Effective Treatment of a Post-renal Transplantation Patient with Early Recurrent Focal Segmental Glomerulosclerosis and Concomitant Hemolytic Uremic Syndrome, a Case Report

While recurrence of primary Focal Segmental Glomerular Sclerosis (FSGS) is common post renal transplantation (30%-80%), a concomitant presentation of hemolytic uremic syndrome (HUS) and recurrent FSGS has never been reported. In addition, treatment of recurrent FSGS and HUS post-renal transplantation is challenging; and usually individualized based on center's experience. Here, we reported a case of a pediatric patient with early recurrence of FSGS and concomitant HUS post-renal transplantation. This patient had a complete hematological and renal response following the administration of Eculizumab and Rituximab, respectively. Withdrawal of Tacrolimus as well as plasmapheresis did not improve kidney function. Therefore, we concluded that both Eculizumab and Rituximab could achieve remission in comparable cases when administered at fixed intervals.

Alternative vanHAX promoters and increased vanA-plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium

Background Vancomycin variable enterococci (VVE) are van-positive isolates with a susceptible phenotype that can convert to a resistant phenotype during vancomycin selection. Objectives To describe a vancomycin-susceptible vanA-PCR positive ST203 VVE Enterococcus faecium isolate (VVESwe-S) from a liver transplantation patient in Sweden which reverted to resistant (VVESwe-R) during in vitro vancomycin exposure. Methods WGS analysis revealed the genetic differences between the isolates. Expression of the van-operon was investigated by qPCR. Fitness and stability of the revertant were investigated by growth measurements, competition and serial transfer. Results The VVESwe-R isolate gained high-level vancomycin (MIC >256 mg/L) and teicoplanin resistance (MIC = 8 mg/L). VVESwe-S has a 5′-truncated vanR activator sequence and the VVESwe-R has in addition acquired a 44 bp deletion upstream of vanHAX in a region containing alternative putative constitutive promoters. In VVESwe-R the vanHAX-operon is constitutively expressed at a level comparable to the non-induced prototype E. faecium BM4147 strain. The vanHAX operon of VVESwe is located on an Inc18-like plasmid, which has a 3–4-fold higher copy number in VVESwe-R compared with VVESwe-S. Resistance has a low fitness cost and the vancomycin MIC of VVESwe-R decreased during in vitro serial culture without selection. The reduction in MIC was associated with a decreased vanA-plasmid copy number. Conclusions Our data support a mechanism by which vancomycin-susceptible VVE strains may revert to a resistant phenotype through the use of an alternative, constitutive, vanR-activator-independent promoter and a vanA-plasmid copy number increase.