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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Foscarnet is an antiviral used to treat herpes virus infections, including ganciclovir-resistant cytomegalovirus retinitis. It is an FDA category C, and the manufacturer “discourages its use during pregnancy.” In rodent and rabbit models given the drug during organogenesis at 1/8 to 1/3 the usual human dose the frequency of birth defects was slightly increased. These results are not usable to evaluate possible teratogenicity because no dose response effect was observed, and the doses were lower than that to which humans are usually exposed.
Antiviral therapeutics for viral infections of the central nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Foscarnet is indicated for the treatment of CMV retinitis and is also effective in the treatment of resistant HSV, VZV, and CMV infections [43–45], an important problem in immunocompromised hosts. Because of the severity of its associated adverse effects, foscarnet is typically reserved as a potent therapeutic option in select situations. Foscarnet is not recommended to treat CNS viral infections.
Herpes Simplex Virus Infections in Immunocompromised Patients
Published in Marie Studahl, Paola Cinque, Tomas Bergström, Herpes Simplex Viruses, 2017
In case of limited lesions, low-dose oral aciclovir or equivalent valaciclovir or famciclovir regimens are sufficient for complete healing of the lesions. In patients with more severe lesions, higher dosages and longer treatments may be required. If lesions persist or recur despite adequate treatment, infection with a resistant strain should be suspected. Ideally, a viral isolate should be obtained for susceptibility testing; however, these tests are not performed routinely in all laboratories. HSV strains resistant to aciclovir are also resistant to valaciclovir and likely to famciclovir. Intravenous foscarnet should be administered in these cases. Mucocutaneous lesions due to foscarnet-resistant strains are also described. Intravenous cidofovir® has also been suggested for treatment of lesions caused by aciclovir-resistant strains (92). Use of this drug, however, is limited by frequent cross-resistance with aciclovir. In the case of aciclovir-resistant HSV infection, topical cidofovir gel (93) or topical trifluridine (94) might also be effective.
Optical Coherence Tomography Angiography Findings of Iris Ischemia and Reperfusion in Cytomegalovirus Panuveitis
Published in Ocular Immunology and Inflammation, 2022
Federico Zicarelli, Salvatore Parrulli, Alessandro Torre, Marta Oldani, Alessandro Invernizzi
Foscarnet is an analogue of inorganic pyrophosphate that selectively inhibits the viral DNA polymerases at concentrations that do not affect human DNA polymerases and can be used intravitreally as an adjunctive therapy or as an alternative treatment to Gancyclovir for CMV retinitis.11–13 After intravitreal Foscarnet injections, we observed regression of the area of active retinitis and partial retinal and iris vessel re-perfusion. The simultaneous involvement of tissues belonging to different eye compartments, along with the partial reversibility of the iris ischemia, suggests the immune system to play a role in the vascular alterations. Unlike direct viral invasion, which determines granular full thickness retinal necrosis, the immune-mediated retinal and iris vascular damage seems to be in fact partially reversible. The reduction in IOP after the first intravitreal Foscarnet administration could also have contributed in facilitating the vascular reperfusion in both the iris and retinal compartments.
Cost-effectiveness of letermovir as cytomegalovirus prophylaxis in adult recipients of allogeneic hematopoietic stem cell transplantation in Hong Kong
Published in Journal of Medical Economics, 2020
Thomas Sau-Yan Chan, Sally Shuk-Yee Cheng, Wei-Ting Chen, Danny Chung Hsu, Rene Wing-Yan Chau, Suk Hyun Kang, Adnan Alsumali, Yok-Lam Kwong
Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT)1. The manifestations range from virologic reactivation (detectable circulating CMV pp65 antigen or CMV DNA) to actual clinical disease (organ involvement with histopathologic changes)2. The risk of CMV infection is nearly double in allogeneic as compared with autologous HSCT2. Without anti-viral prophylaxis, CMV virologic reactivation in high-risk seropositive allogeneic HSCT recipient might approach 100%2. High-risk factors also include HLA (A, B, DR, C, or DRB1) mismatched related or unrelated donor, haploidentical donor, umbilical cord blood donation, ex vivo T-cell depletion, and graft-versus-host disease (GVHD) of > grade 23,4. Treatment of CMV reactivation with antiviral agents may be associated with significant toxicity. For example, around 30% of patients treated with ganciclovir or valganciclovir develop treatment-associated neutropenia5, which in turn leads to greater incidence of bacterial or fungal infections, with resultant increased mortality6. Use of foscarnet is also associated with nephrotoxicity in up to 27% of patients7. Therefore, new anti-CMV drugs with an improved toxicity profile are needed to provide effective and well-tolerated prophylaxis, particularly in high-risk seropositive allogeneic HSCT recipients.
Management of Ganciclovir Resistant Cytomegalovirus Retinitis in a Solid Organ Transplant Recipient: A Review of Current Evidence and Treatment Approaches
Published in Ocular Immunology and Inflammation, 2020
L. Fu, K. Santhanakrishnan, M. Al-Aloul, N. P. Jones, L. R. Steeples
There are four established antiviral drugs for CMV infection: ganciclovir, valganciclovir, foscarnet, and cidofovir (CDV); all target DNA polymerase. Oral or intravenous GCV is standard first-line therapy. In patients with renal impairment or impaired absorption, IV therapy is favored.9 All available antivirals are associated with significant toxicity and emergence of drug resistance. Foscarnet is second-line for resistant or refractory disease. If UL97 resistance is diagnosed during GCV or VGCV therapy the principal approach is to switch to IV FOS and reduce systemic immunosuppression if possible. Alternatively, for mutations conferring low-level GCV resistance, dose escalation or combined GCV/FOS, with monitoring for hematological toxicity, is an alternative approach.12 Systemic adjuvant therapy may be used alongside FOS, particularly leflunomide. Use of cidofovir is limited by toxicity, particularly severe nephrotoxicity and especially with concurrent calcineurin inhibitor therapy.9 If there is inadequate clinical response or toxicity with FOS, one or more investigational medicines must be considered.5 UL54 mutation resistance is treated according to cross-resistance, with FOS, CDV and GCV used according to sensitivity and tolerance. Drug level monitoring is encouraged, particularly in renal-adjusted dosing.13