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Transplant Infectious Disease : An... Dec 2023Valganciclovir is the first-line agent for Cytomegalovirus prophylaxis after lung transplantation. However, its use is associated with a relatively high risk of... (Observational Study)
Observational Study
BACKGROUND
Valganciclovir is the first-line agent for Cytomegalovirus prophylaxis after lung transplantation. However, its use is associated with a relatively high risk of hematological toxicity. This study aimed to investigate the relationship between trough ganciclovir concentration and hematologic toxicity in lung transplantation patients receiving valganciclovir prophylaxis, and identify factors that affect ganciclovir pharmacokinetics in this population.
METHODS
This prospective observational study included 24 lung transplant patients receiving valganciclovir prophylaxis. The cutoff value of trough ganciclovir concentration was estimated using receiver operating characteristic analysis in leukopenia grade 3 and higher. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling program.
RESULTS
The trough ganciclovir concentration was significantly higher in the group with leukopenia grades 3 or higher than in the group with grades less than or equal to 2 (1605.7 ± 860.1 ng/mL [n = 3] vs. 380.5 ± 175.8 ng/mL (n = 21), p < .001). The cutoff value of trough ganciclovir concentration for predicting greater than or equal to grade 3 leukopenia was estimated as 872.0 ng/mL. Creatinine clearance and lung re-transplantation were found to have a significant impact on the total body clearance of valganciclovir. Ganciclovir clearance was decreased in patients with reduced creatine clearance or re-transplantation.
CONCLUSION
These results suggest that higher ganciclovir trough concentrations are associated with an increased risk of leukopenia grade 3 or higher, and that creatinine clearance and lung re-transplantation affected the pharmacokinetics of ganciclovir.
Topics: Humans; Ganciclovir; Valganciclovir; Antiviral Agents; Transplant Recipients; Creatinine; Cytomegalovirus Infections; Lung; Leukopenia
PubMed: 37639301
DOI: 10.1111/tid.14141 -
JAMA Jul 2023
Topics: Humans; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Kidney Transplantation; Valganciclovir
PubMed: 37279971
DOI: 10.1001/jama.2023.9100 -
Journal of Clinical Medicine Dec 2023(1) Background: CMV infections remain a problem after kidney transplantation, particularly if patients are refractory or resistant (r/r) to treatment with valganciclovir...
(1) Background: CMV infections remain a problem after kidney transplantation, particularly if patients are refractory or resistant (r/r) to treatment with valganciclovir (VGCV) or ganciclovir (GCV). (2) Methods: In a single-center retrospective study, kidney transplant recipients (KTR) receiving letermovir (LTV) as rescue therapy for VGCV-/GCV-r/r CMV disease were analyzed regarding CMV history, immunosuppression, and outcomes. (3) Results: Of 201 KTR treated for CMV between 2017 and 2022, 8 patients received LTV following treatment failure with VGCV/GCV. All patients received CMV prophylaxis with VGCV according to the center's protocol, and 7/8 patients had a high-risk (D+/R-) CMV constellation. In seven of eight cases, rising CMV levels occurred during prophylaxis. In seven of eight patients, a mutation in UL97 associated with a decreased response to VGCV/GCV was detected. In four of eight patients, LTV resulted in CMV clearance after 24 ± 10 weeks (16-39 weeks), two of eight patients stabilized at viral loads <2000 cop/mL (6-20 weeks), and two of eight patients developed LTV resistance (range 8-10 weeks). (4) Conclusion: LTV, which is currently evaluated for CMV prophylaxis in kidney transplantation, also shows promising results for the treatment of patients with VGCV/GCV resistance despite the risk of developing LTV resistance. Additional studies are needed to further define its role in the treatment of patients with CMV resistance.
PubMed: 38202107
DOI: 10.3390/jcm13010100 -
Internal Medicine (Tokyo, Japan) Jan 2024Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness....
Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness. Chest computed tomography (CT) revealed bilateral diffuse reticulation and nodules. Laboratory investigations showed atypical lymphocytosis and increased transaminases. She was treated with corticosteroid pulse therapy because of acute lung injury, and her clinical condition improved. Based on the presence of cytomegalovirus antibodies, antigen, and polymerase chain reaction findings, she was diagnosed with primary cytomegalovirus pneumonia and treated with valganciclovir. Primary cytomegalovirus pneumonia is very rare in immunocompetent individuals. The efficacy of corticosteroid and valganciclovir against cytomegalovirus pneumonia in this patient is noteworthy.
Topics: Female; Humans; Adult; Valganciclovir; Cytomegalovirus; Cytomegalovirus Infections; Pneumonia; Tomography, X-Ray Computed; Antiviral Agents
PubMed: 37225488
DOI: 10.2169/internalmedicine.1638-23 -
Clinical Transplantation Dec 2023Recurrence after Cytomegalovirus (CMV) infection in heart transplant recipients is difficult to predict, in spite of its high incidence. Secondary prophylaxis could... (Observational Study)
Observational Study
BACKGROUND
Recurrence after Cytomegalovirus (CMV) infection in heart transplant recipients is difficult to predict, in spite of its high incidence. Secondary prophylaxis could reduce this burden; however, its duration remains unestablished. We evaluated the QuantiFERON®-CMV test to see if it could predict CMV recurrence and help optimize the duration of secondary prophylaxis.
METHODS
This observational retrospective single center study included all heart transplant recipients who developed CMV infection between 2019 and 2021, with the CD8+ T-cell-mediated CMV immunity QuantiFERON®-CMV test assessed at the time of (val)ganciclovir curative treatment completion. The main outcomes were CMV recurrence and duration of secondary prophylaxis. Secondary outcomes included immunosuppressive regimen, rejection, lymphocyte count, CMV viral load, infection type, and duration as possible confounding factors for recurrence.
RESULTS
Among the 15 patients included, five (33%) experienced recurrence, of whom three (60%) had a positive QuantiFERON®-CMV test. The duration of secondary prophylaxis was similar regardless of QF-CMV positivity. No confounding factor was significantly associated with CMV recurrence; however, it occurred in only 1/7 (14%) of the patients receiving an everolimus-containing immunosuppressive regimen.
CONCLUSION
In the population of heart transplant recipients, most of whom received ATG-based induction, the QuantiFERON®-CMV assay may not accurately predict CMV recurrence and would have not helped refining the duration of secondary prophylaxis in our patients. Other cell-mediated immunity tests and strategies in this specific population, including everolimus-containing regimens, may help predict and manage CMV recurrence.
Topics: Humans; Retrospective Studies; Antiviral Agents; Cytomegalovirus; Everolimus; Reproducibility of Results; Cytomegalovirus Infections; Ganciclovir; Immunosuppressive Agents; Heart Transplantation; Transplant Recipients
PubMed: 37641575
DOI: 10.1111/ctr.15109 -
Journal of Nephrology Jun 2024Kidney transplantation in Sudan is funded by the government. Cytomegalovirus prophylaxis is provided for patients who receive biological induction or have...
BACKGROUND
Kidney transplantation in Sudan is funded by the government. Cytomegalovirus prophylaxis is provided for patients who receive biological induction or have recipient-negative donor-positive cytomegalovirus serology. Doctor Selma Center for Kidney Diseases joined the national kidney transplant program in May 2019. Since then, we observed the frequent occurrence of cancer in patients who received modest immunosuppression without viral prophylaxis.
METHODS
We retrospectively divided kidney transplant recipients between 2019 and 2021 into two groups according to cytomegalovirus prophylaxis and compared tumor occurrence rates.
RESULTS
The first group included 77 patients who did not receive biological induction or cytomegalovirus prophylaxis. The second group included 92 patients who received valganciclovir for 3-6 months. There was no other antiviral treatment except entecavir for chronic hepatitis B virus infection in eight patients. Five patients in the first group developed malignancy. The first patient presented eight months post-transplant with Kaposi sarcoma of the stomach and responded to treatment with sirolimus. The second patient presented nine months post-transplant with cutaneous Kaposi sarcoma and also responded to sirolimus. Two patients presented two and four months post-transplant with aggressive non-cutaneous Kaposi sarcoma that involved the gastrointestinal tract and lymphatic system and died soon afterwards. The fifth patient presented three years post-transplant with non-Hodgkin lymphoma of the duodenum and is currently receiving chemotherapy. Malignancy rate (6.5% vs 0.0%, P = 0.02) and Kaposi sarcoma rate (5.2% vs 0.0%, P = 0.04) were significantly higher in the first group.
CONCLUSION
In Sudan, omitting valganciclovir prophylaxis after kidney transplantation was associated with a high rate of virus-induced malignancy.
PubMed: 38847938
DOI: 10.1007/s40620-024-01978-9 -
Ear and HearingCongenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of...
Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.
OBJECTIVES
Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy.
DESIGN
The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic. Chart review identified infants with cCMV, and records were reviewed for information about universal newborn hearing screen (UNHS) results, the clinical course of SNHL, and the use of antiviral therapy.
RESULTS
A total of 44 children were identified with cCMV. In this group, 33 (75%) had SNHL of varying degree and age at onset. Notably, 17 (39%) children passed UNHS bilaterally. Of those children, 6 (35%) ultimately acquired bilateral or unilateral SNHL, detected at a mean age of 20 months (median age, 12 months). Five out of 10 children (50%) that did not pass UNHS in one ear acquired late-onset hearing loss in the contralateral ear, identified at a mean age of 24 months (median age, 4 months). Eleven (25%) children passed UNHS bilaterally and continued to demonstrate normal hearing in both ears at their most recent follow-up visit at a mean age of 19 months (SD, 18 months). Of the 33 children with cCMV and SNHL, 18 (55%) received antiviral medication (ganciclovir and/or valganciclovir). While, on average, both treated and untreated ears experienced a progression of hearing loss over time, the group that received antiviral treatment experienced less overall hearing change compared with the untreated group (baseline-adjusted expected mean difference, -10.5 dB; 95% confidence interval, -28.1 to 7.2 dB).
CONCLUSIONS
Among children with cCMV included in this study who passed UNHS in both ears, 35% demonstrated delayed-onset SNHL. Notably, of those children who referred unilaterally, 50% later demonstrated SNHL in the contralateral ear. These findings have implications for audiological monitoring, and potentially antiviral therapy, of children with cCMV. As implementation of universal cCMV screening moves forward, a key aspect of follow-up will be appropriate long-term audiologic monitoring.
Topics: Infant; Infant, Newborn; Humans; Child; Child, Preschool; Cytomegalovirus; Retrospective Studies; Hearing Loss, Sensorineural; Hearing; Cytomegalovirus Infections; Deafness; Antiviral Agents; Neonatal Screening
PubMed: 37563758
DOI: 10.1097/AUD.0000000000001411 -
JAMA Nov 2023
Topics: Acetates; Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; Kidney Transplantation; Quinazolines; Valganciclovir
PubMed: 37962654
DOI: 10.1001/jama.2023.18025 -
JAMA Nov 2023
Topics: Acetates; Cytomegalovirus; Kidney Transplantation; Valganciclovir; Antiviral Agents; Chemoprevention; Cytomegalovirus Infections
PubMed: 37962657
DOI: 10.1001/jama.2023.18022 -
The Annals of Pharmacotherapy May 2024Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV...
BACKGROUND
Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.
OBJECTIVE
The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.
METHODS
This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.
RESULTS
Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.
CONCLUSION AND RELEVANCE
Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.
PubMed: 38801191
DOI: 10.1177/10600280241255110