micafungin and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking.. We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder.. Of the 19 cases of invasive T asahii infection, the most commonly reported underlying hematologic disorder was acute lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most of the patients (94%) had neutropenia, defined as an absolute neutrophil count of <500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19 cases, and micafungin use was reported in 5 cases. Treatment regimens frequently included voriconazole monotherapy (47%) or the combination of an azole antifungal with amphotericin B (35%). The mortality rate was 58%.. Recognizing that echinocandins, which are increasingly used for prophylaxis in patients with a hematologic malignancy, are not active against Trichosporon species is of critical importance. The recommended first-line therapy for trichosporonosis is voriconazole, but successful outcome depends largely on the underlying immune status of the host.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Drug Therapy, Combination; Echinocandins; Female; Humans; Immunocompromised Host; Invasive Fungal Infections; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporonosis; Voriconazole

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Bacterial; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Chemical and Drug Induced Liver Injury; Early Diagnosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Mannans; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

This observational study was conducted to document the efficacy and safety of the use of micafungin (Mycamine) as an empirical antifungal agent in febrile neutropenic patients.. Micafungin was administered for sustained fever (>38.4°C) on days 3-5 following the initiation of empirical antibiotic therapy. The overall success rate and side effects were evaluated.. A total of 47 patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome and lymphoma were enrolled in the study. The overall success rate of micafungin was 61.7% (29/47). A total of 3 patients (6.4%) experienced grade 3/4 elevations in their aspartate aminotransferase levels, and 10 patients (21%) experienced grade 3/4 hyperbilirubinemia, 9 of which resolved. Four patients died of septic shock. Younger patients (<50 years) and patients with acute lymphoblastic leukemia exhibited a better response to micafungin than other patients. Patients that were less profoundly neutropenic (≥0.05 × 10(9)/l) also had a better response to micafungin, as did the patients who recovered from their fever or neutropenia.. Micafungin has an excellent efficacy (61.7%) and safety profile when used as an empirical antifungal agent in febrile neutropenic patients with hematological disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifungal Agents; Echinocandins; Female; Fever; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Micafungin; Middle Aged; Mycoses; Myelodysplastic Syndromes; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Young Adult

To determine the pharmacokinetics of twice-a-week micafungin prophylaxis in paediatric leukaemic patients to provide the rationale for this approach.. Twice-a-week micafungin at a dose of 9 mg/kg (maximum 300 mg) was given during the leukaemic induction treatment with at least one pharmacokinetic assessment. Non-linear mixed-effects modelling was used for analysis. For model building, our paediatric data were strengthened with existing adult data. Monte Carlo simulations were performed with twice-a-week dosing regimens of 5, 7 and 9 mg/kg and flat dosing per weight band. Simulated paediatric exposures were compared with the exposure in adults after a once-daily 100 mg regimen.. Sixty-one paediatric patients were included with a median age and weight of 4.0 years (range 1.0-17) and 19.5 kg (range 8.60-182), respectively. A two-compartment model best fitted the data. CL and central Vd were lower (P < 0.01) in paediatric patients compared with adults. Predicted exposures (AUC0-168 h) for the 5, 7 and 9 mg/kg and flat dosing per weight band regimens exceeded the adult reference exposure.. All twice-a-week regimens appeared to result in adequate exposure for Candida therapy, with simulated exposures well above the adult reference exposure. These findings provide the rationale for the pharmacokinetic equivalence of twice-a-week and once-daily micafungin regimens. The greater micafungin exposures seem to be caused by a slower-than-anticipated CL in our paediatric leukaemic patients. The generalizability of our results for Aspergillus prophylaxis cannot be provided without assumptions on target concentrations and within-class identical efficacy.

Topics: Adolescent; Adult; Antifungal Agents; Child; Child, Preschool; Echinocandins; Humans; Infant; Invasive Fungal Infections; Lipopeptides; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies

Topics: Adolescent; Antifungal Agents; Candidemia; Child; Echinocandins; Female; Humans; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocan-dins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haema-tological patients on chemotherapy.. A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included.. There were 5 cases of probable or proven fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity.. Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Candidiasis; Female; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Micafungin; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Young Adult

Topics: Adolescent; Adult; Allografts; Aspergillosis; Candidiasis; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies

Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML).. Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity ( Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy.. The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1-68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety.. Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML.. Clinicaltrials.gov NCT02440178, registered May 12th 2015.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Female; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Treatment Outcome; Young Adult

We report the first case of liver abscess due to Sterigmatomyces halophilus. Because this pathogen grows poorly in culture medium without added salts, it was identified by sequencing analysis targeting the rRNA gene internal transcribed spacer (ITS) region. This method could be useful for pathogens that cannot be cultured using standard methods.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Basidiomycota; Biopsy; Bone Marrow Transplantation; Cefozopran; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Child; Hematopoietic Stem Cell Transplantation; Humans; Liver; Liver Abscess; Male; Micafungin; Mycoses; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Topics: Adult; Antifungal Agents; Candida tropicalis; Candidiasis; Combined Modality Therapy; Endophthalmitis; Eye Infections, Fungal; Humans; Male; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retinal Neoplasms; Vitrectomy

The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia.. Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/μL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded.. During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period.. Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy.

Topics: Adolescent; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Ciprofloxacin; Cohort Studies; Drug Costs; Echinocandins; Female; Humans; Infant; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Sepsis; Triazoles; Voriconazole

Topics: Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candida tropicalis; Candidiasis; Drug Therapy, Combination; Echinocandins; Follow-Up Studies; Fungemia; Humans; Infant; Lipopeptides; Male; Micafungin; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Aspergillosis; Pyrimidines; Tomography, X-Ray Computed; Triazoles; Voriconazole

Invasive fungal infection is a major cause of morbidity and mortality in patients with febrile neutropenia unresponsive to antibacterial treatment. Empirical antifungal therapy with amphotericin B has been the standard of care for these patients; however, there remains a need for less toxic alternative drugs.. We conducted a prospective study to evaluate the efficacy and safety of micafungin (MCFG), a novel antifungal agent of the echinocandin class, in an empirical therapy setting for patients with febrile neutropenia.. A total of 31 patients with acute leukemia who developed febrile neutropenia were enrolled in the study. Among them, 18 patients fulfilling the protocol-defined criteria, including 10 with persistent fever and 8 with recurrent fever, received MCFG empirically. Underlying diseases consisted of acute myeloid leukemia (n=15) and acute lymphoblastic leukemia (n=3). The median duration of neutropenia and drug administration was 22 and 9.5 days, respectively. Treatment success, defined as defervescence during the neutropenic period, absence of breakthrough fungal infections, and requiring no replacement of antifungal drugs, was achieved in 14 patients (78%). None of the patients required discontinuation or dose reduction due to adverse events except for one patient with severe hypokalemia.. Although the studied patients were limited in number, our results indicate that MCFG is an encouraging agent for empirical antifungal therapy in patients with febrile neutropenia, and deserves further investigation in large-scale studies.

Topics: Adolescent; Adult; Algorithms; Antifungal Agents; Echinocandins; Female; Fever; Humans; Leukemia, Myeloid; Lipopeptides; Lipoproteins; Male; Micafungin; Middle Aged; Neutropenia; Peptides, Cyclic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies

We treated a 52-year-old woman with acute lymphoblastic leukemia (ALL) who developed invasive pulmonary aspergillosis (IPA) as a result of neutropenia following remission-induction chemotherapy. Although serological test results, such as those for platelia and pastrex, were all negative and the serum level of beta-D-glucan was low, Aspergillus DNA was detected in blood by the polymerase chain reaction method. A clinically documented diagnosis of IPA was made on the basis of chest x-rays, computed tomography scan findings, and the detection of Aspergillus DNA. Micafungin (FK463), a candin class antifungal agent, was administered at a dose of 75 to 150 mg/day, because other antifungal agents were not effective. The increase in serum concentration of micafungin was dose-dependent and was accompanied by improvement of symptoms and objective findings. Micafungin was effective for the treatment of IPA in this patient with ALL.

Topics: Antineoplastic Agents; Aspergillosis; Clinical Trials, Phase II as Topic; Echinocandins; Female; Humans; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Micafungin; Middle Aged; Neutropenia; Opportunistic Infections; Peptides, Cyclic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent.. Haematology department and bone marrow transplantation unit.. Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis.. Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Drug Evaluation; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid; Lipopeptides; Lipoproteins; Male; Micafungin; Mucormycosis; Multiple Organ Failure; Peptides, Cyclic; Periodontal Abscess; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sinusitis; Splenectomy; Systemic Inflammatory Response Syndrome; Transplantation, Homologous