Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.

OBJECTIVES: Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540). PATIENTS AND METHODS: Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected. RESULTS: Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance. CONCLUSIONS: These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.

Cytomegalovirus (CMV) Shedding in French Day-Care Centers: A Nationwide Study of Epidemiology, Risk Factors, Centers' Practices, and Parents' Awareness of CMV.

BACKGROUND: Congenital cytomegalovirus (CMV) remains an important healthcare burden, resulting from primary or secondary infection in pregnant women. Exposure to young children's saliva is a major risk factor, as prevalence of CMV shedding can reach 34%. METHODS: This cross-sectional, multicenter, nationwide study was conducted in randomly selected day care centers (DCCs), and complemented with a survey among parents and DCCs. All children aged >3 months were eligible. The study measured the CMV shedding prevalence in children's saliva and described CMV genotypes epidemiology. The risk factors for CMV shedding and high viral load were evaluated using multivariable models. RESULTS: A total of 93 DCCs participated. Among the 1770 enrolled children with evaluable samples, the CMV shedding prevalence was 40% (713/1770, 95% confidence interval, 34.6-46.1), independently associated with children aged between 12 and 18 months, history of CMV infection in ≥1 parents, a mid-level income. Prevalence increased with DCC staff workload and attending children number. Viral load was ≥5 log-copies CMV/mL in 48% (342/713). Risk factors for higher viral load included children aged between 12 and 18 months, and still being breastfed. The most frequent genotype combinations were gB1-gN4c-gH2 (6.9%), gB1-gN2-gH2 (6.3%), gB4a-gN3a-gH1 (6.3%), and gB1-gN3b-gH2 (5,7%). CMV awareness was low in parents: their serological status was unknown by 72% of mothers and 82% of fathers. Only 41% knew something about CMV. CONCLUSIONS: CMV shedding was independently associated with risk factors related to the children, family and DCC. Some of these risk factors may influence prevention strategies, including through an improved information provided to parents. CLINICAL TRIALS REGISTRATION: NCT01704222.