Browsing by Subject "Amphotericin B"

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    A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.
    (N Engl J Med, 2018-03-16) Le, Thuy; Kinh, Nguyen Van; Cuc, Ngo TK; Tung, Nguyen LN; Lam, Nguyen T; Thuy, Pham TT; Cuong, Do D; Phuc, Pham TH; Vinh, Vu H; Hanh, Doan TH; Tam, Vu Van; Thanh, Nguyen T; Thuy, Tran P; Hang, Nguyen T; Long, Hoang B; Nhan, Ho T; Wertheim, Heiman FL; Merson, Laura; Shikuma, Cecilia; Day, Jeremy N; Chau, Nguyen VV; Farrar, Jeremy; Thwaites, Guy; Wolbers, Marcel; IVAP Investigators
    BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
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    Case 4: Weakness and Headaches in a 14-year-old Boy.
    (Pediatrics in review, 2018-08) White, Alyssa; Liu, Xibei; Das, Samrat U
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    Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance.
    (The Lancet. Infectious diseases, 2021-06) Koehler, Philipp; Bassetti, Matteo; Chakrabarti, Arunaloke; Chen, Sharon CA; Colombo, Arnaldo Lopes; Hoenigl, Martin; Klimko, Nikolay; Lass-Flörl, Cornelia; Oladele, Rita O; Vinh, Donald C; Zhu, Li-Ping; Böll, Boris; Brüggemann, Roger; Gangneux, Jean-Pierre; Perfect, John R; Patterson, Thomas F; Persigehl, Thorsten; Meis, Jacques F; Ostrosky-Zeichner, Luis; White, P Lewis; Verweij, Paul E; Cornely, Oliver A; European Confederation of Medical Mycology; International Society for Human Animal Mycology; Asia Fungal Working Group; INFOCUS LATAM/ISHAM Working Group; ISHAM Pan Africa Mycology Working Group; European Society for Clinical Microbiology; Infectious Diseases Fungal Infection Study Group; ESCMID Study Group for Infections in Critically Ill Patients; Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy; Medical Mycology Society of Nigeria; Medical Mycology Society of China Medicine Education Association; Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology; Association of Medical Microbiology; Infectious Disease Canada
    Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
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    Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.
    (Am J Trop Med Hyg, 2015-02) Rubach, Matthew P; Maro, Venance P; Bartlett, John A; Crump, John A
    We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.
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    Invasive Curvularia Infection in Pediatric Patients With Hematologic Malignancy Identified by Fungal Sequencing.
    (Journal of the Pediatric Infectious Diseases Society, 2019-03) Chang, Yeh-Chung; Graf, Erin; Green, Abby M
    Curvularia is a saprophytic dematiaceous mold and a rare human pathogen. Here, we report three severely immunocompromised pediatric patients who developed invasive Curvularia infection. Diagnosis was achieved or confirmed in all cases by fungal ribosome sequencing, which hastened species identification and targeted treatment for the patients reported. There are no treatment guidelines for invasive Curvularia infection, though we report three patients who were cured of their infection through a combination of surgical resection and various anti-fungal therapies, indicating a relatively low virulence and good prognosis in comparison to other angioinvasive molds.
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    Itraconazole or Amphotericin B for Talaromycosis.
    (The New England journal of medicine, 2017-10) Brüggemann, Roger J; van de Veerdonk, Frank L; Verweij, Paul E
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    Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.
    (The Lancet. Infectious Diseases, 2019-04) Loyse, Angela; Burry, Jessica; Cohn, Jennifer; Ford, Nathan; Chiller, Tom; Ribeiro, Isabela; Koulla-Shiro, Sinata; Mghamba, Janneth; Ramadhani, Angela; Nyirenda, Rose; Aliyu, Sani H; Wilson, Douglas; Le, Thuy; Oladele, Rita; Lesikari, Sokoine; Muzoora, Conrad; Kalata, Newton; Temfack, Elvis; Mapoure, Yacouba; Sini, Victor; Chanda, Duncan; Shimwela, Meshack; Lakhi, Shabir; Ngoma, Jonathon; Gondwe-Chunda, Lilian; Perfect, Chase; Shroufi, Amir; Andrieux-Meyer, Isabelle; Chan, Adrienne; Schutz, Charlotte; Hosseinipour, Mina; Van der Horst, Charles; Klausner, Jeffrey D; Boulware, David R; Heyderman, Robert; Lalloo, David; Day, Jeremy; Jarvis, Joseph N; Rodrigues, Marcio; Jaffar, Shabbar; Denning, David; Migone, Chantal; Doherty, Megan; Lortholary, Olivier; Dromer, Françoise; Stack, Muirgen; Molloy, Síle F; Bicanic, Tihana; van Oosterhout, Joep; Mwaba, Peter; Kanyama, Cecilia; Kouanfack, Charles; Mfinanga, Sayoki; Govender, Nelesh; Harrison, Thomas S
    In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.