Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2014

Antibiotic resistance in the E. coli gut population of ICU patients after cefepime therapy (#447)

Carola Venturini 1 , Sally Partridge 1 , Guy Tsafnat 2 , Ian T Paulsen 3 , Jonathan Iredell 1
  1. Institute of Emerging Infectious Diseases and Biosecurity Marie Bashir Institute, The University of Sydney, Sydney, NSW, Australia
  2. Centre for Health Informatics, The University of New South Wales, Kensington, NSW, Australia
  3. Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia

The spread of antibiotic resistance in bacterial agents causing life-threatening sepsis is a serious immediate global threat.1 Timely antibiotic therapy is critical, with delays in effective therapy being directly associated with increased mortality,2 and preservation of antibiotic susceptibility by controlling inappropriate antibiotic use (“antibiotic stewardship”) has thus become a primary public health agenda.3 Different antibiotics are known to have different effects on the composition of the gut microbiome4, 5 and a better understanding of these effects is needed to guide stewardship decisions, due to possible implications for both the transmission of antibiotic resistance determinants and the establishment of resistant populations.

E. coli are a major cause of life-threatening sepsis, and transmissible antibiotic resistance in this species is increasing.6 In this study, we compared E. coli populations in 12 ICU patients before and after cefepime (FEP) therapy, by sequencing representative pools of perineal E. coli clones from each patient. Extracted DNA was sequenced using paired-end Illumina MiSeq technology. Assembled reads were run against the NCBI database using BLAST7 and we used our automated Attacca system8 to correctly annotate genetic features linked to transmissible antibiotic resistance (resistance, plasmid replicase (rep) and relaxase (mob) genes). In the 'after' FEP sample, the frequency of specific genes with strong links to multiple resistance clusters (e.g. strAB, sul2) was increased, and other genes (e.g. blaCMY-2) and markers of relevant transmission vehicles (e.g. IncI1rep) were detected exclusively in this sample. This increase in transmissible resistance genes is consistent with observed increases in resistance to selected antibiotics after cefepime treatment.9 An explanation for this might be provided by accelerated horizontal gene transfer in proteobacterial blooms,10,11 which are more common and persistent after exposure to drugs like cefepime.11,12

  1. WHO (2014) Antimicrobial resistance: global report on surveillance 2014 http://www.who.int/drugresistance/documents/surveillancereport/en/
  2. Kumar et al. (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 34:1589-96.
  3. National Health and Hospitals Network Act 2011 Australian Commission on Quality and Safety in Health Care Commonwealth of Australia
  4. Jernberg C et al. (2007) Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1:56-66.
  5. Rahal JJ et al. (1998) Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. Jama. 280:1233-7.
  6. Sommer MO et al. (2009) Functional characterization of the antibiotic resistance reservoir in the human microflora. Science. 325:1128-31.
  7. Altschul SF et al. (1990) Basic local alignment search tool. J Mol Biol. 215:403-10.
  8. Tsafnat G et al. (2009) Context-driven discovery of gene cassettes in mobile integrons using a computational grammar. BMC Bioinformatics. 10:281.
  9. Ginn AN et al. (2012) The ecology of antibiotic use in the ICU: homogeneous prescribing of cefepime but not tazocin selects for antibiotic resistant infection. PLoS One. 7(6):e38719.
  10. Stecher B et al. (2012) Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proc Natl Acad Sci U S A. 109:1269-74.
  11. Dethlefsen L et al. (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 108 Suppl 1:4554-61.
  12. de Araujo OR et al. (2007) Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit. Braz J Infect Dis. 11:277-80