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PubMed1998

Treatment of acyclovir-resistant herpetic ulceration with topical foscarnet and antiviral sensitivity analysis.

BACKGROUND: Herpes simplex virus (HSV) can produce persistent mucocutaneous disease in patients with the acquired immunodeficiency syndrome (AIDS). In this case report, we evaluate the efficacy, safety and viral resistance after topical foscarnet in severe genital ulceration due to acyclovir-resistant HSV-2. CASE REPORT: A 45-year-old African woman was known for an HIV infection with severe immunosuppression (CD4 <100/mm3). She had received a long-term prophylaxis with acyclovir (400 mg b.i.d.) for a recurrent genital herpes. Few weeks after stopping this prophylaxis, she developed large genital ulcerations progressing despite valacyclovir treatment (1,000 mg t.i.d.). Cultures were positive for HSV-2, resistance to acyclovir was shown by the plaque reduction assay and topical foscarnet was tried. Treatment consisted of a 20-min application of topical foscarnet 2.4% twice a day. Dramatic improvement was observed with rapid antalgia, and cicatrization of the genital ulcerations was observed after 50 days. HSV could not be detected on the mucosal surface. Initially, HSV-2 was resistant to acyclovir but sensitive to foscarnet. After 1 month of topical treatment, HSV-2 became sensitive to acyclovir and was still sensitive to foscarnet. Finally, after 6 weeks of treatment, no virus could be detected by culture. CONCLUSION: Topical foscarnet (2.4%) is a convenient treatment for chronic genital herpes. Resistance to acyclovir disappears few weeks after stopping this drug and sensitivity to foscarnet persists during the 50 days of treatment.

Acyclovir↗
PubMed2006

Single-dose famciclovir for the treatment of herpes labialis.

BACKGROUND: Approximately 20% to 40% of the population experience recurrent herpes labialis caused by herpes simplex virus type 1 (HSV-1). Since there is no cure, patients typically use antiviral therapy to treat outbreaks as they occur. A large proportion of patients self-administer topical antiviral therapies at the onset of symptoms, but lack of efficacy, frequent dosing, and inconvenient long-term treatment regimens have made the use of oral antiviral therapies more common. Valacyclovir is currently the only oral antiviral approved for the treatment of herpes labialis in immunocompetent individuals. The pharmacokinetic/pharmacodynamic profile of famciclovir suggests that it could be utilized for episodic treatment for immunocompetent individuals as well. FINDINGS: A recent study comparing single-dose vs. single-day bid famciclovir and placebo in the treatment of herpes labialis demonstrated single-dose famciclovir to be as efficacious as single-day bid dosing in time to healing of lesions and more efficacious than single-day bid famciclovir in time to resolution of pain and tenderness. Both were statistically superior to placebo. When results of this study were compared with recently published results of other frequently prescribed treatments, single-dose famciclovir appeared to produce similar or better improvements in healing time and duration of pain. CONCLUSIONS: Single-dose famciclovir appears to be an effective, convenient therapy for recurrent herpes labialis. The convenience of single-dose therapy may lead to better overall management of the condition.

2-Aminopurine↗
PubMed2001

Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice.

BACKGROUND: Acyclovir (ACV) resistant herpes simplex virus (HSV) isolates can be readily selected in animal infection models receiving suboptimal ACV treatment, however no comparative studies of the emergence of resistance following suboptimal treatment with valacyclovir (VCV) or famciclovir (FCV), the prodrugs of acyclovir and penciclovir, respectively, have been reported. METHODS: Mice (n = 30) were infected with HSV type 1 or 2 in the ear pinnae and administered oral prodrugs at one fifth a dose previously shown to be effective. To select and amplify drug-resistant HSV, a total of seven consecutive in vivo passages with suboptimal treatment were performed for each virus sample and progeny virus from each passage was characterized by the plaque reduction (PRA) and plating efficiency assays (PEA). RESULTS: No drug-resistant HSV-2 and only a single drug-resistant HSV-1 variant were identified. Virus recovered from the first three sequential passages of this HSV-1 sample was susceptible by PRA, although the proportion of resistant virus recovered gradually increased upon passage. The resistant HSV-1 phenotype was confirmed by PRA after four sequential passages in mice. Unexpectedly, this in vivo-selected drug-resistant HSV-1 failed to yield an infection completely refractory to treatment in subsequent passages. CONCLUSIONS: Sub-optimal therapy of immunocompetent mice with either VCV or FCV did not readily select for HSV-mutants resistant to either ACV or PCV, suggesting that selection of resistance with either prodrug remains difficult using this system. Futhermore, this study suggests that the PEA may represent a useful adjunct to the PRA for monitoring alterations in the proportion of drug-resistant virus even when no change in IC50 is apparent.

Acyclovir↗
PubMed2005

Herpes zoster: medical and nursing management.

Herpes zoster, the latent descendent of the varicella zoster virus, commonly is seen in clinical practice. Healthcare providers must recognize and treat the virus to decrease the incidence of postherpetic neuralgic pain syndrome. Treatment with an antiviral medication regimen should be initiated rapidly for patients who have had lesions for up to 72 hours. Acyclovir has been the treatment of choice for herpes zoster in the past, but newer drugs, such as valacyclovir, a prodrug of acyclovir, and famciclovir, are as effective for treating the virus and have more convenient dosing regimens and decreased incidence of postherpetic neuralgia.

Antiviral Agents↗
PubMed2005

Clinical update: a nonhealing fractured mandible.

Bisphosphonates have shown significant clinical benefit in reducing skeletal fractures in patients with multiple myeloma or bone: penicillin VK 500 mg or amoxicillin 500 mg; both 4 times daily (QID) initially and twice daily (BID) for maintenance, If penicillin allergic: 1. Clindamycin 150 to 300 mg QID. 2. Vibramycin 100 mg once daily (QD). 3. Erythromycin ethylsuccinate 400 mg 3 times daily (TID). 4. Antifungals when required: 5. Nystatin oral suspension 5 to 15 mL QID or 100,000 IU/mL. 6. Mycelex troches (clotrimazole 10 mg) x 5/day. 7. Fluconazole 200 mg initially, then 100 mg QD. 8. Other potential systemic antifungals include itraconazole or ketoconazole. 9. Antivirals, if required: 10. Acyclovir 400 mg BID. 11. Valacyclovir hydrochloride 500 mg to 2g BID.

Aged↗
PubMed1999

Antiinfectives update: focus on treatment and prevention of viral and associated infections.

OBJECTIVE: To review the clinically significant antiinfectives approved by the Food and Drug Administration (FDA) since 1996, with an emphasis on agents used for treatment, prevention, or suppression of infection in immunocompromised individuals. DATA SOURCES: A MEDLINE search covering November 1994 to March 1998 was conducted to identify all antiinfectives (new medications and old medications with new indications) and the pertinent literature for review. The search was updated in August 1998 and supplemented with an FDA listing of approved drugs to enhance completeness. STUDY SELECTION: Clinically relevant studies were selected to highlight specific points about each medication. Preclinical publications were used when sufficient information was not available from clinical trials and this information was needed for clinical practice. CONCLUSIONS: Several new and promising antiretroviral agents (stavudine, lamivudine, saquinavir soft-gel capsules, nelfinavir, efavirenz) have been approved, which may allow more options to control HIV viremia. New options for treatment, prevention, and suppression of infections in immunocompromised individuals include azithromycin, cidofovir, famciclovir, valacyclovir, and itraconazole suspension. Liposomal-based amphotericin products may be associated with less toxicity than conventional amphotericin B; however, superior efficacy has not been proven.

AIDS-Related Opportunistic Infections↗
PubMed2006

Bell's palsy: a review of treatment using antiviral agents.

OBJECTIVE: To review the evidence evaluating the efficacy and safety of antiviral agents to reduce morbidity associated with Bell's palsy. DATA SOURCES: MEDLINE, EMBASE, and PubMed were searched (all up to April 2006) for English-language, prospective, randomized, controlled clinical trials that evaluated the use of antiviral agents in Bell's palsy. Search terms included Bell's palsy, acyclovir, valacyclovir, famciclovir, and randomized controlled trials. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, controlled trials that evaluated efficacy and safety endpoints of antiviral agents in the treatment of Bell's palsy were included. Primary efficacy outcomes included facial paralysis recovery profile, facial paralysis recovery index, and the House-Brackmann facial nerve grading scale. Safety outcomes were also identified by each trial. DATA SYNTHESIS: Two prospective, randomized clinical trials were included in this review, both involving the use of acyclovir for treatment of Bell's palsy. Acyclovir monotherapy was shown to be inferior to prednisone monotherapy; however, the combination of acyclovir and prednisone was found to be superior to prednisone alone. There are limited data describing the safety of acyclovir in Bell's palsy. CONCLUSIONS: The use of acyclovir in the treatment of Bell's palsy remains controversial. Additional, adequately powered, randomized, placebo-controlled trials are needed to definitively support its use. For the time being, the evidence reviewed in this article would favor the combination of acyclovir and prednisone if commenced within the first 72 hours of symptom onset.

Antiviral Agents↗
PubMed1998

Herpes simplex virus ocular infections.

Herpes simplex ocular infection is the leading cause of infectious corneal blindness in the United States and presents a frequent challenge to ophthalmologists. The epithelial infections are usually readily controlled with trifluridine or vidarabine, but clinical resistance may be emerging, and host toxicity remains a problem in chronic cases. Acyclovir offers an alternative, and the oral form appears to be an effective antiviral prophylaxis in stromal keratitis and post-penetrating keratoplasty, as well as a treatment for epithelial infections in patients where administration of topical therapy is difficult. Valacyclovir and perhaps famciclovir may provide similar efficacy as acyclovir at reduced doses. In addition, better control of inflammation with potent steroids used at the appropriate phases of HSV infection can minimize scarring and vascularization. Newer agents attempt to provide more specific therapy for both the infectious and inflammatory components of HSV ocular infections.

Journal Article↗
PubMed2006

Treatment of acute retinal necrosis syndrome.

Acute retinal necrosis is a distinct ocular viral syndrome with a potentially devastating visual outcome, traditionally treated with intravenous acyclovir followed by oral acyclovir. The goals of therapy include accelerating the resolution of the infection in the affected eye and prevention of contralateral involvement. Recently, several small case series and case reports have described the use of newer oral antivirals such as valacyclovir, famciclovir or valganciclovir, alone or in combination with adjunctive intravitreal foscarnet or ganciclovir injections for the treatment of acute retinal necrosis (1-4). The purpose of this article is to describe various therapies available to practitioners who may treat patients with acute retinal necrosis.

Animals↗
PubMed2005

Agents and strategies in development for improved management of herpes simplex virus infection and disease.

The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity since ancient times, causing mucocutaneous infection such as herpes labialis and herpes genitalis. Disease symptoms often interfere with every-day activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immuno-compromised patient population. After infection the virus persists for life in neurons of the host in a latent form, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. So far, vaccines, ILs, IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or non-specific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. The recently discovered inhibitors of the HSV helicase-primase are the most potent development candidates today. These antiviral agents act by a novel mechanism of action and display low resistance rates in vitro and superior efficacy in animal models. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.

Antiviral Agents↗
PubMed2000

Several options for antiviral treatment trials in multiple sclerosis--but which targets should be selected?

Involvement of viruses in the pathogenesis of multiple sclerosis (MS) is a long-lived hypothesis, which is has not yet been proven nor refuted. This is partly due to difficulties in the evaluation of diagnostic findings on persistent infections by common viruses such as herpesviruses and endogenous retroviruses. Progress in antiviral treatment of central nervous system (CNS) herpesvirus infections has stimulated controlled trials of long-term therapy with acyclovir and valacyclovir in MS, but conclusive results are not yet available. Other treatment possibilities might include anti-retroviral therapy, as well as attempts to counteract the effects of viruses in triggering attacks of MS following upper respiratory tract infections. Before such trials are initiated, however, further diagnostic evidence of the involvement of target viruses seems warranted.

Antiviral Agents↗
PubMed2003

Current treatment options to prevent perinatal transmission of herpes simplex virus.

Neonatal herpes is a potentially devastating consequence of perinatal transmission of the herpes simplex virus (HSV), with significant morbidity and mortality. Treatment options are available, but must begin early in disease with manifestations that are often protean. Thus, preventive measures need to be optimised. Antiviral suppression in late pregnancy of women with a history of recurrent genital herpes will decrease symptomatic recurrence at delivery and appears to reduce caesarian section rates. However, primary HSV Type 2 and primary HSV Type 1 episodes have the highest neonatal transmission rates and thus, effective prevention may require the identification and suppression of the discordant partner. Significant experience has been gained with the use of acyclovir in pregnancy and it is recommended for both episodic and suppressive therapy in pregnant women. Its use has been demonstrated to be cost-effective in suppressive therapy, although issues regarding compliance and the potential for neonatal neutropenia need to be addressed. The more conveniently dosed prodrugs valacyclovir and famciclovir are being evaluated for use in pregnancy.

Antiviral Agents↗
PubMed2005

Main adult herpes virus infections of the CNS.

Herpes viruses are widely involved in human infectious diseases, and some are life threatening, such as CNS infections. These manifestations vary according to the type of virus involved and the immune status of the patient. This article will review the clinical manifestations (encephalitis, myelitis, meningitis and postinfectious encephalomyelitis), the diagnostic strategies and the presently used drugs (acyclovir, valacyclovir, ganciclovir, valgancyclovir, foscarnet and cidofovir). The review will also discuss drugs that are currently in the pipeline and that could be used in the future.

Antiviral Agents↗
PubMed2004

Viral prophylaxis in organ transplant patients.

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu season'.

Antiviral Agents↗
PubMed2004

Peptide transporters: structure, function, regulation and application for drug delivery.

Proton-coupled peptide transporters, localized at brush-border membranes of intestinal and renal epithelial cells, play important roles in protein absorption and the conservation of peptide-bound amino nitrogen. These transporters also have significant pharmacological and pharmacokinetic relevance to the transport of various peptide-like drugs such as beta-lactam antibiotics. The identification and molecular characterization of H(+)/peptide cotransporters (PEPT1 and PEPT2) have facilitated the clarification of many aspects of these transporters such as the structure/function relationship and regulation. Recent findings that intestinal PEPT1 can transport l-valine ester prodrugs such as valacyclovir provided a major step forward toward the development of novel drug delivery systems. It has been demonstrated that peptide transporters, which have a similar substrate specificity to PEPT1 and PEPT2, but possess other distinct functional properties, are localized at basolateral membranes of intestinal and renal epithelial cells. This review highlights the recent advances in our knowledge of the cellular and molecular nature of PEPT1, PEPT2 and the basolateral peptide transporters.

Animals↗
PubMed1999

Recent advances in varicella-zoster virus infection.

Varicella-zoster virus has developed a complex strategy that allows it to remain latent in the body and avoid destruction by the immune system. Although varicella and zoster have been recognized since antiquity, several new clinical syndromes--including chronic chickenpox with persistent verrucous lesions and disseminated varicella without skin lesions--have been noted in patients with AIDS. Acyclovir has been the mainstay for treating severe varicella-zoster virus infections; however, newer antiviral agents, including valacyclovir and famciclovir, have expanded therapeutic options for treating adults with herpes zoster. The recently licensed live attenuated vaccine for varicella-zoster virus is effective in preventing chickenpox, and the vaccine's ability to stimulate immunity in seropositive adults suggests a promising strategy with which to modify the course of herpes zoster.

Adult↗
PubMed2000

[Clinical manifestations of the subfamily alpha-herpesvirinae in childhood].

Herpes simplex virus(HSV) and varicella-zoster virus(VZV) belonging to the subfamily of alpha-herpesvirinae have the capacity to establish latent infection in neural tissues and to reactivate from these sites. HSV infection is characterized by a vesicular eruption, fever, and other constitutional symptoms but frequently inapparent both in primary and recurrent infections. However, the infection produces a wide spectrum of illness ranging from the trivial fever blisters to the most severe fatal sporadic encephalitis and neonatal infection. In contrast, VZV develops varicella, a common contagious disease of childhood during primary infection and zoster by reactivation of latent virus acquired during varicella. In normal children, the systemic symptoms of both diseases are mild, whereas serious complications are often observed in children with deficiencies in cell-mediated immunity. Acyclovir has been the drug of choice for treatment of severe infection with HSV and VZV for approximately 2 decades. Now, two new agents, valacyclovir and famciclovir will supplant acyclovir for certain indications.

Alphaherpesvirinae↗
PubMed2000

Management of herpes zoster (shingles) and postherpetic neuralgia.

Herpes zoster (commonly referred to as "shingles") and postherpetic neuralgia result from reactivation of the varicella-zoster virus acquired during the primary varicella infection, or chickenpox. Whereas varicella is generally a disease of childhood, herpes zoster and post-herpetic neuralgia become more common with increasing age. Factors that decrease immune function, such as human immunodeficiency virus infection, chemotherapy, malignancies and chronic corticosteroid use, may also increase the risk of developing herpes zoster. Reactivation of latent varicella-zoster virus from dorsal root ganglia is responsible for the classic dermatomal rash and pain that occur with herpes zoster. Burning pain typically precedes the rash by several days and can persist for several months after the rash resolves. With postherpetic neuralgia, a complication of herpes zoster, pain may persist well after resolution of the rash and can be highly debilitating. Herpes zoster is usually treated with orally administered acyclovir. Other antiviral medications include famciclovir and valacyclovir. The antiviral medications are most effective when started within 72 hours after the onset of the rash. The addition of an orally administered corticosteroid can provide modest benefits in reducing the pain of herpes zoster and the incidence of postherpetic neuralgia. Ocular involvement in herpes zoster can lead to rare but serious complications and generally merits referral to an ophthalmologist. Patients with postherpetic neuralgia may require narcotics for adequate pain control. Tricyclic antidepressants or anticonvulsants, often given in low dosages, may help to control neuropathic pain. Capsaicin, lidocaine patches and nerve blocks can also be used in selected patients.

Acyclovir↗