acyclovir and Neoplasms

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunity. While diagnosis of more common HSV and/or VZV infections is frequently clinically based, immunocompromised hosts may have atypical skin presentation or visceral involvement. Thus, diagnostic confirmation using virus-specific tests such as polymerase chain reaction or immunohistochemical staining is crucial in some cases. Oral acyclovir, valacyclovir and famciclovir are usually used for mild to moderate infections and intravenous acyclovir is the drug of choice for severe or disseminated infections. Foscarnet can be used when acyclovir-resistance is confirmed or suspected. Pharmaceutical prophylaxis against HSV and/or VZV should be considered in high-risk cancers patients. Currently, there is no commercially available vaccine against HSV, but VZV vaccines are available to prevent varicella and zoster.

Topics: Acyclovir; Chickenpox; Herpes Zoster; Herpesvirus 3, Human; Humans; Neoplasms; Quality of Life; Simplexvirus; Varicella Zoster Virus Infection

The goal was to characterize the clinical-epidemiological profile of patients with mucocutaneous tumoural herpes simplex virus (MCT HSV) lesions across the world. Two researchers extracted and independently reviewed data from the literature search engine PubMed/MEDLINE through October 2018. From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %-69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related. Lesions size varied from 0.2-13 cm, settling in the anogenital region in 76.36 % (84/110) patients; 84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases. On clinical basis, the initial hypothesis was neoplasia in 36/53 patients. Histopathological diagnosis was achieved in 90 % (90/100, missing 10) cases and was sample size-dependent. Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions. MCT HSV lesions recurrence after treatment was reported in 33.96 % (18/53, missing 57) patients. Pathophysiology is poorly understood. Physicians should be aware of MCT HSV lesions in immunosuppressed patients to avoid inappropriate therapeutic strategies.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Female; Herpes Simplex; Humans; Male; Middle Aged; Neoplasms; Recurrence; Simplexvirus; Young Adult

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d]pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d]pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Chemistry, Pharmaceutical; Humans; Inflammation; Neoplasms; Pyrimidines; Structure-Activity Relationship

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

The prevention of varicella in children with cancer is generally agreed to be an important goal, because of their elevated risk of varicella zoster virus (VZV)-associated morbidity and mortality. However, there is a lack of consensus on the best means of achieving this. Here, we review the existing evidence in relation to postexposure prophylaxis against varicella in this group and summarize data regarding the role of active vaccination.. Death from varicella during treatment for cancer is now rare, but VZV disease and its prevention remain significant problems in paediatric oncology practice. Measures to reduce VZV exposure amongst seronegative individuals are often neglected. When exposure is known to have occurred, early administration of varicella zoster immune globulin (VZIG) is generally protective against severe and complicated varicella. However, many centres in the UK and Japan use an oral antiviral agent, aciclovir, in place of VZIG. Published evidence for the efficacy of aciclovir as postexposure prophylaxis (PEP) relates mostly to healthy children, with no controlled studies in the immunocompromised.. Good evidence already supports the administration of varicella vaccine to healthy susceptible family contacts of children with malignancy, but not to patients themselves. Further data are urgently needed to inform the choice of PEP against VZV in the immunocompromised.

Topics: Acyclovir; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Humans; Immune Sera; Japan; Neoplasms; Post-Exposure Prophylaxis; United Kingdom

Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV).. To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer.. We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008.. All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects.. Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models.. Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0).. There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

Topics: Acyclovir; Antiviral Agents; Herpes Labialis; Humans; Immunocompromised Host; Neoplasms; Prostaglandins E; Randomized Controlled Trials as Topic; Simplexvirus; Stomatitis, Herpetic; Valacyclovir; Valine

In the search for novel antiviral molecules from natural products, we have discovered various antiviral molecules with characteristic mechanisms of action. Scopadulciol (SDC), isolated from the tropical medicinal plant Scoparia dulcis L., showed stimulatory effects on the antiviral potency of acyclovir (ACV) or ganciclovir (GCV). This effect of SDC was exerted via the activation of viral thymidine kinase (HSV-1 TK) and, as a result, an increase in the cellular concentration of the active form of ACV/GCV, i.e., the triphosphate of ACV or GCV. On the basis of these experimental results, cancer gene therapy using the HSV-1 tk gene and ACV/GCV together with SDC was found to be effective in suppressing the growth of cancer cells in animals. Acidic polysaccharides such as calcium spirulan (Ca-SP) from Spirulina platensis, nostoflan from Nostoc flagelliforme, and a fucoidan from the sporophyll of Undaria pinnatifida (mekabu fucoidan) were also found to be potent inhibitors against several enveloped viruses. Their antiviral potency was dependent on molecular weight and content of the sulfate or carboxyl group as well as counterion species chelating with sulfate groups, indicating the importance of the three-dimensional structure of the molecules. In addition, unlike dextran sulfate, Ca-SP was shown to target not only viral absorption/penetration stages but also some replication stages of progeny viruses after penetration into cells. When mekabu fucoidan or nostoflan was administered with oseltamivir phosphate, their synergistic antiviral effects on influenza A virus were confirmed in vitro as well as in vivo.

Topics: Abietanes; Acyclovir; Animals; Antiviral Agents; Biological Products; Drug Resistance, Viral; Drug Synergism; Ganciclovir; Genetic Therapy; Herpesvirus 1, Human; Humans; Neoplasms; Polysaccharides; Scoparia; Structure-Activity Relationship; Thymidine Kinase

Recent guidelines for the prevention of opportunistic infections have addressed a variety of issues germane to recipients of hematopoietic stem cell transplant. However, there are several issues regarding postexposure prophylaxis against varicella-zoster virus that remain unresolved. We address these questions and offer several consensus recommendations.

Topics: Acyclovir; Antiviral Agents; Disease Transmission, Infectious; Hematopoietic Stem Cell Transplantation; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Immune Sera; Immunization, Passive; Immunocompromised Host; Neoplasms; Opportunistic Infections; Practice Guidelines as Topic; Secondary Prevention

Antiviral prophylaxis in pediatric oncology and pediatric bone marrow transplantation (BMT)/stem cell transplantation (SCT) focuses herpes viruses: herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV) since these viruses cause significant morbidity and mortality due to primary infection or to reactivation in long term latency. The majority of studies on antiviral prophylaxis, especially those on CMV-prophylaxis, have been conducted in adult patients. Recommendations for antiviral prophylaxis have been published recently by the German "Deutsche Gesellschaft für pädiatrische Infektiologie" and by the following American institutions and societies "Centers for Disease Control and Prevention", "Infectious Diseases Society of America", "American Society of Blood and Marrow Transplantation" who published the "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients". Concerning HSV- and VZV-prophylaxis there are almost no differences between recommendations of the german society and the american institutions, however recommendations for preventing CMV-disease and CMV-recurrence do differ considerably. Controversial aspects of antiviral prophylaxis, e.g. VZV vaccination or CMV prevention, should be studied in oncology and infectious diseases working groups to define consensus in the near future.

Topics: Acyclovir; Adult; Age Factors; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Child; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunization, Passive; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Viral Vaccines; Virus Diseases

Topics: Acyclovir; Animals; Antiviral Agents; Carcinogens; Didanosine; Disease Models, Animal; Evidence-Based Medicine; Humans; Intestinal Absorption; Neoplasms; Risk Factors; Tissue Distribution; Zalcitabine; Zidovudine

Treatment options for peripheral facial palsy (PFP) are an often discussed problem in neurologic practice. Following a short description of the complex anatomy of the seventh cranial nerve we therefore review possible etiologies in the context of leading clinical signs, with idiopathic PFP or Bell's palsy (BP) being most frequent. A rather typical clinical course of BP allows to focus differential diagnostic workup predominantly on the rapid identification of treatable infections such as with Herpes zoster or Borrelia burgdorferi. Neuroimaging studies are needed only in case of trauma, with slowly developing PFP or in the presence of associated signs and symptoms. As BP is characterized by an overall high rate of spontaneous recovery, major emphasis has to be put on avoiding complications by protecting the eye. Meta-analysis of four randomized controlled studies suggests a marginal benefit of steroids concerning eventual achievement of complete recovery. Beneficial effects of a combination of acyclovir and prednisone have also been claimed. While such therapies may be considered in patients with a presumptive bad prognosis, more general recommendations on medical treatment of BP will have to await further trials.

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antiviral Agents; Clinical Trials as Topic; Diabetic Neuropathies; Diagnosis, Differential; Diagnostic Imaging; Eye Injuries; Facial Nerve; Facial Nerve Injuries; Facial Paralysis; Herpes Simplex; Humans; Neoplasms; Pons; Postoperative Complications; Prednisone; Prognosis; Virus Diseases

Topics: Acyclovir; alpha-Fetoproteins; Animals; Bacterial Proteins; Biotransformation; Cytosine Deaminase; Drug Resistance; Escherichia coli Proteins; Ganciclovir; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; Humans; Mice; Mice, Transgenic; Neoplasms; Neoplasms, Experimental; Nucleoside Deaminases; Pentosyltransferases; Precancerous Conditions; Prodrugs; Promoter Regions, Genetic; Proteins; Purine-Nucleoside Phosphorylase; Rats; Recombinant Fusion Proteins; Thymidine Kinase; Viral Proteins

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Azoles; Aztreonam; Cephalosporins; Fluoroquinolones; Foscarnet; Ganciclovir; Humans; Imipenem; Immunocompromised Host; Infections; Neoplasms; Pneumonia, Pneumocystis; Vancomycin

Herpes simplex virus (HSV) infection is common in patients receiving cytotoxic therapy for cancer. Almost all infections result from reactivation of latent virus during treatment-induced immunosuppression. Typical, self-limited orolabial or genital ulceration does not always require laboratory diagnosis or treatment, but HSV may present in an atypical fashion in cancer patients and cause more severe and prolonged mucocutaneous infection or visceral disease. The presence of antibodies to HSV identifies patients at risk for recurrent HSV infection. The treatment of choice is acyclovir, which may also be used to prevent infection in high-risk patients. Acyclovir resistance has been reported in patients with profound and prolonged immune deficiency, but remains rare in patients treated for cancer.

Topics: Acyclovir; Drug Resistance; Herpes Simplex; Humans; Immunocompromised Host; Neoplasms; Simplexvirus

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chickenpox; Child; Chronic Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Immune Tolerance; Neoplasms; Pneumonia, Viral

Topics: Acyclovir; Allopurinol; Animals; Drug Therapy; Folic Acid Antagonists; Herpes Simplex; Herpes Zoster; Humans; Leishmania; Mercaptopurine; Neoplasms; Nucleic Acid Synthesis Inhibitors; Recurrence; Species Specificity

Herpes viruses are among the most common and troublesome opportunistic pathogens infecting patients with neoplastic diseases. The recent development of partially effective and relatively nontoxic antiviral agents offers promise for the prophylaxis or therapy of these infections in high-risk groups. Vidarabine and acyclovir have shown efficacy in several herpes virus infections and are now licensed in the United States. Alpha interferon may also be useful in the prophylaxis or early therapy of certain herpes virus infections. Newer antiviral agents and combination therapies are under study. Early and rapid diagnosis of such infections is critical to the development of effective therapy.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cloning, Molecular; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infectious Mononucleosis; Interferons; Kidney Transplantation; Leukemia; Lymphopenia; Neoplasms; Pulmonary Fibrosis; Vidarabine

Progress in antiviral chemotherapy has taken place as a logical strategy for the design of antiviral agents has emerged. The second-generation nucleoside analogues, led by acyclovir, have proved their worth against herpesviruses and should now become a standard part of medical practice. Meanwhile, recombinant DNA technology has lowered the cost of interferons to the point at which the several human subtypes of these naturally occurring hormones can be subjected individually to controlled clinical trials against the viral diseases in the treatment of which they show promise. Yet, optimism about the future of antiviral chemotherapy must be tempered by the observation that most of the agents discussed in this review are described more accurately as promising rather than proven, and several of these have not yet been released in Australia at the time of writing.

Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Bromodeoxyuridine; Female; Hepatitis B; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; In Vitro Techniques; Interferons; Male; Neoplasms; Papillomaviridae; Respiratory Tract Infections; Ribavirin; Rimantadine; Tumor Virus Infections; Vidarabine

In a randomized, placebo-controlled, double-blind trial of intravenous acyclovir in the treatment of varicella zoster virus (VZV) infections, 8 of 20 immunocompromised children with varicella received acyclovir (500 mg/m2/dose three times daily for 7 days). There was no significant difference in skin healing between the acyclovir and placebo groups although there was a significant reduction in the incidence of development of pulmonary involvement during acyclovir treatment. Nineteen out of 34 patients received vidarabine (10 mg/kg/day for 5 days). Vidarabine significantly shortened the duration of new vesicle formation. Both drugs significantly reduced the incidence of visceral varicella, the most serious complication of VZV infection. An open trial also concluded that early treatment of varicella in these patients is essential. Of the 94 patients with zoster infection, 52 received acyclovir (500 mg/m2/dose infused over one hour three times daily for 7 days). Acyclovir recipients healed more rapidly, had fewer days of pain and shorter duration of viral shedding compared with placebo patients. The most important finding was that acyclovir significantly protected against progression of zoster as defined by development or progression of cutaneous dissemination and development of visceral zoster. Vidarabine seemed to be equally effective in this respect. The likelihood of cutaneous dissemination is related to the nature of the underlying condition. The in vitro sensitivity of VZV isolates from patients with second episode VZV infection during the trial did not change appreciably which suggests that VZV does not become resistant to acyclovir during therapy.

Topics: Acyclovir; Adolescent; Adult; Aged; Bone Marrow Transplantation; Chickenpox; Child; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunosuppression Therapy; Injections, Intravenous; Kidney Transplantation; Lymphoproliferative Disorders; Male; Middle Aged; Neoplasms; Random Allocation; Vidarabine

Topics: Abnormalities, Drug-Induced; Acyclovir; Animals; Animals, Newborn; Antiviral Agents; Cell Transformation, Neoplastic; Eye; Female; Growth; Guanine; Immunity; Lethal Dose 50; Male; Mutagenicity Tests; Mutation; Neoplasms; Pregnancy; Reproduction; Skin; Wound Healing

Topics: Acyclovir; Amantadine; Antiviral Agents; Bromodeoxyuridine; Clinical Trials as Topic; Guanine; Hepatitis B; Herpesviridae Infections; Humans; Interferons; Ketones; Neoplasms; Phosphonoacetic Acid; Vidarabine; Virus Diseases

To determine the likely rate of patient randomisation and to facilitate sample size calculation for a full-scale phase III trial of varicella zoster immunoglobulin (VZIG) and aciclovir as postexposure prophylaxis against chickenpox in children with cancer.. Multicentre pilot randomised controlled trial of VZIG and oral aciclovir.. England, UK.. Children under 16 years of age with a diagnosis of cancer: currently or within 6 months of receiving cancer treatment and with negative varicella zoster virus (VZV) serostatus at diagnosis or within the last 3 months.. Study participants who have a significant VZV exposure were randomised to receive PEP in the form of VZIG or aciclovir after the exposure.. Number of patients registered and randomised within 12 months of the trial opening to recruitment and incidence of breakthrough varicella.. The study opened in six sites over a 13-month period. 482 patients were screened for eligibility, 32 patients were registered and 3 patients were randomised following VZV exposure. All three were randomised to receive aciclovir and there were no cases of breakthrough varicella.. Given the limited recruitment to the PEPtalk2 pilot, it is unlikely that the necessary sample size would be achievable using this strategy in a full-scale trial. The study identified factors that could be used to modify the design of a definitive trial but other options for defining the best means to protect such children against VZV should be explored.. ISRCTN48257441, EudraCT number: 2013-001332-22, sponsor: University of Birmingham.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; England; Female; Herpesvirus 3, Human; Humans; Immune Sera; Immunization, Passive; Male; Neoplasms; Pilot Projects; Post-Exposure Prophylaxis; Treatment Outcome

Oral acyclovir has been demonstrated to prevent reactivation of herpes simplex virus (HSV) infections when administered prophylactically to autologous bone marrow transplant (BMT) recipients or patients undergoing stem cell rescue therapy. Oral valacyclovir, which is converted in the body to acyclovir, has greater oral bioavailability than oral acyclovir and compared with oral acyclovir yields similar acyclovir plasma concentrations with less frequent (twice-daily) dosing. This study compared the efficacy of oral valacyclovir with that of oral acyclovir at preventing HSV mucositis in BMT recipients. A total of 60 HSV-1-positive patients scheduled for BMT or stem cell rescue therapy were treated prophylactically with valacyclovir 500 mg twice daily until resolution of neutropenia. Data from these patients were compared with those of a historical control group of 60 patients who had received acyclovir 600 mg every 6 h until resolution of neutropenia or acyclovir 125 mg/m(2) intravenously every 6 h. The results show that none of the patients developed oral or oropharyngeal HSV infection while receiving either treatment. Of the 60 patients receiving valacyclovir, 38 (63%) completed treatment without the need for intravenous acyclovir compared with 12 of 60 (20%) patients in the acyclovir group. Additionally, the total number of doses of drug administered to the valacyclovir group was significantly less than the number received by patients in the acyclovir group. No serious adverse events occurred in either group of patients. This study demonstrates that oral valacyclovir and acyclovir are comparably effective and safe in preventing reactivation of HSV infections in autologous BMT and stem cell recipients. The less frequent dosing schedule with valacyclovir compared with acyclovir offers a potential advantage for patients undergoing BMT who frequently suffer with severe mucositis and have difficulty taking oral medications.

Topics: Acyclovir; Administration, Oral; Adult; Biological Availability; Bone Marrow Transplantation; Female; Herpes Simplex; Humans; Male; Middle Aged; Neoplasms; Patient Selection; Stem Cell Transplantation; Transplantation, Autologous; Valacyclovir; Valine

Patients who are seropositive for herpes simplex virus (HSV) and are undergoing autologous marrow or peripheral blood stem cell transplantation require prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used to achieve plasma concentrations equivalent to levels achieved with intravenous ACY. In this study, adults undergoing autologous stem cell transplantation were randomized to receive ACY, 250 mg/m2 intravenously (IV) every 12 hours from day 0 to engraftment, or VAL, 1 g orally every 12 hours from day 0 to engraftment. The primary study objective was to compare cost of HSV prophylaxis between study groups. Thirty patients were randomized to receive either oral VAL (n = 14) or IV ACY (n = 16) prophylaxis. Mean pharmacy cost of HSV prophylaxis in the patient group randomized to IV ACY was $1080 versus $320 for the group randomized initially to VAL. This study demonstrates the feasibility and significant cost savings of using oral VAL for HSV prophylaxis.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Female; Herpes Simplex; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Stem Cell Transplantation; Valacyclovir; Valine

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Opportunistic Infections; Valacyclovir; Valine

Immunocompromised patients with varicella-zoster virus (VZV) infection are at greater risk for dissemination and the development of complications than immunocompetent individuals. Consequently, they are generally hospitalized in strict isolation rooms and treated with parenterally administered acyclovir. Although effective, this approach is expensive and creates logistic difficulties in the hospital. We treated 38 immunosuppressed cancer patients presenting to our ambulatory treatment center with VZV infections with intravenous acyclovir (500 mg/m2 8-hourly) in an ambulatory/home setting. Patients were monitored for success or failure of therapy, progression of infection, development of complications or drug toxicity, and satisfaction/compliance with therapy. Most patients (33, or 87%) responded to therapy. Among the failures, 2 patients had progressive VZV infection, 2 were hospitalized due to renal toxicity, and 1 developed a superinfection. All patients eventually responded and there were no deaths on this study. Two patients relapsed within 1 month of initial response. Both responded to retreatment with acyclovir, without hospitalization. The median duration of parenteral therapy with acyclovir was 7.5 days. Seven patients (18%) had to be switched to oral acyclovir (800 mg, 5 times a day) before complete response, owing to problems with venous access. All 7 completed therapy successfully. Overall, patients expressed a high level of satisfaction with outpatient therapy, and there were no instances of noncompliance or patient requests for withdrawal from study. The results of this study indicate that VZV infections in clinically stable immunosuppressed cancer patients are relatively benign and do not require hospitalization. Parenterally administered acyclovir in an ambulatory setting is effective therapy for such infections.

Topics: Acyclovir; Adolescent; Adult; Aged; Ambulatory Care; Antiviral Agents; Costs and Cost Analysis; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Injections, Intravenous; Male; Middle Aged; Neoplasms; Prognosis; Treatment Outcome

To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem.. Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection.. Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients.. Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.

Topics: Acyclovir; Adolescent; Adult; Aged; Bacterial Infections; Cause of Death; Ceftazidime; Child; Child, Preschool; Female; Fever; Fever of Unknown Origin; Humans; Imipenem; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Vancomycin

The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.

Topics: Acyclovir; Adult; Bacteremia; Bone Marrow Transplantation; Female; Fever; Fluconazole; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Norfloxacin; Penicillins; Premedication; Streptococcal Infections; Vancomycin

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

Topics: Acyclovir; Adult; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Male; Neoplasms; Opportunistic Infections; Safety; Zidovudine

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Child; Child, Preschool; Clinical Trials as Topic; Herpes Zoster; Humans; Immune Tolerance; Infant; Neoplasms; Opportunistic Infections

Topics: Acyclovir; Chickenpox; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Drug Interactions; Female; Humans; Immunosuppressive Agents; Infant; Lymphoma; Male; Neoplasms

A comparative assessment of vidarabine and acyclovir in the treatment of varicella and disseminated zoster in immunosuppressed patients was undertaken. Thirty-eight immunosuppressed patients with varicella (N = 18) or disseminated zoster (N = 20) were treated intravenously with 10 mg/kg/day of vidarabine or 30 mg/kg/day of acyclovir for 5 days according to a preestablished code within each diagnosis group--varicella and disseminated zoster. Two deaths, although not directly related to VZV infection, were observed in the vidarabine-treated varicella group. The times to cessation of formation of new lesions and to the disappearance of fever were similar for vidarabine and acyclovir in each group. In the varicella group, VZV was isolated on day 5 in four out of five vidarabine patients versus one out of five acyclovir patients. No severe adverse effects were observed with either drug. Neutropenia present in patients of both drug groups was transitory and most often related to previous cytolytic chemotherapy. These data suggest that either vidarabine or acyclovir could be used in the treatment of severe VZV infections in immunosuppressed patients, although a larger number of patients would be required for definitive conclusion. Because of the large amount of solute required for vidarabine administration, acyclovir may be preferred when the risk of cardiorespiratory failure is high.

Topics: Acyclovir; Chickenpox; Clinical Trials as Topic; Female; Herpes Zoster; Humans; Male; Neoplasms; Random Allocation; Vidarabine

In a randomized, placebo-controlled, double-blind trial of intravenous acyclovir in the treatment of varicella zoster virus (VZV) infections, 8 of 20 immunocompromised children with varicella received acyclovir (500 mg/m2/dose three times daily for 7 days). There was no significant difference in skin healing between the acyclovir and placebo groups although there was a significant reduction in the incidence of development of pulmonary involvement during acyclovir treatment. Nineteen out of 34 patients received vidarabine (10 mg/kg/day for 5 days). Vidarabine significantly shortened the duration of new vesicle formation. Both drugs significantly reduced the incidence of visceral varicella, the most serious complication of VZV infection. An open trial also concluded that early treatment of varicella in these patients is essential. Of the 94 patients with zoster infection, 52 received acyclovir (500 mg/m2/dose infused over one hour three times daily for 7 days). Acyclovir recipients healed more rapidly, had fewer days of pain and shorter duration of viral shedding compared with placebo patients. The most important finding was that acyclovir significantly protected against progression of zoster as defined by development or progression of cutaneous dissemination and development of visceral zoster. Vidarabine seemed to be equally effective in this respect. The likelihood of cutaneous dissemination is related to the nature of the underlying condition. The in vitro sensitivity of VZV isolates from patients with second episode VZV infection during the trial did not change appreciably which suggests that VZV does not become resistant to acyclovir during therapy.

Topics: Acyclovir; Adolescent; Adult; Aged; Bone Marrow Transplantation; Chickenpox; Child; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunosuppression Therapy; Injections, Intravenous; Kidney Transplantation; Lymphoproliferative Disorders; Male; Middle Aged; Neoplasms; Random Allocation; Vidarabine

We conducted a placebo-controlled, double-blind study of acyclovir therapy for acute herpes zoster in immunocompromised patients. Of the 94 patients enrolled in the study, 52 had localized skin lesions at entry, and 42 had disseminated cutaneous zoster. A one-week course of intravenous acyclovir (1500 mg per square meter of body-surface area per day) halted progression of zoster in both groups, as determined by development or progression of cutaneous dissemination, development of visceral zoster, or proportion of cases deemed treatment failures. Significantly fewer patients treated with acyclovir within the first three days after the onset of exanthem had complications of zoster, as compared with patients treated with placebo (P = 0.02 by Fisher's exact test), but acyclovir also stopped progression of zoster in patients treated after three days of rash (P = 0.05 by Fisher's exact test). Acyclovir recipients with disseminated cutaneous zoster had a significantly accelerated rate of clearance of virus from vesicles, as compared with placebo recipients (P = 0.05 by the Breslow test).

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Leukemia; Lymphoma; Male; Middle Aged; Neoplasms; Transplantation, Homologous

The clinical effects of a new anti-viral 9-(2-hydroxymethoxymethyl) guanine (Aciclovir) against Herpes virus infections have been investigated. The patients had malignant tumours or auto-immune disease complicated by shingles and chicken pox due to Vaicella zoster virus (VZV) (43 cases), Herpes simplex virus (HSV) (10 cases) and 9 cases which were clinically diagnosed as Herpes, though the virus was not confirmed as the causative agent. As a general principle the dosage of Aciclovir was 5 mg/kg, t. i. d. for 5 days by slow intravenous infusion. The clinically effective rate against VZV was 93%, being excellent in 42% and against HSV it was 80%, being excellent in 40% and when the results of the cases of unknown origin were included it was excellent in 40% and the cumulative effective rate was 88%. Concerning the efficacy in reduction of pain, swelling, disappearance of vesicles and new scab formation, the effect was most noticeable after the third day of treatment. Treatment given early in the disease is likely to provide better results. Concerning side effects, one of 62 patients had proteinuria and the other had a drug rash and an abnormal liver function test. It is likely that the combination of treatment and the primary disease had some influence, but the cause/effect relationship to Aciclovir treatment is not clear.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Female; Herpes Simplex; Herpes Zoster; Humans; Leukemia; Male; Middle Aged; Neoplasms

A randomized double-blind, placebo-controlled, multicenter investigation assessed the usefulness of acyclovir in the treatment of immunosuppressed children with chickenpox. Twelve patients received placebo and eight received acyclovir. If the event of clinical deterioration, patients could be removed from the study to receive acyclovir. Eighteen patients had skin lesions within 96 hours of admission to the study. Nineteen patients had malignancies. The two groups of patients were similar in age, in concomitant or preceding immunosuppressive therapy, in status of malignancy, and in presenting granulocyte and lymphocyte counts. Zoster immune globulin or plasma had been given to 50% of the placebo group but to only 25% of the acyclovir group. One patient in each group had pneumonitis at entry. Of the patients without pneumonitis at entry, five of the 11 placebo patients compared with none of the seven acyclovir patients developed pneumonitis during treatment (P = 0.054). No evidence of toxicity related to acyclovir was observed.

Topics: Acyclovir; Chickenpox; Child; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Immunization, Passive; Immunosuppression Therapy; Male; Neoplasms; Random Allocation

We evaluated Acyclovir therapy in 16 immunodeficient children with varicella (7 cases) and zoster (9 cases) in a controlled open study. infections were serious in 12 patients. Each patient had daily clinical, biological and virological tests. Sixty minutes intra-venous infusions of Acyclovir were given three times a day (5 to 10 mg/kg/8 hours) for 6 ou 11 days. All patients who received therapy before the first four days, ahd a more rapid cessation of new vesicles formation and more rapid scaring, than those with delayed treatment. Ten controlled children had accelerated clearance of viral antigens from vesicles. In 15 cases, virus was not isolated after the third day. Two children with varicellous interstitial pneumonia died, 8 and 25 days after the end of treatment. Fourteen patients recovered in 8 to 10 days. No relapses of varicella-zoster virus infections had been observed 1 to 14 months after therapy. The drug was well-tolerated, but supervising of renal functions is necessary. Acyclovir had a good therapeutic efficacy to treat chickenpox and shingles in the immunocompromised patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Chickenpox; Child; Child, Preschool; Clinical Trials as Topic; Female; Herpes Zoster; Humans; Male; Neoplasms

Topics: Acyclovir; Amantadine; Antiviral Agents; Bromodeoxyuridine; Clinical Trials as Topic; Guanine; Hepatitis B; Herpesviridae Infections; Humans; Interferons; Ketones; Neoplasms; Phosphonoacetic Acid; Vidarabine; Virus Diseases

The clinical presentations of herpes simplex virus (HSV) infections are varied and range from asymptomatic to a prodrome of tingling and burning followed by painful vesicles, erosions and ulcers. Resolution leads to latent infection of the sensory ganglia. HSV-1 is associated with most of the nongenital HSV-induced infections and HSV-2 is generally associated with anogenital lesions; however, lesions at either site may be caused by both viruses. In persons living with HIV (PLHIV), the lesions have been described as verrucous/hypertrophic, exophytic or vegetative and may suggest a neoplastic rather than an infective process and this can be a diagnostic dilemma in resource-limited countries with no access to confirmatory diagnostic testing for HSV. We report on two PLHIV who developed rapidly growing lesions on the face that clinically mimicked neoplasia but were found to be HSV-associated squamous proliferative lesions which responded to high dose acyclovir.

Topics: Acyclovir; Antiviral Agents; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Neoplasms

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.

Topics: Acyclovir; Antiviral Agents; Disease Management; Germany; Hematologic Neoplasms; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Neoplasms; Vaccination; Varicella Zoster Virus Infection; Virus Activation

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Herpesvirus 3, Human; Humans; Molecular Docking Simulation; Neoplasms; Oxadiazoles; Pyrimidines; Structure-Activity Relationship

The objective of this study was to describe the incidence of acute kidney injury (AKI) in children receiving intravenous acyclovir and determine risk factors that may be associated with it.. This was a retrospective cohort study, conducted by chart review.. The study was conducted across two paediatric hospitals.. All inpatients that received intravenous acyclovir in records from January 2015 to December 2015 were reviewed. Only patients with creatinine measurements taken before and after starting acyclovir were included in the study.. The main outcome measure was the development of AKI following intravenous acyclovir administration, with AKI defined according to change in serum creatinine.. AKI following intravenous acyclovir exposure is common in children. This study raises the possibility that glomerular hyperfiltration is a previously unrecognised risk factor for acyclovir-induced AKI.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adolescent; Antiviral Agents; Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Infant; Infant, Newborn; Male; Neoplasms; Retrospective Studies; Risk Factors

Topics: Acyclovir; Administration, Oral; Chickenpox; Child; Child, Preschool; Disease Outbreaks; Female; Humans; Infant; Male; Neoplasms

Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many highincome countries, but in most low-income and middleincome countries, the burden of varicella in children treated for malignancy is poorly defined.. We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost.. Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquantile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD.. Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden.

Topics: Acyclovir; Adolescent; Age Distribution; Antineoplastic Agents; Chickenpox; Child; Child, Preschool; Comorbidity; Databases, Factual; Developing Countries; Female; Follow-Up Studies; Guatemala; Humans; Incidence; Infant; Infusions, Intravenous; Male; Needs Assessment; Neoplasms; Retrospective Studies; Risk Assessment; Sex Distribution; Survival Rate; Treatment Outcome

Topics: Acyclovir; Administration, Oral; Antibiotic Prophylaxis; Antineoplastic Agents; Chickenpox; Child; Disease Outbreaks; Hospitals, Teaching; Humans; Immunocompromised Host; India; Infection Control; Neoplasms; Outcome Assessment, Health Care

We report 2 children with life-threatening breakthrough varicella. Both had received 1 varicella vaccination before onset of cancer. Despite treatment with intravenous acyclovir, 1 child died of disseminated varicella. Because similar fatal cases have been reported, high-risk immunocompromised children with 1 varicella vaccination may warrant the same varicella prophylaxis as immunocompromised children who have never been vaccinated.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Child, Preschool; Fatal Outcome; Female; Humans; Immunization Schedule; Immunocompromised Host; Male; Neoplasms

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) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~70%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (p<0.05-0.005) of A-LCP NPs, suggests excellent in vivo efficacy. Whereas, two free drugs (ACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug.

Topics: Acyclovir; Animals; Antineoplastic Agents; Antiviral Agents; Calcium Phosphates; Cell Line, Tumor; Cell Survival; Female; Humans; Lipids; Mice; Mice, Nude; Nanoparticles; Neoplasms; Simplexvirus; Thymidine Kinase; Tumor Burden; Viral Proteins; Xenograft Model Antitumor Assays

The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233) displays great potential to produce nucleoside analogues in industry and can be exploited in the development of new anti-tumor gene therapies. In order to provide structural basis for enzyme and substrates rational optimization, aiming at those applications, the present work shows a thorough and detailed structural description of the binding mode of substrates and nucleoside analogues to the active site of the hexameric BsPNP233. Here we report the crystal structure of BsPNP233 in the apo form and in complex with 11 ligands, including clinically relevant compounds. The crystal structure of six ligands (adenine, 2'deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine) in complex with a hexameric PNP are presented for the first time. Our data showed that free bases adopt alternative conformations in the BsPNP233 active site and indicated that binding of the co-substrate (2'deoxy)ribose 1-phosphate might contribute for stabilizing the bases in a favorable orientation for catalysis. The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5' hydroxyl group of adenosine and Arg(43*) side chain contributes for the ribosyl radical to adopt an unusual C3'-endo conformation. The structures with 6-chloroguanosine and 8-bromoguanosine pointed out that the Cl(6) and Br(8) substrate modifications seem to be detrimental for catalysis and can be explored in the design of inhibitors for hexameric PNPs from pathogens. Our data also corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for hexameric PNPs than aciclovir. Furthermore, comparative structural analyses indicated that the replacement of Ser(90) by a threonine in the B. cereus hexameric adenosine phosphorylase (Thr(91)) is responsible for the lack of negative cooperativity of phosphate binding in this enzyme.

Topics: Acyclovir; Adenosine; Bacillus subtilis; Catalysis; Catalytic Domain; Crystallography, X-Ray; Ganciclovir; Genetic Therapy; Humans; Ligands; Models, Molecular; Molecular Conformation; Neoplasms; Phosphates; Prodrugs; Protein Structure, Quaternary; Purine-Nucleoside Phosphorylase; Serine; Threonine; Tubercidin

To describe postexposure prophylaxis (PEP) against varicella zoster virus (VZV) in children being treated for malignancy in the UK and Ireland: the population at risk, frequency of exposure, clinical practice and attitudes among healthcare providers.. An observational study in three parts: (1) a retrospective survey of serostatus at diagnosis of malignancy, (2) collation of varicella zoster immune globulin (VZIG) dispensing data over a 3-year period and (3) an online survey of paediatric oncologists' clinical practice and beliefs in relation to VZV disease and its prevention.. UK and Ireland.. Children diagnosed with malignancy in 2009 (serostatus survey) or receiving VZIG between April 2006 and March 2009 (VZIG dispensing study). Paediatric oncologists and haematologists working in tertiary paediatric oncology centres and related shared care units in the UK and Ireland (physician survey).. Of 1500 children diagnosed with malignancy each year, at least 24% are VZV seronegative. Few centres make efforts to prevent household exposure by vaccinating VZV-susceptible family members. Exposures to VZV result in the administration of PEP to approximately 250 children with cancer annually: half receive an intramuscular injection of VZIG while the remainder receive a course of oral aciclovir. The choice of PEP is made by doctors. There is no consensus among paediatric oncologists as to which is the better option, reflecting the lack of a secure evidence base.. A randomised controlled trial to compare the effectiveness and acceptability of VZIG and aciclovir as PEP against varicella is both desirable and feasible.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Attitude of Health Personnel; Chickenpox; Child; Child, Preschool; Drug Utilization; Epidemiologic Methods; Herpesvirus 3, Human; Humans; Immune Sera; Neoplasms; Opportunistic Infections; Post-Exposure Prophylaxis; Professional Practice; Randomized Controlled Trials as Topic

Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The aim of this study was to characterize the population pharmacokinetics of acyclovir observed following treatment with intravenous acyclovir and oral valacyclovir (valaciclovir) in young people with malignancy. Plasma acyclovir concentration-time data were collected from 43 patients (age range, 9 months to 20 years) who had been given multiple doses of acyclovir (5 mg/kg of body weight) and/or valacyclovir (10 mg/kg). Nonlinear mixed-effect modeling was employed to analyze acyclovir population pharmacokinetics and identify influential covariates. Simulations (n = 1,000) were conducted to explore the ability of the current doses to maintain acyclovir concentrations above the recommended 50% inhibitory concentration for HSV or VZV (0.56 mg/liter or 1.125 mg/liter, respectively) for more than 12 h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. The population mean estimates for clearance (CL), volume of distribution (V), absorption rate (k(a)), and bioavailability (F) were 3.55 liters/h, 7.36 liters, 0.63 h(-1), and 0.60, respectively. Inclusion of body weight and estimated creatinine CL (CL(CR)) in the final model reduced the interindividual variabilities in CL and V from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that with the use of the current doses, maximal efficacy can be achieved in over 45% of patients weighing 25 to 50 kg and with CL(CR) levels of 2.0 to 4.0 liters/h/m(2), but only in a much smaller proportion of patients, with low weights (10 kg) and high CL(CR)s (5.5 liters/h/m(2)), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Humans; Infant; Infusions, Intravenous; Neoplasms; Prospective Studies; Valacyclovir; Valine

The clinical significance of herpes simplex virus (HSV) isolated in lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is unknown. In the current study, the authors attempted to determine the clinical relevance of this finding among ST patients.. The authors reviewed records of ST patients admitted to the study institution between April 2000 and April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified in LRTS by culture alone or culture and cytology. Patients were categorized as having proven (HSV identified by culture and cytology from the LRTS), probable (HSV as the sole pathogen by culture alone), and possible (HSV along with copathogens identified by culture) HSV pneumonia.. Forty-five ST patients with either proven (6 patients), probable (25 patients), or possible (14 patients) HSV pneumonia were identified. When compared with patients with probable or possible HSV pneumonia, more patients with proven infection were on mechanical ventilation (40% vs 50% vs 100%, respectively; P=.03), and had longer length of stay in the intensive care unit (12 days vs 13 days vs 26 days, respectively; P=.05). The overall mortality rate was 22% (10 patients). Four of 25 (16%) patients who received HSV-directed antiviral therapy died during their hospital stay versus 6 of 20 (30%) who were not treated (P=.3). None of the 6 patients with proven HSV pneumonia who were treated with acyclovir died. On univariate analysis, risk factors for mortality included underlying breast cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score>15, admission to the intensive care unit, and use of mechanical ventilation and vasopressors (all P15 being found to be independent predictors of death by multiple logistic regression analysis (all P

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Neoplasms; Pneumonia, Viral; Respiration, Artificial; Retrospective Studies; Simplexvirus

The aim of this study was to create an alternative mutant of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene with reduced phosphorylation capacity for acycloguanosine derivatives, but not pyrimidine-based compounds that will allow for successful PET imaging.. A new mutant of HSV1-tk reporter gene, suitable for PET imaging using pyrimidine-based radiotracers, was developed. The HSV1-tk mutant contains an arginine-to-glutamine substitution at position 176 (HSV1-R176Qtk) of the nucleoside binding region of the enzyme.. The mutant-gene product showed favorable enzymatic characteristics toward pyrimidine-based nucleosides, while exhibiting reduced activity with acycloguanosine derivatives. In order to enhance HSV1-R176Qtk reporter activity with pyrimidine-based radiotracers, we introduced the R176Q substitution into the more active HSV1-sr39tk mutant. U87 human glioma cells transduced with the HSV1-R176Qsr39tk double mutant reporter gene showed high (3)H-FEAU pyrimidine nucleoside and low (3)H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high (18)F-FEAU and low (18)F-FHBG accumulation in HSV1-R176Qsr39tk+ xenografts. The feasibility of imaging two independent nucleoside-specific HSV1-tk mutants in the same animal with PET was demonstrated. Two opposite xenografts expressing the HSV1-R176Qsr39tk reporter gene and the previously described acycloguanosine-specific mutant of HSV1-tk, HSV1-A167Ysr39tk reporter gene, were imaged using a short-lived pyrimidine-based (18)F-FEAU and an acycloguanosine-based (18)F-FHBG radiotracer, respectively, administered on 2 consecutive days.. We conclude that in combination with acycloguanosine-specific HSV1-A167Ysr39tk reporter gene, a HSV1-tk mutant containing the R176Q substitution could be used for PET imaging of two different cell populations or concurrent molecular biological processes in the same living subject.

Topics: Acyclovir; Amino Acid Substitution; Animals; Cell Line, Tumor; Drug Resistance, Viral; Gene Expression Regulation, Neoplastic; Genes, Reporter; Herpesvirus 1, Human; Humans; Mice; Mutation; Neoplasms; Phosphorylation; Positron-Emission Tomography; Pyrimidines; Radioactive Tracers; Substrate Specificity; Thymidine Kinase

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.

Topics: Acyclovir; Adolescent; Adult; Aged; Chickenpox; Child; Child, Preschool; Female; Genetic Diseases, Inborn; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Humans; Incidence; Infant; Infant, Newborn; Japan; Male; Middle Aged; Neoplasms; Neuralgia, Postherpetic; Postoperative Complications; Retrospective Studies; Risk; Transplantation, Autologous; Transplantation, Homologous; Valacyclovir; Valine; Virus Activation; Young Adult

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer.

Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells

Topics: Acyclovir; Administration, Oral; Antineoplastic Agents; Antiviral Agents; Child; Herpes Simplex; Humans; Neoplasms; Simplexvirus; Time Factors

Cytomegalovirus (CMV) disease remains an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We evaluated high-dose acyclovir (HDACV) and pre-emptive ganciclovir to prevent CMV disease in 76 children who underwent peripheral blood stem cell transplantation (PBSCT) and were at risk for CMV reactivation and disease (both recipient and donor seropositive) from May 1998 to April 2003. All received HDACV from day -9 to 6 months post transplant in conjunction with weekly CMV pp65 antigenemia monitoring. The incidence of antigenemia in this cohort was 19.7%, at a median of 22 days post-PBSCT. The frequencies were 26.4 and 4.4% in allogeneic and autologous groups, respectively (P=0.03). Patients with nonmalignant disease had higher CMV antigenemia than those with malignant disease (30.8 vs 8.1%, P=0.02). Age at PBSCT, sex, graft-versus-host disease (GVHD) prophylaxis regimen and presence of acute GVHD did not affect the risk of CMV antigenemia. None of the patients who had positive pp65 antigenemia developed CMV disease during the study period. We conclude that pp65 antigenemia-guided HDACV and pre-emptive ganciclovir may prevent CMV disease in children undergoing PBSCT.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Cohort Studies; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Neoplasms; Phosphoproteins; Risk Factors; Time Factors; Treatment Outcome; Viral Matrix Proteins

Infections caused by Varicella Zoster virus in children with cancer have a high rate of complications and mortality.. To report the outcome of this infection in children with cancer.. Retrospective analysis of medical records of 216 children aged less than 15 years old with the diagnosis of an hematological or solid tumor, admitted to the National Program of Antineoplastic Drugs (PINDA).. Eighty seven children had a Varicella Zoster virus infections, 73 (84%) had varicella, 8 (9%) had herpes zoster and 6 (7%) had varicella and herpes zoster. Ninety four percent acquired the infection during antineoplastic treatment and 78% received Acyclovir as antiviral therapy. During a nosocomial outbreak of varicella, three patients with an Acute Lymphoblastic leukemia died in the initial phase of chemotherapy, in spite of an early administration of Acyclovir. No patient with herpes zoster died.. The incidence of varicella was higher in children with leukemia or lymphoma than in children with other types of cancer. Virus reactivation was uncommon and had a benign course. Varicella mortality in these children could be favorably modified through an active immunization of immunocompetent children.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Child; Child, Preschool; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Infant; Infant, Newborn; Neoplasms; Retrospective Studies

Shingles are caused by an endogenous or exogenous reinfection with varicella zoster virus (VZV). Up to 50% of individuals with Hodgkin's disease develop herpes zoster; however, no association could be shown between the occurrence of herpes zoster and underlying subclinical malignancies.. This study was conducted to investigate whether VZV DNA could be detected by polymerase chain reaction (PCR) in the blood of herpes zoster patients and whether there was an association between VZV viraemia and previous or concurrent neoplasias.. At least five blood samples from 28 patients with herpes zoster were investigated by internally controlled PCR enzyme-linked immunosorbent assay prior to and during therapy with aciclovir.. None of 13 patients, two with a history of neoplasia and two with a neoplasia at the time of the study, showed any signs of viraemia with VZV, and 14 patients had inconsistent viraemia, one with a history of neoplasia and two with neoplasia at the time of the study. In one patient VZV DNA was detected in the blood for 6 days. This patient died soon after from metastatic malignant melanoma.. VZV viraemia may occur during herpes zoster episodes, even in patients without evidence of immunosuppression; however, this viraemia is, in most cases, inconsistent and does not provide any specific information concerning underlying unrecognized malignancies.

Topics: Acyclovir; Adult; Aged; Base Sequence; DNA, Viral; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Molecular Sequence Data; Neoplasms; Polymerase Chain Reaction; Prognosis; Prospective Studies; Risk Factors; Sampling Studies; Sensitivity and Specificity; Viremia

In most tissue culture cell lines tested, infection with the paramyxovirus simian virus 5 (SV5) results in very little cell death. To determine if SV5 could be used as a vector for controlled killing of tumor cells, a recombinant SV5 (rSV5-TK) was constructed to encode the herpes simplex virus thymidine kinase (TK) gene. MDBK cells infected with rSV5-TK showed a time-dependent loss of viability when infected cells were cultured in the presence of the prodrug acyclovir (ACV) or ganciclovir (GCV) while no significant toxicity was observed in the absence of prodrug. Cells infected with a control rSV5 expressing GFP and cultured with prodrug showed only a slight reduction in growth rate and little cell death. Time-lapse video microscopy of rSV5-TK-infected MDBK cells that were cultured in the presence of ACV showed an accumulation of cells with morphological effects characteristic of apoptotic cell death. An MDBK cell line persistently infected with rSV5-TK retained long-term expression of TK and sensitivity to prodrug-mediated cell killing that were comparable to those found in an acute infection. Titration experiments showed that the rSV5-TK plus GCV combination resulted in cell death for all mouse and human cell lines tested, although the kinetics and efficiency of cell death varied between cell types. Our results demonstrating controlled cell killing by a recombinant paramyxovirus support the use of negative-strand RNA viruses as therapeutic vectors for targeted killing of cancer cells.

Topics: Acyclovir; Animals; Cell Death; Cell Line; Dose-Response Relationship, Drug; Ganciclovir; Genetic Therapy; Genetic Vectors; Neoplasms; Recombinant Proteins; Respirovirus; Simplexvirus; Thymidine Kinase; Tumor Suppressor Protein p53

The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.

Topics: Acyclovir; Adolescent; Adult; Anti-Infective Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Ciprofloxacin; Combined Modality Therapy; Communicable Diseases; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Itraconazole; Male; Middle Aged; Neoplasms; Prospective Studies; Staphylococcal Infections; Staphylococcus epidermidis; Transplantation, Autologous; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans; Neoplasms; Recurrence; Time Factors

To determine the frequency of, risk factors for, and clinical course of herpes zoster (HZ) after bone marrow transplantation (BMT) in children.. A total of 107 children with hematologic malignancy or solid tumor who underwent allogeneic or autologous BMT were studied retrospectively.. Of the 107 patients, HZ developed in 35 (33%) after BMT; 31 (89%) of these 35 patients had localized HZ. The median onset of infection was day 96 after BMT, and 89% of cases of HZ occurred before day 365 after BMT. HZ developed in 26 (58%) of 45 patients (13/21 (62%) allogeneic and 13/24 (54%) autologous patients) with hematologic malignancy; most of these patients had undergone total body irradiation. Of 33 patients with solid tumor, HZ developed in 9 (27%). All patients with HZ were treated with acyclovir, and no patients died of complications directly resulting from HZ.. Herpes zoster occurred earlier after BMT than in adults, and it occurred frequently in children who had hematologic malignancy and/or had undergone total body irradiation. Prompt antiviral therapy reduced the mortality rate and significant morbidity associated with HZ.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Case-Control Studies; Chickenpox; Child; Female; Herpes Zoster; Humans; Incidence; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Whole-Body Irradiation

The Durable Medical Equipment Regional Carriers has recommended excluding ganciclovir, acyclovir, and vancomycin from the list of Medicare-covered drugs. Only drugs infused by a pump, as indicated in the drug's product labeling, will be covered. IV ganciclovir is not covered, even though it is the drug of choice for treating cytomegalovirus retinitis. IV acyclovir, a standard therapy for disseminated herpes simplex infection among people with AIDS, is also not covered.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Retinitis; Foscarnet; Ganciclovir; Humans; Infusions, Intravenous; Insurance, Pharmaceutical Services; Medicare; Neoplasms; Vancomycin

Topics: Acyclovir; Animals; Drug Resistance; Female; Ganciclovir; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Mice; Mice, Inbred C57BL; Neoplasms; Retroviridae; Simplexvirus; Thymidine Kinase; Tumor Cells, Cultured

Immunocompromised children are potentially threatened by infections, among which, the highly contagious chickenpox infection is the most common. In the past six months, there has been a spate of five chickenpox infections in children with malignancy, all of whom were receiving chemotherapy at that time.. The cases of 17 children with malignancies, who suffered from varicella-zoster infection during a period of chemotherapy at Taichung Veterans General Hospital were reviewed.. The diagnoses of their neoplasms were 12 acute lymphoblastic leukemia (ALL), 2 lymphoma, 3 solid tumors. The mean age was 6.8 +/- 4.0 year-old (range 3 to 15 year-old). The average duration from chickenpox skin eruption to admission was 3.3 +/- 1.8 days. Four patients suffered from abdominal pain and three of them died soon; three of them suffered from back pain and one died later. Seven of these 11 patients had impaired liver function (GOT > 45 U/L), of whom 4 died later. There were seven patients with pneumonitis, of whom five died later. Among 12 patients with ALL, 3 had absolute lymphocyte counts (ALC) < 500/mm3, but only 1 died later; 9 had ALC > 500/mm3, of whom 4 had pneumonitis, and all died later. Four patients developed disseminated intravascular coagulopathy, and three of them died later. Seven patients were prescribed acyclovir within three days after first skin eruption, none of these died. Ten patients were prescribed acyclovir three days or more after first skin eruption and five of them died later. Five patients were prescribed intravenous immunoglobulin (IVIG) within three days after first skin eruption, and none of them died; of the seven patients prescribed IVIG three days or more after first skin eruption, three died later.. Abdominal pain and disseminated intravascular coagulopathy (DIC) were signs of visceral dissemination. Severe liver function impairment, pneumonitis and DIC were the principal causes of death. Early administration of acyclovir and intravenous immunoglobulin (IVIG) can probably effectively prevent the dissemination of varicella-zoster virus (VZV). While varicella-zoster immunoglobulin (VZIG) was unavailable, IVIG was still valuable in treating VZV infection.

Topics: Acyclovir; Adolescent; Chickenpox; Child; Child, Preschool; Female; Humans; Immunoglobulins, Intravenous; Male; Neoplasms

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Agranulocytosis; Bacterial Infections; Breast Neoplasms; Candidiasis; Female; Herpes Zoster; Hodgkin Disease; Humans; Immunocompromised Host; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Neutropenia

To determine the sensitivity of herpes simplex virus isolates to acyclovir and the importance of resistant isolates in hospitalized patients.. Retrospective incidence cohort study.. All herpes simplex virus isolates cultured over 1 year from patients followed at a tertiary care center.. Consecutive herpes simplex virus isolates were collected from 207 patients, including immunocompetent patients, patients with malignancy, neonates, bone marrow and organ transplant recipients, and patients seropositive for human immunodeficiency virus.. A rapid nucleic acid hybridization method was used to assess susceptibility to acyclovir. Acyclovir-resistant herpes simplex viruses were recovered from 7 of 148 immunocompromised patients (4.7%) but from none of 59 immunocompetent hosts. Clinical disease was found in all 7 patients with resistant herpes simplex virus and was more severe in pediatric patients. All resistant isolates were from acyclovir-treated patients and had absent or altered thymidine kinase activity by plaque autoradiography.. Herpes simplex virus resistant to acyclovir arises relatively frequently in immunocompromised patients and may cause serious disease. Rapid detection of resistance permits antiviral therapy to be individualized. Antiviral susceptibility testing to monitor viral resistance should be encouraged, especially in tertiary care settings.

Topics: Acyclovir; Adult; Bone Marrow Transplantation; Drug Resistance, Microbial; Female; HIV Infections; Hospitals, University; Humans; Infant; Infant, Newborn; Male; Middle Aged; Minnesota; Neoplasms; Nucleic Acid Hybridization; Simplexvirus; Transplantation Immunology

Oral ulcerations are frequently observed in cancer patients receiving chemotherapy or radiation therapy. Herpes simplex virus is the most common viral pathogen association with lesions. Reactivation of latent virus is responsible for the vast majority of culture-positive infections. The natural history of this virus has been well studied in selected patient populations. These infections may cause local complications and, if untreated, may not heal for weeks. Reactivation of the virus may occur predictably in patients after bone marrow transplantation or acute leukemia. Recognition that herpes simplex virus is present in oral lesions is of importance because of the availability of safe, effective antiviral therapy. Prospective, randomized, double-blind clinical trials have demonstrated that acyclovir is the most effective agent to treat or prevent herpes simplex virus infections in immunocompromised patients.

Topics: Acute Disease; Acyclovir; Herpes Simplex; Humans; Neoplasms

Topics: Acyclovir; Herpes Zoster; Humans; Injections, Intravenous; Laryngeal Neoplasms; Neoplasms

Topics: Acyclovir; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Herpes Labialis; Humans; Mouth Diseases; Mycoses; Neoplasms

Topics: Acyclovir; Adult; Female; Herpes Zoster; Humans; Male; Neoplasms; Poly I-C; Vidarabine

Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day -12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cytomegalovirus Infections; Drug Combinations; Drug Therapy, Combination; gamma-Globulins; Herpesviridae Infections; Humans; Immune Tolerance; Infant; Neoplasms; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The effects of low-dose and short-time acyclovir therapy in 14 children with malignant disease of ages 4-18 years who had developed varicella zoster virus infections while receiving aggressive chemo-/+radiotherapy are reported. Ten of them had chickenpox and 4 herpes zoster. Acyclovir 5 mg/kg was infused IV every 12 h in 9 patients and every 8 h in 5 patients for a median of 4 days' duration. We resumed the primary therapy when the patients' lesions had dried out and became crusted and new lesions had not reappeared. The period of initiation of the acyclovir therapy to the resumption of oncological treatment was 8.4 +/- 2.7 days for chickenpox and 12.0 +/- 3.4 days for herpes zoster patients. After restarting the oncological therapy, no adverse effects of acyclovir or complication of infection were observed. The efficiency of early, short-term, and relatively low dose acyclovir therapy is discussed and compared to the results in the relevant literature.

Topics: Acyclovir; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chickenpox; Child; Child, Preschool; Drug Evaluation; Female; Herpes Zoster; Humans; Male; Neoplasms

Considerable progress has been made in the supportive care of patients undergoing cancer therapy. This progress has been associated with the improved survival of some patients. However, infection continues to be the major fatal complication in cancer. patients. The response of granulocytopenic patients with infections to some of the current available antibiotics is suboptimal. Since neutropenia is common during cancer treatment, there is a continual risk of infection in cancer patients; thus it is important for medical oncologists to become aware of these complications and their management. The most frequent types of acute infections, their clinical manifestations, and available antibiotic therapies were reviewed.

Topics: Acyclovir; Anti-Bacterial Agents; Bacterial Infections; Fever; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Neoplasms; Neutropenia; Vidarabine; Virus Diseases

A short review on available toxicological data of acyclovir is given. In principle, a substance which interferes with the nucleic acid metabolism should be judged with special care for carcinogenic and mutagenic properties. Although the substance is mainly incorporated into the viral genome, very high doses have also shown genotoxic effects in mammalian cell systems. However, since such effects are found only in doses where also naturally occurring nucleosides show the same effect, this manifestation does not appear to represent a potential hazard. In general, acyclovir seems to have a low toxic potential. Data from available investigations do not give support for a mutagen, teratogen or carcinogen hazard in patients receiving recommended clinical doses. An awareness of a potential risk for the fetus, especially with infusion treatment should nonetheless be kept in mind. The possibility of kidney damage with accumulation of the drug should also be taken into account. Such damage seems to have less importance with p.o. administration, and has little or no importance with the proposed use of eye ointment.

Topics: Abnormalities, Drug-Induced; Acyclovir; Animals; Dogs; Female; Humans; Lethal Dose 50; Mice; Mutagenicity Tests; Neoplasms; Pregnancy; Rabbits; Rats

21 patients, aged 1 to 15 years, who developed manifest varicella/zoster-virus infection while on chemotherapy for malignant disease were treated with acyclovir. Drug dosage was 10 mg/kg every eight hours for 5 days as a one hour infusion. The clinical course of the infection in all patients was mild. 1 to 4 (median 2,2) days after beginning of acyclovir therapy the formation of new lesions stopped. Within 4 to 8 (median 5,9) days all vesicles were scabbed . In 13 patients with fever in the beginning the temperature fell within 2 to 6 (median 2,6) days of treatment. The development of visceral involvement was not observed during or after acyclovir therapy. Acyclovir was well tolerated. Tests of the hematopoietic, liver and renal functions before and after acyclovir therapy revealed no adverse effects of the drug. Also the immunologic response seemed not to be impaired. With one exception, all patients investigated had antibodies against varicella/zoster-virus after recovery. In order to prevent varicella infection after household exposure two immunocompetent patients were treated prophylactically with acyclovir tablets (400 mg 5 times a day for 5 days). Both children did not exhibit manifest varicella/zoster infection, but five weeks later they had antibodies against varicella/zoster-virus (KBR 1:10, resp. KBR 1:20).

Topics: Acyclovir; Adolescent; Adult; Antibodies, Viral; Antineoplastic Combined Chemotherapy Protocols; Chickenpox; Child; Child, Preschool; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunosuppression Therapy; Infant; Liver Function Tests; Neoplasms

Topics: Acute Kidney Injury; Acyclovir; Adult; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Neoplasms; Pregnancy; Pregnancy Complications; Virus Diseases

Topics: Acyclovir; Administration, Oral; Adolescent; Chickenpox; Child; Female; Herpes Zoster; Humans; Immune Tolerance; Male; Neoplasms

The therapeutic efficacy of 9-(2-hydroxyethoxymethyl) guanine (Acyclovir, ACV) was evaluated using Oncorhynchus masou virus (OMV) and chum salmon fry. The fish, which were experimentally infected with OMV, were treated with ACV either orally or by the immersion method. Daily immersion of fish into ACV solution (25 microgram/ml, 30 min/day, 15 times) reduced mortality of the infected fish. Oral administration of the drug (25 microgram/fish per day, 60 times) did not affect survival of the chum salmon. On the contrary, the group administered 5-iodo-2'-deoxyuridine (IUdR) by the oral route showed a higher survival than the ACV-administered group. This suggested that an effective level of ACV was not maintained in fish given the drug by the oral route. Daily immersion of infected fish into ACV solution (25 microgram/ml, 30 min/day, 60 times) considerably suppressed the development of tumors induced by OMV.

Topics: Acyclovir; Animals; Fish Diseases; Herpesviridae Infections; Neoplasms; Salmon

Sixty minutes intravenous infusions of Acyclovir were given at 5 to 10 mg/kg 3 times daily for 6 to 11 days in 20 immunodeficient children with varicella (9 cases) and herpes zoster (11 cases) in a controlled open study. Twelve patients had a life-threatening illness. All patients who received therapy before the first 4 days had a more rapid cessation of new vesicles formation and more rapid scarring. Fourteen controlled children had accelerated clearance of viral antigens from vesicles. In 19 cases, virus was no longer isolated after the 3rd day. Eighteen patients recovered within 6 to 10 days. No relapse of varicella zoster virus infections had been observed 1 to 18 months after the end of treatment. Two children with varicellous interstitial pneumonia died 8 and 32 days after the end of treatment. In 3 cases, zoster pains reappeared 8 days after Acyclovir therapy was stopped. The drug was well-tolerated, but control of renal functions is necessary.

Topics: Acyclovir; Adolescent; Antigens, Viral; Chickenpox; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Herpes Zoster; Humans; Immune Tolerance; Infusions, Parenteral; Leukemia; Lymphoma; Male; Neoplasms