acyclovir and Stomatitis

Herpes simplex virus (HSV) has been implicated as a major etiologic factor in the development of ulcerative mucositis in bone marrow transplant (BMT) recipients. In this study, 60 patients who received BMTs were evaluated for at least 30 days post-transplant for ulcerative mucositis and the presence of culturable HSV. Fifty-nine patients received prophylactic acyclovir. Forty-six patients developed ulcerative lesions and 45 of these were culture negative for HSV. Neither the source of transplant (autologous versus allogenic) nor the HSV antibody status of the patient affected the frequency of mucositis. The conditioning regimen appeared to be the most significant factor contributing to the severity of ulcerative mucositis. While the majority of ulcers occurred on movable nonkeratinized mucosa in BMT recipients, the usual sites of reactivation of intraoral HSV are nonmovable, keratinized mucosa. We conclude that HSV is probably not a major etiologic agent of mucositis in BMT recipients and that acyclovir is an effective agent in preventing HSV reactivation.

Topics: Acyclovir; Adolescent; Adult; Bone Marrow Transplantation; Child; Female; Humans; Male; Middle Aged; Mouth Mucosa; Serologic Tests; Simplexvirus; Stomatitis

We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT).. HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir.. Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived.. ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Antiviral Agents; Cidofovir; Drug Resistance, Viral; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Stomatitis; Treatment Outcome

Topics: Acrodermatitis; Acyclovir; Child, Preschool; Gingivitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Stomatitis

We report 3 children who, after undergoing hematopoietic stem cell transplant, developed herpes simplex virus (HSV) stomatitis while receiving weekly cidofovir as preemptive treatment for cytomegalovirus infection. All patients responded well to treatment with either acyclovir or ganciclovir. Despite the in vitro susceptibility of HSV to cidofovir, once-weekly treatment with this agent may not be adequate prophylaxis in pediatric patients.

Topics: Acyclovir; Antiviral Agents; Chemoprevention; Child; Child, Preschool; Cidofovir; Cytomegalovirus Infections; Cytosine; Ganciclovir; Humans; Male; Organophosphonates; Simplexvirus; Stem Cell Transplantation; Stomatitis; Treatment Outcome

The aim of the study was to investigate the incidence of herpes simplex virus-1 (HSV-1) infection in mucositis during head and neck cancer radiotherapy.. Sixty patients with malignant head and neck tumor, eligible to receive radiotherapy, who were referred to the Dental Oncology Unit, entered the study. Sixteen patients (26.6%) received concomitant chemotherapy. Mucositis was recorded weekly. Smears taken from the ulcers of mucositis grade 2, or 3, or 4 were stained with Papanicolaou and alkaline phosphatase/antialkaline phosphatase immunocytochemical method to identify HSV-1.. Forty-eight of all 60 patients developed ulcerative mucositis. Smear was available from 29 of 48 patients with ulcerations. HSV-1 infection was identified in 14 of 29 smears available (48.2%). Mucositis healed or was reduced after 1 week of antiviral treatment in 11 of those 14 HSV-1-positive patients; 3 patients responded to 1 g/day of valacyclovir, 7-2 g/day, and 1 patient responded to i.v. acyclovir. Ulcerations recurred after quitting antivirals. Three patients did not respond to 1 g/day of valacyclovir. No HSV-1-negative patient responded to acyclovir (P = 0.000).. HSV-1 was isolated from 14 of 29 available smears taken from 48 patients with ulcerative mucositis. The incidence of HSV-1 infection during radiotherapy was estimated as being 14 of all 48 patients at risk (29.1%). Healing or reduction in the grade of mucositis after antivirals in HSV-1 positive patients, combined with the negative response to antivirals in HSV-1 negative patients, denoted that HSV-1 infection was a component of ulcerative radiation mucositis in those HSV-1-positive patients.

Topics: Abnormalities, Radiation-Induced; Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Candidiasis, Oral; Dose-Response Relationship, Radiation; Female; Head and Neck Neoplasms; Herpes Simplex; Herpesvirus 1, Human; Humans; Incidence; Male; Middle Aged; Oral Ulcer; Radiotherapy; Recurrence; Stomatitis; Treatment Outcome; Valacyclovir; Valine

Herpes simplex virus (HSV) oral excretions are common after bone marrow transplantation (BMT).. We report a 4-year systematic survey of HSV excretions in an adult population who underwent BMT (289 transplantations).. Patients received either intravenous ACV treatment when mucositis occurred or systematic intravenous ACV prophylaxis from initiation of the BMT conditioning until the end of aplasia. All patients were followed up for HSV excretions.. Twenty-eight patients (9.7%) excreted HSV. The occurrence of HSV excretions was similar in both allogeneic and autologous transplant patients. The incidence was significantly lower when ACV was systematically used after transplantation (2.5%) compared to when ACV was implemented for mucositis (12%). ACV-resistant HSV was detected in three patients who received allogeneic transplantation, representing 27% of allogeneic recipients excreting HSV.. HSV infection prophylaxis with high dose of intravenous ACV resulted in a decreased incidence of HSV excretion. Nevertheless, the risk of emergence of ACV resistance, especially among allogeneic transplant patients, appears to be identical whatever the route and dose of ACV prophylaxis.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Bone Marrow Transplantation; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Incidence; Male; Middle Aged; Mouth; Stomatitis; Virus Shedding

The efficacy of oral acyclovir, a purine nucleoside analogue with activity against human herpes viruses, is limited as a result of its low bioavailability. Valacyclovir, the L-valyl ester of acyclovir, has been developed as a pro-drug to improve the bioavailability. The aim of the present study was to compare the pharmacokinetics of acyclovir after intravenous administration and after oral administration of valacyclovir.. The pharmacokinetics of acyclovir were studied in 18 children aged 1.4-18.1 years (median: 6.9 years; 9 females) after intravenous infusion (1 hr; median dose: 10.5 mg/kg). In 10 of the children the pharmacokinetics of acyclovir were also studied after oral administration of valacyclovir (median dose: 34.1 mg/kg). Quantification of acyclovir in serum was performed by reversed-phase liquid chromatography with fluorometric detection. The pharmacokinetic analysis was performed by pharmacokinetic modelling.. The serum concentration versus time curves of acyclovir were described by the two compartment model after intravenous administration and by the one compartment model with a zero- or first-order absorption phase after oral administration of valacyclovir. The bioavailability of acyclovir after oral administration of valacyclovir was 45% (median value; 95% CI: 37-55%).. It is possible to substitute intravenous acyclovir therapy by oral valacyclovir therapy in children with leukopenia and mucositis after chemotherapy. This finding can at present not be fully implemented in clinical practice, since a commercial pharmaceutical formulation of valacyclovir aimed for children not able to swallow intact tablets is lacking. Crushed valacyclovir tablets have a very unpleasant taste, but can be administered to children through nasogastric tubes.

Topics: Acyclovir; Administration, Oral; Adolescent; Antineoplastic Agents; Antiviral Agents; Biological Availability; Child; Child, Preschool; Female; Herpes Simplex; Humans; Immunocompromised Host; Infant; Infusions, Intravenous; Leukopenia; Male; Mouth Mucosa; Prodrugs; Stomatitis; Valacyclovir; Valine

This study was conducted to compare the survival rates of bone marrow transplantation (BMT) patients who were affected with the survival rates of those who were not affected by oral recrudescent human herpes virus-1 infection (HHV-1) after transplantation.. Fifty-two consecutive patients who underwent BMT were included in the study. The time of death after BMT was displayed, by means of the Kaplan-Meier method, for the following parameters: age and gender of the patient, donor gender, primary disease, stem cells, conditioning regimen, platelet number after day 100, acute and chronic graft-versus-host disease, oral recurrent HHV-1 infection post-BMT, oral lichenoid lesions of graft-versus-host disease, graft-versus-host disease at the salivary glands, parenteral nutrition, and oral mucositis. The data were initially analyzed by means of the log-rank test and then included in the Cox proportional hazards model.. The multivariate analysis demonstrated a significance of 5% for only the platelet numbers and oral recurrent HHV-1 infection.. The present study provides evidence that platelet numbers below 100,000 cells/mm(3) after day 100 and oral recurrent HHV-1 infection are independent negative prognostic variables in BMT patients' 24-month survival rates.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Age Factors; Anemia, Aplastic; Antiviral Agents; Bone Marrow Transplantation; Chronic Disease; Female; Graft vs Host Disease; Humans; Leukemia; Linear Models; Lymphoma; Male; Middle Aged; Multivariate Analysis; Platelet Count; Prognosis; Proportional Hazards Models; Recurrence; Salivary Gland Diseases; Sex Factors; Stomatitis; Stomatitis, Herpetic; Survival Rate; Tissue Donors; Transplantation Conditioning

A leukemic child developed recurrent herpes simplex virus lesions shortly after receiving a bone marrow transplant and while taking acyclovir. The isolate was resistant to acyclovir and foscarnet in vitro. The lesions responded to a course of cidofovir.

Topics: Acyclovir; Antiviral Agents; Bone Marrow Transplantation; Child; Cidofovir; Cytosine; Drug Resistance, Multiple, Viral; Female; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Injections, Intravenous; Organophosphonates; Organophosphorus Compounds; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Stomatitis

Mucositis is a common complication following chemotherapy. Clinical findings similar to herpetic infection are observed in some patients. Acyclovir administered in addition to empirical, antibiotic treatment improves the course of mucositis, and can also bring down the temperature. The aim of our study was to define the etiological influence of herpetic infection on the course of febrile neutropenia in patients with mucositis. A total of 34 patients with febrile neutropenia were divided into 2 groups: 15 with typical herpetic eruption, and 19 with non-specific mucositis. Both groups received 5-10 mg/kg acyclovir every eight hours together with empiric antibiotic treatment. The effect of acyclovir was studied, and results compared in the two patient groups. Body temperatures decreased in both groups, clinical symptoms, however, disappeared more slowly in the group with non-specific mucositis. The beneficial effect of acyclovir treatment was particularly well expressed in seropositive patients. In this group of patients, herpetic infections may recur under further chemotherapy. Thus, it would be useful to administer acyclovir to them prophylactically during risk periods.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Diagnosis, Differential; Female; Fever of Unknown Origin; Hematologic Neoplasms; Herpes Simplex; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Stomatitis; Virus Activation

Various studies were done during a spontaneous outbreak of stomatitis-rhinitis-complex (mouth rot) in a collection of Mediterranean land tortoises (21 Testudo hermanni, Hermann's tortoises, and three Testudo graeca, spur-thighed tortoises) in southern Germany. These studies were intended to help diagnose the causative agent, establish a possible diagnostic method in vivo and provide information on the efficacy of aciclovir and ganciclovir against chelonian herpesviruses. Thirteen T. hermanni and no T. graeca died within a period of 6 weeks following the introduction of one apparently healthy T. graeca. Two of the dead Testudo hermanni were submitted for post-mortem examination. In addition, blood samples from 11 of the 12 tortoises still surviving at the beginning of this study were cultured for virus content and for the presence of neutralizing antibodies to chelonian herpesviruses and swabs from conjunctiva, pharynx and cloaca were cultured for the presence of viruses. Herpesviruses were isolated from tissues of the two dead Testudo hermanni (tongue, intestine, trachea, lung, spleen, heart and brain). Peripheral leukocytes from one of 11 blood samples were positive for herpesvirus isolation, indicating viremia in at least one animal. Nine of 11 pharyngeal swabs but none of the conjunctival and cloacal swabs yielded herpesviruses. Circulating neutralizing antibodies were present in two of two tested T. graeca, but absent in all of the nine samples from T. hermanni. Aciclovir and ganciclovir were effective when tested in vitro against one of the herpesvirus isolates.

Topics: Acyclovir; Animals; Antibodies, Viral; Antiviral Agents; Cells, Cultured; Conjunctivitis; Ganciclovir; Herpesviridae; Herpesviridae Infections; Leukocytes; Pharynx; Rhinitis; Stomatitis; Turtles

Few longitudinal studies have investigated the onset, duration, and resolution of ulcerative mucositis in bone marrow transplant recipients. This study prospectively followed a group of such patients on a daily basis to obtain data on the incidence of ulcerative mucositis, location and duration of lesions, severity with different conditioning regimens, and the relationship of such mucositis to the absolute neutrophil count.. Fifty-nine bone marrow transplant recipients on prophylactic acyclovir were examined daily for 26 days after marrow infusion, and all oral ulcerative lesions were recorded.. Oral ulcers occurred in 76.3% of patients, began at a mean of 5 days after marrow infusion (day + 5), and lasted for a median of 6 days. More than 90% of patients showed complete resolution of ulcers on or before day + 15, and all showed resolution when the absolute neutrophil count was > 500 cells/ml. Persistence of ulcers was noticed in patients who had oral graft-versus-host disease and in some patients who initially developed more severe ulcerations. Ninety-six percent of ulcers were located on nonkeratinized mucosa.. Ulcerative mucositis occurs in about 75% of bone marrow transplant recipients in the absence of herpes simplex virus infection. Most lesions occur on nonkeratinized mucosae which are vulnerable to trauma, especially if such mucosae are rendered atrophic by conditioning regimens. Oral ulcers may persist beyond day + 15 and after recovery of the neutrophil count in patients who initially develop more severe ulcerations or in patients who develop graft-versus-host disease.

Topics: Acyclovir; Adolescent; Adult; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Candidiasis, Oral; Child; Cohort Studies; Diagnosis, Differential; Female; Graft vs Host Disease; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Mouth Diseases; Prospective Studies; Stomatitis; Time Factors; Ulcer

The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.

Topics: Acyclovir; Alveolar Process; Animals; Biopsy; Dissection; Epithelium; Female; Mouth Mucosa; Rats; Rats, Inbred Strains; Stomatitis; Stomatitis, Herpetic; Tooth Extraction; Wound Healing