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

Front Cell Infect Microbiol. 2023 May 2:13:1180714. doi: 10.3389/fcimb.2023.1180714. eCollection 2023.

Abstract

Introduction: Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients.

Methods: RLs of bla CTX-M-1-Family, bla OXA-1, bla OXA-48 and bla VIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients' demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates.

Results and discussion: 76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for bla OXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem β-lactams, and glycopeptides were statistically associated with testing negative for bla CTX-M-1-Family and bla OXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.

Keywords: antibiotic consumption; extra-intestinal multi-drug resistant organisms; intestinal dominance; microbiome; pediatric patients; qPCR; relative intestinal load; β-lactamase genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Carbapenems / pharmacology
  • Child
  • Critical Illness*
  • Gram-Negative Bacteria
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamases* / genetics

Substances

  • carbapenemase
  • beta-Lactamases
  • Bacterial Proteins
  • Anti-Bacterial Agents
  • Carbapenems

Grants and funding

This work has been possible thanks to funding allocated to ED from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Individual Fellowship grant agreement No. 796084 (qMAR). After qMAR termination, ED has been funded from the Agencia Estatal de Investigación of the Spanish Ministry of Science and Innovation in the form of a Juan de la Cierva – Incorporación grant number IJC2019-038832-I. Follow-up work has been allowed by support provided by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, grants PI16/01209 and PI19/01356 to JM. Co-financed by European Development Regional Fund “A way to achieve Europe”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.