Successful Treatment of Life-threatening Candida Peritonitis in a Child With Abdominal Non-Hodgkin Lymphoma Using Efungumab and Amphotericin B Colloid Dispersion

Křenová, Zdenka; Pavelka, Zdeněk; Lokaj, Petr; Skotáková, Jarmila; Kocmanova, Ivana; Teyschl, O; Křen, Leoš; Múdrý, Peter; Štěrba, Jaroslav

doi:10.1097/mph.0b013e3181cb49a8

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…Efungumab binds to the middle region of HSP 90, preventing communication between the terminal regions, hence preventing necessary conformational changes . In addition to promising data from preclinical investigations and patient case reports with efungumab, a randomised, double‐blinded trial in patients with culture‐confirmed invasive candidiasis, compared L‐AmB or ABLC alone with L‐AmB or ABLC in combination with efungumab . The primary outcome, the composite of complete clinical response and mycological clearance on day 10, favoured combination therapy (84 vs. 48%, P < 0.001).…”

Section: Investigational Antifungal Agents and Vaccines No Longer In mentioning

confidence: 99%

“…29 In addition to promising data from preclinical investigations and patient case reports with efungumab, a randomised, double-blinded trial in patients with culture-confirmed invasive candidiasis, compared L-AmB or ABLC alone with L-AmB or ABLC in combination with efungumab. [32][33][34][105][106][107][108] The primary outcome, the composite of complete clinical response and mycological clearance on day 10, favoured combination therapy (84 vs. 48%, P < 0.001). The rate of mycological clearance was more than twice as fast with efungumab and mycological resolution was achieved in 89% of the combination therapy group compared with 54% in the amphotericin group at day 10 (P < 0.001).…”

Section: Efungumabmentioning

confidence: 99%

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Emerging drugs and vaccines for Candidemia

Moriyama

Gordon

McCarthy

et al. 2014

Mycoses

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Summary Candidemia and other forms of invasive candidiasis are important causes of morbidity and mortality. The evolving challenge of antimicrobial resistance among fungal pathogens continues to highlight the need for potent, new antifungal agents. MEDLINE, EMBASE, Scopus, and Web of Science searches (up to January 2014) of the English-language literature were performed with the keywords “Candida” or “Candidemia” or “Candidiasis” and terms describing investigational drugs with activity against Candida spp. Conference abstracts and the bibliographies of pertinent articles were also reviewed for relevant reports. ClinicalTrials.gov was searched for relevant clinical trials. Currently available antifungal agents for the treatment of candidemia are summarized. Investigational antifungal agents with potential activity against Candida bloodstream infections and other forms of invasive candidiasis and vaccines for prevention of Candida infections are also reviewed as are selected antifungal agents no longer in development. Antifungal agents currently in clinical trials include isavuconazole, albaconazole, SCY-078, VT-1161, and T-2307. Further data are needed to determine the role of these compounds in the treatment of candidemia and other forms of invasive candidiasis. The progressive reduction in antimicrobial drug development may result in a decline in antifungal drug discovery. Still there remains a critical need for new antifungal agents to treat and prevent invasive candidiasis and other life-threatening mycoses.

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Section: Investigational Antifungal Agents and Vaccines No Longer In mentioning

confidence: 99%

Section: Efungumabmentioning

confidence: 99%

Emerging drugs and vaccines for Candidemia

Moriyama

Gordon

McCarthy

et al. 2014

Mycoses

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“…In another study, a human recombinant MAb to heat shock protein 90 was used in the treatment of patients with invasive candidiasis (Pachl et al, 2006). Recently, Krenova et al (2010) reported the successful treatment of life-threatening Candida peritonitis in a child with abdominal non-Hodgkin lymphoma using a MAb against heat shock protein 90 in association with amphotericin B.…”

Section: Therapeutic Monoclonal Antibodies and Fungal Infectionmentioning

confidence: 99%

Therapeutic monoclonal antibody for sporotrichosis

Almeida¹

2012

Front. Microbio.

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Sporotrichosis is a chronic subcutaneous mycosis that affects both humans and animals worldwide. This subcutaneous mycosis had been attributed to a single etiological agent, Sporothrix schenckii. S. schenckii exhibits considerable genetic variability, and recently, it was suggested that this taxon consists of a complex of species. Sporotrichosis is caused by traumatic inoculation of the fungus, which is a ubiquitous environmental saprophyte that can be isolated from soil and plant debris. The infection is limited to cutaneous forms, but recently, more severe clinical forms of this mycosis have been described, especially among immunocompromised individuals. The immunological mechanisms involved in the prevention and control of sporotrichosis are not well understood. Some studies suggest that cell-mediated immunity plays an important role in protecting the host against S. schenckii. In contrast, the role of the humoral immune response in protection against this fungus has not been studied in detail. In a previous study, we showed that antigens secreted by S. schenckii induced a specific humoral response in infected animals, primarily against a 70-kDa molecule, indicating a possible role of specific antibodies against this molecule in infection control. In another study by our group, we produced a mAb against a 70-kDa glycoprotein of S. schenckii to better understand the effect of the passive immunization of mice infected with S. schenckii. The results showed a significant reduction in the number of CFUs in various mice organs when the mAb was injected before or during S. schenckii infection. Similar results were observed when T-cell-deficient mice were used. The drugs of choice in the treatment of sporotrichosis require long periods, and relapses are frequently observed, primarily in immunocompromised patients. The strong protection induced by the mAb against a 70-kDa glycoprotein makes it a strong candidate as a therapeutic vaccine against sporotrichosis.

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“…These very promising results have attracted the attention of the scientific community, and some case reports have been published on the use of antifungal agents in combination with Mycograb for treatment of severe, also pediatric, cases of disseminated C. albicans infections [47–49]. …”

Section: Introductionmentioning

confidence: 99%

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Bugli

Cacaci

Martini

et al. 2013

Clinical and Developmental Immunology

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Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum of Candida species. Furthermore, recent studies have established an important role for Hsp90 in mediating Candida resistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model.

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Successful Treatment of Life-threatening Candida Peritonitis in a Child With Abdominal Non-Hodgkin Lymphoma Using Efungumab and Amphotericin B Colloid Dispersion

Cited by 11 publications

References 10 publications

Emerging drugs and vaccines for Candidemia

Emerging drugs and vaccines for Candidemia

Therapeutic monoclonal antibody for sporotrichosis

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

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