-
BMJ Case Reports Oct 2019A follow-up blood count was performed on a 74-year-old woman diagnosed with colitis due to cytomegalovirus and under treatment with valganciclovir. The automated...
A follow-up blood count was performed on a 74-year-old woman diagnosed with colitis due to cytomegalovirus and under treatment with valganciclovir. The automated complete blood count revealed an abnormal white blood cells (WBC) scattergram together with WBC alert flags. The peripheral blood smear showed neutrophils with markedly hyposegmented nuclei or bilobed nuclei and very condensed chromatin or clumping chromatin all consistent with Pelger-Huët anomaly (PHA). We checked previous blood counts, ruling out an inherited PHA. We assessed the haematological, infectious and iatrogenic aetiologies for an acquired PHA. Once the valganciclovir treatment was completed and the drug was withdrawn, without changing the rest of the treatment, the morphological abnormalities of neutrophils were completely resolved. We conclude therefore that the acquired PHA presented by our patient is probably related to valganciclovir treatment.
Topics: Aged; Antiviral Agents; Colitis; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Pelger-Huet Anomaly; Valganciclovir
PubMed: 31611226
DOI: 10.1136/bcr-2019-230958 -
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 -
British Journal of Clinical Pharmacology Aug 2021Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high...
AIMS
Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high pharmacokinetic (PK) interindividual variability and PK data are scarce, especially in paediatric stem cell transplant (SCT) recipients. We sought to determine the optimal GCV and VGCV dosing in transplanted children.
METHODS
We conducted a single-centre retrospective population PK (POPPK) study of IV GCV and enteral VGCV in paediatric solid organ transplant (SOT) and SCT recipients. We included children who were transplanted and had available plasma GCV concentrations, done per standard of care. POPPK analysis was performed using a nonlinear mixed effects modelling approach with NONMEM. Optimal dosing was determined based on the achievement of the surrogate efficacy target: GCV 24 h area under the concentration-time curve (AUC ) of 40-60 mg.h.L .
RESULTS
Fifty children with a median [range] age of 7.5 years [0.5-17.4] contributed 580 PK samples. A two-compartment model with first-order absorption with a lag time and first-order elimination fit the data well. Creatinine clearance and body weight (WT) were significant covariates for GCV clearance (CL); and WT for the volumes of distribution. IV GCV 15-20 mg.kg .day divided every 12 hours achieved the highest probability of target achievement (PTA) (33.0-33.8%). Enteral VGCV 30 and 40 mg.kg .day divided every 12 hours in children 0-<6 years, and 6-18 years, respectively, achieved the highest PTA (29.1-33.0%).
CONCLUSION
This is the first POPPK model developed in children with either SOT or SCT. Concentration target achievement was low, suggesting a potential benefit for therapeutic drug monitoring to ensure optimal exposure.
Topics: Antiviral Agents; Child; Ganciclovir; Humans; Retrospective Studies; Stem Cell Transplantation; Transplant Recipients; Valganciclovir
PubMed: 33373493
DOI: 10.1111/bcp.14719 -
Leukemia Apr 2009
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cytomegalovirus; Drug Evaluation; Ganciclovir; Humans; Premedication; Valganciclovir; Virus Activation
PubMed: 18843288
DOI: 10.1038/leu.2008.282 -
European Journal of Pediatrics Aug 2006
Topics: Administration, Oral; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Infant, Newborn; Neutropenia; Valganciclovir; Viral Load
PubMed: 16534589
DOI: 10.1007/s00431-006-0109-0 -
Current Opinion in Organ Transplantation Apr 2024Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT). (Review)
Review
PURPOSE OF REVIEW
Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT).
RECENT FINDINGS
Universal prophylaxis and preemptive therapy are the most adopted strategies for prevention of CMV disease globally. Prophylaxis with valganciclovir is the most widely used approach to CMV prevention, however leukopenia and late onset CMV disease after discontinuation of prophylaxis requires new strategies to prevent this complication. The use of assays detecting CMV-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Letermovir has been recently approved for prophylaxis in kidney transplant recipients. CMV-RNAemia used together with CMV-DNAemia in the viral surveillance of CMV infection provides accurate information on viral load kinetics, mostly in patients receiving letermovir prophylaxis/therapy. The development of refractory and resistant CMV infection remains a major challenge and a new treatment with maribavir is currently available. In the present paper we will review the most recent advances in prevention and treatment of CMV diseases in SOT recipients.
SUMMARY
Recent findings, summarized in the present paper, may be useful to optimize prevention and treatment of CMV infection in SOT.
Topics: Humans; Antiviral Agents; Cytomegalovirus Infections; Valganciclovir; Transplant Recipients; Organ Transplantation; Acetates; Quinazolines
PubMed: 38288947
DOI: 10.1097/MOT.0000000000001139 -
Editorial commentary: Use of valganciclovir for prevention and treatment of cytomegalovirus disease.Clinical Infectious Diseases : An... Jan 2008
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Humans; Immunocompromised Host; Postoperative Complications; Transplantation; Valganciclovir
PubMed: 18171209
DOI: 10.1086/523589 -
Farmacia Hospitalaria : Organo Oficial... Feb 2021Immunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients...
OBJECTIVE
Immunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver.
METHOD
This is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days posttransplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients.
RESULTS
144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29- 45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binarylogistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00].
CONCLUSIONS
Our study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.
Topics: Child; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Neutropenia; Retrospective Studies; Valganciclovir
PubMed: 33709891
DOI: 10.7399/fh.11571 -
International Journal of Molecular... Mar 2019Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital...
Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; = 20) or 6 months (July 2015 to March 2018, = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61⁻90 dB; and moderate, 41⁻60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Although, 16 (84%) of 19 ears with moderate or severe hearing dysfunction improved after treatment ( < 0.001), 10 ears with the most severe form did not. In conclusion, VGCV treatment is effective in improving moderate and severe hearing dysfunction in infants with congenital CMV infection.
Topics: Cytomegalovirus Infections; Evoked Potentials, Auditory, Brain Stem; Female; Hearing Loss, Sensorineural; Humans; Infant; Male; Severity of Illness Index; Treatment Outcome; Valganciclovir; Viral Load
PubMed: 30893926
DOI: 10.3390/ijms20061388 -
Transplant Infectious Disease : An... Aug 2019Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear.
BACKGROUND
Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear.
METHODS
This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66).
RESULTS
Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively.
CONCLUSION
Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.
Topics: Adult; Antiviral Agents; Cytomegalovirus Infections; Delayed Graft Function; Electronic Health Records; Female; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Risk Factors; Transplant Recipients; Treatment Outcome; Valganciclovir; Viremia
PubMed: 31165548
DOI: 10.1111/tid.13125