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Revista de Neurologia Apr 2022The SARS-CoV-2 virus, which causes COVID-19, could give rise to damage the nervous system. Many studies have been conducted on this topic, but few have focused...
INTRODUCTION
The SARS-CoV-2 virus, which causes COVID-19, could give rise to damage the nervous system. Many studies have been conducted on this topic, but few have focused specifically on encephalitis. The effect of SARS-CoV-2 on the clinical expression of other neurotropic viruses, such as Herpesviridae, is unknown.
CASE REPORTS
We describe the cases of two young men (39 and 18 years old) in whom SARS-CoV-2 had been detected -reverse transcription polymerase chain reaction (RT-PCR)-, and with a clinical diagnosis and cerebrospinal fluid (CSF) analysis consistent with encephalitis. The first patient had a positive PCR for varicella zoster virus in CSF, while the second had a positive PCR for herpes simplex virus types 1 and 2. The first patient, who was recently diagnosed with human immunodeficiency virus, presented with fever, headache, vomiting, cough, inappropriate behaviour and epileptic seizures; the second was seen to have fever, headache, myalgia and exanthema. Both offered the same laboratory findings (lymphopenia and high interleukin 6). CSF showed pleocytosis with a predominance of monomorphonuclear cells, hyperproteinorrachia and normal glycorrhachia. A cranial CT scan showed only mild diffuse cerebral oedema in the first case. Both cases were treated with corticosteroids, antibiotics and acyclovir. The second progressed favourably, while the first did not.
CONCLUSIONS
Little is known about co-infection of SARS-CoV-2 with neurotropic viruses, such as Herpesviridae, and we have only limited evidence of direct neurological involvement of SARS-CoV-2, due to the technical difficulty of detecting it in the nervous system, thus making it important to take co-infection into account in order to be able to establish an early diagnosis and treatment to improve prognosis.
Topics: Acyclovir; COVID-19; Encephalitis; Herpesvirus 3, Human; Humans; Male; SARS-CoV-2
PubMed: 35383876
DOI: 10.33588/rn.7408.2021121 -
Pharmacogenetics and Genomics Jul 2022
Topics: Acyclovir; Antiviral Agents; Ganciclovir; Humans
PubMed: 35665708
DOI: 10.1097/FPC.0000000000000474 -
Canadian Family Physician Medecin de... May 2016Every year I see preschool children with gingivostomatitis. There seems to be quite a substantial burden of illness with this condition. Because it is caused by herpes... (Review)
Review
QUESTION
Every year I see preschool children with gingivostomatitis. There seems to be quite a substantial burden of illness with this condition. Because it is caused by herpes simplex virus type 1, should I prescribe antiherpetic therapy with oral acyclovir?
ANSWER
While most children with primary gingivostomatitis will be asymptomatic, some will experience considerable pain and discomfort and are at risk of dehydration. There are no large, well designed studies to clearly determine appropriate therapy for all children. Based on a single randomized study, treatment should be started only within the first 72 hours of symptom onset if substantial pain or dehydration are documented.
Topics: Acyclovir; Antiviral Agents; Child; Dehydration; Humans; Pain; Pediatrics; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Stomatitis, Herpetic
PubMed: 27255621
DOI: No ID Found -
Therapeutic Drug Monitoring Feb 2022Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of Cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such... (Review)
Review
BACKGROUND
Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of Cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such as myelosuppression, which often leads to therapy cessation. Underdosing, as an attempt to prevent side effects, can lead to drug resistance and therapy failure. Therapeutic drug monitoring (TDM) has been used to overcome these problems. The purpose of this narrative review was to give an overview of ganciclovir TDM, available assays, population pharmacokinetic models, and discuss the current knowledge gaps.
METHODS
For this narrative review, a nonsystematic literature search was performed on the PubMed database in April 2021. The following search terms were used: ganciclovir, valganciclovir, pharmacokinetics, pharmacodynamics, population pharmacokinetics, therapeutic drug monitoring, bioassay, liquid chromatography coupled with tandem mass spectrometry, liquid chromatography, chromatography, spectrophotometry, and toxicity. In addition, the reference lists of the included articles were screened.
RESULTS
The most common bioanalysis method identified was liquid chromatography coupled with tandem mass spectrometry. There are different models presenting ganciclovir IC50; however, establishing a pharmacokinetic/pharmacodynamic target for ganciclovir based on preclinical data is difficult because there are no studies combining dynamic drug exposure in relation to inhibition of viral replication. The data on ganciclovir TDM show large interindividual variability, indicating that TDM may play a role in modifying the dose to reduce toxicity and prevent treatment failure related to low concentrations. The main hurdle for implementing TDM is the lack of robust data to define a therapeutic window.
CONCLUSIONS
Although the pharmacokinetics (PK) involved is relatively well-described, both the pharmacodynamics (PD) and pharmacokinetic/pharmacodynamic relationship are not. This is because the studies conducted to date have mainly focused on estimating ganciclovir exposure, and owing to the limited therapeutic options for CMV infections, future studies on ganciclovir are warranted.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Monitoring; Ganciclovir; Humans; Valganciclovir
PubMed: 34610621
DOI: 10.1097/FTD.0000000000000925 -
Journal of Healthcare Engineering 2022The aim of this study was to systematically evaluate the efficacy and prognosis of acyclovir combined with naloxone in the treatment of patients with viral encephalitis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to systematically evaluate the efficacy and prognosis of acyclovir combined with naloxone in the treatment of patients with viral encephalitis (VE).
METHODS
PubMed, Web of Science, Embase, CNKI, and WanFang Data were searched for relevant literature published between 2000 and 2021. Meta-analysis was performed using Stata16.0 software. The treatment group was treated with acyclovir combined with naloxone, and the control group was treated with acyclovir alone.
RESULTS
A total of 12 studies with 986 participants were included. Compared with the control group, the treatment group could not only significantly improve the treatment response rate (OR = 5.53, 95% CI: 3.50, 8.74; ≤ 0.001), but also reduce the incidence of adverse reactions (OR = 0.25, 95% CI: 0.17, 0.38; ≤ 0.001). In addition, the combined treatment significantly inhibited the levels of inflammatory factors and neuron-specific enolase (NSE) in VE patients. The time for cerebrospinal fluid to return to normal (SMD = -2.73, 95% CI: -2.96, -2.51; ≤ 0.001), as well as the disappearance time of meningeal irritation (SMD = -3.58, 95% CI: -4.96, -2.20; ≤ 0.001), headache (SMD = -3.87, 95% CI: -5.84, -1.91; ≤ 0.001), convulsion (SMD = -3.65, 95% CI: -4.56, -2.75; < 0.001), tic (SMD = -4.083, 95% CI: -5.18, -2.98; ≤ 0.001) and disturbance of consciousness (SMD = -4.96, 95% CI: -6.28, -3.63; ≤ 0.001) in the treatment group were significantly shorter than those in the control group.
CONCLUSION
A combination of acyclovir and naloxone can reduce the inflammatory response and shorter the time to symptom relief and disappearance, which is worthy of clinical promotion.
Topics: Acyclovir; Drugs, Chinese Herbal; Encephalitis, Viral; Humans; Naloxone; Prognosis
PubMed: 35399846
DOI: 10.1155/2022/8593251 -
International Journal of Oral Science Mar 2016Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital... (Review)
Review
Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.
Topics: Acyclovir; Antiviral Agents; Drug Resistance; Herpes Labialis; Humans; Immunocompromised Host; Molecular Structure; Mutagenesis; Nucleosides; Plant Extracts; Simplexvirus; Stomatitis, Herpetic
PubMed: 27025259
DOI: 10.1038/ijos.2016.3 -
Cancer Biology & Therapy Dec 2023Gene edited and engineered cell-based therapies are a promising approach for treating a variety of disorders, including cancer. However, the ability of engineered cells...
Gene edited and engineered cell-based therapies are a promising approach for treating a variety of disorders, including cancer. However, the ability of engineered cells to persist for prolonged periods along with possible toxicity raises concerns over the safety of these approaches. Although a number of different one-dimensional suicide systems have been incorporated into therapeutic cell types, the incorporation of a two-layered suicide system that allows controlled killing of therapeutic cells at different time points is needed. In this study, we engineered a variety of therapeutic cells to express two different kill switches, RapaCasp9 and HSV-TK and utilized Rapamycin and Ganciclovir respectively to activate these kill switches. We show that the function of both RapaCasp9 and HSV-TK molecules is preserved and can be activated to induce apoptosis detected early (24 h) and late (48 h) post-activation respectively, with no toxicity. In vivo, we show the eradication of a majority of cells after treatment in subcutaneous and orthotopic models. Furthermore, we demonstrate how both suicide switches work independently and can be activated sequentially for an improved killing, thus ensuring a failsafe mechanism in case the activation of a single one of them is not sufficient to eliminate the cells. Our findings highlight the reliability of the double suicide system, effective on a variety of cells with different biological characteristics, independent of their anatomic presence.
Topics: Humans; Genes, Transgenic, Suicide; Genetic Therapy; Reproducibility of Results; Ganciclovir; Apoptosis
PubMed: 37439774
DOI: 10.1080/15384047.2023.2232146 -
BMC Pediatrics Feb 2020Prompt initiation of empiric therapy is common practice in case of suspected meningitis or encephalitis. However, in children the most common pathogens are viruses that...
Comparison of antibiotic and acyclovir usage before and after the implementation of an on-site FilmArray meningitis/encephalitis panel in an academic tertiary pediatric hospital: a retrospective observational study.
BACKGROUND
Prompt initiation of empiric therapy is common practice in case of suspected meningitis or encephalitis. However, in children the most common pathogens are viruses that usually do not require and are not covered by the applied anti-infective treatment. Novel multiplex PCR (mPCR) panels provide rapid on-site diagnostic testing for a variety of pathogens. This study compared empiric antibiotic and acyclovir usage before and after the introduction of an on-site FilmArray Meningitis/Encephalitis Panel (FA ME Panel).
METHODS
We retrospectively compared data for empiric antibiotic and acyclovir usage between pediatric patients with suspected central nervous system (CNS) infection receiving mPCR testing and a matched historical control group. Patients were matched by age and suspected CNS infection. We included all patients for whom empiric antibiotics and/or acyclovir were prescribed.
RESULTS
Each study group consisted of 46 patients with 29 (63.0%) infants and 17 (37.0%) older children. A viral pathogen was diagnosed in 5/46 (10.9%) patients in the control group (all enteroviruses) and in 14/46 (30.4%) patients in the mPCR group (enterovirus n = 9; human herpesvirus 6 (HHV-6) n = 5), (p = 0.038)). Length of Therapy (LoT) and Days of Therapy (DoT) for antibiotics were significantly lower for infants (4.0 vs. 3.0, p = 0.038 and 8.0 vs. 6.0, p = 0.015, respectively). Acyclovir therapy was significantly shorter for both, infants and older children (3.0 vs. 1.0 day, p < 0.001 for both age groups).
CONCLUSION
The findings of our study suggest that the introduction of a FA ME Panel into clinical routine procedures is associated with a significantly reduced LoT and DoT of empiric anti-infective treatment in children with suspected meningoencephalitis. The largest effect was observed in infants.
Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Encephalitis; Female; Hospitals, Pediatric; Humans; Infant; Male; Meningitis; Retrospective Studies; Young Adult
PubMed: 32020860
DOI: 10.1186/s12887-020-1944-2 -
Nature Communications Jul 2021Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of...
Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
Topics: Acyclovir; Adolescent; Adult; Aged; Animals; Antibiotic Prophylaxis; Antiviral Agents; Biological Variation, Population; Cell Line; Child; Child, Preschool; Crystallography, X-Ray; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Disease Models, Animal; Drug Resistance, Viral; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Host Microbial Interactions; Humans; Infant; Infant, Newborn; Male; Middle Aged; Muromegalovirus; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Pyrophosphatases; Treatment Outcome; Young Adult
PubMed: 34234136
DOI: 10.1038/s41467-021-24509-7 -
Antimicrobial Agents and Chemotherapy Nov 2020Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to...
Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.).
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Child; Humans; Valacyclovir; Valine
PubMed: 32988829
DOI: 10.1128/AAC.01426-20