Combination therapy for multidrug‐resistant cytomegalovirus disease

Stuehler, Claudia; Stüssi, Georg; Nowakowska, Justyna; Schibli, Adrian; Battegay, Manuel; Dirks, Jan; Passweg, Jakob; Heim, Dominik; Rovó, Alicia; Kalberer, Christian P.; Bucher, Christoph; Weisser, Maja; Dumoulin, Alexis; Hirsch, Hans H.; Khanna, Nina

doi:10.1111/tid.12435

Cited by 20 publications

(10 citation statements)

References 17 publications

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“…A third case report of a patient with multidrug-resistant HCMV infection is difficult to interpret due to the complicated series of treatments after two hematopoietic stem cell transplantations and consequent acute graft-versus-host disease episodes. In this patient, AS given in association with maribavir was withdrawn two weeks after initiation because of orthostatic hypotension [47]. Wolf and colleagues described six cases of stem cell transplant recipients who received pre-emptive AS treatment for HCMV infection.…”

Section: Artesunate and Hcmvmentioning

confidence: 99%

“…Herpesviridae HCMV Artesunate [12,13,[46][47][48] Artesunate-amodiaquine [49] Arthemeter-lumefantrine [64] HHV6 Artesunate [52] Polyomaviridae JCPyV Artesunate [54,55] Mefloquine [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][122][123][124][125][126] Mefloquine and mirtazapine [86,87,127,128] Mefloquine, mirtazapine and a third drug [118,119] Mefloquine and risperidone [75] Mefloquine, risperidone and cytarabine [120] Mefloquine and cidofovir [121] Mefloquine and PML standard of care [129] Filoviridae EBOV Artesunate-amodiaquine [58,60] Nevertheless, some drugs have already been used in several clinical trials, as summarized in Table 1. Most of them regard the use of antimalarial drugs against HIV infection, but some of them failed, and...…”

Section: Virus Family Virus Species Drug Referencesmentioning

confidence: 99%

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The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

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Section: Artesunate and Hcmvmentioning

confidence: 99%

Section: Virus Family Virus Species Drug Referencesmentioning

confidence: 99%

The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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“…This study also found longer persistence of investigational cell lines with CD4 cells, as well as expansion of CMV-specific CD8 T cells through adoptive transfer of CD4 lymphocytes. In another case report, a 50 year old man with follicular lymphoma (CMV R+/D-) who received a matched unrelated allogenic HSCT complicated by GVHD incurred UL97 mutations on valganciclovir treatment during the fourth recurrence of CMV [22]. Cidofovir, foscarnet and leflunomide were administered, which failed to control viremia.…”

Section: Cmv-specific T-lymphocytesmentioning

confidence: 99%

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

Santos

Rhee

Czapka

et al. 2020

JCM

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Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key "safety net" in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible "safety net" for these immunocompromised hosts.

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“…Interestingly, in a case report of a patient with a multidrug-resistant CMV infection, adoptive transfer of CMV-specific T cells was preceded with retransplantation from a CMV-seropositive donor. 134 However, major adverse events, such as graft failure and transplantation-associated microangiopathy, have been reported in a very small number of patients undergoing donor-derived CTL infusions. 132 …”

Section: Cmv-specific Ctlsmentioning

confidence: 99%

How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

Chaer

Shah

Chemaly

2016

Blood

154

137

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Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV.

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Combination therapy for multidrug‐resistant cytomegalovirus disease

Cited by 20 publications

References 17 publications

The Use of Antimalarial Drugs against Viral Infection

The Use of Antimalarial Drugs against Viral Infection

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

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