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Progress and Challenges in Implementing the Research on ESKAPE Pathogens

  • Louis B. Rice (a1)

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are responsible for a substantial percentage of nosocomial infections in the modern hospital and represent the vast majority of isolates whose resistance to antimicrobial agents presents serious therapeutic dilemmas for physicians. Over the years, improved molecular biology techniques have led to detailed information about individual resistance mechanisms in all these pathogens. However, there remains a lack of compelling data on the interplay between resistance mechanisms and between the bacteria themselves. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking. The difficulty in identifying novel antimicrobial agents with reliable activity against these pathogens argues for an augmentation of research in the basic and population science of resistance, as well as careful studies to identify optimal strategies for infection control and antimicrobial use.

Corresponding author
Medical Service 111(W), Louis Stokes Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106 (
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1. P Pronovost , D Needham , S Berenholtz , et al.An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355(26):27252732.

2. LB Rice . Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008;197(8):10791081.

, , , . ;():–.3. AI Hidron JR Edwards J Patel et al.NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007 Infect Control Hosp Epidemiol 2008 29 11 9961011

7. LB Rice , S Bellais , LL Carias , et al.Impact of specific pbp5 mutations on expression of β-lactam resistance in Enterococcus faecium. Antimicrob Agents Chemother 2004;48(8):30283032.

8. CC Fuda , JF Fisher , S Mobashery . β-Lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome. Cell Mol Life Sci 2005;62(22):26172633.

, . . ;():–.9. GA Jacoby AA Medeiros More extended-spectrum β-lactamases Antimicrob Agents Chemother 1991 35 9 16971704

10. DA Schiappa , MK Hayden , MG Matushek , et al.Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. J Infect Dis 1996;174(3):529536.

11. JD Pitout . Multiresistant Enterobacteriaceae: new threat of an old problem. Expert Rev Anti Infect Ther 2008;6(5):657669.

, , , , , . . ;():–.12. LB Rice LL Carias RA Hutton SD Rudin A Endimiani RA Bonomo The KQ element, a complex genetic region conferring transferable resistance to carbapenems, aminoglycosides, and fluoroquinolones in Klebsiella pneumoniae Antimicrob Agents Chemother 2008 52 9 34273429

13. AY Peleg , H Seifert , DL Paterson . Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008;21(3):538582.

14. H Nikaido . Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 2003;67(4):593656.

15. PE Fournier , D Vallenet , V Barbe , et al.Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2006;2(1):e7.

. . ;():–.17. DM Livermore Interplay of impermeability and chromosomal β-lactamase activity in imipenem-resistant Pseudomonas aeruginosa Antimicrob Agents Chemother 1992 36 9 20462048

, , , . ;:–.18. VH Tam KT Chang K Abdelraouf et al.Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa Antimicrob Agents Chemother 2010 54 11601164

, , . . ;():–.19. C Jacobs J-M Frere S Normark Cytosolic intermediates for cell wall biosynthesis and degradation control inducible β-lactam resistance in gram-negative bacteria Cell 1997 88 6 823832

21. C Jacobs , B Joris , M Jamin , et al.AmpD, essential for both β-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase. Mol Microbiol 1995;15(3):553559.

, . . ;:–.22. CC Sanders WE Sanders Jr RV Goering In vitro antagonism of β-lactam antibiotics by cefoxitin Antimicrob Agents Chemother 1982 21 968975

, . . ;():–.23. AJ Schmidtke ND Hanson Role of homologs in overproduction of AmpC in clinical isolates of ampDPseudomonas aeruginosa Antimicrob Agents Chemother 2008 52 11 39223927

, , , . ;():–.25. LB Rice LL Carias S Rudin et al.Role of class A penicillin-binding proteins in the expression of β-lactam resistance in Enterococcus faecium J Bacteriol 2009 191 11 36493656

26. J Strahilevitz , GA Jacoby , DC Hooper , A Robicsek . Plasmid-mediated quinolone resistance: a multifaceted threat. Clin Microbiol Rev 2009;22(4):664689.

27. S Hernandez-Alles , S Alberti , D Alvarez , et al.Porin expression in clinical isolates of Klebsiella pneumoniae. Microbiology 1999;145(3):673679.

. . ;:.29. I Brook The role of beta-lactamase-producing-bacteria in mixed infections BMC Infect Dis 2009 9 202

30. G Yim , HH Wang , J Davies . Antibiotics as signalling molecules. Philos Trans R Soc Lond B Biol Sci 2007;362(1483):11951200.

31. SJ Projan , DM Shlaes . Antibacterial drug discovery: is it all downhill from here? Clin Microbiol Infect 2004;10(Suppl 4):1822.

, , , . ;():–.32. HW Boucher GH Talbot JS Bradley et al.Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America Clin Infect Dis 2009 48 1 112

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Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
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