Comprehensive modeling reveals proximity, seasonality, and hygiene practices as key determinants of MRSA colonization in exposed households.

BACKGROUND: Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs). To develop interventions to prevent recurrent infections, household attributes and individual practices influencing S. aureus colonization must be discerned. METHODS: Households of healthy children with methicillin-resistant S. aureus (MRSA) SSTI (n = 150; 671 participants) were interviewed regarding health history, activities, and hygiene practices. S. aureus colonization was assessed in household members, and recovered isolates were typed by repetitive sequence-based PCR. RESULTS: The number of unique strain types in a household (median 1, range 0-7) correlated with the number of colonized individuals (p < 0.001). The MRSA infecting strain type colonized a household member in 57% of 91 households with an available infecting strain, and was the most common strain type recovered in 45% of these households. In multivariable models, household MRSA colonization burden (p < 0.001), sharing a bedroom with MRSA-colonized individuals (p = 0.03), renting dwelling (p = 0.048), and warmer seasons (p = 0.02) were associated with increased MRSA colonization. Increasing age (p = 0.02), bathing at least daily (p = 0.01), and antibacterial soap use (p = 0.03) correlated with reduced MRSA colonization. CONCLUSIONS: This study identified practices that correlate with MRSA colonization, which will inform physician counseling and multifaceted interventions among MRSA-affected households to mitigate MRSA in the community.

Letermovir Discontinuation at Day 100 After Allogeneic Stem Cell Transplant Is Associated With Increased CMV-Related Mortality.

Letermovir is approved by the Food and Drug Administration for cytomegalovirus (CMV) prophylaxis in CMV seropositive recipients of allogeneic stem cell transplantation (alloSCT) up to day 100. Letermovir use up to day 100 after alloSCT has demonstrated a significantly lower incidence of clinically significant CMV infection (csCMVi) at 24 weeks and an overall mortality benefit as far as 48 weeks after transplantation. We report data on csCMVi incidence beyond 24 weeks and overall survival (OS) beyond 48 weeks and outcomes for patients who had a prior alloSCT, are CMV seronegative with seropositive donor (D+/R-), or are high risk (defined as those receiving haploidentical transplants, mismatched transplants, T-cell-depleted grafts, umbilical cord blood transplants, prednisone ≥1 mg/kg or equivalent steroid use, or the use of 2 or more immunosuppressants). Additionally, risk factors for CMV-related mortality and possible extended duration of letermovir are reported. This is a single-center, retrospective cohort study of 333 alloSCTs with CMV seropositive donors or recipients performed at Siteman Cancer Center and Barnes-Jewish Hospital from January 2016 to June 2019. The primary endpoint of csCMVi at day 180 was 19.46% with letermovir and 39.13% without letermovir (P < .0001). The secondary endpoints are as follows: day 100 csCMVi was 8.1% with letermovir and 34.8% without (P < .0001), day 365 csCMVi was 24.8% with letermovir and 41.3% without (P = .001). Our multivariate analyses demonstrated that exposure to letermovir was associated with improved OS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.25-0.77), nonrelapse mortality (HR 0.50; 95% CI 0.27-0.94) and CMV-related mortality (HR 0.40; 95% CI 0.16-0.95) during day 0 to day 99 but worse CMV-related mortality during day 180 to day 364 (HR 3.19; 95% CI 1.29-7.92). Patients with serum IgG levels <400 mg/dL at day 100, high-risk transplants (P = .004), post-transplantation cyclophosphamide (PTCy; P = .001), and mismatched-unrelated donors (MMUD; P = .02) experienced increased CMV reactivation. The CMV D+/R- cohort demonstrated no difference in CMV reactivation overall (P = .19), but the subset receiving PTCy showed decreased reactivation with letermovir (P = .03). Discontinuation of letermovir at day 100 leads to increased incidence of late CMV reactivation and CMV-related mortality. Letermovir use in CMV recipient seropositive alloSCT may need to be extended. Serum IgG levels <400 mg/dL at day 100 was associated with increased CMV reactivation. Patients with subclinical CMV viremia before transplantation, high-risk transplants, PTCy, or MMUD had decreased CMV reactivation with letermovir. Although there was no difference in CMV reactivation in the CMV D+/R- cohort, the subset treated with PTCy for acute graft-versus-host disease prophylaxis had decreased CMV reactivation with letermovir.