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Neonatal Network : NN Apr 2024Cytomegalovirus (CMV), a beta-herpes virus, is the most common viral infection in infants. Transmission may occur congenitally (cCMV) or postnatally (pCMV). Early... (Review)
Review
Cytomegalovirus (CMV), a beta-herpes virus, is the most common viral infection in infants. Transmission may occur congenitally (cCMV) or postnatally (pCMV). Early detection and intervention are crucial in reducing morbidities, notable developmental delays, and sensorineural hearing loss. However, more than 90% of infants are asymptomatic at birth. Treatment involves intravenous ganciclovir or the oral prodrug, valganciclovir, drugs usually reserved for use with symptomatic infants because of the toxicity profile. Research currently supports standardized antenatal CMV screening and treatment of affected pregnant patients with hyperimmune globulin as well as vaccination against CMV in unaffected pregnant patients, although widespread adoption is lacking. Standardized postnatal CMV screening is a proven, cost-effective way to detect and diagnose CMV and optimize outcomes across the lifespan. This article presents a case series of cCMV and pCMV and a review of the state of science of CMV as well as promising scientific advances that are on the horizon.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Neonatal Screening; Valganciclovir
PubMed: 38599771
DOI: 10.1891/NN-2023-0069 -
BMJ Case Reports Apr 2024We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an...
We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an immunocompetent patient. Treatment with oral valganciclovir for 2 weeks successfully led to complete clinical recovery. CMV is traditionally associated with infection in immunocompromised patients and neonates; however, evidence of severe CMV infections in immunocompetent hosts is emerging. It is important to highlight the broad range of clinical presentations of CMV infections to prevent diagnostic delay and associated morbidity and expense.
Topics: Female; Infant, Newborn; Humans; Cytomegalovirus; Purpura, Thrombocytopenic, Idiopathic; Ganciclovir; Delayed Diagnosis; Queensland; Cytomegalovirus Infections; Pneumonia; Antiviral Agents
PubMed: 38594194
DOI: 10.1136/bcr-2023-259136 -
Clinical and Experimental Medicine Apr 2024Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in... (Review)
Review
Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.
Topics: Humans; Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Lung; Off-Label Use; Quinazolines; Retrospective Studies; Transplant Recipients
PubMed: 38578337
DOI: 10.1007/s10238-024-01330-2 -
Pediatrics International : Official... 2024
Topics: Infant; Infant, Newborn; Humans; Valganciclovir; Cytomegalovirus; Infant, Premature; Cytomegalovirus Infections; Antiviral Agents; Infant, Newborn, Diseases; Hearing Loss, Sensorineural
PubMed: 38563289
DOI: 10.1111/ped.15755 -
Cureus Feb 2024This case report presents a 24-year-old female with a history of ulcerative colitis (UC) who sought care for symptoms initially suggestive of the disease exacerbation...
This case report presents a 24-year-old female with a history of ulcerative colitis (UC) who sought care for symptoms initially suggestive of the disease exacerbation but was later diagnosed as acute cytomegalovirus (CMV) colitis. The patient's clinical course, marked by watery diarrhea, blood in stools, vomiting, and fever, raised suspicion of a UC flare. However, a nuanced diagnostic approach revealed CMV superinfection, including computed tomography, colonoscopy, and tissue polymerase chain reaction (PCR). The patient's immunosuppressive history, with prior treatment, including intravenous infliximab and azathioprine, contributed to CMV infection. Treatment involved initiation of tofacitinib and antiviral therapy with valganciclovir. This case underscores the diagnostic challenges in distinguishing between infectious complications and UC exacerbations, necessitating a tailored, multidisciplinary approach for optimal management. It highlights the delicate balance required when managing UC patients on immunosuppressive regimens, emphasizing the importance of timely diagnosis and individualized treatment strategies in complex clinical scenarios.
PubMed: 38544631
DOI: 10.7759/cureus.54903 -
Infection & Chemotherapy Mar 2024Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV... (Review)
Review
Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients: Guidelines by the Korean Society of Infectious Diseases and the Korean Society for Transplantation.
Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.
PubMed: 38527780
DOI: 10.3947/ic.2024.0016 -
The Annals of Pharmacotherapy Mar 2024The article reviews the safety and efficacy of treatments for cytomegalovirus (CMV) in solid organ transplantation. (Review)
Review
OBJECTIVE
The article reviews the safety and efficacy of treatments for cytomegalovirus (CMV) in solid organ transplantation.
DATA SOURCES
A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from database inception through January 2024, using terms CMV, therapy, and solid organ transplantation.
STUDY SELECTION AND DATA EXTRACTION
Clinical trials, meta-analyses, cohort studies, case reports, and guidelines were included. Letters to the editor, reviews, and commentaries were excluded.
DATA SYNTHESIS
After abstract screening and full-text review of 728 citations for eligibility, 53 were included. Valganciclovir and intravenous ganciclovir are drugs of choice for CMV management and, until recently, the availability of alternative options has been restricted due to toxicity. For instance, foscarnet and cidofovir serve as second-line agents due to potential bone marrow and renal toxicity. In patients with refractory or resistant CMV, maribavir, a novel oral agent, has proven efficacy and a lower adverse effect profile. However, in refractory or resistant CMV, foscarnet and cidofovir are preferred in invasive disease (CMV gastritis, CMV retinitis, and CMV encephalitis), high viral loads, and inability to tolerate oral preparations.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Consensus guidelines have not been revised since approval of novel antivirals in solid organ transplantation. Valganciclovir and ganciclovir remain drugs of choice for initial CMV therapy. Foscarnet, cidofovir, and maribavir are treatments for refractory or resistant-CMV.
CONCLUSIONS
Selection of CMV antiviral treatment should be determined by patient-specific factors, including severity of illness, resistant or refractory disease, dose-limiting adverse effects, and the preferred route of administration.
PubMed: 38501850
DOI: 10.1177/10600280241237534 -
Clinical Pharmacokinetics Apr 2024Ganciclovir (GCV) and valganciclovir (VGCV) show large interindividual pharmacokinetic variability, particularly in children. The objectives of this study were (1) to...
BACKGROUND AND OBJECTIVES
Ganciclovir (GCV) and valganciclovir (VGCV) show large interindividual pharmacokinetic variability, particularly in children. The objectives of this study were (1) to develop machine learning (ML) algorithms trained on simulated pharmacokinetics profiles obtained by Monte Carlo simulations to estimate the best ganciclovir or valganciclovir starting dose in children and (2) to compare its performances on real-world profiles to previously published equation derived from literature population pharmacokinetic (POPPK) models achieving about 20% of profiles within the target.
MATERIALS AND METHODS
The pharmacokinetic parameters of four literature POPPK models in addition to the World Health Organization (WHO) growth curve for children were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles. ML algorithms were developed and benchmarked to predict the probability to reach the steady-state, area-under-the-curve target (AUC within 40-60 mg × h/L) based on demographic characteristics only. The best ML algorithm was then used to calculate the starting dose maximizing the target attainment. Performances were evaluated for ML and literature formula in a test set and in an external set of 32 and 31 actual patients (GCV and VGCV, respectively).
RESULTS
A combination of Xgboost, neural network, and random forest algorithms yielded the best performances and highest target attainment in the test set (36.8% for GCV and 35.3% for the VGCV). In actual patients, the best GCV ML starting dose yielded the highest target attainment rate (25.8%) and performed equally for VGCV with the Franck model formula (35.3% for both).
CONCLUSION
The ML algorithms exhibit good performances in comparison with previously validated models and should be evaluated prospectively.
Topics: Humans; Ganciclovir; Valganciclovir; Machine Learning; Child; Antiviral Agents; Child, Preschool; Monte Carlo Method; Male; Female; Adolescent; Infant; Models, Biological; Algorithms; Area Under Curve; Computer Simulation
PubMed: 38492206
DOI: 10.1007/s40262-024-01362-7 -
Transplant Infectious Disease : An... Apr 2024The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported...
BACKGROUND
The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis.
METHODS
This retrospective cohort study included lung transplant recipients newly initiated on letermovir between 2019-2022 following valganciclovir intolerance. Tacrolimus doses and concentrations were collected up to 30 days before and after the letermovir start date. No pre-emptive FK dose adjustments occurred prior to letermovir initiation. Patients admitted to the hospital or lacking an appropriately timed trough in the pre- or post-period were excluded.
RESULTS
A total of 78 lung transplant recipients receiving FK (1.5 mg median total daily dose) and itraconazole (56.4%), isavuconazole (25.6%) or posaconazole (17.9%) prophylaxis were included. Letermovir was started at a median of 8.4 months post-transplant. The pre-/post-letermovir median FK trough was 9.6/9.0 ng/mL (p = .151), median dose-corrected trough was 4.2/4.7 ng/mL/mg (+11.9%, p = .032), and median weight-based dose-corrected trough was 362/326 [ng/mL]/[mg/kg/day] (-9.9%, p = .036). There was no significant difference in the proportion of patients within their goal trough range before and after letermovir initiation (62% vs. 72%, p = .229).
CONCLUSION
Empiric FK dose adjustments do not appear warranted before letermovir initiation in lung transplant recipients receiving antifungal prophylaxis with moderate-to-strong CYP3A4 inhibitors.
Topics: Humans; Antifungal Agents; Tacrolimus; Azoles; Transplant Recipients; Retrospective Studies; Lung; Antiviral Agents; Acetates; Quinazolines
PubMed: 38488776
DOI: 10.1111/tid.14267 -
Journal of Infection and Chemotherapy :... Mar 2024Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital...
Assessment of patients' characteristics associated with the efficacy and safety of oral valganciclovir treatment for infants with symptomatic congenital cytomegalovirus disease.
INTRODUCTION
Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing.
MATERIALS AND METHODS
We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count.
RESULTS
Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019).
CONCLUSIONS
Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening.
PubMed: 38484931
DOI: 10.1016/j.jiac.2024.03.006