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Indian Journal of Dermatology,... 2022Varicella gangrenosa is a rare but life-threatening dermatological complication of infection with varicella-zoster virus. A healthy 37-year-old male who had been...
Varicella gangrenosa is a rare but life-threatening dermatological complication of infection with varicella-zoster virus. A healthy 37-year-old male who had been diagnosed with varicella 20 days back was admitted to our hospital with complaints of fever and painful necrotic skin lesions. Physical examination revealed multiple round to oval ulcers covered with eschar predominantly over arms, lower limbs, back of trunk and flanks. Streptococcus pyogenes and Staphylococcus aureus grew in wound culture. Biopsy revealed ulceration and necrosis of epidermis, and edema, hemorrhage and granulation tissue formation involving the dermis and subcutaneous tissue. The patient was treated with acyclovir - parenteral followed by oral, antibiotics and supportive measures. The lesions healed and he was discharged after 20 days. We report this case to draw attention to the fact that varicella gangrenosum, even though a rare complication, may occur in the lesions of chicken pox and that the survival of patient depends on early diagnosis and aggressive treatment.
Topics: Male; Humans; Chickenpox; Herpesvirus 3, Human; Acyclovir; Necrosis
PubMed: 34491686
DOI: 10.25259/IJDVL_65_20 -
Pain Physician Jul 2023The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to... (Meta-Analysis)
Meta-Analysis
A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.
BACKGROUND
The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain.
OBJECTIVES
The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020.
METHODS
Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events.
RESULTS
A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo.
LIMITATIONS
The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors.
CONCLUSIONS
For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated.
CLINICAL TRIAL REGISTRATION INFORMATION
PROSPERO under the identification CRD42020212834.
Topics: Humans; Antiviral Agents; Valacyclovir; Famciclovir; Network Meta-Analysis; Acute Pain; Randomized Controlled Trials as Topic; Acyclovir; Herpes Zoster; Neuralgia, Postherpetic
PubMed: 37535772
DOI: No ID Found -
Early Human Development Jul 2022Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.
BACKGROUND
Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.
AIMS
Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).
STUDY DESIGN
We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model.
SUBJECTS
Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals.
OUTCOME MEASURES
We identified clinical and laboratory adverse events (AEs).
RESULTS AND CONCLUSIONS
We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2-37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.
Topics: Acyclovir; Antiviral Agents; Child; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Pregnancy Complications, Infectious; Simplexvirus
PubMed: 35763957
DOI: 10.1016/j.earlhumdev.2022.105616 -
The Cochrane Database of Systematic... Nov 2016Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the... (Review)
Review
BACKGROUND
Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications.
OBJECTIVES
To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016.
SELECTION CRITERIA
We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach.
MAIN RESULTS
One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir.
AUTHORS' CONCLUSIONS
This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.
Topics: Acyclovir; Antiviral Agents; Herpes Zoster Ophthalmicus; Humans; Immunocompetence; Randomized Controlled Trials as Topic; Valacyclovir; Valine
PubMed: 27841441
DOI: 10.1002/14651858.CD011503.pub2 -
The Cochrane Database of Systematic... Jan 2016The Cochrane Oral Health Group withdrew this review as of Issue 1, 2016. The review is out of date and does not meet current Cochrane methodological standards. It will... (Meta-Analysis)
Meta-Analysis Review
The Cochrane Oral Health Group withdrew this review as of Issue 1, 2016. The review is out of date and does not meet current Cochrane methodological standards. It will be superseded by a new expanded Cochrane review on Interventions for treating primary herpetic gingivostomatitis. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Female; Gingivitis; Humans; Infant; Male; Randomized Controlled Trials as Topic; Stomatitis, Herpetic
PubMed: 26784280
DOI: 10.1002/14651858.CD006700.pub3 -
Italian Journal of Pediatrics Sep 2022Intraosseous (IO) access offers a fast and reliable route for administration of fluids and drugs when intravenous (IV) accesses like umbilical, peripheral, or...
Intraosseous (IO) access offers a fast and reliable route for administration of fluids and drugs when intravenous (IV) accesses like umbilical, peripheral, or peripherally inserted central lines fail in critically ill neonates. Several medications can be successfully administered via the IO route, however only limited information is available regarding IO administration of antiviral agents.We present the case of a 2-week-old neonate, admitted to the Neonatal Intensive Care Unit (NICU) due to suspected meningitis, who received acyclovir through IO infusion after the venous access was lost and a new one could not be established. No complications were reported within 12 months of follow up.This report highlights the feasibility of IO acyclovir infusion when IV accesses fail in a critically ill neonate.
Topics: Acyclovir; Critical Illness; Humans; Infant, Newborn; Infusions, Intraosseous; Tibia
PubMed: 36068631
DOI: 10.1186/s13052-022-01353-z -
Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1.Acta Pharmacologica Sinica Sep 2023Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis...
Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg·d, i.g.) or acyclovir (ACV, 206 mg·kg·d, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 μM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 μM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.
Topics: Humans; Animals; Mice; Herpesvirus 1, Human; Lipid Peroxidation; Neuroblastoma; Acyclovir; Herpes Simplex
PubMed: 37193755
DOI: 10.1038/s41401-023-01095-6 -
British Journal of Clinical Pharmacology May 2023Letermovir inhibits renal tubular organic anion transporter 3 (OAT3) in vitro and is predicted to inhibit OAT3 in vivo. Acyclovir, a substrate for OAT3, is likely to be...
Letermovir inhibits renal tubular organic anion transporter 3 (OAT3) in vitro and is predicted to inhibit OAT3 in vivo. Acyclovir, a substrate for OAT3, is likely to be coadministered with letermovir; therefore, letermovir may increase acyclovir concentrations. A drug-drug interaction study was conducted in healthy participants (N = 16) to assess the effect of letermovir on acyclovir pharmacokinetics. On Day 1, participants received a single oral dose of 400 mg acyclovir; on Days 2-7, participants received oral doses of 480 mg letermovir once daily with a single oral dose of 400 mg acyclovir coadministered on Day 7. Coadministration with letermovir resulted in geometric mean ratios (90% confidence intervals) for acyclovir area under the concentration-time curve from administration to infinity and maximum plasma concentration of 1.02 (0.87-1.20) and 0.82 (0.71-0.93), respectively. No notable safety issues were reported. No clinically significant interaction was observed between letermovir and acyclovir in healthy participants and no dose adjustment is required for coadministration.
Topics: Humans; Acyclovir; Healthy Volunteers; Drug Interactions; Area Under Curve
PubMed: 36537620
DOI: 10.1111/bcp.15648 -
Viruses Nov 2022Herpes viruses are widespread in the human population and can cause many different diseases. Genital herpes is common and can increase the risk of HIV infection and...
Herpes viruses are widespread in the human population and can cause many different diseases. Genital herpes is common and can increase the risk of HIV infection and neonatal herpes. Acyclovir is the most used drug for herpes treatment; however, it presents some disadvantages due to its poor oral bioavailability. In this study, some ethylene vinyl acetate devices with different acyclovir amounts (0, 10, and 20 wt.%) were manufactured by fused filament fabrication in two different geometries, an intrauterine device, and an intravaginal ring. Thermal analyses suggested that the crystallinity of EVA decreased up to 8% for the sample loaded with 20 wt.% of acyclovir. DSC, SEM, and FTIR analyses confirmed that the drug was successfully incorporated into the EVA matrix. Moreover, the drug release tests suggested a burst release during the first 24 h followed by a slower release rate sustained up to 80 days. Biological assays showed the biocompatibility of the EVA/ACV device, as well as a 99% reduction in vitro replication of HSV-1. Finally, the EVA presented a suitable performance for 3D printing manufacturing that can contribute to developing personalized solutions for long-term herpes treatment.
Topics: Humans; Infant, Newborn; Acyclovir; Antiviral Agents; Genitalia; HIV Infections; Printing, Three-Dimensional; Simplexvirus
PubMed: 36423110
DOI: 10.3390/v14112501 -
Journal of Medical Case Reports Jun 2024Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the...
OBJECTIVE
Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation.
CASE REPORT
A female newborn (Iranian, Asian) with gestational age 37 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase.
CONCLUSION
Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.
Topics: Humans; Acyclovir; Female; Infant, Newborn; Antiviral Agents; Extravasation of Diagnostic and Therapeutic Materials; Herpes Simplex; Hyaluronoglucosaminidase
PubMed: 38845030
DOI: 10.1186/s13256-024-04585-1