Foscarnet sodium 6g/250ml solution for infusion bottles

Our case demonstrated unique cytomegalovirus (CMV) encephalitis post-haploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HID-HSCT. After HSCT, the patient developed CMV viremia and severe acute graft-versus-host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusion-weighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient's consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes.

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Acute kidney injury (AKI) occurs commonly in hospitalized patients, especially patients in intensive care units (ICUs). Medications are among the major causative factors of AKI. This narrative review addressed and updated different aspects of anti-infective-associated AKI, including amphotericin B, cidofovir, foscarnet, polymyxins, vancomycin, and aminoglycosides. There is no standard definition or operational criteria to describe anti-infective-associated AKI. Characteristically, it usually occurs during the first two weeks of treatment and is typically dose dependent. Functional resolution occurs, but kidney injury can affect renal functional reserve and increase susceptibility to future AKI events. A variety of pathophysiological mechanisms impacting glomerular, tubular, and interstitial components of the kidney are usually responsible for the development of AKI from anti-infective medications. Oxidative stress and inflammation play a pivotal role in the pathogenesis of antibiotic-related AKI. Numerous patient-related, medication-related, and co-administered-related scenarios have been demonstrated as risk factors for anti-infective-induced AKI. Apart from traditional indexes of kidney function (serum creatinine and urine output), novel biomarkers of kidney function (e.g., serum cystatin C) and damage (e.g., urinary kidney-injury molecule-1 and neutrophil gelatinase-associated lipocalin) have been noticed in recent clinical studies with promising findings. The efficiency of preventive strategies against anti-infective-associated AKI in most cases appears to be variable, relative, and modest. Close and regular monitoring of kidney function parameters is crucial during treatment with nephrotoxic antibiotics. Currently, there is no definitive treatment modalities for the management of AKI with anti-infectives. Therefore, supportive care is the mainstay of treatment.

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Acute retinal necrosis (ARN) is a sight-threatening ophthalmic emergency that requires aggressive treatment to prevent irreversible vision loss. However, primary treatment failure (PTF), where the initial antiviral therapy is ineffective, is a common challenge in ARN management. This comprehensive review examines PTF in ARN, drawing insights from a systematic literature search spanning 1997 to 2022, which identified 35 relevant cases from 23 reports. The analysis focuses on drug resistance patterns, alternative antiviral agents, combination therapies, and emerging treatments. Potential causes of drug resistance, including host factors, viral mutations, and drug-related considerations, are elucidated. Alternative agents such as foscarnet, cidofovir, and brivudine, as well as combination approaches involving systemic and intravitreal administration, high-dose therapy, judicious use of steroids, and potential treatment-related complications, are discussed. The review also highlights emerging therapies, including vaccines, monoclonal antibodies, and natural compounds, offering insights into future directions for addressing this challenging condition.

Abstract licence: CC BY-NC-SA

Objective: Therapy for vision-threatening CMV retinitis is often limited by drug resistance or systemic toxicity. Maribavir, a novel UL97 kinase inhibitor that has been FDA-approved for refractory CMV viremia, is a potential alternative to traditional antiviral therapy but remains understudied for CMV retinitis. The objective of this series is to describe the clinical courses and outcomes of patients with CMV retinitis after initiation of maribavir therapy. Design: Retrospective case series. Subjects: Six patients (11 eyes) with CMV retinitis from two tertiary uveitis centers. All were immunocompromised due to chemotherapy, immunotherapy, or AIDS and were initially treated with standard therapy (systemic and/or intravitreal ganciclovir, valganciclovir, or foscarnet) before developing drug resistance, toxicity, or intolerance prompting a transition to maribavir as alternative therapy. Intervention: Oral maribavir 400 mg twice daily. Main Outcome Measures: Time to retinitis quiescence, visual acuity (VA), and adverse effects of therapy. Results: 4/11 eyes had active retinitis upon initiation of maribavir and all achieved quiescence within 6 weeks. The remaining 7/11 eyes were already quiescent and remained so. VA remained stable or improved in all eyes. Notable clinical courses included (1) rapid decline in aqueous CMV titer and resolution of retinitis in a patient with multidrug-resistant CMV failing intravitreal ganciclovir/foscarnet; (2) a patient with UL54-resistant CMV and bilateral macula-involving retinitis rapidly achieving inactivity and preserved visual acuity on maribavir; and (3) successful substitution of maribavir in patients who were unable to continue conventional antiviral therapy due to drug-induced neutropenia or nephrotoxicity. Maribavir was generally well-tolerated, and only mild adverse effects were reported (dysgeusia, myalgia). Review of the literature identified 2 additional cases of patients with similar clinical courses achieving resolution of retinitis on maribavir. Conclusions: In this descriptive case series, patients with multidrug-resistant CMV retinitis or intolerance to traditional antiviral therapy were observed to achieve or maintain quiescence of retinitis following initiation of maribavir. These findings suggest maribavir as a potential novel systemic option for challenging cases of CMV retinitis. Prospective studies are necessary to further characterize the efficacy and safety of maribavir for the treatment of CMV retinitis, as well as optimal duration of therapy after quiescence.

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Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.

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Background: Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized. Methods: This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance. Results: Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction. Conclusions: Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.

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