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Romanian Journal of Ophthalmology 2021To report a case of acute retinal necrosis (ARN) and to emphasize special aspects of the management. Factors that must be considered. We present the case of an...
To report a case of acute retinal necrosis (ARN) and to emphasize special aspects of the management. Factors that must be considered. We present the case of an 83-year-old woman examined for acute vision loss in her left eye (LE). Background: diabetes, pseudophakic in her LE; subluxated intraocular lens (IOL) and advanced pseudoexfoliative glaucoma in her right eye (RE). The visual acuity (VA) was hand movements in both eyes. Funduscopic examination revealed vitritis, temporal area of retinal necrosis with peripapillary choroiditis spots and macular haemorrhages in her LE and OCT showed a cystic macular edema. A positive polymerase chain reaction (PCR) test for Varicella Zoster Virus (VZV) in aqueous humor of her LE was found. She underwent intravenous Acyclovir 10 mg per kg every 8 hours. She received two doses of adjunctive intravitreal Foscarnet (2.4 mg/ 0.1 mL) in the first 3 days of treatment (2 days between doses). After 3 days of treatment, she started with intravenous prednisone 60 mg per day. The VA of her LE was 0,8 and the retinal necrosis activity was stationary. In fundoscopic examination, vitritis and retinal hemorrhages have disappeared. At that moment there were no foci of chorioretinitis or macular edema although retinal ischemia persisted at the inferior nasal level. The role of adjunctive intravitreal antiviral therapy in combination with systemic treatment revealed promising results. Corticosteroids can be used topically and orally to decrease the severe inflammatory response associated with ARN. Early treatment is crucial to optimize visual and anatomic outcomes.
Topics: Acyclovir; Aged, 80 and over; Eye Infections, Viral; Female; Foscarnet; Herpesvirus 3, Human; Humans; Retinal Necrosis Syndrome, Acute
PubMed: 35036649
DOI: 10.22336/rjo.2021.53 -
Rapid Communications in Mass... Apr 2022Foscarnet (FCV) is used to treat cytomegalovirus, human herpesvirus, and human immunodeficiency virus infections. It is a low-molecular-weight compound containing...
RATIONALE
Foscarnet (FCV) is used to treat cytomegalovirus, human herpesvirus, and human immunodeficiency virus infections. It is a low-molecular-weight compound containing carboxylate and phosphate groups. There are no reports on the use of liquid chromatography-tandem mass spectrometry (LC/MS/MS) to analyze FCV via bioanalysis. In the present study, we developed the ion-pair LC/MS/MS method to analyze FCV in human serum and cerebrospinal fluid (CSF).
METHODS
FCV was extracted from human serum and CSF by weak anion exchange (WAX) solid-phase extraction. The LC/MS/MS systems were coated with 0.1% phosphoric acid in methanol to avoid nonspecific absorption. FCV was detected using ion-pair LC/MS/MS with dibutylammonium acetate. Selected reaction monitoring transition of FCV in the negative ion mode was selected at m/z 125.1 → 62.9.
RESULTS
FCV was selectively detected in human serum and CSF, and the liner range was 5-1000 μM (R = 0.99). The intraday and interday accuracy and precision were within ±15%. FCV was constantly extracted from human serum and CSF by WAX solid-phase extraction (recovery ratio = 76.0-77.9%). No matrix effect was observed.
CONCLUSIONS
A robust LC/MS/MS method to analyze FCV was successfully developed. FCV was selectively measured using LC/MS/MS in very low extract volumes (20 μL). The method will be useful in evaluating the FCV level in human serum and CSF.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Foscarnet; Humans; Reproducibility of Results; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 35001441
DOI: 10.1002/rcm.9255 -
BMJ Case Reports Dec 2021The early engraftment phase of allogeneic haematopoietic stem cell transplantation can be associated with a number of oromucosal infective complications. While the...
The early engraftment phase of allogeneic haematopoietic stem cell transplantation can be associated with a number of oromucosal infective complications. While the routine use of prophylactic acyclovir has reduced the incidence of herpes simplex virus (HSV) reactivation, there is an increasing prevalence of acyclovir resistance within this cohort of patients. The authors present a case of acyclovir-resistant HSV reactivation in a 26-year-old woman 7 days post T-deplete sibling allograft on a background of combined cyclophosphamide and total body irradiation myeloablative conditioning, successfully treated with foscarnet and cidofovir therapy and discuss the differential diagnoses for early/late engraftment oral disease.
Topics: Acyclovir; Adult; Antiviral Agents; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans
PubMed: 34969809
DOI: 10.1136/bcr-2021-247109 -
Clinical Infectious Diseases : An... Sep 2022Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase.
METHODS
In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16.
RESULTS
352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs.
CONCLUSIONS
Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dichlororibofuranosylbenzimidazole; Drug Resistance, Viral; Foscarnet; Ganciclovir; Humans; Valganciclovir; Viremia
PubMed: 34864943
DOI: 10.1093/cid/ciab988 -
Cutis Oct 2021Patients with dedicator of cytokinesis 8 (DOCK8) deficiency are susceptible to development of severe viral cutaneous infections, including herpes simplex virus (HSV). We...
Patients with dedicator of cytokinesis 8 (DOCK8) deficiency are susceptible to development of severe viral cutaneous infections, including herpes simplex virus (HSV). We report a 32-month-old girl with homozygous DOCK8 deficiency who developed a posterior auricular cutaneous lesion that was culture positive for HSV despite acyclovir prophylaxis. Resolution of this lesion was only observed after addition of foscarnet to the treatment regimen. Prophylactic acyclovir may be insufficient for suppression of cutaneous HSV in patients with DOCK8 deficiency, and a high index of suspicion for viral resistance is necessary for prompt initiation of appropriate antiviral treatment in these patients.
Topics: Acyclovir; Antiviral Agents; Child, Preschool; Drug Resistance, Viral; Female; Foscarnet; Guanine Nucleotide Exchange Factors; Herpes Simplex; Humans; Simplexvirus
PubMed: 34847003
DOI: 10.12788/cutis.0364 -
Journal of Renal Nutrition : the... Mar 2022Vascular calcification (VC) is an important risk factor for cardiovascular disease in maintenance hemodialysis (MHD) patients. Hyperphosphatemia and microinflammation...
OBJECTIVE
Vascular calcification (VC) is an important risk factor for cardiovascular disease in maintenance hemodialysis (MHD) patients. Hyperphosphatemia and microinflammation statement are known major contributors to the development of VC; however, the mechanisms are unknown. The aims of this study were to explore the risk factors of VC in MHD patients and to explore whether high phosphate could increase the secretion of inflammatory cytokines via PiT-1 in monocytes.
METHODS
A cross-sectional study was conducted on 65 MHD patients to assess the relevance of coronary artery calcification (CAC), inflammatory factors, serum phosphate, and sodium-dependent phosphate cotransporter (NPT) mRNA expression of peripheral blood mononuclear cells (PBMCs). Multivariate logistic regression analysis was used to analyze the predictors of CAC. The calcification effects of high phosphate (HP), TNF-α, and supernatants of healthy human monocytes treated with HP were further evaluated in cultured HASMCs.
RESULTS
Diabetes, longer dialysis vintage, higher serum TNF-α levels, and PiT-1 mRNA expression of PBMCs) were independent risk factors of CAC in MHD patients. The mRNA levels of PiT-1 in PBMCs were positively correlated with serum phosphate, CAC scores, and Pit-2 mRNA levels of PBMCs. The expressions of TNF-α, IL-6, and PiT-1 in human monocytes were significantly increased in a dose-dependent manner after treatment with HP, which was subsequently inhibited by NPT antagonist phosphonoformic acid. Neither TNF-α alone nor supernatants of monocytes stimulated with HP promoted the expression of osteopontin and Runt-related transcription factor 2 (Runx2) or caused mineralization in human aortic smooth muscle cells, but combined with HP intervention, the calcification effects were markedly increased in human aortic smooth muscle cells and ameliorated by phosphonoformic acid treatment.
CONCLUSION
Hyperphosphatemia directly increased the synthesis and secretion of TNF-α by monocytes may via PiT-1 pathway, resulting in elevated systemic inflammatory response, which may further aggravate VC induced by phosphate overload in MHD patients.
Topics: Cells, Cultured; Cross-Sectional Studies; Female; Foscarnet; Humans; Hyperphosphatemia; Leukocytes, Mononuclear; Male; Muscle, Smooth, Vascular; Phosphates; RNA, Messenger; Sodium-Phosphate Cotransporter Proteins, Type III; Tumor Necrosis Factor-alpha; Uremia; Vascular Calcification
PubMed: 34688540
DOI: 10.1053/j.jrn.2021.03.008 -
Clinical NephrologyFoscarnet (trisodium phosphonoformate hexahydrate) is standard treatment for ganciclovir-resistant cytomegalovirus (CMV) infections. In the kidney, foscarnet-induced...
INTRODUCTION
Foscarnet (trisodium phosphonoformate hexahydrate) is standard treatment for ganciclovir-resistant cytomegalovirus (CMV) infections. In the kidney, foscarnet-induced injury may be attributed to reversible tubulointerstitial lesions, but foscarnet crystals have also been observed within glomerular capillaries, suggesting that foscarnet can lead to glomerular lesions such as crescentic glomerulonephritis. We present biopsy and autopsy findings of foscarnet induced nephropathy in a transplanted kidney, with a particular emphasis on the histopathology and electron micrographic peculiarities of drug crystal deposits.
CASE PRESENTATION
A 72-year-old Caucasian male patient with a deceased donor kidney was treated with several foscarnet applications due to ganciclovir-resistant CMV infection. Transplant kidney biopsy revealed massive glomerular crystalline precipitates, resulting in crescentic glomerulonephritis and tubular damage. The last foscarnet application was complicated with several infections and kidney graft failure. Autopsy revealed multi-organ damage due to foscarnet crystal precipitations associated with systemic CMV and fungal infection. On autopsy of kidney specimens, we succeeded in preserving the rectangular flat plate-like foscarnet crystals in stacks detected by transmission electron microscopy (TEM) after 100% alcohol fixation. The chemical composition of the crystals was confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy.
CONCLUSION
Transplant kidney biopsy remains the gold standard in distinguishing between foscarnet crystalline glomerular and/or tubulointerstitial lesions, and various forms of rejection and other causes of impaired renal function in transplant kidney.
Topics: Aged; Allografts; Antiviral Agents; Foscarnet; Ganciclovir; Humans; Kidney; Kidney Transplantation; Male; Nephritis, Interstitial
PubMed: 34643504
DOI: 10.5414/CNP96S23 -
Antiviral Research Nov 2021Acyclovir (ACV) and penciclovir and their prodrugs are recommended for therapy or prophylaxis of Herpes simplex virus 1 (HSV-1) infections. Their administration,...
Acyclovir (ACV) and penciclovir and their prodrugs are recommended for therapy or prophylaxis of Herpes simplex virus 1 (HSV-1) infections. Their administration, however, can lead to the emergence of resistant strains with altered viral thymidine kinase (TK) function, especially in immunocompromised patients. Furthermore, amino acid (aa) changes of the viral deoxyribonucleic acid polymerase (POL) may contribute to resistance to the aforementioned nucleoside analogues. Given this, treatment with foscarnet (FOS) or cidofovir (CDV) may represent an important alternative. Both drugs directly affect POL activity. Several aa changes of POL, such as L49I, E70K, L359I, E421V, P829S, T1121M, and M1226I, have been observed in ACV-resistant clinical strains which also carried relevant aa changes in their TK. Their contribution to ACV, FOS, and CDV resistance is not fully understood. In this study, these seven aa changes with unknown significance for ACV, FOS and CDV resistance were introduced separately into the POL of a recombinant HSV-1 strain rHSV-1(17+)Lox, equipped with or without information for expression of green fluorescent protein (GFP). The GFP-expressing variants were tested for susceptibility to ACV, FOS and CDV. An rHSV-1(17+)Lox GFP strain with the S724N change conferring resistance to ACV and FOS was generated and included as a control. Only the S724N change was confirmed to induce ACV and FOS resistance, whereas the other changes did not contribute to resistance. The underlying nucleotide substitutions of the POL gene should be therefore considered as natural polymorphism. These data will improve sequence-based prediction of antiviral susceptibility.
Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Cidofovir; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Foscarnet; Guanine; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Thymidine Kinase; Vero Cells
PubMed: 34419483
DOI: 10.1016/j.antiviral.2021.105166 -
Clinical Transplantation Nov 2021Letermovir (LTV) might be an alternative treatment to nephrotoxic foscarnet (FOS) in Ganciclovir (GCV) resistant cytomegalovirus (CMV) infection. However, its efficacy...
BACKGROUND
Letermovir (LTV) might be an alternative treatment to nephrotoxic foscarnet (FOS) in Ganciclovir (GCV) resistant cytomegalovirus (CMV) infection. However, its efficacy in controlling active CMV viremia is unclear, as it is only approved for CMV prophylaxis in hematopoietic stem-cell transplantation.
METHODS
This case series describes 14 kidney transplant recipients (KTR) with moderate-level GCV resistant CMV infection, treated by different step-down strategies after initial FOS therapy: (1) Observation without antiviral follow-up or switch to valganciclovir (VGCV) (pre-LTV era), and (2) Switch to LTV±VGCV (LTV era).
RESULTS
One patient died under FOS. Thirteen patients were followed under step-down regimens. All but two patients had ongoing CMV viremia when stopping FOS. In pre-LTV era, 5/9 (56%) experienced a CMV breakthrough > 10 000 IU/ml calling for another course of FOS, as compared to 1/4 (25%) in the LTV era. Addition of VGCV to LTV at low-level viral breakthrough, addressing a possible developing resistance against LTV, prevented viral surge in two patients. In the pre-LTV era, CMV-related death or graft loss occurred in three of nine (33%), compared to no death or graft loss in the LTV era.
CONCLUSION
A step-down strategy combining LTV+VGCV, might allow to safely stop FOS at ongoing low-level viremia.
Topics: Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Kidney Transplantation; Quinazolines; Transplant Recipients; Valganciclovir
PubMed: 34181768
DOI: 10.1111/ctr.14401 -
Retina (Philadelphia, Pa.) Jul 2021To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment...
PURPOSE
To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment options.
METHODS
The study evaluated 22 eyes in 18 patients of polymerase chain reaction-positive acute retinal necrosis at the University of Pittsburgh Medical Center from 2007 to 2018. Outcome measures included final visual acuity, treatment paradigms, and retinal detachment rate.
RESULTS
Eight eyes were polymerase chain reaction-positive for varicella zoster virus, two eyes for herpes simplex virus Type 1 (HSV-1), and 12 eyes for herpes simplex virus Type 2 (HSV-2). Final Snellen best-corrected visual acuity averaged 20/51 for varicella zoster virus, 20/25 for HSV-1, and 20/814 for HSV-2. Retinal detachment occurred in 2 (25%) of varicella zoster virus eyes and 8 (75%) of HSV-2 eyes. One eye with HSV-1 and three eyes with HSV-2 received cidofovir for treatment of refractory retinitis.
CONCLUSION
Acute retinal necrosis secondary to HSV-2 tended to have persistent active retinitis with a higher rate of retinal detachment despite similar treatment protocols, suggesting that in some cases combination intravenous acyclovir and adjuvant intravitreal foscarnet injections are not sufficient. Despite the risk of renal toxicity, intravenous cidofovir may be a consideration in select patients.
Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; DNA, Viral; Eye Infections, Viral; Female; Follow-Up Studies; Foscarnet; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male; Middle Aged; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Treatment Outcome; Visual Acuity
PubMed: 34137387
DOI: 10.1097/IAE.0000000000003058