RESUMEN
Background: Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods: We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score-weighted sensitivity, and subgroup analyses were performed. Results: Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%-1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31-0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21-8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92-55.5; subdistribution aHR, 7.15; 95% CI, 0.95-53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions: MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.
RESUMEN
Caenorhabditis elegans are free-living nematodes with a relatively short life cycle and a wealth of genomic information across multiple databases. Uridine diphosphate-glycosyltransferases (UGTs) are a family of enzymes involved in Phase II modification of xenobiotics in C. elegans , which is the addition of a sizeable water-soluble molecule to a xenobiotic to allow for its excretion out of a cell. Little is known about the variation in UGTs across wild isolates and how that might affect their innate immune response. We analyzed the diversity in ugt genes across C. elegans isolates from different geographical locations from the Caenorhabditis elegans Natural Diversity Resource (CaeNDR) database. This was accomplished using whole genome data and data identifying genome regions as hyper-divergent for each isotype. We implemented three steps to identify ugt genes and make inferences based on their variation. First, we created a catalog of UGTs in the N2 reference strain and used them to create a phylogenetic tree that depicts the relationships between the UGT protein sequences. We then quantified ugt variation using the strains from the CaeNDR database and used their data to remove hyper-divergent ugt genes. The third step was to catalog the occurrence of minor allele frequency (MAF) > 0.05 for all the ugts to compare how that aligned with genes classified as hyper-divergent by CaeNDR. Of the 67 ugt genes analyzed, 18 were hyper-divergent. This research will help improve our understanding of ugt variation in C. elegans .
