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Pharmacology Research & Perspectives Jun 2024Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of...
Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CL) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CL and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CL), suggesting different dosing requirement for pre-term neonates.
Topics: Humans; Acyclovir; Infant, Newborn; Antiviral Agents; Herpes Simplex; Female; Male; Models, Biological; Creatinine; Dose-Response Relationship, Drug; Metabolic Clearance Rate; Computer Simulation
PubMed: 38775304
DOI: 10.1002/prp2.1193 -
BMC Ophthalmology May 2024Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We...
BACKGROUND
Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We describe the first case of Spiroplasma infection initially presenting as a corneal infiltrate.
CASE PRESENTATION
A 1-month-old girl was referred for a corneal infiltrate in the left eye. She presented in our hospital with unilateral keratouveitis. Examination showed a stromal corneal infiltrate and dense white keratic precipitates in the left eye. Herpetic keratouveitis was suspected and intravenous acyclovir therapy was initiated. Two weeks later, the inflammation in the left eye persisted and was also noticed in the right eye. Acute angle-closure glaucoma and a cataract with dilated iris vessels extending onto the anterior lens capsule developed in the left eye. The inflammation resolved after treatment with azithromycin. Iridectomy, synechiolysis and lensectomy were performed. Bacterial metagenomic sequencing (16 S rRNA) and transmission electron microscopy revealed Spiroplasma ixodetis species in lens aspirates and biopsy. Consequently, a diagnosis of bilateral Spiroplasma uveitis was made.
CONCLUSIONS
In cases of congenital cataract with concomitant intraocular inflammation, Spiroplasma infection should be considered. The purpose of this case report is to raise awareness of congenital Spiroplasma infection as a cause of severe keratouveitis, cataract and angle-closure glaucoma in newborns. Performing molecular testing on lens aspirates is essential to confirm diagnosis. Systemic macrolides are suggested as the mainstay of treatment.
Topics: Humans; Female; Eye Infections, Bacterial; Cataract; Uveitis; Spiroplasma; Keratitis; Infant, Newborn; Anti-Bacterial Agents; Infant
PubMed: 38773506
DOI: 10.1186/s12886-024-03480-z -
Cureus Apr 2024Neuroretinitis is a potentially vision-threatening condition distinguished by swelling of the optic disc followed by the emergence of a macular star pattern. The...
Neuroretinitis is a potentially vision-threatening condition distinguished by swelling of the optic disc followed by the emergence of a macular star pattern. The majority of these clinical observations are typically linked to infections caused by bacteria, parasites, or viruses. We report a case of dual infections in neuroretinitis complicated with severe macular edema. A 49-year-old lady presented with sudden onset left eye blurring of vision of one-week duration. Visual acuity was 6/6 in the right eye and 6/60 in the left eye. There was a left positive relative afferent pupillary defect with impaired optic nerve functions. A fundoscopy of the left eye showed optic disc swelling with a macular star. The right optic disc was also swollen. Vasculitis changes were observed in both posterior poles. The ocular coherence tomography of the left eye revealed the existence of macular edema, subretinal fluids, and an epiretinal membrane that extended from the optic disc to the fovea. Serological examinations were positive for toxoplasma and herpes simplex virus type 1. The patient was started on oral azithromycin, oral acyclovir, and oral corticosteroids. Left macular edema persisted despite the treatment. The patient was given a trial of a single injection of intravitreal ranibizumab. A remarkable reduction of subretinal fluids was seen post-intravitreal injection and continuation of medications. Intravitreal ranibizumab has shown significant outcomes in neuroretinitis with severe macula edema.
PubMed: 38765323
DOI: 10.7759/cureus.58444 -
Dermatology Online Journal Mar 2024The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised...
The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.
Topics: Humans; Herpes Simplex; Immunocompromised Host; Middle Aged; Female; Male; Antiviral Agents; Aged; Herpesvirus 1, Human; Adult; Valacyclovir; Herpesvirus 2, Human; Acyclovir; Valine; Immunosuppressive Agents; Foscarnet
PubMed: 38762853
DOI: 10.5070/D330163281 -
Dermatology Online Journal Mar 2024Herpetic geometric glossitis is a unique morphologic variant of HSV (herpes simplex virus) type 1 infection on the dorsum of the tongue that presents as an extremely...
Clinical features of atypical presentations of mucocutaneous herpes simplex virus infection observed in immunosuppressed individuals. Part I: herpetic geometric glossitis.
Herpetic geometric glossitis is a unique morphologic variant of HSV (herpes simplex virus) type 1 infection on the dorsum of the tongue that presents as an extremely painful linear central lingual fissure with a branched pattern. in the center of the tongue; there is a branched pattern of fissures that extend bilaterally from the central linear fissure. Herpetic geometric glossitis has been reported in 11 patients; 8 of these individuals were immunocompromised. Medical conditions and immunosuppressive medication treatment (7 patients) or only medical disorders (3 patients) or neither (1 patient) were present. HSV type 1 infection was diagnosed by viral culture in (7 patients), Tzanck preparation (2 patients) or clinically (2 patients). Mucocutaneous HSV infection at non-lingual locations--including the lips, labial mucosa, face and chest--were observed in 5 patients. All patients' symptoms and lesions responded to treatment with oral antiviral therapy: acyclovir (9 patients), famciclovir (1 patient) or valacyclovir (1 patient). The lingual pain and dorsal tongue fissures completely resolved completely within two to 14 days. In summary, herpetic geometric glossitis is a unique HSV type 1 infection, usually in immunocompromised patients, that occurs on the dorsal tongue and responds completely after treatment with orally administered antiviral therapy.
Topics: Humans; Glossitis; Middle Aged; Female; Immunocompromised Host; Male; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Adult; Aged; Acyclovir; Valacyclovir; Valine; Famciclovir
PubMed: 38762852
DOI: 10.5070/D330163280 -
The Journal of Surgical Research Jul 2024Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation....
INTRODUCTION
Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration.
METHODS
This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group.
RESULTS
During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection.
CONCLUSIONS
CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.
Topics: Humans; Cytomegalovirus Infections; Male; Female; Retrospective Studies; Middle Aged; Lung Transplantation; Adult; Risk Factors; Antiviral Agents; Recurrence; Valganciclovir; Aged; Cytomegalovirus; Postoperative Complications
PubMed: 38754251
DOI: 10.1016/j.jss.2024.04.012 -
Transplant Infectious Disease : An... Jun 2024Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with... (Comparative Study)
Comparative Study
BACKGROUND
Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.
METHODS
This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes.
RESULTS
A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).
CONCLUSION
LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.
Topics: Humans; Lung Transplantation; Cytomegalovirus Infections; Male; Valganciclovir; Antiviral Agents; Female; Middle Aged; Retrospective Studies; Transplant Recipients; Cytomegalovirus; Adult; Acetates; Quinazolines; Treatment Outcome; Aged
PubMed: 38742601
DOI: 10.1111/tid.14279 -
Cureus Apr 2024Atopic dermatitis (AD) characterized by pruritus and eczematous lesions makes individuals susceptible to various viral and bacterial infections. Eczema herpeticum (EH),...
Atopic dermatitis (AD) characterized by pruritus and eczematous lesions makes individuals susceptible to various viral and bacterial infections. Eczema herpeticum (EH), also known as Kaposi's varicelliform eruption, is a severe herpes simplex virus infection that can be observed in individuals with AD. EH manifests with monomorphic vesicles and "punched-out" erosions accompanied by hemorrhagic crusts, primarily affecting eczematous areas. Misdiagnosis, often as impetigo, can lead to severe complications and even death. Timely diagnosis and treatment with acyclovir are crucial to avert these outcomes. Here we present a case of a 19-year-old male with AD who presented with a monomorphic vesicular rash.
PubMed: 38738145
DOI: 10.7759/cureus.58102 -
Indian Pediatrics May 2024To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES).
OBJECTIVE
To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES).
METHODS
A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available. Electronic medical records were reviewed for details including demographic profile, clinical presentation, investigations and outcome.
RESULTS
Out of 157 CSF samples sent for FAME panel testing, 49 were positive (31.4%.) Viral pathogens were identified in 42 (Enterovirus: 31, Human herpes virus 6: 9, Varicella zoster virus: 1, and Cytomegalovirus: 1) Bacterial pathogens were identified in 6 (Streptococcus pneumoniae: 2, Streptococcus agalactiae: 2, Hemophilus influenzae: 1, and Escherischia coli: 1). Fungal etiology (Cryptococcus neoformans) was detected in one child. Antibiotics could be stopped within 72 hours of initiation in 42 children in whom a viral etiology was established. Acyclovir could be stopped in 21 out of 32 children within 72 hours after the FAME panel testing. FAME panel was presumed to be false positive in 4 children.
CONCLUSION
Etiology of AES could be established in nearly a third of children with AES using the rapid diagnostic FAME panel testing in CSF and it was found to be effective in reducing empirical antibiotic/antiviral therapy.
Topics: Humans; India; Retrospective Studies; Child; Child, Preschool; Female; Male; Infant; Acute Febrile Encephalopathy; Adolescent; Meningoencephalitis
PubMed: 38736224
DOI: No ID Found -
Antiviral Research Jul 2024Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase,...
Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.
Topics: Humans; Herpesvirus 4, Human; Virus Activation; B-Lymphocytes; Apoptosis; Cell Line, Tumor; Virus Replication; Epstein-Barr Virus Infections; Antiviral Agents; Ascomycota; Lymphoma, B-Cell; Virus Latency
PubMed: 38735576
DOI: 10.1016/j.antiviral.2024.105906