Stewardship: it's going viral.

Introduction: Historically, antimicrobial stewardship (AMS) has considered the judicious use of antibiotics. AMS is widely adopted across Europe and the US; recently antifungal AMS is gaining momentum but antiviral AMS has been little described. Here we describe the introduction of AMS virology reviews at University Hospitals Birmingham (UHBFT); a novel concept and an opportunity to broaden the beneficial aspects of AMS to virology, termed anti-viral stewardship (AVS). Method: In June 2022, a UK supply issue with aciclovir injection (ACV IV) was announced. In order to review and preserve parenteral ACV for those in greatest need, UHBFT pharmacist and virologists implemented a specialist review for patients prescribed more than 48 hours of treatment. This review initially lasted 10 weeks and data was collected on the advice offered, whether it was accepted, and time required completing the review. Results: AVS rounds halved IV ACV consumption, compared to pre or post intervention levels, with more than half of patients advised to stop or switch to oral therapy. Diagnostics and sampling guidance was offered in one quarter of reviews, whilst the remaining interventions were more stewardship focused. In almost all cases stewardship advice was readily accepted by clinical teams. Due to positive feedback from clinicians and its effective management of supply, the anti-viral stewardship (AVS) programme was re-introduced in June 2023. Conclusions: Antiviral AMS rounds provide an opportunity to optimise sampling, diagnosis and improve patient management. Introduction of regular AVS at UHBFT are now well established and plan to be implemented in other hospitals.

Analyses of the onset mechanisms of cardio-stimulatory action by aciclovir.

Cardio-stimulatory actions of aciclovir have been considered to primarily depend on the sympathetically-mediated reflex resulting from its hypotensive effect. To further clarify onset mechanisms of the cardio-stimulatory actions, we initially studied them using isoflurane-anesthetized dogs under thorough ß1-adrenoceptor blockade with atenolol (1 mg/kg, i.v.) (n = 4). Aciclovir (20 mg/kg/10 min, i.v.) decreased mean arterial blood pressure by 10 mmHg, whereas it increased heart rate by 10 bpm and maximum upstroke velocity of ventricular pressure by 928 mmHg/s, and shortened AH interval by 2 ms, indicating that cardio-stimulatory actions were not totally abolished by ß1-adrenoceptor blockade. Then, unknown mechanisms of cardio-stimulatory action were explored. Since aciclovir has a similar chemical structure to theophylline, in silico molecular docking simulation was performed, indicating aciclovir as well as theophylline possesses strong likelihood of interactions with phosphodiesterase 1A, 1C and 3A. Indeed, aciclovir inhibited phosphodiesterase 1A derived from the bovine heart (n = 4), moreover it exerted positive chronotropic action on the atrial tissue preparation of rats along with an increase of tissue cyclic AMP concentration (n = 4). These results indicate that cardio-stimulatory actions of aciclovir could result from not only hypotension-induced, reflex-mediated increase of sympathetic tone but also its inhibitory effects on phosphodiesterase in the heart.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Ramsay Hunt syndrome and concurrent varicella-zoster virus meningitis in Denmark: A nationwide cohort study.

Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.

Viral lumbosacral radiculitis (Elsberg syndrome) in Denmark.

PURPOSE: To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). METHODS: Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. RESULTS: Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). CONCLUSIONS: Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.

Ophthalmic herpes zoster in an immunocompetent five-year-old child.

OBJECTIVE: The goal of this clinical case is to report a case of ophthalmic zoster in a five-year-old boy and to insist on the relevance of early antiviral treatment (aciclovir) so as to minimize corneal affection and preserve visual function. OBSERVATION: We report the case of a five-year-old boy of preschool age with no notable pathological history who came for consultation with a painful eruption affecting the forehead, the upper eyelid, the nose. The clinical examination showed many erythematous vesicles affecting the left hemi-face. The diagnosis of ophthalmic zoster has been retained. Minimum biological laboratory assessment is normal. The treatment was local antiseptic and systemic aciclovir with high dose for ten days. The evolution was favorable. Zoster is rare in children. The ophthalmic form is exceptional. The diagnosis is clinical and should mention some bladdery lesions grouped in bunches with a disposition which follows a metamere. It can be responsible for serious ocular complications. CONCLUSION: The particularity of our observation is the presence of zoster in an immunocompetent child and the ophthalmic localization, that remains exceptional in children.

Reduction in Herpes Zoster Antiviral Use Since the Introduction of the Live-Attenuated Zoster Vaccine on Australia's National Immunisation Program: A Population-Based Study from 1994 to 2019.

INTRODUCTION: Zostavax, the live-attenuated vaccine used to prevent herpes zoster (HZ), has been available to individuals aged 70 and 71-79 years (phased catch-up) via Australia's National Immunisation Program (NIP) since 2016. There are limited data characterising the incidence of HZ at the level of the Australian population. National prescription data for antivirals used to treat HZ may be used as a proxy for HZ incidence. We aimed to examine trends in antiviral prescriptions supplied for the treatment of HZ in Australia pre- and post-2016, and to assess whether Zostavax's inclusion on the NIP correlated with a reduction in HZ antiviral prescription rates. METHODS: Using the Australian Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme prescribing data, we analysed antiviral prescriptions supplied for the treatment of HZ Australia-wide between 1994 and 2019. Annual prescription rates were calculated, and trends and changes in HZ antiviral use were explored descriptively and using Poisson models. RESULTS: HZ antiviral prescription rates increased 2.6-fold (160%) between 1995 and 2015 [25.4 (95% CI 25.2, 25.6) and 65.3 (95% CI 64.9, 65.6) prescriptions per 10,000 people, respectively], and then decreased 0.45-fold (55%) between 2016 and 2018 [60.9 (95% CI 60.6, 61.2) and 27.5 (95% CI 27.3, 27.9) prescriptions per 10,000 people, respectively]. The prescription rate for the antiviral famciclovir restricted specifically for treating HZ in immunocompromised individuals increased 8.5-fold (750%) between 2006 (year first listed) and 2019 [0.3 (95% CI 0.3, 0.3) and 2.5 (95% CI 2.4, 2.6) prescriptions per 10,000 people, respectively]. CONCLUSION: The introduction of the live-attenuated HZ vaccine on Australia's formal national vaccination program was associated with a reduction in HZ antiviral prescription rates within the Australian population. The data suggest that the introduction of Shingrix, the non-live subunit zoster vaccine, may also be associated with a similar reduction in HZ antiviral prescriptions used to treat the immunocompromised, as well as the general population, given its accepted greater efficacy over Zostavax.

Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse nuclear magnetic resonance spectroscopy.

Favipiravir (brand name Avigan), a widely known anti-influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA-dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir-ribofuranosyl-5'-monophosphate (favipiravir-RMP), by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate-determining step in the generation of the active metabolite, quantitative and real-time monitoring of the HGPRT-catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19 F- or 31 P-based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target-selective, nondestructive, and real-time observation of HGPRT-catalyzed conversion of favipiravir to favipiravir-RMP by performing time-lapse 19 F-NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31 P-NMR can be used for real-time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir-RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km . This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir-analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.

Despigmentação precoce em caso de ceratopigmentação / Early depigmentation in case of keratopigmentation

RESUMO A ceratopigmentação teve seu primeiro registro pelo filósofo Galeno há muitos séculos como uma estratégia utilizada para o tratamento estético de pacientes com leucomas. As córneas com leucoma são patológicas e, muitas vezes, intolerantes a lentes de contato cosméticas ou próteses oculares, sendo comum a queixa de desconforto excessivo, proporcionado pela superfície corneana irregular. Assim, a ceratopigmentação é uma alternativa para a melhora estética de pacientes com opacidades corneanas. Descrevemos o caso de um paciente do sexo masculino, 39 anos, que apresentou despigmentação precoce em caso de ceratopigmentação associado a quadro de ceratite herpética necrotizante. O paciente foi submetido ao tratamento com aciclovir 2g ao dia e doxiciclina 200mg ao dia, evoluindo com melhora do quadro clínico, apesar da má adesão medicamentosa.

ABSTRACT Keratopigmentation was first recorded many centuries ago by the philosopher Galeno, as a strategy used for the aesthetic treatment of patients with leukomas. Corneas with leucoma are pathological and often intolerant of cosmetic contact lenses or ocular prostheses, with complaints of excessive discomfort provided by the irregular corneal surface being common. Therefore, keratopigmentation is an alternative for the aesthetic improvement of patients with corneal opacities. We describe the case of a 39-year old male patient, who presented early depigmentation in a case of keratopigmentation associated with necrotizing herpetic keratitis. The patient was treated with Acyclovir 2g/day and Doxycycline 200mg/day, evolving with clinical improvement, despite poor medication adherence.

Encefalitis por Virus Herpes Simplex con PCR persistentemente positivo en líquido cefalorraquídeo. A propósito de un caso neonatal

RESUMEN Las infecciones por herpes virus en la etapa neonatal pueden causar una alta morbimortalidad. La persistencia del virus, a pesar del tratamiento de primera línea, puede llevar a consecuencias devastadoras para el paciente. Presentamos el caso de un paciente neonato con persistencia de Virus Herpes Simplex en LCR, en el cual fue necesario iniciar foscarnet para contener la infección.

ABSTRACT Herpes virus infections in the neonatal stage can cause high morbidity and mortality. The persistence of the virus, despite first-line treatment, can lead to devastating consequences for the patient. We present the case of a neonatal patient with persistence of Herpes Simplex Virus in the CSF, in whic foscarnet treatment was required to contain the infection.

Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG.

OBJECTIVES: Although often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. Until April 2022, the UK recommendations were that varicella immunoglobulin (VZIG) should be administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG was recommended if exposure occurred at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox. METHODS: We identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes. RESULTS: 171/186 (91.9%) of these women received either VZIG or oral aciclovir. Of the 145 women who received VZIG, 53/145 (36.6%) went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p = 0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p = 0.75). CONCLUSIONS: These findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed to varicella as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG.

Incidence and Outcome of Patients with Cardiogenic Shock and Detection of Herpes Simplex Virus in the Lower Respiratory Tract.

(1) Herpes simplex virus (HSV) reactivation in critically ill patients can cause infection in the lower respiratory tract, prolonging mechanical ventilation. However, the association of HSV reactivation with cardiogenic shock (CS) is unclear. As CS is often accompanied by pulmonary congestion and reduced immune system activity, the aim of our study was to determine the incidence and outcome of HSV reactivation in these patients. (2) In this retrospective, single-center study, bronchial lavage (BL) was performed on 181 out of 837 CS patients with mechanical ventilation. (3) In 44 of those patients, HSV was detected with a median time interval of 11 days since intubation. The occurrence of HSV was associated with an increase in C-reactive protein and the fraction of inspired oxygen at the time of HSV detection. Arterial hypertension, bilirubin on ICU admission, the duration of mechanical ventilation and out-of-hospital cardiac arrest were associated with HSV reactivation. (4) HSV reactivation could be detected in 24.3% of patients with CS on whom BL was performed, and its occurrence should be considered in patients with prolonged mechanical ventilation. Due to the limited current evidence, the initiation of treatment for these patients remains an individual choice. Dedicated randomized studies are necessary to investigate the efficacy of antiviral therapy.

A proof-of-concept study for the efficacy of dispirotripiperazine PDSTP in a rabbit model of herpes simplex epithelial keratitis.

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

The effect of Gamma and Ethylene Oxide Sterilization on a Selection of Active Pharmaceutical Ingredients for Ophthalmics.

Ensuring the sterility of life science products plays a pivotal role in the healthcare sector. Gamma irradiation and ethylene oxide sterilization are two commonly applied methods for the sterilization of medical devices, packaging components and Active Pharmaceutical Ingredients (API) for medicinal products. Focussed studies on the effects of sterilization processes on APIs remain limited. In this research study, five APIs, frequently used in sterile ophthalmic preparations were subjected to both gamma irradiation and ethylene oxide under different process conditions. The following APIs of GMP quality were selected: dexamethasone, aciclovir, tetracycline hydrochloride, triamcinolone and methylprednisolone. Analyses were performed using High Performance Liquid Chromatography equipped with UV detection and the effect of sterilization conditions on the APIs was evaluated by the assay and related substances test prescribed by the European Pharmacopoeia (Ph. Eur.). It was concluded that exposure to ethylene oxide resulted in compliance with Ph. Eur. for all APIs. While dexamethasone and methylprednisolone did not meet the requirement for the Ph. Eur. after exposure to gamma irradiation, the other three APIs did meet the requirement under the specified irradiation conditions. Subsequent optimization of sterilization parameters positively influenced the compliance to the Ph. Eur. requirements.

Insuficiencia renal aguda secundaria al tratamiento con Aciclovir por herpes zoster en pacientes con lupus eritematoso sistémico: reporte de dos casos / Acute renal failure secondary to Acyclovir treatment for herpes zoster in patients with systemic lupus erythematosus: report of two cases

Descripción del plan de cuidados:El plan de cuidados estuvo abocado a tratar las necesidades alteradas según la clasificación de Virginia Henderson. Estas necesidades alteradas fueron: la necesidad de eliminación, higiene e integridad de la piel, dolor y movilización. Para el proceso de atención de enfermería se aplicó la taxonomía NANDA.Evaluación del plan:Tras aplicar el proceso de atención de enfermería se logró mejorar la función renal, recuperar la integridad cutánea, se evitó infecciones por las lesiones en la piel producidas por el herpes zoster, se controló el dolor, y se mejoró la movilidad del brazo izquierdo de una de las pacientes que padecía paresia.Conclusiones:Es menester para enfermería realizar un seguimiento minucioso de los pacientes que presentan tratamiento con Aciclovir, especialmente de aquellos que presentan patologías crónicas de base, como lupus erite­matoso sistémico en recidivas con herpes zoster, para prevenir eventos adversos asociados al fármaco. (AU)

Description of the care plan:The care plan was aimed at addressing the altered needs according to the Virginia Henderson classification. These altered needs were the need for elimination, hygiene and skin integrity, pain and mobilisation. The NANDA taxonomy was applied for the nursing care process.Evaluation of the plan:After applying the nursing care process, renal function was improved, skin integrity was restored, infections were avoided due to skin lesions caused by herpes zoster, pain was controlled, and the mobility of the left arm of one of the patients suffering from paresis was improved.Conclusions:Close monitoring by nursing staff of patients treated with acyclovir is necessary, especially those with chronic underlying pathologies, such as systemic lupus erythematosus in relapses with herpes zoster, in order to prevent adverse events associated with the drug. (AU)

Encefalopatía como forma de presentación de la COVID-19

RESUMEN Introducción: El virus SARS-CoV-2, responsable de la COVID-19 presenta una alta tasa de contagio y es capaz de producir afecciones a diferentes niveles en el organismo, e incluye el sistema nervioso central, con manifestaciones como crisis convulsiva febril y afebril, estado de mal epiléptico, encefalopatías y encefalitis. Objetivo: Describir un paciente con encefalopatía, como forma de presentación de la COVID-19. Caso clínico: Paciente de 25 años con antecedentes de hidrocefalia obstructiva postraumática, con derivación ventrículo - peritoneal, positivo a la COVID-19, quien desarrolló manifestaciones neurológicas, en ausencia de manifestaciones respiratorias. Fue tratado según el protocolo para pacientes con la COVID-19, medidas antiedema cerebral y uso del péptido CIGB-258. Tuvo una evolución favorable hacia la recuperación. Conclusiones: En pacientes con encefalopatía de causa desconocida, en el contexto de la pandemia por la COVID-19, debe considerarse la infección por SARS-CoV-2. La evolución puede ser favorable con el uso de medidas generales y antiedema cerebral.

ABSTRACT Introduction: SARS-CoV-2 virus, responsible for COVID-19, has a high contagion rate and is capable of producing conditions at different levels in the body, and includes the central nervous system, with manifestations such as febrile and afebrile seizures, status epilepticus, encephalopathies and encephalitis. Objective: To describe a patient with encephalopathy, as a form of presentation of COVID-19. Clinical case: A 25-year-old patient with a history of post-traumatic obstructive hydrocephalus, with ventricular peritoneal shunt, positive for COVID-19, who developed neurological manifestations, in the absence of respiratory manifestations. He was treated according to the protocol for patients with COVID-19, anti-cerebral edema measures and use of the CIGB-258 peptide. The patient had a favorable evolution towards recovery Conclusions: In patients with encephalopathy of unknown cause, in the context of the COVID-19 pandemic, SARS-CoV-2 infection should be considered. The evolution can be favorable with the use of general measures and anti-cerebral edema.

A UHPLC-MS/MS Method for Therapeutic Drug Monitoring of Aciclovir and Ganciclovir in Plasma and Dried Plasma Spots.

The role of therapeutic drug monitoring (TDM) of valaciclovir (VA)/aciclovir (A) and valganciclovir/ganciclovir (VG/G) in critically ill patients is still a matter of debate. More data on the dose-concentration relationship might therefore be useful, especially in pediatrics where clinical practice is not adequately supported by robust PK studies. We developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) micro-method to simultaneously quantify A and G from plasma and dried plasma spots (DPS). The method was based on rapid organic extraction from DPS and separation on a reversed-phase C-18 UHPLC column after addition of deuterated internal standards. Accurate analyte quantification using SRM detection was then obtained using a Thermo Fisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. It was validated following international (EMA) guidelines for bioanalytical method validation and was tested on samples from pediatric patients treated with A, VG, or G for cytomegalovirus infection following solid organ or hematopoietic stem cell transplantation. Concentrations obtained from plasma and DPS were compared using Passing-Bablok and Bland-Altman statistical tests. The assay was linear over wide concentration ranges (0.01-20 mg/L) in both plasma and DPS for A and G, suitable for the expected therapeutic ranges for both Cmin and Cmax, accurate, and reproducible in the absence of matrix effects. The results obtained from plasma and DPS were comparable. Using an LC-MS/MS method allowed us to obtain a very specific, sensitive, and rapid quantification of these antiviral drugs starting from very low volumes (50 µL) of plasma samples and DPS. The stability of analytes for at least 30 days allows for cost-effective shipment and storage at room temperature. Our method is suitable for TDM and could be helpful for improving knowledge on PK/PD targets of antivirals in critically ill pediatric patients.

Aciclovir endovenoso como tratamiento en la parálisis facial periférica e idiopática en un recién nacido. Reporte de caso

Introducción: la parálisis facial neonatal debida a la parálisis de Bell es rara. El mecanismo de parto traumático representa una etiología más común. Caso clínico: neonato, previamente sano, con parto espontáneo no instrumentalizado y sin complicaciones obstétricas, que cursó con parálisis facial derecha aguda. La imagen cerebral fue normal y los hallazgos clínicos compatibles con parálisis de Bell, con buena respuesta al manejo antirretroviral y fisioterapia. Discusión: la mayoría de infantes con parálisis de Bell mejora con o sin tratamiento y sin secuelas graves. No hay evidencia concluyente en la población pediátrica sobre el beneficio de usar esteroides, solos o con antirretrovirales. Actualmente, tampoco existe un consenso sobre la seguridad de usar esteroides posnatales tardíos, que se deben reservar para neonatos sin otra opción. El aciclovir a dosis de 60 mg/Kg/día es seguro en neonatos. Conclusiones: la parálisis de Bell neonatal puede presentar una respuesta favorable a la terapia antirretroviral y fisioterapia, prescindiendo del uso de esteroides.

SUMMARY Introduction: Neonatal facial palsy due to Bell's palsy is rare. A traumatic delivery mechanism represents a common etiology. Clinical case: Neonate, without previous illnesses, born by spontaneous non-instrumentalized delivery and without any obstetric complications; who presented acute right facial palsy, with normal brain imaging and clinical findings compatible with Bell's palsy, who had a good response to antiretroviral management and physical therapy. Discussion: Most infants with Bell's palsy improve with or without treatment, with no serious sequelae. In pediatric population, evidence on benefits of steroids use, alone or with antiretrovirals, has not been conclusive. There is not a current consensus on the safety of late postnatal steroid use, and they should be reserved for neonates who have no other treatment choice. Acyclovir use at 60/mg/Kg/day it's safe in neonates. Conclusions: Neonatal Bell's palsy may present a favorable response to antiretroviral therapy and an adherent physical rehabilitation program, irrespective of steroids use.