acyclovir and Skin-Diseases--Infectious

Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting > or = 2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to compl

Topics: 2-Aminopurine; Acetamides; Acyclovir; Aged; Anti-Bacterial Agents; Antidepressive Agents, Tricyclic; Antiviral Agents; Famciclovir; Herpes Zoster; Humans; Itraconazole; Linezolid; Onychomycosis; Oxazolidinones; Skin Diseases, Infectious; Virginiamycin

A case of cutaneous herpes relapse with meningitis is reported in a 1.5 month-old infant treated during the first three weeks of life with acyclovir (ACV) for a neonatal herpes infection. Such a relapse has previously been described in older children as well as in adults. In this case report, there was immunological response to herpes virus infection, 2.5 months after the onset of the infection. The relapse is discussed taking into account the mechanism of action of ACV, the age of the patient and the immunological response profile. Because of the high risk of neurological involvement, we suggest that the relapse should be treated with ACV for a period of time longer than actually recommended.

Topics: Acyclovir; Administration, Oral; Herpes Simplex; Humans; Infant, Newborn; Injections, Intravenous; Male; Recurrence; Skin Diseases, Infectious

The introduction of new protocols of immune suppression and especially the use of cyclosporine have led to a marked reduction of infective pathology in children receiving transplants. Nevertheless, infections still represent a major factor of morbidity and mortality in these patients. The above study lists the main viral infections, according to apparatus involved, that may arise, also with reference to the time elapsed since transplantation. The most up-to-date diagnostic possibilities for each infection are reviewed together with some indications on therapy which may subsequently be examined in greater detail.

Topics: Acyclovir; Age Factors; Child; Child, Preschool; Gastrointestinal Diseases; Heart Transplantation; Humans; Immunoglobulins; Immunosuppressive Agents; Infant; Infant, Newborn; Kidney Transplantation; Lymphoproliferative Disorders; Pneumonia, Viral; Skin Diseases, Infectious; Urinary Tract Infections; Virus Diseases

Chronic zoster represents an infrequent presentation of varicella zoster virus infection. It is observed with increased frequency in patients infected with human immunodeficiency virus, especially when their lymphocyte counts are depressed. We report a child infected with human immunodeficiency virus who showed a long-standing cutaneous zoster lesion and was treated for a prolonged period of time with acyclovir. The occurrence of resistance to acyclovir by varicella zoster virus was suspected based on the clinical picture. The clinical and laboratory features of this case and a review of the literature are presented.

Topics: Acyclovir; Child; Chronic Disease; Herpes Zoster; HIV Infections; Humans; Male; Skin; Skin Diseases, Infectious

Affecting millions of Americans each year, herpes simplex virus infections are among the most common human viral infections. Many clinical forms exist, depending on the site of infection and the patient's age and immune status. Clinical evaluation and laboratory studies help establish the diagnosis. Acyclovir is the drug most often used to treat herpes simplex virus infections, although newer agents, such as phosphonoformate trisodium, may be required for acyclovir-resistant infections.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Diagnosis, Differential; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Idoxuridine; Infusions, Intravenous; Phosphonoacetic Acid; Recurrence; Skin Diseases, Infectious; Trifluridine; Vidarabine

Herpes simplex and varicella-zoster infections of the skin are commonly seen in primary care practice. For the patient to be managed most effectively, clinical diagnoses must be accurately made and supported by laboratory confirmation using the Tzanck smear and/or viral culture. Topical therapy and systemic acyclovir can be of help to most patients with these infections.

Topics: Acyclovir; Herpes Simplex; Herpes Zoster; Humans; Recurrence; Skin Diseases, Infectious

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Herpesviridae Infections; Humans; Recurrence; Skin Diseases, Infectious

Topics: Acyclovir; Chickenpox; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Infant, Newborn; Interferons; Papillomaviridae; Skin Diseases, Infectious; Tumor Virus Infections

Intravenous acyclovir had a significant effect on the resolution of the skin rash in patients with acute zoster, but the 5-day course of therapy was not, in itself, sufficient to treat coexisting ocular involvement. In an open study, topical acyclovir was found to control herpes zoster kerato-uveitis, without recurrences and in a shorter time than if steroids alone were used. The use of steroids in combination with acyclovir led to prolonged treatment and high recurrence rates. A comparative trial of topical acyclovir versus steroids in the treatment of acute herpes zoster kerato-uveitis showed significant differences in favour of acyclovir in terms of the time to resolution of corneal epithelial disease, total treatment duration and the numbers of patients having a recurrence of infection. The reductions in treatment duration and recurrence rate would be expected to result in a reduced incidence of ocular damage and visual loss in acyclovir treated patients.

Topics: Acyclovir; Administration, Topical; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Recurrence; Skin Diseases, Infectious; Steroids

Host defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections.. Two controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q(10), RRR-α-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNα/γ) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions.. In both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups.. Results document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections.

Topics: Acyclovir; Administration, Oral; Adult; alpha-Tocopherol; Alphapapillomavirus; Antioxidants; Antiviral Agents; Chronic Disease; Cryotherapy; Dietary Supplements; DNA Virus Infections; DNA, Viral; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Herpes Genitalis; Herpes Zoster; Host-Pathogen Interactions; Humans; Male; Methionine; Middle Aged; Reactive Nitrogen Species; Reactive Oxygen Species; Recurrence; Selenium; Skin Diseases, Infectious; Ubiquinone; Viral Load; Vitamin E; Young Adult

To assess the efficacy of oral acyclovir in treating adults with varicella and to describe the natural history of adult varicella.. Double-blind, placebo-controlled randomized trial.. A naval hospital.. One hundred forty-eight of 206 consecutive adult active duty Navy and Marine Corps personnel who were hospitalized for isolation and inpatient therapy of varicella and who could be treated within 72 hours of rash onset completed the study. The diagnosis of varicella was confirmed by acute and convalescent serology in 143 of 144 patients with available paired sera.. Patients were randomly assigned to receive either acyclovir, 800 mg orally five times per day for 7 days, or an identical placebo. Separate randomization codes were used for patients presenting within 24 hours of rash onset and for those presenting 25 to 72 hours after rash onset.. Daily lesion counts, symptom scores, temperature measurements, and laboratory tests were used to monitor the course of the illness.. Early treatment (initiated within 24 hours of rash onset) reduced the total time to (100%) crusting from 7.4 to 5.6 days (P = 0.001) and reduced the maximum number of lesions by 46% (P = 0.04). Duration of fever and severity of symptoms were also reduced by early therapy. Late therapy (25 to 72 hours after rash onset) had no effect on the course of illness. Only four patients had pneumonia, and no encephalitis or mortality was noted.. Early therapy with oral acyclovir decreases the time to cutaneous healing of adult varicella, decreases the duration of fever, and lessens symptoms. Initiation of therapy after the first day of illness is of no value in uncomplicated cases of adult varicella. The low frequency of serious complications of varicella (pneumonia, encephalitis, or death) precluded any evaluation of the possible effect of acyclovir on these outcomes.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Antibodies, Viral; Chickenpox; Double-Blind Method; Female; Fever; Herpesvirus 3, Human; Humans; Immunoglobulin G; Male; Skin Diseases, Infectious

Seventy-three immunocompromised patients with disseminated herpes zoster were evaluated in a double-blind controlled trial of acyclovir (n = 37) versus vidarabine (n = 36) therapy. Acyclovir was administered at 30 mg/kg/day at 8-h intervals and vidarabine was given as a continuous 12-h infusion at 10 mg/kg/day for 7 days (longer if resolution of cutaneous or visceral disease was incomplete). No demographic differences existed between treatment groups. No deaths attributable to varicella-zoster virus infection occurred within 1 month of treatment. Neither rates of cutaneous healing, resolution of acute neuritis, and frequency of postherpetic neuralgia nor adverse clinical and laboratory events differed between treatment groups. Acyclovir recipients were discharged from the hospital more promptly than vidarabine recipients (P = .04, log rank test). These data indicate that disseminated herpes zoster is amenable to therapy with either acyclovir or vidarabine; resultant mortality is low.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Child; Cost-Benefit Analysis; Double-Blind Method; Female; Hepatitis, Viral, Human; Herpes Zoster; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Meningoencephalitis; Middle Aged; Neuritis; Pneumonia, Viral; Skin Diseases, Infectious; Vidarabine

Neonatal herpes simplex virus (HSV) infections are recognized to be severe because of their association with significant morbidity and mortality. Through ongoing studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, the presentation, natural history, outcome and value of antiviral chemotherapy have been considered. Infants developing neonatal HSV infections can be classified according to the extent of disease, disseminated or localized. Localized infection can be subdivided into either central nervous system (CNS) disease, occurring in 35% of infected infants, or skin, eye and mouth (SEM) disease, in 41% of infants. Disseminated disease accounts for 24% of neonatal HSV infection. Therapeutic outcome depends upon disease classification. Administration of either 15 or 30 mg/kg/day of vidarabine resulted in significantly decreased mortality for infants with life-threatening disseminated and CNS disease as compared to placebo recipients. Approximately one-third of children developed normally following disseminated disease or CNS infection. When disease was localized to the SEM, no death occurred, and 88% of treated infants developed normally. While these data indicate that therapy is effective for management of infants with neonatal HSV infection, improvements are necessary. Hopefully, a study in progress will demonstrate improved outcome with acyclovir treatment.

Topics: Acyclovir; Central Nervous System Diseases; Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Risk; Skin Diseases, Infectious; Stomatitis, Herpetic; Vidarabine

Intravenous acyclovir had a significant effect on the resolution of the skin rash in patients with acute zoster, but the 5-day course of therapy was not, in itself, sufficient to treat coexisting ocular involvement. In an open study, topical acyclovir was found to control herpes zoster kerato-uveitis, without recurrences and in a shorter time than if steroids alone were used. The use of steroids in combination with acyclovir led to prolonged treatment and high recurrence rates. A comparative trial of topical acyclovir versus steroids in the treatment of acute herpes zoster kerato-uveitis showed significant differences in favour of acyclovir in terms of the time to resolution of corneal epithelial disease, total treatment duration and the numbers of patients having a recurrence of infection. The reductions in treatment duration and recurrence rate would be expected to result in a reduced incidence of ocular damage and visual loss in acyclovir treated patients.

Topics: Acyclovir; Administration, Topical; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Recurrence; Skin Diseases, Infectious; Steroids

The effect of acyclovir on the skin rash and herpes zoster keratouveitis has been studied. It has been shown to have a significant effect on both disease processes, and to be superior to topical steroids in the treatment of herpes zoster keratouveitis. Steroids have been found to have an adverse effect with prolonged treatment and frequent recurrences.

Topics: Acyclovir; Administration, Topical; Betamethasone; Clinical Trials as Topic; Female; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Keratitis; Male; Recurrence; Retrospective Studies; Skin Diseases, Infectious; Uveitis

Varicella zoster infection (VZI) is well recognized as a potential cause of morbidity and mortality in immunocompromised pediatric oncology patients (POP). The purpose of this study was to describe the clinical profile and risk factors for complications and outcomes of VZI in POP treated with acyclovir.. Medical records of all POP with a discharge diagnosis of VZI over a period of seven years (2005-2011) were reviewed. The demographic features, underlying malignancy, risk factors for VZI, complications, and outcomes were recorded.. Thirty-six POP with VZI were identified. Leukemia was the most common underlying malignancy (n = 20, 58.8%), followed by lymphoma (n = 7, 20.6%) and solid organ tumors (n = 7, 20.6%). Most of the cases (41%) were observed in children under five. All patients were treated with acyclovir. Varicella-related complications developed in 10 (29%) patients. The most frequent complication was bloodstream infection (n = 3, 8.8%), followed by pneumonia (n = 2, 5.9%), skin infection (n = 2, 5.9%), hepatitis, renal failure, and encephalitis. Independent risk factors associated with complications were age < five years, weight for age < fifth percentile, delay in seeking care (> seven days after onset of symptoms) and severe neutropenia (ANC < 500/cm). One child died secondary to varicella encephalitis.. Our data suggests that young age, poor health-seeking behavior, severe neutropenia, and being underweight are the major risk factors for the development of varicella-related complications in POP in developing countries. These complications could be favorably modified through active immunization of immunocompetent children.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Child; Child, Preschool; Humans; Immunocompromised Host; Infant; Logistic Models; Neoplasms; Pakistan; Retrospective Studies; Risk Factors; Skin Diseases, Infectious; Tertiary Care Centers

Anti-herpes simplex virus (HSV) activities of oxyresveratrol in vitro and topical administration in cutaneous HSV-1 infection in mice were examined. The inhibitory concentrations for 50% plaque formation (IC(50)) of oxyresveratrol against HSV-1 clinical isolates and HSV-2 clinical isolates were 20.9-29.5 and 22.2-27.5 μg/ml, respectively. In topical administration in cutaneous HSV-1 infection in mice, 2.5%, 5%, 10% and 20% oxyresveratrol in cream vehicle applied three times daily for 7 days after infection were evaluated and 10% and 20% oxyresveratrol cream were significantly effective in delaying the development of skin lesions and protection from death (P < 0.01). The concentration of 10% oxyresveratrol in cream was significantly more effective than that of 30% oxyresveratrol in vaseline applied three times daily (P < 0.01). Oxyresveratrol cream at 20% was as effective as 5% ACV cream applied three times daily (P < 0.01). Both 10% and 20% oxyresveratrol cream were as effective as that of 5% ACV cream applied two times daily (P > 0.05). Therapeutic efficacy of oxyresveratrol in cream vehicle was dose-dependent and the maximum efficacy observed on day 6 after infection was shown at 10% oxyresveratrol in cream applied three times daily. The frequency of application of 10% oxyresveratrol cream at three, four and five times daily was as effective as that of 5% ACV cream applied five times daily (P > 0.05). These results demonstrated that topical administration of oxyresveratrol in novel cream vehicle reduced the concentration of oxyresveratrol to 10% and was suitable for cutaneous HSV infection.

Topics: Acyclovir; Administration, Cutaneous; Animals; Antiviral Agents; Artocarpus; Chlorocebus aethiops; Dose-Response Relationship, Drug; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Inhibitory Concentration 50; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Plant Extracts; Skin Diseases, Infectious; Stilbenes; Vero Cells; Viral Plaque Assay

In order to investigate the antiviral effect of chinonin against Herpes simplex virus (HSV), the encephalitis model in mice and skin infection model in guinea pigs were established by HSV- I and HSV-II infection respectively. Acyclovir was used as the positive reference drug to evaluate the antiviral capacity of chinonin. Chinonin showed an obvious therapeutic effect on encephalitis in mice at doses of 25 and 50 mg/kg. At both dosages, chinonin demonstrated stronger protection than acyclovir (1 and 5 mg/kg) to the infected mice from death. It was also found that chinonin could treat the skin infection in guinea pigs effectively. The therapeutic effect of chinonin was similar to that of acyclovir (5 mg/kg) at 25 mg/kg but obviously better than that at 50 and 75 mg/ kg. In conclusion, chinonin is a potential candidate for the treatment against HSV.

Topics: Acyclovir; Animals; Antiviral Agents; Encephalitis; Glycosides; Guinea Pigs; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Simplexvirus; Skin Diseases, Infectious; Xanthenes; Xanthones

Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. Recurrence of skin vesicles is common.. To determine the features of relapse and identify the factors related to relapse.. Thirty two surviving patients with neonatal herpes virus infections were enrolled. All patients received acyclovir treatment. Clinical and virological data were analysed and compared between relapsed and non-relapsed cases.. Thirteen (41%) had either local skin or central nervous system relapse between 4 and 63 days after completing the initial antiviral treatment. Nine patients exhibited local skin relapses, and four developed central nervous system relapses. In one skin and two central nervous system relapse cases, neurological impairment later developed. Type 2 virus infection was significantly related to relapse (odds ratio 10.4, 95% confidence interval 1.1 to 99.0). Patients with relapse had worse outcomes than those without relapse.. Neonates with HSV type 2 infections have a greater risk of relapse. Relapsed patients have poorer prognoses.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Viral Diseases; Female; Gestational Age; Herpes Simplex; Humans; Infant, Newborn; Male; Recurrence; Skin Diseases, Infectious; Treatment Outcome; Viral Load

The current communication describes clinical findings in two recipients of allogeneic bone marrow transplantation (BMT) with varicella zoster virus infection who complained of acute severe abdominal pain preceding cutaneous manifestations. Physical examination, laboratory data and gastroscopic findings were nonspecific. In these cases, acyclovir was very effective for the symptoms. Varicella zoster virus infection should be suspected in BMT recipients who have rebellant acute abdominal pain but no characteristic skin eruptions.

Topics: Abdominal Pain; Acute Disease; Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Skin Diseases, Infectious; Transplantation, Homologous

Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its antiviral actions by a systemic effect. When topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:linoleic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated HSV-2 HG-52 infection. At 1 h following topical application of 1.7% w/v ACV the plasma and skin concentrations of ACV were 5.5 nmoles/ml and 120 nmoles/g. At 1 h following an oral dose of ACV with antiviral efficacy comparable to topically applied ACV (1.7% w/v) the plasma and skin concentrations of ACV were 21.3 nmoles/ml and 51 nmoles/g. These findings imply that when applied topically to the HM, ACV can mediate a portion of its antiviral activity through a systemic mode of action.

Topics: Acyclovir; Administration, Cutaneous; Administration, Oral; Animals; Herpes Simplex; Herpesvirus 1, Human; In Vitro Techniques; Mice; Mice, Hairless; Skin Absorption; Skin Diseases, Infectious

A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy. Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity. Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity. Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens. Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity. This report is an example of acyclovir hypersensitivity and successful oral desensitization.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Aged; Desensitization, Immunologic; Drug Hypersensitivity; Female; Herpes Simplex; Humans; Skin Diseases, Infectious

To determine whether foscarnet has potential efficacy in the treatment of acyclovir-resistant mucocutaneous varicella-zoster infection in patients with the acquired immunodeficiency syndrome (AIDS).. Open-label study.. Three university medical centers.. Five patients with AIDS who were infected with thymidine-kinase-deficient or -altered strains of varicella-zoster virus.. Foscarnet, 40 mg/kg body weight every 8 hours in 1-hour infusions for 10 or more days.. Four patients had healing in response to foscarnet therapy, and each of four tested patients became culture negative for virus during foscarnet therapy. Results of fluorescent antigen testing remained positive during therapy in two patients; one of these patients had concomitant clinical failure but the other patient healed fully. One patient had complete healing despite the emergence of resistance to foscarnet in serial specimens obtained during foscarnet therapy.. Foscarnet is a potentially effective and tolerable antiviral agent for patients with acyclovir-resistant, varicella-zoster virus infection; however, the optimal dosage and duration of therapy require further study, as does the relation between clinical findings and in-vitro susceptibility results.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cohort Studies; Drug Resistance, Microbial; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans; Middle Aged; Phosphonoacetic Acid; Skin Diseases, Infectious

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; HIV Infections; Humans; Male; Phosphonoacetic Acid; Skin Diseases, Infectious

The phosphonylmethoxyalkyl derivative (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was evaluated for its in vivo efficacy in several model infections for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and thymidine kinase-deficient (TK-) HSV-1 in mice. In hairless mice infected intracutaneously with HSV-1 or HSV-2, HPMPC completely suppressed all manifestations of the disease (skin lesions, paralysis of the hind legs, and mortality) if it was administered topically at a concentration of as low as 0.1, 0.3, or 1%. Similarly, HPMPC completely suppressed TK- HSV-1 infection in athymic nude mice if it was administered topically at 0.1 or 0.3% or intraperitoneally at 100 or 250 mg/kg/day. HPMPC was also effective against intraperitoneal HSV infection if it was given orally at a dose of 50 mg/kg/day or higher. In mice inoculated intracerebrally with HSV-2, intraperitoneal HPMPC treatment achieved a significant and dose-dependent protection at doses ranging from 5 to 400 mg/kg/day. The protective effect of HPMPC (at 200 mg/kg/day) was accompanied by a complete inhibition of virus multiplication in the brain. In all models of infections studied, the efficacy of HPMPC proved to be superior to that of acyclovir. The most remarkable feature of HPMPC was that a single administration of the compound, even as late as 4 days after infection, conferred significant protection against HSV-1 or HSV-2 infection. Topical or systemic HPMPC treatment is efficacious in murine models of HSV-1, HSV-2, and TK- HSV infections.

Topics: Acyclovir; Animals; Antiviral Agents; Brain Diseases; Cidofovir; Cytosine; Herpes Simplex; Mice; Mice, Hairless; Mice, Nude; Organophosphonates; Organophosphorus Compounds; Peritoneal Cavity; Skin Diseases, Infectious

We described the development of prolonged disseminated cutaneous herpes zoster in two patients with acquired immunodeficiency syndrome. Both patients developed hyperkeratotic, verrucous lesions that progressed despite acyclovir therapy. The biopsy specimens were typical of herpes infection. The development of acyclovir-resistant varicella-zoster virus during therapy was suspected clinically in the first patient and documented in vitro in the second patient. The inability to mount an effective cell-mediated immune response contributed to the prolonged course of cutaneous zoster in our patients. The hyperkeratotic nature of the skin lesions may reflect their chronic nature. Treatment with inadequate doses of acyclovir, allowing viral persistence and the selection of resistant strains of virus, may also be implicated. We recommend prolonged high-dose intravenous acyclovir therapy in the initial management of herpes zoster in patients with acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Chronic Disease; Drug Resistance, Microbial; Herpes Zoster; Herpesvirus 3, Human; Humans; Injections, Intravenous; Male; Recurrence; Skin Diseases, Infectious

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Chickenpox; Child; Drug Resistance, Microbial; Herpes Zoster; Humans; Keratosis; Male; Recurrence; Skin Diseases, Infectious

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Female; Foscarnet; Herpes Genitalis; Herpes Simplex; Humans; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Skin Diseases, Infectious

Amniotic band syndrome, which is frequently seen in association with prolonged rupture of membranes, is due to the amnion forming fibrous strands that encircle fetal parts. This causes compression and necrosis of the underlying skin. We report a case of herpes simplex virus infection localized to these lesions.

Topics: Acyclovir; Amniotic Band Syndrome; Female; Fetal Membranes, Premature Rupture; Herpesviridae Infections; Humans; Infant, Newborn; Injections, Intravenous; Pregnancy; Skin Diseases, Infectious

We report a case of orofacial herpes simplex virus (HSV) infection that was progressive despite multiple courses of acyclovir sodium in a patient with the acquired immunodeficiency syndrome. The viral isolate was shown to be resistant to acyclovir in vitro, but proved susceptible to vidarabine and foscarnet sodium (trisodium phosphonoformate). The patient failed to respond to a 2-week course of intravenous vidarabine. However, rapid improvement in the orofacial lesion occurred with intravenous foscarnet. Most HSV isolates that are resistant to acyclovir are spontaneous mutants partially or completely lacking in thymidine kinase. Because foscarnet is a direct inhibitor of HSV DNA polymerase, this compound is expected to have efficacy against acyclovir-resistant strains. This report documents successful treatment of clinically significant HSV with intravenous administration of foscarnet, suggesting that further study is indicated.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Herpes Simplex; Humans; Male; Simplexvirus; Skin Diseases, Infectious

Pathologic changes in the skin of elderly individuals increase their susceptibility to skin infections. These changes include thinning, decreased secretions, and reduced immune function. This paper will discuss the most important viral, fungal, bacteriologic, and parasitic infections of the skin in the elderly and the appropriate treatment of these infections.

Topics: Acyclovir; Aged; Anti-Bacterial Agents; Antifungal Agents; Antiparasitic Agents; Dermatomycoses; Diagnosis, Differential; Humans; Middle Aged; Skin Diseases, Infectious; Skin Diseases, Parasitic; Virus Diseases

The herpesvirus DNA polymerase inhibitor foscarnet, applied topically, and the anti-herpesvirus guanosine analogue buciclovir, given orally, decreased virus replication and disease development in primary skin infections of mice caused by herpes simplex virus type 1 (HSV-1). If the same tissues were infected via sensory nerves, following zosteriform spread of the virus the same treatments showed strongly decreased efficacy, or were inefficacious, when started before development of clinical signs in the infected tissues. These results were obtained in murine models of zosteriform spread of HSV-1 to the ear (following inoculation of the ventral side of the neck) or to the lower flank (following inoculation of the upper flank). In these models the immune system played a dominant role in virus clearance. The topically applied foscarnet could not prevent disease development in these models of recrudescent disease even when applied before the virus was detected in the skin, but a decrease in virus titre was obtained. Orally administered buciclovir lost efficacy when administered at the time of virus entry into the skin, i.e. 1 or 2 days before development of clinical signs. In the flank model, measuring lesion development, orally administered acyclovir also had a strongly decreased efficacy, when compared with its effect during infections in which lesion development did not involve translocation of virus through nerves. In the presence of developing immunity the inhibitors could not accelerate the clearance of virus from infected tissues. Furthermore, all treatments (topical foscarnet and oral buciclovir or acyclovir) were without effect on disease development when treatment was initiated on appearance of the first clinical signs of disease. As disease development following zosteriform spread of HSV resembles that in recurrent herpes in humans, and as the limited efficacy of the inhibitors observed resembles the poor results obtained with inhibitors of herpesvirus DNA synthesis in clinical studies on the treatment of symptomatic recurrent herpes, we suggest the use of animal models of zosteriform spread for pre-clinical evaluation of new antiherpes drugs.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Animals; Antiviral Agents; Disease Models, Animal; DNA Replication; DNA, Viral; Foscarnet; Herpes Simplex; Male; Mice; Nervous System Diseases; Organophosphorus Compounds; Phosphonoacetic Acid; Recurrence; Simplexvirus; Skin; Skin Diseases, Infectious; Virus Replication

We investigated the influence of disodium phosphonic formate (PFA-Na2) and trisodium thiophosphonic formate (TPFA-Na3), in comparison with acyclovir (Zovirax) and trisodium phosphonic formate (PFA-Na3) (Triapten) ointment, on the course of primary cutaneous herpes simplex virus infection in a guinea pig skin model. PFA-Na2 at 3.0%, TPFA-Na3 at 0.5% and PFA-Na3 at 0.5% as well as Triapten ointment (2.0% PFA-Na3) completely inhibited virus infection. Zovirax cream (5.0% acyclovir), applied five times (15 min., 4, 20, 24, and 28 h) after virus inoculation did not prevent virus infection. Similarly, application of Zovirax cream 5 times daily for 5 days did not prevent a vesicle formation following cutaneous herpes simplex virus infection of the guinea pig.

Topics: Acyclovir; Animals; Diphosphates; Female; Guinea Pigs; Herpes Simplex; Male; Simplexvirus; Skin Diseases, Infectious

The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection. BRL 39123 was as active as acyclovir (ACV) when applied topically to guinea pigs with a cutaneous HSV type 1 (HSV-1) infection and was also active topically in an HSV-2 genital infection. Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography. When given systemically to mice infected cutaneously with HSV-1, BRL 39123 was as active as ACV. In mice infected intranasally with HSV-1 or HSV-2, single daily subcutaneous doses of BRL 39123 were more effective than equivalent treatment with ACV, reflecting the more persistent activity seen in cell culture and a more stable triphosphate within the infected cell. When the compounds were supplied in drinking water for this infection, BRL 39123 and ACV had similar potencies against HSV-1, although ACV was more active against an HSV-2 infection than BRL 39123 was. In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection. Although BRL 39123 failed to eradicate the virus from mice latently infected with HSV-1, treatment initiated 5 h after infection of the ear pinna reduced the numbers of mice that developed latent infections.

Topics: Acyclovir; Animals; Antiviral Agents; Biological Availability; Chromatography, High Pressure Liquid; Female; Guanine; Guinea Pigs; Herpes Simplex; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Nude; Peritoneal Diseases; Skin Diseases, Infectious

Chronic cutaneous herpes simplex virus infection is described in a 68-year-old man who was immunocompromised because of chronic lymphocytic leukemia. The herpes infection was not amenable to therapy with acyclovir. Clinical isolates of herpes simplex virus were assessed for viral thymidine kinase activity, which was markedly decreased in two isolates. By the method of viral plaque autoradiography, these isolates were determined to be composed primarily of mutant thymidine kinase-negative herpes simplex virus mixed with occasional standard thymidine kinase-positive herpes simplex virus. Viral plaque autoradiography permitted the quantitation of proportions of thymidine kinase-negative and thymidine kinase-positive herpes simplex virus in the mixed virus populations. The chronic cutaneous infection persisted, unlike other reported infections by thymidine kinase-negative herpes simplex virus.

Topics: Acyclovir; Aged; Chronic Disease; Drug Resistance, Microbial; Herpes Simplex; Humans; Lip; Male; Simplexvirus; Skin Diseases, Infectious; Thymidine Kinase

Topics: Acyclovir; Diaper Rash; Female; Herpes Simplex; Humans; Infant; Skin Diseases, Infectious

The vast majority of the more than 300,000 annual cases of herpes zoster in the United States occur among healthy, immunocompetent persons. Most patients recover from reactivated varicella-zoster infection, but some experience complications. The most common of these is postherpetic neuralgia, but other neurologic as well as ocular and dermatologic complications can occur as well. Zoster during pregnancy is not of serious concern. Ongoing trials of antiviral agents are aimed at resolving the infection quickly and decreasing the incidence and severity of postherpetic neuralgia.

Topics: Acyclovir; Adenosine Monophosphate; Eye Diseases; Female; Herpes Zoster; Humans; Immunocompetence; Nervous System Diseases; Pregnancy; Skin Diseases, Infectious

The synthesis of acyclovir-phospholipid conjugate (2) is reported through an unambiguous one-step preparation of L-alpha-dimyristoyl phosphatidic acid triethylammonium salt (5). The biological activity of 2 as an antiviral drug has also been investigated.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line; Chemical Phenomena; Chemistry; Fibroblasts; Guinea Pigs; Herpes Simplex; Humans; Mice; Phospholipids; Simplexvirus; Skin Diseases, Infectious; Virus Replication

Antiviral effects of acyclovir (ACV) and antibody were studied in athymic nude mice inoculated intracutaneously in the midflank with herpes simplex virus type 1. Three hours after virus inoculation, treatment was initiated. In ACV-treated mice, the development of skin lesions was inhibited and the mean survival time was prolonged as compared with controls. Treatment with ACV markedly reduced the viral titers both at the inoculation site and in the neural tissues (dorsal root ganglia, spinal cord and brain). Transfer of antibody was also effective in controlling infection as described previously. The use of ACV plus antibody was more effective than the use of ACV alone and in 5 of 17 mice the disease was completely inhibited. Furthermore, in the mice that survived, latent infections in the ganglia were also prevented. These results indicate that treatment with ACV plus antibody is highly effective against herpes simplex virus infection in the immunocompromised host.

Topics: Acyclovir; Animals; Female; Herpes Simplex; Immunization, Passive; Mice; Mice, Inbred BALB C; Mice, Nude; Simplexvirus; Skin Diseases, Infectious

The effect of topical and systemic treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the evolution of herpes simplex virus-induced skin infection in hairless mice was investigated. Systemic (subcutaneous) treatment with a 10-mg/kg dose and topical applications with a 5% cream started up to 48 h after infection prevented the development of severe skin lesions and a fatal outcome. However, the establishment of latent infections was prevented only by topical treatment started at 6 h after infection. Systemic (50 mg/kg) and topical treatments started 48 h after infection reduced virus titers in the skin and ganglia and promoted rapid clearance of virus from these sites. The clearance of infectious virus from ganglia during the acute phase of infection was followed by early establishment of latency. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (0.03 microgram/ml) significantly inhibited the synthesis of infectious virus in explant cultures of latently infected ganglia, and at concentrations higher than 8 micrograms/ml no infectious virus was detectable in ganglia explant cultures.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Female; Ganciclovir; Ganglia; Herpes Simplex; Injections, Subcutaneous; Mice; Mice, Hairless; Skin; Skin Diseases, Infectious; Time Factors

Dermatologic diseases of the genitalia are of several types: congenital diseases, acquired diseases (those caused by viruses, bacteria, fungi, or physical or chemical toxins), tumors, and atrophic dermatoses. The methods available to diagnose these diseases vary. Some conditions may be recognized by appearance alone, whereas others require histopathologic examination of involved skin for correct diagnosis. Some do not need treatment, while others call for an aggressive approach. Some types of genital dermatologic diseases, such as herpes infections and condylomata acuminata, appear to be associated with genital carcinogenesis. Patients with these diseases should be carefully examined.

Topics: Acyclovir; Condylomata Acuminata; Dermatitis, Contact; Female; Genital Diseases, Female; Genital Diseases, Male; Herpes Genitalis; Humans; Male; Skin Diseases; Skin Diseases, Infectious

Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10-fold greater than those shown by ACV in ointment formulation (0.56 versus 0.05 microgram/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 micrograms/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Deoxyuridine; Disease Models, Animal; Emulsions; Female; Guinea Pigs; Herpes Simplex; Ointments; Skin Absorption; Skin Diseases, Infectious

Guinea pigs were infected cutaneously with HSV1 and treated topically with acyclovir or phosphonoformic acid (0.1% to 0.5% solution), or with a combination of both. The therapy was clinically effective and the virus content in the skin diminished. Virus harvests from skin areas in no case showed increased drug resistance, as tested by plaque reduction.

Topics: Acyclovir; Administration, Topical; Animals; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Foscarnet; Guinea Pigs; Herpes Simplex; Male; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Skin Diseases, Infectious

Cutaneous infection of guinea pigs with HSV1 was topically treated from 2 to 6 days post infection with 7 antiherpetic substances. Phosphonoformic acid and acyclovir were found to be highly effective; trifluorothymidine, thymine arabinoside, ethyldeoxyuridine, and adenine arabinoside monophosphate all had some therapeutic effect in decreasing order, whereas iododeoxyuridine was ineffective. The efficacy of treatment was evaluated from cutaneous lesion scores by the Wilcoxon rank test. The substances were combined in marginally effective concentrations. From the 21 combinations, acyclovir + phosphonoformic acid, acyclovir + thymine arabinoside, and phosphonoformic acid + thymine arabinoside suggested a synergistic interaction, which appeared significant for acyclovir + phosphonoformic acid.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinonucleosides; Deoxyuridine; Drug Therapy, Combination; Female; Foscarnet; Guinea Pigs; Herpes Simplex; Idoxuridine; Male; Phosphonoacetic Acid; Skin Diseases, Infectious; Thymidine; Trifluridine; Vidarabine Phosphate

Topics: Acyclovir; Antiviral Agents; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpesviridae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Keratoconjunctivitis; Male; Skin Diseases, Infectious; Vidarabine

Systemic or topical treatment with E-5-(2-bromovinyl)2'-deoxyuridine (BVDU) showed significant efficacy against orofacial infection with herpes simplex virus type 1 (HSV-1) in hairless mice. The chemotherapeutic response to BVDU was dose-dependent and clearly evident even when the treatment was initiated during the clinical manifestation of HSV-1 infection at 72 hr after inoculation. Early initiation of therapy with BVDU at 3 or 24 hr after inoculation significantly prevented the establishment of latent HSV infection in the trigeminal ganglia of mice, but systemic treatment with BVDU did not influence already established latent HSV-1. The chemotherapeutic efficacy of BVDU was comparable to that of acyclovir in the present animal model.

Topics: Acyclovir; Administration, Topical; Animals; Bromodeoxyuridine; Face; Guanine; Herpes Labialis; Herpes Simplex; Male; Mice; Mice, Inbred BALB C; Skin Diseases, Infectious; Time Factors; Trigeminal Ganglion

The chemotherapeutic efficacy of acyclovir was evaluated by observing the potential of topical acyclovir to reduce the severity of herpes viral lesions and to control the multiplication of this virus in the experimentally induced primary cutaneous infection of guinea pigs. Topical acyclovir showed a substantially high therapeutic efficacy when treatment was initiated after the development of clinically overt skin lesions. The therapeutic response was dose dependent and clearly evident even when the treatment was initiated on day 2 after inoculation. Our results indicate that topical acyclovir treatment improved the cutaneous herpes simplex virus type 1 (HSV-1) infectious process by inhibiting multiplication of HSV-1 in the skin of guinea pigs.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Female; Guanine; Guinea Pigs; Herpes Simplex; Skin Diseases, Infectious; Time Factors