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Mechanisms of Nonretroviral Resistance

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Overcoming Antimicrobial Resistance of the Skin

Part of the book series: Updates in Clinical Dermatology ((UCD))

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Abstract

The development of the nucleoside analogues acyclovir and penciclovir was a milestone in antiviral therapy. Their success in treating herpes simplex virus (HSV) and varicella zoster virus (VZV) demonstrated the potential of drug therapy in the management of viral infections. The subsequent development of the nucleoside analogue ganciclovir, and its prodrug valganciclovir, provided effective antiviral therapy against human cytomegalovirus (CMV) infections. Newer agents such as the pyrophosphate analogue foscarnet and nucleotide analogue cidofovir, that bypassed the need for viral protein kinase phosphorylation for activation, offered an even wider antiviral spectrum of activity. Since the introduction of these groundbreaking antiviral medications, drug-resistant isolates of HSV and VZV have been reported, primarily among severely immunocompromised patients such as transplant recipients and patients with human immunodeficiency virus (HIV). Other antiviral agents, developed to treat a variety of additional viruses, are now in widespread use, but their success has also been challenged by the emergence of drug resistance. In this chapter, we review antiviral therapies for HSV and VZV, mechanisms of drug resistance, and strategies for managing skin infections with resistant strains. We also briefly discuss the influenza virus and its mechanism of resistance to drug therapy.

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Abbreviations

AIDS:

Acquired immunodeficiency syndrome

CMV:

Cytomegalovirus

CRISPR:

Clustered regularly interspaced short palindromic repeats

dCTP:

Deoxycytidine triphosphate

dGTP:

Deoxyguanosine triphosphate

dsDNA:

Double-stranded DNA

EBV:

Epstein-Barr Virus

FDA:

Food and Drug Administration

GvHD:

Graft-versus-host disease

HA:

Hemagglutinin

HCT:

Hematopoietic cell transplantation

HHV:

Human herpes virus

HIV:

Human immunodeficiency virus

HSCT:

Hematopoietic stem cell transplantation

HSV:

Herpes simplex virus

IV:

Intravenous

NA:

Neuraminidase

N-MCT:

N-methanocarbathymidine

TFT:

Trifluorothymidine

TK:

Tyrosine kinase

VZV:

Varicella zoster virus

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Authors and Affiliations

  1. MD Anderson Cancer Center, Department of Dermatology, Houston, TX, USA

    Saira George

  2. Department of Dermatology, University of Nebraska Medical Center, Omaha, TX, USA

    Ritu Swali

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  1. Saira George
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  2. Ritu Swali
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Correspondence to Saira George .

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Editors and Affiliations

  1. Department of Dermatology, University of Texas Health Science Center, Houston, TX, USA

    Stephen K. Tyring

  2. Arlington Center for Dermatology, Arlington, TX, USA

    Stephen Andrew Moore

  3. Division of Dermatology, Baylor University Medical Center, Dallas, TX, USA

    Angela Yen Moore

  4. Immunology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Omar Lupi

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George, S., Swali, R. (2021). Mechanisms of Nonretroviral Resistance. In: Tyring, S.K., Moore, S.A., Moore, A.Y., Lupi, O. (eds) Overcoming Antimicrobial Resistance of the Skin. Updates in Clinical Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-030-68321-4_4

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