micafungin and Opportunistic-Infections

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

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cryptococcus; Cytarabine; Dermatomycoses; Echinocandins; Exanthema; Fever; Fungemia; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipopeptides; Male; Micafungin; Opportunistic Infections; Retrospective Studies; Saccharomyces; Salvage Therapy; Trichosporon; Ustilaginales; Vidarabine; Voriconazole; Yeasts

Hematopoietic stem transplant recipients are subject to increased risk for invasive fungal infections.. This meta-analysis was undertaken to explore the comparative effectiveness of systemic antifungal prophylaxis in hematopoietic stem cell transplant recipients.. We searched PubMed and The Cochrane Register of Randomized Controlled Trials up to March 2013 for randomized studies on systemic antifungal prophylaxis after hematopoietic stem cell transplantation. We performed a meta-analysis on the relative effectiveness of systemic antifungal prophylaxis on proven or probable invasive fungal infections using direct and indirect effects. Relative effectiveness was reported as odds ratio (OR) for invasive fungal infections, causative agent, empirical antifungal therapy, and withdrawals due to drug adverse events.. Twenty evaluable studies provided data on 4823 patients. The risk for invasive fungal infections while on prophylaxis was 5.1% (95% CI, 3.6-6.8%). In patients receiving fluconazole, risks of proven or probable invasive fungal infections (OR = 0.24; 95% CI, 0.11-0.50; number needed to treat [NNT] = 8), systemic candidiasis (OR = 0.11; 95% CI, 0.05-0.24; NNT = 7), and overall need for empiric antifungal treatment (OR = 0.60; 95% CI, 0.44-0.82; NNT = 8) were reduced compared with patients receiving placebo. Itraconazole was more effective than fluconazole for the prevention of aspergillosis (OR = 0.40; 95% CI, 0.19-0.83; NNT = 23) at the expense of more frequent withdrawals (OR = 3.01; 95% CI, 1.77-5.13; number needed to harm = 6). Micafungin was marginally more effective than fluconazole for the prevention of all mold infections (OR = 0.35; 95% CI, 0.10-1.18; NNT = 79) and invasive aspergillosis (OR = 0.19; 95% CI, 0.03-1.11; NNT = 78) and reducing the need for empiric antifungal treatment (OR = 0.40; 95% CI, 0.13-1.21; NNT = 8). There was a relative lack of comparisons between different antifungal prophylactic strategies, including the newer azoles, voriconazole and posaconazole, in this population. Direct effects derived from single studies showed marginally significant effects for voriconazole compared with fluconazole regarding invasive aspergillosis (OR = 0.50; 95% CI, 0.20-1.20; NNT = 35) and the need for empiric treatment (OR = 0.72; 95% CI, 0.50-1.06; NNT = 15). Voriconazole compared with itraconazole (OR = 0.59; 95% CI, 0.40-0.88; NNT = 8) and posaconazole compared with amphotericin B (OR = 0.28; 95% CI, 0.06-1.24, marginal significance; NNT = 3) were better regarding empirical antifungal treatment.. Even when on antifungal therapy, invasive fungal infection will develop in 1 of 20 patients undergoing hematopoietic stem cell transplantation. There is evidence for the comparable effectiveness of different antifungal drugs used for prophylaxis. Fluconazole is the most widely studied agent, but micafungin might prove to be more effective. There is a relative paucity of studies for the newer azoles, although both voriconazole and posaconazole give proof of their comparative or higher effectiveness to fluconazole in single randomized studies.

Topics: Antibiotic Prophylaxis; Antifungal Agents; Echinocandins; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Micafungin; Opportunistic Infections; Randomized Controlled Trials as Topic; Treatment Outcome

Serious infections caused by opportunistic molds remain a major problem for public health. Immune deficiency following organ transplantation and aggressive cancer treatment has greatly increased the incidence of systemic mycoses, and invasive aspergillosis in patients with AIDS is associated with significant morbidity and mortality. Amphotericin B is the first-line therapy for systemic infection because of its broad-spectrum and fungicidal activity. However, considerable side effects limit its clinical utility. The echinocandins are large lipopeptide molecules that inhibit the synthesis of 1,3-beta-D-glucan, a key component of the fungal cell wall. Three echinocandins have reached the market, and some others are in early clinical development. Caspofungin was the first echinocandin to be licensed for clinical use in most countries. Micafungin is licensed for clinical use in Japan, China, Taiwan, Jordan, Korea, Hong-Kong and the US, and anidulafungin is currently licensed in the US. The novel class of echinocandins represents a milestone in antifungal drug research that has further expanded our therapeutic options. Studies to date have shown that micafungin exhibits extremely potent antifungal activity against clinically important fungi, including Aspergillus and azole-resistant strains of Candida. In animal studies, micafungin is as efficacious as amphotericin B with respect to improvement of survival rate. Micafungin is also characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions are described. No dose adjustments of the drug are required in the presence of mycophenolate mofetil, cyclosporin, tacrolimus, prednisolone, or sirolimus. Strategies using this new echinocandin agent will benefit a large number of patients with severe immune dysfunction.

Topics: Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cell Wall; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Fungal; Echinocandins; Hematopoietic Stem Cell Transplantation; Hemolytic Agents; Humans; Lipopeptides; Lipoproteins; Micafungin; Mice; Mycoses; Opportunistic Infections; Peptides, Cyclic; Structure-Activity Relationship

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Azoles; Caspofungin; Drug Design; Drug Resistance, Fungal; Echinocandins; Fluconazole; Fluorouracil; Fungi; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Opportunistic Infections; Peptides; Peptides, Cyclic; Polyenes; Pyrimidines

Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised patients with cancer. Current treatment strategies for these infections are limited by antifungal resistance, toxicity, drug interactions, and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve our therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk patients with neoplastic diseases.

Topics: Anidulafungin; Antifungal Agents; Echinocandins; Humans; Immunocompromised Host; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Neoplasms; Opportunistic Infections; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Invasive fungal infection (IFI) is a serious complication of chemotherapy for hematological malignancies and autologous/allogeneic hematopoietic stem cell transplantation in children and shows a high mortality rate. We performed a randomized trial comparing micafungin (MCFG), a new anti-fungal agent, with fosfluconazole, a prodrug of fluconazole (FF) conventionally used as a prophylactic agent, for prophylaxis against IFI. Cefpirome was administered as prophylaxis against bacterial infection, and meropenem+minocycline as an empiric window therapy for febrile neutropenia. MCFG 2 mg/kg/day (max 100 mg/day) and FF 10 mg/kg/day (max 400 mg/day) were both safe and effective (event free ratio of IFI, MCFG 94.4% vs FF 94.3%) without significant difference. Thus, MCFG is safe and can be used for prophylaxis against IFI in children.

Topics: Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Echinocandins; Female; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lipopeptides; Male; Meropenem; Micafungin; Minocycline; Mycoses; Neutropenia; Opportunistic Infections; Organophosphates; Prodrugs; Thienamycins

Tocilizumab, an interleukin-6 receptor antagonist, has been used to treat critically ill patients with coronavirus disease-2019. We present the case of a previously immunocompetent man with coronavirus disease-2019 who developed invasive pulmonary aspergillosis after treatment with tocilizumab, illustrating the importance of considering opportunistic infections when providing immune modulating therapy.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antiviral Agents; Aspergillus; COVID-19 Drug Treatment; Humans; Immunomodulation; Invasive Pulmonary Aspergillosis; Male; Micafungin; Opportunistic Infections; Receptors, Interleukin-6; SARS-CoV-2; Voriconazole

The in vitro activities of isavuconazole, micafungin, and 8 comparator antifungal agents were determined for 1613 clinical isolates of fungi (1320 isolates of Candida spp., 155 of Aspergillus spp., 103 of non-Candida yeasts, and 35 non-Aspergillus molds) collected during a global survey conducted in 2013. The vast majority of the isolates of the 21 different species of Candida, with the exception of Candida glabrata (MIC90, 2 μg/mL), Candida krusei (MIC90, 1 μg/mL), and Candida guilliermondii (MIC90, 8 μg/mL), were inhibited by ≤0.25 μg/mL of isavuconazole. C. glabrata and C. krusei were largely inhibited by ≤1 μg/mL of isavuconazole. Resistance to fluconazole was seen in 0.5% of Candida albicans isolates, 11.1% of C. glabrata isolates, 2.5% of Candida parapsilosis isolates, 4.5% of Candida tropicalis isolates, and 20.0% of C. guilliermondii isolates. Resistance to the echinocandins was restricted to C. glabrata (1.3-2.1%) and C. tropicalis (0.9-1.8%). All agents except for the echinocandins were active against 69 Cryptococcus neoformans isolates, and the triazoles, including isavuconazole, were active against the other yeasts. Both the mold active triazoles as well as the echinocandins were active against 155 Aspergillus spp. isolates belonging to 10 species/species complex. In general, there was low resistance levels to the available systemically active antifungal agents in a large, contemporary (2013), global collection of molecularly characterized yeasts and molds. Resistance to azoles and echinocandins was most prominent among isolates of C. glabrata, C. tropicalis, and C. guilliermondii.

Topics: Antifungal Agents; Drug Resistance, Fungal; Echinocandins; Fungi; Global Health; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mycoses; Nitriles; Opportunistic Infections; Pyridines; Triazoles

The Sporopachydermia cereana species lives in decaying stems of cactus and is exceptionally rare as a human pathogen. A 57-year-old man with therapy-refractory acute promyelocytic leukaemia developed severe neutropaenia. After about 3 weeks of micafungin used as prophylaxis, he developed high fever, multiple pulmonary nodular infiltrates and a painful leg lesion. Blood culture yielded a yeast which was not identified by the Vitek 2 system. On ITS1-5.8S-ITS2 gene sequencing, the isolate was identified as S. cereana. Antifungal sensitivity by the Etest showed that the minimum inhibitory concentration for fluconazole was 0.75 μg/mL, and for anidulafungin, it was >32 μg/mL. He responded to liposomal amphotericin B but later died of Escherichia coli septicaemia. There were no cactus plants in the vicinity, suggesting that S. cereana might have alternative habitats.

Topics: Antifungal Agents; Chemoprevention; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Echinocandins; Escherichia coli Infections; Fatal Outcome; Fungemia; Humans; Immunocompromised Host; Leukemia, Promyelocytic, Acute; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Opportunistic Infections; Radiography, Thoracic; Saccharomycetales; Sepsis; Sequence Analysis, DNA; Skin; Tomography, X-Ray Computed

Mucormycosis is a rapidly progressive fungal infection that usually occurs in patients with diabetes mellitus or in immunocompromised patients. Sinus involvement is the most common clinical presentation and the rates of mortality increase with the orbital extension. The treatment of mucormycosis includes aggressive surgical debridement and systemic antifungal therapy. Early diagnosis and prompt initiation of effective antifungal drugs are essential for successful outcome. However, the role of orbital exenteration for the case of orbital involvement remains controversial, and the drugs effective against mucormycosis are limited. We present a successfully treated case with rhino-orbital mucormycosis caused by Rhizopus oryzae in a diabetic and dialysis patient. The early diagnosis, surgical debridement and a new combination therapy with liposomal amphotericin B and micafungin were effective. This new combination antifungal therapy will be useful for the treatment of mucormycosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Drug Therapy, Combination; Echinocandins; Endoscopy; Humans; Lipopeptides; Magnetic Resonance Imaging; Male; Maxillary Sinus; Maxillary Sinusitis; Micafungin; Necrosis; Opportunistic Infections; Orbital Diseases; Rhinitis; Rhizopus; Tomography, X-Ray Computed; Turbinates

In 2005, several groups, including the European Group for Blood and Marrow Transplantation, the European Organization for Treatment and Research of Cancer, the European Leukemia Net and the Immunocompromised Host Society created the European Conference on Infections in Leukemia (ECIL). The main goal of ECIL is to elaborate guidelines, or recommendations, for the management of infections in leukemia and stem cell transplant patients. The first sets of ECIL slides about the management of invasive fungal disease were made available on the web in 2006 and the papers were published in 2007. The third meeting of the group (ECIL 3) was held in September 2009 and the group updated its previous recommendations. The goal of this paper is to summarize the new proposals from ECIL 3, based on the results of studies published after the ECIL 2 meeting: (1) the prophylactic recommendations for hematopoietic stem cell transplant recipients were formulated differently, by splitting the neutropenic and the GVHD phases and taking into account recent data on voriconazole; (2) micafungin was introduced as an alternative drug for empirical antifungal therapy; (3) although several studies were published on preemptive antifungal approaches in neutropenic patients, the group decided not to propose any recommendation, as the only randomized study comparing an empirical versus a preemptive approach showed a significant excess of fungal disease in the preemptive group.

Topics: Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia; Lipopeptides; Micafungin; Mycoses; Neutropenia; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress.

Topics: Animals; Antifungal Agents; Base Sequence; Calcineurin; Candida glabrata; Candidiasis; DNA Primers; DNA, Fungal; Drug Resistance, Fungal; Female; Fungal Proteins; Genes, Fungal; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mutation; Opportunistic Infections; Transcription Factors; Virulence

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

A 35-year-old man developed invasive pulmonary aspergillosis (IPA) with severe neutropenia after umbilical cord stem cell transplantation for chronic myelogenous leukemia. Filamentous fungus isolated from his sputum was identified as Aspergillus terreus. Despite systemic amphotericin B (AMPH) administration, IPA progressed. However, intravenous administration of micafungin (MCFG) and oral itraconazole improved clinical data and symptoms, although he later died of massive hemoptysis. Examination of the in vitro susceptibility of this A. terreus isolate to MCFG revealed a good minimum inhibitory concentration and good time-kill assay results compared to AMPH. Thus, MCFG might be useful for IPA caused by A. terreus.

Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus; Drug Therapy, Combination; Echinocandins; Humans; Itraconazole; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Neutropenia; Opportunistic Infections; Peptides, Cyclic; Sputum; Stem Cell Transplantation

Invasive fungal infections are fatal complications for patients on chemotherapy, and antifungal prophylactic treatment has been commonly recommended. Because its clinical and economic impact is not well known, we evaluated cost-effectiveness of anti-fungal treatment for patients who were neutropoenic as a result of chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$), and incremental cost-effectiveness ratio (US$/YLS). The following treatment strategies for fungal infections were compared: (1) prophylactic fluconazole strategy: oral fluconazole administration concurrently with chemotherapy; (2) empirical amphotericin B strategy: empirical intravenous amphotericin B administration at the point where fever is detected; and (3) no prophylaxis strategy: intravenous micafangin administration at the point where fungal infections is diagnosed. Baseline analyses showed that prophylactic fluconazole strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS). The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was 625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to empirical amphotericin B strategy. Baseline result was found to be robust through sensitivity analyses. Our study showed that concurrent administration of oral fluconazole during induction chemotherapy appears to ensure clinical benefits together with acceptable cost-effectiveness.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Cohort Studies; Cost-Benefit Analysis; Echinocandins; Fluconazole; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Opportunistic Infections; Peptides, Cyclic

Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Debridement; DNA, Fungal; Drug Therapy, Combination; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Itraconazole; Lipopeptides; Lipoproteins; Lymphoma, Non-Hodgkin; Male; Maxillary Diseases; Maxillary Sinus; Micafungin; Middle Aged; Opportunistic Infections; Peptides, Cyclic; Renal Insufficiency; Sinusitis; Treatment Outcome

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