scholarly journals Emergence of antiviral resistance during oral valganciclovir treatment of an infant with congenital cytomegalovirus (CMV) infection

2013 ◽  
Vol 57 (4) ◽  
pp. 356-360 ◽  
Author(s):  
K. Yeon Choi ◽  
B. Sharon ◽  
H.H. Balfour ◽  
K. Belani ◽  
T.C. Pozos ◽  
...  
Keyword(s):  
Antiviral Resistance ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus ◽  
Oral Valganciclovir

scholarly journals Incidence of UL97 Resistance Mutations in Infants with Congenital Cytomegalovirus Disease Receiving 6 Months of Oral Valganciclovir Therapy

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S23-S23 ◽  
Author(s):  
Scott H James ◽  
Ra’Shun L Conner ◽  
David W Kimberlin ◽  
Richard Whitley ◽  
Mark N Prichard
Keyword(s):  
Antiviral Therapy ◽  
Antiviral Resistance ◽  
Sequence Variants ◽  
Resistance Mutations ◽  
Phase 3 ◽  
Congenital Cytomegalovirus ◽  
Study Population ◽  
Oral Valganciclovir ◽  
Cmv Disease ◽  
Ul97 Gene

Abstract Background A recently completed Phase 3 randomized, controlled, double-blind, multicenter study of infants with symptomatic congenital cytomegalovirus (CMV) disease receiving 6 months of oral valganciclovir (VGCV) therapy represents the largest such population in which to evaluate treatment-emergent antiviral resistance. The most common mechanism of CMV antiviral resistance occurs through mutations in the CMV UL97 gene that confer resistance to ganciclovir (GCV). Genotypic resistance analyses were performed on infants receiving 6 months of VGCV to assess the incidence of antiviral resistance due to UL97 sequence variants. Methods Resistance analyses were performed by conventional DNA sequencing of the UL97 gene at multiple time points. Following CMV DNA extraction from frozen whole blood specimens, the UL97 gene was amplified with a double nested polymerase chain reaction method and sequenced to identify polymorphisms and mutations that might confer GCV resistance. Results Forty-six infants with symptomatic CMV disease who received a 6-month course of VGCV underwent resistance analysis to identify UL97 sequence variants. In addition to a range of natural polymorphisms known to have no effect on antiviral susceptibility, 2 subjects developed UL97 mutations known to confer resistance to GCV (A594V and G598S detected in one subject; E596G detected in another), yielding an incidence of 4%. Each of these resistance mutations occurred in specimens collected after at least 4 months of antiviral therapy. As evaluated in the original Phase 3 trial, neither of these infants showed an improvement in hearing outcome. Conclusion The development of treatment-emergent UL97 resistance mutations was determined in a controlled study population of infants with congenital CMV disease receiving 6 months of VGCV. This targeted resistance analysis demonstrated an incidence approaching the total incidence of antiviral resistance for CMV disease in some immunocompromised populations, such as solid-organ transplant recipients. Further studies within this study population are warranted to elucidate the risk of emerging antiviral resistance and to assess clinical impact as well as the potential need for combination antiviral therapy. Disclosures All authors: No reported disclosures.

Congenital cytomegalovirus infection in twin pregnancy

2021 ◽  
Vol 14 (7) ◽  
pp. e242712
Author(s):  
Ana Araújo Carvalho ◽  
Cláudia B Silva ◽  
Maria Luísa Martins ◽  
Gonçalo Cassiano Santos
Keyword(s):  
Intrauterine Growth Restriction ◽  
Twin Pregnancy ◽  
Viral Infections ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus Infection ◽  
Congenital Cytomegalovirus ◽  
Postnatal Treatment ◽  
Oral Valganciclovir ◽  
Maternal Administration ◽  
Infected Newborn

Cytomegalovirus (CMV) infection is one of the preeminent congenital viral infections, and despite its potential morbidity, uncertainty about its physiopathology, prevention and treatment remains until now. We report a case of a dichorionic and diamniotic twin pregnancy in which only one of the fetus had signs of being affected. The first twin had prenatal diagnosis of intrauterine growth restriction and hyperechogenic bowel, attributable to CMV infection, while there was no evidence of infection of the second one. Prenatal treatment was done with maternal administration of valacyclovir and postnatal treatment of the infected newborn with oral valganciclovir with normal neurodevelopment assessment at 12 months corrected age. In this case, maternal CMV infection was not equally transmitted to both fetuses, suggesting that there may be intrinsic fetal and placental factors influencing both transmission and the clinical features of the infection.

CMV pneumonitis in a patient with Crohn’s disease taking azathioprine

2021 ◽  
Vol 14 (4) ◽  
pp. e241256
Author(s):  
Timothy Zef Hawthorne ◽  
Rachel Shellien ◽  
Lucy Chambers ◽  
Graham Devereux
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Low Dose ◽  
Antiviral Treatment ◽  
Cmv Infection ◽  
Rare Presentation ◽  
Intravenous Ganciclovir ◽  
Increased Risk ◽  
Oral Valganciclovir

This case report discusses the rare presentation of cytomegalovirus (CMV) pneumonitis in a young patient with moderately severe Crohn’s disease managed with low dose azathioprine. CMV pneumonitis was initially suspected on CT chest images and confirmed by PCR for CMV. She was treated with intravenous ganciclovir and later stepped down to oral valganciclovir. Although this patient had a prolonged and complicated hospital admission, a good clinical outcome was achieved. CMV infection was raised as an early differential and antiviral treatment was started without delay. This case study, therefore, makes the case for increased awareness of the possibility of, and recognition of CMV pneumonitis among healthcare professionals as a way of preventing significant morbidity and mortality. It also raises awareness of checking for slow metabolisers of azathioprine before initiation to look for individuals who may be at increased risk of azathioprine’s adverse effects.

Severe fetal anaemia caused by congenital cytomegalovirus infection

2021 ◽  
Vol 14 (10) ◽  
pp. e244585
Author(s):  
Claudia Salazar-Sanchez ◽  
Pedro Llancarí ◽  
Rommy H Novoa ◽  
Walter Ventura
Keyword(s):  
Pregnant Woman ◽  
Fetal Growth ◽  
Umbilical Cord Blood ◽  
Cytomegalovirus Infection ◽  
Peak Systolic Velocity ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus Infection ◽  
Congenital Cytomegalovirus ◽  
Fetal Medicine ◽  
Fetal Infection

A 22-year-old pregnant woman was referred to our fetal medicine unit due to severe fetal growth restriction at 26 weeks of gestation. An extensive detailed ultrasound revealed signs of bilateral periventricular hyperechogenicity, suggesting fetal infection potentially due to cytomegalovirus (CMV). Doppler ultrasound showed a high peak systolic velocity in the middle cerebral artery. Percutaneous umbilical cord blood sampling confirmed fetal CMV infection and severe fetal anaemia. We present this case to highlight the importance of fetal anaemia, which can be fatal regardless of whether it is associated with generalised oedema or hydrops fetalis.

scholarly journals Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hitomi Imafuku ◽  
Hideto Yamada ◽  
Akiko Uchida ◽  
Masashi Deguchi ◽  
Tokuro Shirakawa ◽  
...  
Keyword(s):  
Preterm Delivery ◽  
Medical Center ◽  
Clinical Manifestations ◽  
High Sensitivity ◽  
Clinical Findings ◽  
Youden Index ◽  
Cmv Infection ◽  
Fetal Abnormality ◽  
Congenital Cytomegalovirus ◽  
Fetal Abnormalities

AbstractThis prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1–6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6–11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8–27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1–6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

scholarly journals Pharmacokinetic and Pharmacodynamic Assessment of Oral Valganciclovir in the Treatment of Symptomatic Congenital Cytomegalovirus Disease

2008 ◽  
Vol 197 (6) ◽  
pp. 836-845 ◽  
Author(s):  
David W. Kimberlin ◽  
Edward P. Acosta ◽  
Pablo J. Sánchez ◽  
Sunil Sood ◽  
Vish Agrawal ◽  
...  
Keyword(s):  
Cytomegalovirus Disease ◽  
Congenital Cytomegalovirus ◽  
Oral Valganciclovir

Congenital Cytomegalovirus Infection: A Cause of Renal Dysplasia?

2007 ◽  
Vol 10 (4) ◽  
pp. 300-304 ◽  
Author(s):  
Maren Chan ◽  
Jonathan L. Hecht ◽  
Theonia Boyd ◽  
Seymour Rosen
Keyword(s):  
Viral Infections ◽  
Tissue Injury ◽  
Clinical Manifestations ◽  
Renal Dysplasia ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus Infection ◽  
Congenital Cytomegalovirus ◽  
Wide Range ◽  
The Central Nervous System ◽  
Multicystic Dysplasia

Cytomegalovirus (CMV) infection is one of the most frequently encountered viral infections of the fetus and induces a wide range of histologic and clinical manifestations. Congenital abnormalities are typically restricted to the central nervous system despite evidence of CMV inclusions occurring in most epithelial cells. Although tissue injury and even glomerulonephritis have been observed in congenital CMV infections, renal multicystic dysplasia has not been reported. Herein, we describe a case of unilateral renal dysplasia in a 19-week fetus with concurrent CMV infection. We believe the present case to be the first description of a virus apparently inducing renal multicystic dysplasia.

The obstetrician, congenital cytomegalovirus, clinical and diagnostic approaches to the pregnant woman

2015 ◽  
Vol 36 (4) ◽  
pp. 194
Author(s):  
Antonia W Shand
Keyword(s):  
Magnetic Resonance Imaging ◽  
Pregnant Woman ◽  
Fetal Mri ◽  
Maternal Infection ◽  
Resonance Imaging ◽  
Cmv Infection ◽  
Serological Screening ◽  
Congenital Cytomegalovirus ◽  
Fetal Infection ◽  
Diagnostic Approaches

There is low awareness of congenital cytomegalovirus (CMV) in Australia. Routine pregnancy serological screening for CMV is not recommended, but all pregnant women should be given advice about CMV prevention. Obstetricians may be asked to see a pregnant woman when serology suggests CMV infection or when features of fetal infection are present on ultrasound. If maternal CMV infection is confirmed, the timing of infection (pre-pregnancy or gestation of pregnancy), must be determined to predict the fetal risks. In addition, it is important to establish whether maternal infection is primary or reactivation. If there is fetal infection, ultrasound can be used to attempt to establish whether the fetus may have been affected. Serial serology, CMV IgG avidity, maternal viraemia (using serum PCR), amniotic fluid CMV PCR, serial fetal ultrasounds, and possibly fetal MRI (magnetic resonance imaging) are investigations that may be useful to predict neonatal outcomes. Timely and accurate counselling is important to optimise maternal and neonatal management.

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