.The first site of infection was the lung in 62 pts. CT scan was positive(halo sign or air-crescent sign)in all the pts with a lung localization. BAL was performed in 37 pts.The mean time of treatment was 18 days. Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion were seen, and it was not necessary to administer any premedication. The global (partial and complete) response was 50/63 (79%); 13 pts died for fungal infection. The responses were generally similar for probable and proven infections. No breakthrough infections were seen. All surviving patients, upon discharge from the hospital, received oral treatment with voriconazole. For all the cured pts, there was a concomitant recovery of neutrophils and this seems crucial for the resolution of the infection. Among the 50 responsive patients, 25 died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 pts there was the recurrence of the fungal infection. Conclusions: The resolution rate of the infections is very high; Caspo seems safe, it does not preclude any other treatment, it is well tolerated and the cost is lower than other antifungal treatments. No significant financial relationships to disclose.

scholarly journals Rapidly expanded partially HLA DRB1–matched fungus-specific T cells mediate in vitro and in vivo antifungal activity

2020 ◽  
Vol 4 (14) ◽  
pp. 3443-3456
Author(s):  
Gloria Castellano-González ◽  
Helen M. McGuire ◽  
Fabio Luciani ◽  
Leighton E. Clancy ◽  
Ziduo Li ◽  
...  
Keyword(s):  
T Cells ◽  
Fungal Infection ◽  
Fungal Infections ◽  
Interferon Γ ◽  
Third Party ◽  
Interleukin 17 ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Invasive fungal infections are a major cause of disease and death in immunocompromised hosts, including patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Recovery of adaptive immunity after HSCT correlates strongly with recovery from fungal infection. Using initial selection of lymphocytes expressing the activation marker CD137 after fungal stimulation, we rapidly expanded a population of mainly CD4+ T cells with potent antifungal characteristics, including production of tumor necrosis factor α, interferon γ, interleukin-17, and granulocyte-macrophage colony stimulating factor. Cells were manufactured using a fully good manufacturing practice–compliant process. In vitro, the T cells responded to fungal antigens presented on fully and partially HLA-DRB1 antigen–matched presenting cells, including when the single common DRB1 antigen was allelically mismatched. Administration of antifungal T cells lead to reduction in the severity of pulmonary and cerebral infection in an experimental mouse model of Aspergillus. These data support the establishment of a bank of cryopreserved fungus-specific T cells using normal donors with common HLA DRB1 molecules and testing of partially HLA-matched third-party donor fungus-specific T cells as a potential therapeutic in patients with invasive fungal infection after HSCT.

Micafungin Is Extremely Effective Against Fungal Infections Complicating Hematological Malignancies: Report of a Multicenter Study by N-FISH (Niigata Fungal Infection Study Group in Hematology).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5350-5350
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Yoshinobu Seki ◽  
Kazue Takai ◽  
Koji Nikkuni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Multicenter Study ◽  
Liver Dysfunction ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
The United States ◽  
Study Group ◽  
The Mean ◽  
Infection Study

Abstract [Background]Micafungin (MCFG) is a candin antifungal agent, and was marketed in Dec. 2002 in Japan and in Apr. 2005 in the United States. The Niigata Fungal Infection Study Group in Hematology (N-FISH) performed a multicenter prospective study to clarify the therapeutic effects of MCFG on deep fungal infections complicating hematological malignancies. [Methods]A total of 36 pts. who had been treated in centers belonging to N-FISH between Oct. 2003 and Apr. 2005 were included in this study. They consisted of 14 men and 22 women with a mean age of 53.5 years: 14 pts. with AML, 10 pts. with malignant lymphoma, 6 pts. with ALL, and 6 pts with other diseases. They had a proven fungal infection, or were suspected of having a fungal infection because of fever unresponsive to antimicrobial agents or from laboratory data. Three of them had a proven infection, and 33 were suspected of having a fungal infection. Three of these 33 pts. failed to respond to fluconazole. As a rule, MCFG was administered for more than 14 days until infectious symptoms improved or disappeared. When MCFG was judged ineffective because of the worsening of clinical symptoms despite the administration of MCFG, or when the administration of MCFG was judged difficult because of adverse effects, the drug was discontinued or replaced by other drugs. Two pts. orally received amphotericin B syrup singly. [Results]The mean dose of MCFG was 2.6 mg/kg (1.5–4.2 mg/kg), and the mean duration of administration was 15.9 days (5–85 days). Complete or partial response was achieved in 31 (86.1%) of the 36 pts., who showed improvements in infectious symptoms. In 4 pts, MCFG was discontinued because of insufficient effects. There were no breakthrough fungal infections within 7 days after the completion of MCFG therapy. Of the 36 pts., 31 (86.1%) and 24 (66.7%) survived 1 and 3 months after MCFG therapy, respectively. The cause of death was exacerbation of the primary disease, and not exacerbation or the onset of a fungal infection. Eight adverse events occurred in 7 pts.: hypoglycemia in 1, liver dysfunction in 3, eosinophilia in 1, kidney dysfunction in 2, and hypokalemia in 1. In 1 of the 3 pts. with liver dysfunction (grade 3), MCFG therapy was discontinued, with rapid improvement of the liver dysfunction. All other adverse events were mild, allowing continued MCFG therapy. [Conclusion]This multicenter study demonstrated the effectiveness and safety of MCFG therapy for deep fungal infections complicating hematological malignancies. The results suggest that MCFG should be promptly used for fever associated with a fungal infection complicating hematological malignancies.

scholarly journals Diagnostic Significance of Serum and BAL Galactomannan (GM) Enzyme Immune Assay in Invasive Aspergillosis (IA) with Reference to EORTC/MSG - A Short Review

2018 ◽  
Vol 2 (2) ◽  
Keyword(s):  
Invasive Aspergillosis ◽  
Fungal Infections ◽  
Signs And Symptoms ◽  
Lavage Fluid ◽  
Short Review ◽  
Severe Neutropenia ◽  
Cell Transplant ◽  
Diagnostic Significance ◽  
Hematopoietic Stem ◽  
Mortality And Morbidity

Invasive aspergillosis is a life-threatening mycelial fungal infection in immunocompromised patients and is associated with high mortality and morbidity. Patients undergoing hematopoietic stem cell transplant (HSCT) and neutropenic patients are particularly at risk. The degree and duration of neutropenia is an independent risk factor for invasive fungal infections. Patients with prolonged and severe neutropenia (ANC less than 500cells/cumm) are more susceptible. The lung is the most common site of infection and vascular invasion by Aspergillus species is a common histopathological feature of invasive aspergillosis (IA). As there is a lack of adequate immune response, patients with IA fail to develop classical signs and symptoms of the disease making diagnosis of IA more difficult. The results of fungal cultures are often delayed and cytopathological examination, yields negative results as there is lack of sensitivity and specificity. Biopsy specimens may be unproductive if the sample is collected at an advanced stage of the disease. Galactomannan (GM) detection in serum and Broncho alveolar lavage fluid (BAL) seems to be useful in establishing or excluding the diagnosis of invasive aspergillosis. Multicentre studies reported that there was no conclusive benefit of determining serum and BAL GM levels in the diagnosis of invasive aspergillosis among immunocompetent hosts. A serum and BAL GM test should not be ordered routinely in non-immunocompromised hosts.

Prevention, Diagnosis, and Treatment of Invasive Fungal Infections in Patients with Cancer and Neutropenia

2004 ◽  
Vol 2 (5) ◽  
pp. 455-469 ◽  
Author(s):  
Thomas A. Cumbo ◽  
Brahm H. Segal
Keyword(s):  
Fungal Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Detection Methods ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Effective Prevention ◽  
Nccn Guidelines ◽  
Patients With Cancer

Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.

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