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Clinical Transplantation Aug 2021Incidence and impact of CMV infection in pancreas-transplant recipients (PTRs) in the valganciclovir prophylaxis era has not been completely elucidated.
PROBLEM
Incidence and impact of CMV infection in pancreas-transplant recipients (PTRs) in the valganciclovir prophylaxis era has not been completely elucidated.
METHODS
Adult D+/R- PTRs were divided into a current era (1/1/2011-12/31/17; 6-month PPX) and a historic era (1/1/2003-12/31/09; 3-month PPX).
PRIMARY OBJECTIVE
effect of prophylaxis extension on the incidence of CMV infection.
SECONDARY OBJECTIVE
impact of extension on valganciclovir-related toxicity (leukopenia) and transplant outcomes.
RESULTS
There were 177 D+/R- PTRs in the study period (historic:98, current:79). Prophylaxis extension resulted in significant reduction of CMV infection from 25.4% to 10.9% at 6 months, (57% reduction, p = .021). However, 1-year rates of CMV infection (historic:31% vs current:36%) and end-organ disease (historic:7.7% vs current:6.9%) were not different (p = .93). Prophylaxis extension significantly increased leukopenia (white blood cell count<3 K/uL) at 6 months (historic:9.5% vs current:28.6%, p = .018). On multivariable analysis prophylaxis extension was not associated with reduced rates of CMV infection (p = .99) or CMV end-organ disease (p = .3). Additionally, there was no significant difference in rejection (p = .2), graft survival (p = .08), death-censored graft survival(p = .07) or patient survival (p = .6).
CONCLUSIONS
Prophylaxis extension in D+/R- PTRs appears to delay time to first CMV but not reduce overall incidence. These findings suggest a hybrid approach, incorporating antiviral withdrawal and protocolized monitoring, may be needed to improve CMV-related outcomes.
Topics: Cytomegalovirus Infections; Ganciclovir; Humans; Incidence; Pancreas; Retrospective Studies; Transplant Recipients; Valganciclovir
PubMed: 34075624
DOI: 10.1111/ctr.14379 -
Journal of the Pediatric Infectious... Aug 2022Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received...
Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received valganciclovir only, for a median of 8 and 171 days, starting at a median of 15 and 45 days of life, respectively, with neutropenia diagnosed in 25% and 17%.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Electronic Health Records; Ganciclovir; Humans; Infant; United States; Valganciclovir
PubMed: 35532552
DOI: 10.1093/jpids/piac034 -
Transplant Infectious Disease : An... Aug 2021
Topics: Antiviral Agents; Ganciclovir; Heart Transplantation; Humans; Retrospective Studies; Tissue Donors; Transplant Recipients; Valganciclovir
PubMed: 33529417
DOI: 10.1111/tid.13581 -
Transplantation and Cellular Therapy Jan 2023Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our...
Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our experience using letermovir as CMV prophylaxis in pediatric hematopoietic cell transplantation (HCT) recipients. Pediatric patients (age <20 years) undergoing allogeneic HCT and receiving letermovir prophylaxis in the Mayo Clinic Pediatric Bone Marrow Transplant Program were eligible for inclusion in this retrospective chart review. Medical records were reviewed to evaluate letermovir dosing, CMV levels, laboratory values, and reports of adverse effects. Between October 2020 and April 2022, 9 patients age 4 to 19 years undergoing allogeneic HCT in the Pediatric Bone Marrow Transplant Program received letermovir prophylaxis, either 240 mg or 480 mg daily at a mean and median dose of 10 mg/kg/day. Letermovir was crushed and administered via nasogastric tube in 4 of 9 patients. Two patients received letermovir for secondary CMV prophylaxis after initial treatment with ganciclovir/valganciclovir, and the remaining 7 received letermovir for primary prophylaxis. One patient, a 20-kg 6-year-old female receiving 240 mg (12 mg/kg), experienced low-level CMV viremia while on letermovir. No other patients experienced CMV reactivation while on letermovir prophylaxis. In 2 patients, transient mild transaminitis was noted within the first weeks of letermovir therapy, which resolved without intervention, and its relationship to letermovir could not be clearly established. Letermovir administration was feasible and well tolerated as CMV prophylaxis in our small cohort of pediatric patients undergoing HCT. Larger, prospective studies are warranted to confirm the safety and efficacy of letermovir in children. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Topics: Female; Humans; Child; Young Adult; Adult; Child, Preschool; Adolescent; Cytomegalovirus; Antiviral Agents; Retrospective Studies; Cytomegalovirus Infections; Valganciclovir
PubMed: 36244677
DOI: 10.1016/j.jtct.2022.10.005 -
Clinical Infectious Diseases : An... Jan 2008Cytomegalovirus (CMV) infection causes morbidity in solid organ transplant (SOT) recipients, either by direct injury or in association with chronic allograft rejection... (Clinical Trial)
Clinical Trial
BACKGROUND
Cytomegalovirus (CMV) infection causes morbidity in solid organ transplant (SOT) recipients, either by direct injury or in association with chronic allograft rejection or other opportunistic infections. Ganciclovir is the treatment of choice, but this agent requires intravenous administration, which affects its feasibility for long-term use. Valganciclovir, which has an oral bioavailability of 60%, has proven to be useful for prophylaxis of CMV infection in high-risk SOT recipients and for treating retinitis in persons with acquired immunodeficiency syndrome.
OBJECTIVE
To compare the efficacy of valganciclovir (alone or as sequential therapy after a regimen of intravenous ganciclovir) with intravenous ganciclovir alone for preemptive therapy or treatment of CMV disease (viral syndrome or focal disease) in SOT recipients and to determine the incidence of adverse effects and relapses.
METHODS
In this 2-year prospective, comparative cohort study, 376 episodes of preemptive therapy or treatment of CMV disease were recorded among 334 of 3467 SOT recipients included in the Spanish Network for Research on Infection in Transplantation (RESITRA) database. Intravenous ganciclovir was the first-line treatment in 170 episodes; valganciclovir followed by intravenous ganciclovir was administered in 82 episodes, and valganciclovir alone was administered in 112 episodes.
RESULTS
Valganciclovir was used as preemptive therapy or treatment for CMV disease in 84 and 28 episodes, respectively. Duration of treatment was longer in valganciclovir recipients than in ganciclovir recipients for both preemptive therapy (21 vs. 15 days; P < .001) or viral syndrome treatment (21 vs. 18 days; P < .01). In the valganciclovir arm, 94 (83.9%) of 112 episodes were treated successfully, with no statistical difference in the success rates versus the ganciclovir arm (85.8%) or ganciclovir-valganciclovir arm (95.1%). Eighteen episodes (16.1%) treated with valganciclovir were considered to have resulted in treatment failure (because of persistent antigenemia in 4 [3.6%], on the basis of clinical decision in 7 [6.2%], and because of recurrent disease in 7 [6.2%]). There were no incidents in which valganciclovir treatment was withdrawn because of toxicity.
CONCLUSION
Valganciclovir is safe and useful for preemptive therapy and treatment of CMV disease.
Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Antiviral Agents; Cohort Studies; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Humans; Immunocompromised Host; Male; Middle Aged; Postoperative Complications; Prospective Studies; Transplantation; Transplantation Immunology; Valganciclovir
PubMed: 18171208
DOI: 10.1086/523590 -
The Journal of Antimicrobial... May 2023Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Reference anti-CMV treatment is valganciclovir/ganciclovir, which is contraindicated in...
Assessing the risk of adverse pregnancy outcomes and birth defects reporting in women exposed to ganciclovir or valganciclovir during pregnancy: a pharmacovigilance study.
OBJECTIVES
Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Reference anti-CMV treatment is valganciclovir/ganciclovir, which is contraindicated in pregnancy given questions about teratogenicity.
METHODS
We analysed reports from VigiBase, the world's largest safety database, and performed a disproportionality analysis of adverse pregnancy outcomes associated with (val)ganciclovir compared with any other drugs or with (val)aciclovir as comparators.
RESULTS
Among 3 104 984 reports related to childbearing-age women or to pregnancy topics, 6186 were exposed to (val)ganciclovir or (val)aciclovir including 251 adverse pregnancy outcomes with (val)ganciclovir (n = 34) or (val)aciclovir (n = 217). We did not evidence any increased reporting of any adverse pregnancy outcome [miscarriage, stillbirth, small weight for gestational age, preterm birth (<37 weeks of gestation)] or birth defects with (val)ganciclovir compared with the use of (val)aciclovir during pregnancy. Four cases of oesophageal and anorectal atresia were identified with (val)ganciclovir, which may be related to concomitant drugs/medical conditions and require further analyses.
CONCLUSIONS
These preliminary results require confirmation but suggest the possibility for trial evaluation of val(ganciclovir) in severe maternal or fetal CMV infections.
Topics: Humans; Infant, Newborn; Female; Pregnancy; Infant; Ganciclovir; Valganciclovir; Antiviral Agents; Pregnancy Outcome; Pharmacovigilance; Premature Birth; Acyclovir; Cytomegalovirus
PubMed: 36964746
DOI: 10.1093/jac/dkad087 -
Clinical Pharmacokinetics Jun 2023The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV)...
Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach.
BACKGROUND AND OBJECTIVE
The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV) or oral administration of valganciclovir (VGCV), both adjusted to the renal function. In both instances, there is a high interindividual pharmacokinetic variability, mainly owing to the wide range of variation of both the renal function and body weight. Therefore, accurate estimation of the renal function is crucial for GCV/VGCV dose optimization. This study aimed to compare three different formulas for estimating the renal function in solid organ transplantation patients with cytomegalovirus infection, for individualizing antiviral therapy with GCV/VGCV, using a population approach.
METHODS
A population pharmacokinetic analysis was performed using NONMEM 7.4. A total of 650 plasma concentrations obtained after intravenous GCV and oral VGCV administrations were analyzed, from intensive and sparse sampling designs. Three different population pharmacokinetic models were built with the renal function given by Cockcroft-Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formulas. Pharmacokinetic parameters were allometrically scaled to body weight.
RESULTS
The CKD-EPI formula was identified as the best predictor of between-patient variability in GCV clearance. Internal and external validation techniques showed that the CKD-EPI model had better stability and performed better compared with the others.
CONCLUSIONS
The model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.
Topics: Humans; Ganciclovir; Valganciclovir; Antiviral Agents; Cytomegalovirus Infections; Organ Transplantation; Renal Insufficiency, Chronic; Kidney
PubMed: 37140726
DOI: 10.1007/s40262-023-01237-3 -
Clinical Therapeutics Mar 2018The aim of this study was to assess the clinical characteristics and trends in valganciclovir use among infants diagnosed with congenital cytomegalovirus (CMV) disease...
PURPOSE
The aim of this study was to assess the clinical characteristics and trends in valganciclovir use among infants diagnosed with congenital cytomegalovirus (CMV) disease in the United States.
METHODS
We analyzed data from medical claims dated 2009-2015 from the Truven Health MarketScan Commercial Claims and Encounters and Medicaid databases. We identified infants with a live birth code in the first claim who were continuously enrolled for at least 45 days. Among infants diagnosed with congenital CMV disease, identified by an ICD-9-CM or ICD-10-CM code for congenital CMV infection or CMV disease within 45 days of birth, we assessed data from claims containing codes for any CMV-associated clinical condition within the same period, and data from claims for hearing loss and/or valganciclovir within the first 180 days of life.
FINDINGS
In the commercial and Medicaid databases, we identified 257 (2.5/10,000) and 445 (3.3/10,000) infants, respectively, diagnosed with congenital CMV disease, among whom 135 (53%) and 282 (63%) had ≥1 CMV-associated condition, 30 (12%) and 32 (7%) had hearing loss, and 41 (16%) and 78 (18%) had a claim for valganciclovir. Among infants with congenital CMV disease who had a claim for valganciclovir, 37 (90%) among commercially insured infants and 68 (87%) among Medicaid-insured infants had ≥1 CMV-associated condition and/or hearing loss. From 2009 to 2015, the percentages with a claim for valganciclovir increased from 0% to 29% among commercially insured infants and from 4% to 37% among Medicaid-insured infants (P < 0.0001).
IMPLICATIONS
During 2009-2015, there was a strong upward trend in valganciclovir claims among insured infants who were diagnosed with congenital CMV disease, the majority of whom had CMV-associated conditions and/or hearing loss.
Topics: Antiviral Agents; Cytomegalovirus Infections; Databases, Factual; Female; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; International Classification of Diseases; Male; Medicaid; United States; Valganciclovir
PubMed: 29397198
DOI: 10.1016/j.clinthera.2018.01.006 -
Retinal Cases & Brief Reports Mar 2024To determine whether maribavir is effective at treating ganciclovir-resistant cytomegalovirus retinitis.
PURPOSE
To determine whether maribavir is effective at treating ganciclovir-resistant cytomegalovirus retinitis.
METHODS
Retrospective case report of a lung-transplant patient with bilateral cytomegalovirus retinitis documented with serum and aqueous humor studies and color fundus photographs.
RESULTS
A 72-year-old lung-transplant patient with active ganciclovir-resistant cytomegalovirus was treated with intravitreal foscarnet therapy in one eye. Retinitis developed in the contralateral eye and was managed with systemic maribavir alone. Active retinitis regressed in both the eye treated with intravitreal foscarnet and the uninjected eye.
CONCLUSION
This patient's results suggest that systemic maribavir is an effective treatment for treatment-resistant cytomegalovirus retinitis.
Topics: Humans; Aged; Cytomegalovirus Retinitis; Valganciclovir; Foscarnet; Retrospective Studies; Ganciclovir; Antiviral Agents; Dichlororibofuranosylbenzimidazole
PubMed: 36730596
DOI: 10.1097/ICB.0000000000001372 -
Clinical Transplantation Dec 2023Valganciclovir (VGC) is the gold-standard for cytomegalovirus (CMV) prophylaxis (PPX) after solid organ transplant (SOT). Letermovir (LTV) was recently approved in...
Real world experience with conversion from valganciclovir to letermovir for cytomegalovirus prophylaxis: Letermovir reverses leukopenia and avoids mycophenolate dose reduction.
PURPOSE
Valganciclovir (VGC) is the gold-standard for cytomegalovirus (CMV) prophylaxis (PPX) after solid organ transplant (SOT). Letermovir (LTV) was recently approved in high-risk kidney transplant and has reduced myelosuppressive toxicity. Conversion from VGC to LTV may be pursued in the setting of leukopenia. It is unknown if this strategy is effective.
METHODS
Adult patients receiving abdominal SOT were included if converted from VGC to LTV between January 1, 2018 and January 31, 2023. Primary objective was to describe the impact of LTV conversion as measured by WBC recovery, mycophenolate modification, and use of GCSF, and prophylaxis efficacy assessed by course completion and breakthrough DNAemia. Secondary objective was to evaluate rates of post-prophylaxis CMV.
RESULTS
Seventy five SOT recipients met inclusion criteria. Mean change in WBC in response to LTV conversion by day 14 was +2.02 ± 2.52 k/uL. 75%(56/75) of the population did not require mycophenolate adjustment or had their dose increased after conversion. GCSF was required in 38.7%(29/75) prior to conversion; only 21.3%(16/75) of patients required GCSF after conversion. Early termination was uncommon, 14.7%(11/75) stopped due to lack of ongoing insurance approval, only one patient stopped due to adverse effects (1.3%). One patient had clinically significant breakthrough (1.3%) that was successfully managed with VGC. Incidence of post prophylaxis CMV was 40%.
CONCLUSION
Withholding of VGC with LTV conversion may improve leukopenia without need for additional supportive measures. Most importantly, this strategy avoided additional mycophenolate modifications. In our study, LTV was associated with low rates of breakthrough. Post-prophylaxis CMV was similar to VGC prophylaxis.
Topics: Adult; Humans; Valganciclovir; Cytomegalovirus; Antiviral Agents; Ganciclovir; Cytomegalovirus Infections; Drug Tapering; Thrombocytopenia; Leukopenia; Immunosuppressive Agents
PubMed: 37755141
DOI: 10.1111/ctr.15142