Intestinal Dominance by Multidrug-Resistant Bacteria in Pediatric Liver Transplant Patients

Abstract

In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients.

Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients

“…They were also different from those determined for pediatric liver transplant patients that receive prolonged and repeated treatments with antibiotics ( Dahdouh et al., 2022 ). Nevertheless, in all three studies, the consumption of antibiotics was associated with intestinal RLs, where in adults the consumption of non-β-lactams and carbapenems were associated with high RLs for bla OXA-48 ( Lázaro-Perona et al., 2020 ), and additionally to bla CTX-M-1-Family and bla OXA-1 for pediatric liver transplanted patients ( Dahdouh et al., 2022 ). In contrast, this current study showed that the consumption of β-lactams and glycopeptides is associated with a lower incidence of detecting bla CTX-M-1-Family and bla OXA-1 , and the consumption of aminoglycosides and TMX with a lower incidence of detecting bla OXA-48 in the critically ill pediatric patient population.…”

“…In this study, we analyzed the intestinal RLs of the four genes of β-lactamases that are endemic at our hospital ( bla CTX-M-1-Family , bla OXA-1 , bla OXA-48 , and bla VIM ) using a previously validated qPCR assay ( Dahdouh et al., 2022 ). The %RLs of bla CTX-M-1-Family and bla OXA-1 , which are commonly found on the same plasmid ( Livermore et al., 2019 ), for the most part had values that ranged between 1% (-1) and 10% (-2) of the total bacterial population.…”

“…Also, no results were communicated in real time to neither the clinicians nor the patients, and therefore the results obtained from this study did not interfere with the clinical management of the patients involved. Pediatric liver transplant patients were excluded since they received extensively more antibiotics than other patient groups and were included in a previous study performed by our group ( Dahdouh et al., 2022 ).…”

“…The qPCR assays designed in one of our previous studies were used to determine the Relative intestinal Loads (RLs) of the beta-lactamase genes that are endemic at HULP ( bla CTX-M-1-Family , bla OXA-1 , bla OXA-48 , and bla VIM ) ( Dahdouh et al., 2022 ). Briefly, reaction mixtures containing 10µl 2X PowerUP™ SYBR ® Green Master Mix (Applied Biosystems, Waltham, MA, USA), 0.05µM of each respective primer pair, 6µl H 2 O and 2µl DNA were prepared.…”

“…present at such low amounts that it is not detected by traditional culture media, but has the potential to quickly expand and dominate the intestinal microbiome in response to antibiotic pressure ( Sim et al., 2022 ). Previous studies have shown associations between high intestinal Relative Loads (RLs) of carbapenemase-producing Klebsiella pneumoniae , antibiotic consumption, and development of infections in hospitalized adult patient populations ( Migliorini et al., 2022 ;, Lázaro-Perona et al., 2020 ), and in pediatric liver transplant patients ( Dahdouh et al., 2022 ). The aim of this study is to use the qPCR assay developed and validated in these previous studies to determine the relationship between the intestinal RLs of selected ESBL and carbapenemase genes, antibiotic consumption, occult colonization, gut microbiome dysbiosis, and extra-intestinal spread of MDROs among critically ill pediatric patients.…”