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Cureus Mar 2023Viral infections, such as cytomegalovirus (CMV) infection, may affect the clinical course of ulcerative colitis (UC). CMV can cause chronic inflammation of the...
Viral infections, such as cytomegalovirus (CMV) infection, may affect the clinical course of ulcerative colitis (UC). CMV can cause chronic inflammation of the intestinal mucosa. In inflammatory bowel disease, chronic inflammation caused by CMV can deter the regeneration of the mucosa of the colon. However, the relationship between CMV and inflammatory bowel disease still needs to be clarified, especially in immunocompetent patients, such as younger patients not treated with immunosuppressants. Herein, we describe our experience with a middle-aged immunocompetent female patient diagnosed with fulminant UC positive for myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Her initial response to high-dose prednisolone was favorable; however, remission was not achieved. Immunohistochemical staining revealed the presence of CMV. Subsequently, the patient was successfully treated with prednisolone, adalimumab, and azathioprine, along with the anti-CMV treatment comprising valganciclovir. This case shows that the presence of CMV in the mucosa and blood may make patients with UC refractory to immunosuppression; furthermore, the positivity of MPO-ANCA in patients with UC can necessitate the administration of high-dose immunosuppressants to taper the dose of prednisolone.
PubMed: 37065392
DOI: 10.7759/cureus.36092 -
Clinical Transplantation Jun 2023The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations...
BACKGROUND
The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations mostly extrapolated from other groups. We evaluated the incidence and severity of CMV infection in R+ HTR, to identify risk factors and describe outcomes.
METHODS
R+ HTR from 2010 to 2019 were included. Antiviral prophylaxis was not routinely used, with clinically guided monitoring the local standard of care. The primary outcome was CMV infection within one-year post-transplant; secondary outcomes included other herpesvirus infections and mortality.
RESULTS
CMV infection occurred in 27/155 (17%) R+ HTR. Patients with CMV had a longer hospitalization (27 vs. 20 days, unadjusted HR 1.02, 95% CI 1.00-1.02, p = .01), higher rate of intensive care readmission (26% vs. 9%, unadjusted HR 3.46, 1.46-8.20, p = .005), and increased mortality (33% vs. 8%, unadjusted HR 10.60, 4.52-24.88, p < .001). The association between CMV and death persisted after adjusting for multiple confounders (HR 24.19, 95% CI 7.47-78.30, p < .001). Valganciclovir prophylaxis was used in 35/155 (23%) and was protective against CMV (infection rate 4% vs. 27%, adjusted HR .07, .01-.72, p = .025), even though those receiving it were more likely to have received thymoglobulin (adjusted OR 10.5, 95% CI 2.01-55.0, p = .005).
CONCLUSIONS
CMV infection is common in R+ HTR and is associated with a high burden of disease and increased mortality. Patients who received valganciclovir prophylaxis were less likely to develop CMV infection, despite being at higher risk. These findings support the routine use of antiviral prophylaxis following heart transplantation in all CMV R+ patients.
Topics: Humans; Valganciclovir; Antiviral Agents; Ganciclovir; Incidence; Cytomegalovirus Infections; Heart Transplantation; Transplant Recipients; Retrospective Studies
PubMed: 36988473
DOI: 10.1111/ctr.14982 -
IDCases 2023Cytomegalovirus (CMV) pneumonitis infections might present mild or severe illnesses and need sophisticated diagnostic tools, so it remains a diagnostic challenge. We...
Cytomegalovirus (CMV) pneumonitis infections might present mild or severe illnesses and need sophisticated diagnostic tools, so it remains a diagnostic challenge. We reported five infants diagnosed with CMV pneumonitis who were initially and undiagnosed by the pediatrician in secondary private or public health hospitals with no improvement with standard and escalation of antibiotics treatment for bronchopneumonia as the initial diagnoses. As all cases occurred during the COVID-19 pandemic, they proved negative COVID-19 identified by polymerase chain reaction (PCR) SARS-CoV-2. We diagnosed acquired perinatal pneumonitis CMV in all claims based on clinical criteria, imaging studies, CMV serology, and PCR-CMV urinary tests as diagnostic tools. They showed clinical improvement after two weeks of valganciclovir therapy. Other organs' involvement was considered to be evaluated, including brain-evoked response audiometry (BERA) and eye examination. The physician should consider the possibility of CMV pneumonitis, who did not respond to standard and escalation of antibiotics treatment after initial diagnoses of bronchopneumonia.
PubMed: 36938338
DOI: 10.1016/j.idcr.2023.e01724 -
Clinical Case Reports Mar 2023Cytomegalovirus (CMV) retinitis is an uncommon presentation post allogeneic transplant and can be vision-threatening. Our case demonstrates the occurrence of polymerase...
Cytomegalovirus (CMV) retinitis is an uncommon presentation post allogeneic transplant and can be vision-threatening. Our case demonstrates the occurrence of polymerase chain reaction (PCR) proven mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogeneic stem cell transplant despite multiple prophylactic antiviral therapies, including letermovir, and in the documented absence of CMV DNAemia. A 21-year-old female with acute myeloid leukemia presented with mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogenic transplant. This presentation occurred despite ongoing standard prophylaxis for both of these viruses, as well as following two courses of treatment for CMV viremia, with a documented negative CMV PCR in the blood prior to the presentation with retinitis. The patient was treated with intravenous ganciclovir and subsequently transitioned to oral valganciclovir with durable resolution of the retinitis. We report a rare case of mixed viral retinitis occurring despite multiple antiviral prophylaxes including letermovir and with PCR-documented absence of preceding CMV viremia, in a post-allogeneic stem cell transplant patient, with PCR of the aqueous fluid demonstrating two viral populations. With very little existing literature on either mixed viral retinitis or CMV retinitis during letermovir prophylaxis, this case expands the literature on both topics. CMV retinitis is an uncommon potentially vision threatening presentation post hematopoietic stem cell transplant, and can occur due to early CMV reactivation, low CD4 count, and delayed CD4 lymphocyte recovery. Letermovir has poor CNS and retinal penetration. This case highlights the need for more research on secondary prophylaxis with letermovir.
PubMed: 36937625
DOI: 10.1002/ccr3.7095 -
Therapeutic Drug Monitoring Apr 2023Therapeutic drug monitoring (TDM) results for ganciclovir in 12 different treatment episodes showed large intraindividual and interindividual variabilities in the trough...
Therapeutic drug monitoring (TDM) results for ganciclovir in 12 different treatment episodes showed large intraindividual and interindividual variabilities in the trough concentration and area under the 24-hour concentration-time curve (AUC24). Despite adequate valganciclovir dosing, subtherapeutic concentrations were found in 30% of the treatment episodes. A decrease in viral load was observed regardless of subtherapeutic exposure. These findings show the need for target concentration evaluation and assessment of the applicability of ganciclovir TDM in children.
Topics: Child; Humans; Ganciclovir; Antiviral Agents; Cytomegalovirus Infections; Valganciclovir; Drug Monitoring
PubMed: 36920505
DOI: 10.1097/FTD.0000000000001050 -
Frontiers in Pediatrics 2023In immunocompetent individuals, cytomegalovirus (CMV) infection is usually mild but may cause severe complications such as retinitis, pneumonitis, and encephalitis in...
In immunocompetent individuals, cytomegalovirus (CMV) infection is usually mild but may cause severe complications such as retinitis, pneumonitis, and encephalitis in immunocompromised individuals. So far, cases of CMV retinitis in patients with medulloblastoma undergoing chemotherapy and radiotherapy, have not been reported. We herein report the case of a pediatric patient with high-risk medulloblastoma who experienced an unexpected CMV retinopathy and leukoencephalopathy following high dose thiotepa and proton irradiation. The patient underwent a four-course induction therapy (1st cycle: methotrexate and vinorelbine; 2nd cycle: etoposide and hematopoietic stem cells apheresis; 3rd cycle: cyclophosphamide and vinorelbine; 4th cycle: carboplatin and vinorelbine) and then a consolidation phase consisting in high dose thiotepa followed by autologous HSC transplant and proton cranio-spinal irradiation plus boost to the primary tumor site and pituitary site with concomitant vinorelbine. After two months of maintenance treatment with lomustine and vinorelbine, the patient showed complete blindness and leukoencephalopathy. A diagnosis of CMV retinopathy was made and oral valganciclovir was administered. CMV retinopathy was judged to be possibly related to the use of high dose thiotepa worsened by radiotherapy. This case report suggests that in pediatric patients undergoing immunosuppressive chemo-radiotherapy, CMV reactivation should be carefully monitored to prevent serious complications such as retinopathy and visual loss.
PubMed: 36896395
DOI: 10.3389/fped.2023.1145941 -
Antimicrobial Agents and Chemotherapy Apr 2023Valganciclovir, the ganciclovir prodrug, is an antiviral agent used to prevent cytomegalovirus infection in renal transplant children. Therapeutic drug monitoring is...
Valganciclovir, the ganciclovir prodrug, is an antiviral agent used to prevent cytomegalovirus infection in renal transplant children. Therapeutic drug monitoring is still necessary to ensure optimal therapeutic area under the concentration-time curve from 0 to 24 h (AUC) of 40 to 60 μg·h/mL since valganciclovir presents a high pharmacokinetic variability. To calculate ganciclovir AUC with the trapezoidal method, 7 samples are needed. The objective of this study was to develop and validate a reliable and clinically applicable limited sampling strategy (LSS) for individualizing valganciclovir dose in renal transplant children. Rich pharmacokinetic data from ganciclovir plasmatic dosages measured in renal transplant children who received valganciclovir to prevent cytomegalovirus infection at Robert Debré University Hospital were collected retrospectively. Ganciclovir AUCs were calculated using the trapezoidal method. The LSS was developed using a multilinear regression approach to predict AUC. The patients included were divided into two groups for model development (50 patients) and validation (30 patients). A total of 80 patients were included between February 2005 and November 2018. Multilinear regression models were developed on 50 pharmacokinetic profiles (50 patients) and validated with an independent group of 43 pharmacokinetic profiles (30 patients). Regressions based on samples collected at T1h-T4h-T8h, T2h-T4h-T8h, or T1h-T2h-T8h presented the best AUC predictive performances with an average difference between reference and predicted AUC of -0.27, 0.34, and -0.40 μg·h/mL, respectively. In conclusion, valganciclovir dosage adaptation was required in children to achieve the target AUC. Three LSS models using three pharmacokinetic blood samples instead of seven will be useful for individualizing valganciclovir prophylaxis in renal transplant children.
Topics: Humans; Child; Valganciclovir; Ganciclovir; Kidney Transplantation; Retrospective Studies; Antiviral Agents; Cytomegalovirus Infections
PubMed: 36880779
DOI: 10.1128/aac.01597-22 -
Open Forum Infectious Diseases Feb 2023Prolonged (val)ganciclovir [(V)GCV] exposure for ≥6 weeks is a known predisposing factor for cytomegalovirus (CMV) drug resistance. However, the selection of this...
BACKGROUND
Prolonged (val)ganciclovir [(V)GCV] exposure for ≥6 weeks is a known predisposing factor for cytomegalovirus (CMV) drug resistance. However, the selection of this threshold was based on limited data. In this study, we sought to reappraise the risk factors for the development of (V)GCV resistance through a specific focus on kidney transplant recipients (KTRs).
METHODS
This single-center retrospective study included 313 consecutive KTRs treated for a first CMV episode. Adjusted Cox multivariate regression analysis was used for identifying independent risk factors.
RESULTS
Antiviral drug resistance was identified in 20 (6%) KTRs. A cumulative (V)GCV exposure for more than 6 weeks (regardless of the viral load) was not associated with antiviral drug resistance (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 0.33-18.30, = .38). In contrast, persistent CMV DNAemia requiring (V)GCV treatment for more than 8 weeks was the main independent risk factor for antiviral drug resistance (HR = 11.68, 95% CI = 2.62-52.01, = .001). The (V)GCV treatment for more than 8 weeks was given to 9% and 18% of patients who had persistent or recurrent CMV DNAemia, respectively. These scenarios were associated with the occurrence of drug resistance in 39% and 12% of cases, respectively.
CONCLUSIONS
Cumulative (V)GCV exposure ≥6 weeks regardless of the viral load is not associated with antiviral drug resistance. In contrast, prolonged exposure to (V)GCV during CMV replication (with a cutoff ³8 weeks) seems to be a key factor.
PubMed: 36817745
DOI: 10.1093/ofid/ofad018 -
Antimicrobial Agents and Chemotherapy Mar 2023Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and... (Observational Study)
Observational Study
Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and resistance. This study aimed to develop an intravenous ganciclovir population pharmacokinetic model for post-alloHCT patients and to determine dosing regimens likely to achieve suggested therapeutic exposure targets. We performed a prospective observational single-center pharmacokinetic study in adult alloHCT patients requiring treatment with intravenous ganciclovir for CMV viremia or disease. Samples were analyzed using a validated ultraperformance liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (=1000) were performed using Pmetrics for R. Twenty patients aged 18 to 69 years were included in the study. A 2-compartment model with linear elimination from the central compartment and between occasion variability best described the data. Incorporating creatinine clearance (CL) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and presence of continuous renal replacement therapy as covariates for ganciclovir clearance improved the model. Compared to current dosing recommendations, simulations demonstrated loading doses were required to achieve a target AUC of 80 to 120 mg.h/L on day 1 of induction therapy. Increased individualization of post-loading induction and maintenance doses based on CL is required to achieve the suggested exposures for efficacy (AUC >80/>40 mg.h/L for induction/maintenance) while remaining below the exposure thresholds for toxicity (AUC <120/<60 mg.h/L for induction/maintenance). Intravenous ganciclovir dosing in alloHCT patients can be guided by CL estimated by CKD-EPI. Incorporation of loading doses into induction dosing regimens should be considered for timely achievement of currently suggested exposures.
Topics: Adult; Humans; Ganciclovir; Valganciclovir; Cytomegalovirus Infections; Organ Transplantation; Hematopoietic Stem Cell Transplantation; Antiviral Agents
PubMed: 36815858
DOI: 10.1128/aac.01550-22 -
Antimicrobial Agents and Chemotherapy Mar 2023This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in...
This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. A population PK/PD model was developed with Monolix. Ganciclovir concentrations and CMV viral loads were obtained retrospectively from kidney transplant patients receiving routine clinical care. Ten thousand Monte Carlo simulations were performed with the licensed dosages adjusted for renal function to assess the probability of attaining a viral load target of ≤290 and ≤137 IU/mL. Fifty-seven patients provided 343 ganciclovir concentrations and 328 CMV viral loads for PK/PD modeling. A one-compartment pharmacokinetic model coupled with an indirect viral turnover growth model with stimulation of viral degradation pharmacodynamic model was devised. Simulations showed that 1- and 2-log reduction of CMV viral load mostly occurred between a median of 5 to 6 and 12 to 16 days, respectively. The licensed dosages achieved a probability of reaching the viral load target ≥90% at days 35 to 49 and 42 to 56 for the thresholds of ≤290 and ≤137 IU/mL, respectively. Simulations indicate that in patients with an estimated glomerular filtration rate of 10 to 24 mL/min/1.73m, a dose increase to 450 mg every 36 h may reduce time to optimal viral load target to days 42 and 49 from a previous time of 49 and 56 days for the thresholds of ≤290 and ≤137 IU/mL, respectively. Currently licensed dosages of valganciclovir for preemptive therapy of CMV infection may achieve a viral load reduction within the first 2 weeks, but treatment should continue for ≥35 days to ensure viral load suppression.
Topics: Humans; Valganciclovir; Antiviral Agents; Kidney Transplantation; Retrospective Studies; Cytomegalovirus Infections; Ganciclovir; Transplant Recipients
PubMed: 36815856
DOI: 10.1128/aac.01665-22