Acyclovir resistance

Catechins and proanthocyanidins have a documented antiviral activity. Catechins from an extract of Cocos nucifera husk fibre exhibited a strong inhibitory activity against acyclovir-resistant herpes simplex virus type 1 (HSV-l-ACVr) [62]. The use of 10 to 20ngml of ECG and EGCG has been reported to cause 50% inhibition of human immunodeficiency virus reverse transcriptase [89], while Kara and Nakayama [90] reported that a patented chewing gum containing tea catechins is claimed to prevent viral infections against influenza and to inhibit dissemination of this virus. 

Foscarnet, cidofovir, and trifuridine have been administered in acyclovir-resistant patients.30 These agents are usually reserved for use after other agents have failed because of their associated toxicities. 

Cidofovir 0.3%, 1%, and 3% topical agent used on a compassionate basis for acyclovir-resistant herpes lesions (3-7 days) Application site reactions, lesion recrudescence... 

Trifluridine 1% topical agent used for acyclovir-resistant herpes infections for 7-14 days Transient burning or stinging, palpebral edema, superficial punctuate, keratopathy, changes in intraocular pressure... 

Herpes simplex virus (HSV) /nfecf/ons Treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

Cidofovir is approved for the treatment and prophylaxis of CMV retinitis in AIDS patients. It has also been used in the treatment of acyclovir-resistant (viral thymidine kinase-dehcient) HSV infections, polyomavirus-associated progressive multifocal leukoencephalopathy, condylomata acuminata (anogenital warts), and mollus-cum contagiosum. 

Mutations in DNA polymerase or thymidine kinase may result in resistance. Acyclovir-resistant HSV strains that exhibit thymidine kinase deficiency are also resistant to famciclovir and penciciovir. 

Foscarnet is approved for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised individuals. A clinical study indicated that it is more effective than vidarabine. Foscarnet has also been used for the treatment of acyclovir-resistant VZV and nonretinitis forms of CMV infection, although its efficacy is not so well established. 

Unlabeled Uses Treatment of acyclovir-resistant herpes simplex virus, adenovirus, foscarnet-resistant CMV, ganciclovir-resistant CMV, varicella-zoster virus... 

Foscarnet1 Intravenous Acyclovir-resistant HSV and VZV infections 40 mg/kg q8h until healed... 

Acyclovir-resistant HSV infection Thin film covering lesion 5 times daily until healed... 

Trifluridine (trifluorothymidine) is a fluorinated pyrimidine nucleoside that inhibits viral DNA synthesis in HSV-1, HSV-2, CMV, vaccinia, and some adenoviruses. It is phosphorylated intracellularly by host cell enzymes, and then competes with thymidine triphosphate for incorporation by the viral DNA polymerase (Figure 49-3). Incorporation of trifluridine triphosphate into both viral and host DNA prevents its systemic use. Application of a 1% solution is effective in treating keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 or HSV-2. Cutaneous application of trifluridine solution, alone or in combination with interferon alfo, has been used successfully in the treatment of acyclovir-resistant HSV infections. 

In a recent investigation of phenolic compounds tested, using herpes simplex virus type 1 (HSV-1) infected Vero cells, caffeic acid has been reported to inhibit virus replication [91], In a related study [92], chlorogenic acid significantly inhibited acyclovir-resistant HSV-1 replication without any cytotoxicity. However, flavonoids have exhibited cytotoxicity at the same concentration [92],... 

Resistance to acyclovir can develop in HSV or VZV through alteration in either the viral thymidine kinase or the DNA polymerase. Infections that are clinically resistant to acyclovir have been reported in immunocompromised hosts. Most clinical isolates are resistant on the basis of deficient thymidine kinase activity and thus are cross-resistant to valacyclovir, famciclovir, and ganciclovir. Agents such as foscarnet, cidofovir, and trifluridine do not require activation by viral thymidine kinase and thus have preserved activity against the most prevalent acyclovir-resistant strains. 

Foscarnet Inhibition of viral DNA polymerase and reverse transcriptase at the pyrophosphate-binding site Cytomegalovirus, acyclovir-resistant herpes simplex, acyciovir-resistant variceila-zoster 6... 

Malvy D, TreRhaud M, Boues S, et al. A retrospective, case-control smdy of acyclovir resistance in herpes simplex virus. Clin Infect Dis 2005 41(3) 320-326. 

Shin YK, Cai G, Weinberg A, et al. Frequency of acyclovir-resistant herpes simplex virus in clinical specimens and laboratory isolates. J Chn Microbiol 2001 39(3) 913-917. 

Foscamet is used for the treatment of cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant herpes simplex virus (HSV) infections. It may also be beneficial in other types of CMV or HSV infections (Wagstaff and Bryson, 1994). 

Erlich KS, Mills J, Chatis P, Mertz GJ, Busch DF, Follansbee SE, Grant RM, Crumpacker CS. Acyclovir-resistant Herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989 320(5) 293-6. 

Sacks SL, Wanklin RJ, Reece DE, Hicks KA, Tyler KL, Coen DM. Progressive esophagitis from acyclovir-resistant Herpes simplex. Clinical roles for DNA polymerase mutants and viral heterogeneity Ann Intern Med 1989 lll(ll) 893-9. 

Cidofovir is an acyclic nucleotide analogue of the monophosphate of cytosine. When phosphoiylated by host cellular enzymes, the active compound cidofovir diphosphate has broad activity against the herpes viruses, including CMV, HSV 1 and 2, VZV, Epstein-Barr virus, and the BK polyomavirus. Cidofovir has primarily been used in the treatment of CMV retinitis in patients who have failed treatment with ganciclovir or foscarnet and in acyclovir-resistant herpes simplex infections. More recently, there is also a growing experience with the use of this medication in kidney transplant patients who have BK virus-associated nephropathy [31], although this interest has been dampened by significant toxicity and only modest clinical activity [32]... 

Acyclovir is the drug of choice for herpes simplex encephalitis. In patients with normal renal function, acyclovir is usually administered as 10 mg/kg intravenously every 8 hours for 2 to 3 weeks. Herpes virus resistance to acyclovir has been reported with increasing incidence, particularly from immunocompromised patients with prior or chronic exposures to acyclovir. The alternative treatment for acyclovir-resistant herpes simplex virus is foscarnet. The major toxicity of foscarnet is renal impairment, and doses must be individualized for renal function. The dose for patients with normal renal function is 40 mg/kg infused over 1 hour every 8 to 12 hours for 2 to 3 weeks. Ensuring adequate hydration is imperative. In addition, patients receiving foscarnet should be monitored for seizures related to alterations in plasma electrolyte levels. 

Acyclovir-resistant HSV has been reported occasionally in HSCT patients receiving acyclovir prophylaxis. Foscarnet is the drug of choice for treatment of acyclovir-resistant HSV. Foscarnet, however, has not been well studied for HSV prophylaxis. ... 

Darville JM, Ley BE, Roome AP, et al. Acyclovir-resistant herpes simplex virus infections in a bone marrow transplant transplant population. Bone Marrow Tranplant 1998 22 587-589. 

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