Temporal trends, risk factors and outcomes of infections due to extended-spectrum β-lactamase producing Enterobacterales in Swiss solid organ transplant recipients between 2012 and 2018

Abstract

Background The burden of antimicrobial resistance is high in solid organ transplant (SOT) recipients. Among Swiss SOT recipients, we assessed temporal trends of ESBL-producing Enterobacterales (ESBL-E), identified risk factors for ESBL-E, and assessed the impact of resistance on patient outcome. Methods Data from the Swiss Transplant Cohort Study (STCS), a nationwide prospective cohort of SOT-recipients, were analysed. Temporal trends were described for ESBL-detection among Escherichia coli and non-Escherichia coli. In a nested case–control study, cases with ESBL-E infection were 1:1 matched (by time since transplantation, organ transplant, pathogen) to controls infected with non-ESBL-E. Factors associated with resistance and with unfavourable 30-day outcome (death, infection relapse, graft loss) were assessed. Results From 2012 to 2018, we identified 1′212 infection episodes caused by Enterobacterales in 1′074 patients, thereof 11.4% (138/1′212) caused by ESBL-E. The proportion of ESBL-production among Escherichia coli remained stable over time (p = 0.93) but increased for non-E. coli (p = 0.02) Enterobacterales. In the case–control study (n = 102), antibiotic pre-treatment was independently associated with ESBL-production (aOR = 2.6, 95%-CI: 1.0–6.8, p = 0.046). Unfavourable outcome occurred in 24/51 (47%) cases and 9/51 (18%) controls (p = 0.003). Appropriate empiric antibiotic therapy was the only modifiable factor associated with unfavourable outcome. Conclusions In Swiss SOT-recipients, proportion of infections with ESBL-producing non-E. coli Enterobacterales increased in recent years. Antibiotic pre-treatment represents a risk factor for ESBL-E. Improving appropriateness of empiric antibiotic treatment might be an important measure to reduce unfavourable outcome, which was observed in almost half of SOT-recipients with ESBL-E infections.

Gram‐negative bacteremia in solid organ transplant recipients: Clinical characteristics and outcomes as compared to immunocompetent non‐transplant recipients

“…The higher rate of MDR infections in SOT has been attributed to their frequent antibiotic exposure (e.g., from post‐transplant antimicrobial prophylaxis regimens and increased susceptibility to infections) 1,23 . Interestingly, MDR GNB was not significantly associated with mortality among our SOT recipients, in contrast to other reports 42,43 . Aggressive, broad‐spectrum empiric antibiotic administration at the first signs of sepsis in our SOT recipients, or possibly the administration of prolonged courses of antibiotics could explain this observation.…”

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

“…A further study analyzing the etiology of post‐transplant BSI in a Spanish center detected an increasing rate of ESBL‐producing strains, mainly K. pneumoniae , from 7% in the period 2007–2008 to 34% in 2015–2016 2 . A nationwide study carried out in Switzerland reported that the proportion of ESBL‐E infections in SOT recipients rose in recent years to 11.4%, although the proportion of ESBL produces among E. coli isolates remained stable over time (in contrast to the increasing trend observed for non‐ E. coli strains) 18 …”

“…2 A nationwide study carried out in Switzerland reported that the proportion of ESBL-E infections in SOT recipients rose in recent years to 11.4%, although the proportion of ESBL produces among E. coli isolates remained stable over time (in contrast to the increasing trend observed for non-E. coli strains). 18 Risk factors for developing post-transplant ESBL-E infection include previous antibiotic exposure, pre-transplant colonization, perioperative prophylaxis, prolonged tracheal intubation, long-term hospitalization, urinary tract obstruction and instrumentation, kidneypancreas transplantation, post-transplant renal replacement therapy (RRT), and recurrent urinary tract infection (UTI), as reviewed elsewhere. 3,19 A recent multicenter case-control study in the USA comprising 988 ESBL-E BSI episodes identified various risk factors of relevance, including the isolation of ESBL-E in a prior culture, a corticosteroid-containing immunosuppression regimen, acute rejection treated with corticosteroids, and previous exposure to third-generation cephalosporins, echinocandins and trimethoprimsulfamethoxazole.…”

Antimicrobial stewardship programs in solid‐organ transplant recipients in Switzerland

“…A subsequent publication detailed the epidemiology and risk factors of ESBL‐producing Enterobacterales. 12 Out of 1212 Enterobacterales infections, 138 (11%) were ESBL‐producing. The main risk factor for acquisition of ESBL‐producing Enterobacterales infection was a previous antibiotic exposure (aOR = 2.6, 95%‐CI: 1.0–6.8).…”

“…and Escherichia coli produced extended‐spectrum β‐lactamase (ESBL), but no infection due to carbapenemase‐producing bacteria was identified. A subsequent publication detailed the epidemiology and risk factors of ESBL‐producing Enterobacterales 12 . Out of 1212 Enterobacterales infections, 138 (11%) were ESBL‐producing.…”