Daptomycin-Resistant Enterococcus Bacteremia Is Associated With Prior Daptomycin Use and Increased Mortality After Liver Transplantation

Abstract

Background Risk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact daptomycin-resistant Enterococcus (DRE) in this patient population. Methods We conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within one year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest. Results We identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total ICU days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within one year of transplantation (aOR 2.648 [1.025-6.840], p = 0.044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR 30.62 (10.087-92.955), p <0.001). Conclusions In this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared to VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin

“…It is predominately used to prevent recurrent hepatic encephalopathy in patients with liver cirrhosis 18, 31 . Importantly, this patient cohort is high-risk for VREfm colonisation within the gastrointestinal tract 32 . Since the Bayesian phylodynamic analyses highlighted a putative correlation between the S491F RpoB mutation in VREfm and use of rifaximin, we hypothesised rifaximin use may be driving the emergence of this mutation and therefore, daptomycin-resistant VREfm within the gastrointestinal tract of patients receiving this antibiotic.…”

“…Rifaximin is a non-absorbable oral agent with direct antimicrobial activity in the gastrointestinal tract, predominately prescribed to prevent recurrent hepatic encephalopathy in patients with liver cirrhosis 17,30 . This patient cohort is high-risk for VREfm gastrointestinal colonisation 31 . Since the Bayesian phylodynamic analyses highlighted a correlation between the S491F RpoB substitution in VREfm and use of rifaximin, we hypothesised rifaximin use in VREfm colonised patients may be associated with the presence of substitutions in RpoB and, therefore, daptomycin resistance.…”

Controlling infections in hospitalized pretransplant candidates

“…Pretransplant patients are at increased risk for colonization with organisms such as Pseudomonas , methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and extended spectrum beta-lactamase-producing organisms [11 ▪▪ ,12,14]. Knowledge of colonizing flora can assist in developing posttransplant and peri-operative prophylactic regimens.…”

“…While most studies exclude pretransplant patients, studies in kidney transplant recipients and in non-SOT immunocompromised patients suggest that shorter courses of antibiotics have similar efficacy to longer courses with less antibiotic exposure [11 ▪▪ ]. Patients with prior receipt of antimicrobials have increased risk of developing infection with resistant organisms and, in some studies, higher posttransplant mortality [12,13]. Shorter duration of antibiotics can be considered in pretransplant patients provided clinical improvement has been demonstrated.…”

Isolation and phenotypic characterization of bacteriophage SA14 with lytic- and anti-biofilm activity against multidrug-resistant Enterococcus faecalis

“…Moreover, they can acquire resistance to glycopeptides, tetracycline, erythromycin, fluoroquinolones, rifampin, chloramphenicol, fusidic acid, nitrofurantoin, and high concentrations of β-lactams and aminoglycosides [9]. This exceptional AMR pattern complicates their management [10][11][12][13]. So, the protocol for managing enterococcal infections is typically a combination of antibiotics [5].…”