Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T03:03:46.288Z Has data issue: false hasContentIssue false

Progress and Challenges in Implementing the Research on ESKAPE Pathogens

Published online by Cambridge University Press:  02 January 2015

Louis B. Rice*
Affiliation:
Medical Service, Louis Stokes Cleveland VA Medical Center, and the Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio
*
Medical Service 111(W), Louis Stokes Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106 ([email protected])

Abstract

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.

Type
Supplement Article
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Pronovost, P, Needham, D, Berenholtz, S, et al.An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355(26):27252732.Google Scholar
2.Rice, LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008;197(8):10791081.Google Scholar
3.Hidron, AI, Edwards, JR, Patel, J, 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.CrossRefGoogle Scholar
4.European Antimicrobial Resistance Surveillance System (EARSS). EARSS annual report 2007. Bilthoven, the Netherlands: EARSS; 2008. http://www.rivm.nl/earss/Images/EARSS%202007_FINAL_tcm61-55933.pdf. Accessed 1 July 2010.Google Scholar
5.Arthur, M, Molinas, C, Depardieu, F, Courvalin, P. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol 1993;175(1):117127.Google Scholar
6.Carias, LL, Rudin, SD, Donskey, CJ, Rice, LB. Genetic linkage and cotransfer of a novel, vonB-containing transposon (Tn5382) and a low-affinity penicillin-binding protein 5 gene in a clinical vancomycin-resistant Enterococcus faecium isolate. J Bacteriol 1998;180(17):44264434.CrossRefGoogle Scholar
7.Rice, LB, Bellais, S, Carias, LL, et al.Impact of specific pbp5 mutations on expression of β-lactam resistance in Enterococcus faecium. Antimicrob Agents Chemother 2004;48(8):30283032.Google Scholar
8.Fuda, CC, Fisher, JF, Mobashery, S. β-Lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome. Cell Mol Life Sci 2005;62(22):26172633.CrossRefGoogle ScholarPubMed
9.Jacoby, GA, Medeiros, AA. More extended-spectrum β-lactamases. Antimicrob Agents Chemother 1991;35(9):16971704.CrossRefGoogle ScholarPubMed
10.Schiappa, DA, Hayden, MK, Matushek, MG, 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.Google Scholar
11.Pitout, JD. Multiresistant Enterobacteriaceae: new threat of an old problem. Expert Rev Anti Infect Ther 2008;6(5):657669.CrossRefGoogle ScholarPubMed
12.Rice, LB, Carias, LL, Hutton, RA, Rudin, SD, Endimiani, A, Bonomo, RA. 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.Google Scholar
13.Peleg, AY, Seifert, H, Paterson, DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008;21(3):538582.CrossRefGoogle ScholarPubMed
14.Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 2003;67(4):593656.CrossRefGoogle ScholarPubMed
15.Fournier, PE, Vallenet, D, Barbe, V, et al.Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2006;2(1):e7.CrossRefGoogle ScholarPubMed
16.Whitecar, JP JrLuna, M, Bodey, GP. Pseudomonas bacteremia in patients with malignant diseases. Am J Med Sci 1970;60(4):216223.CrossRefGoogle ScholarPubMed
17.Livermore, DM. Interplay of impermeability and chromosomal β-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 1992;36(9):20462048.CrossRefGoogle ScholarPubMed
18.Tam, VH, Chang, KT, Abdelraouf, K, et al.Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2010;54:11601164.CrossRefGoogle ScholarPubMed
19.Jacobs, C, Frere, J-M, Normark, S. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible β-lactam resistance in gram-negative bacteria. Cell 1997;88(6):823832.CrossRefGoogle ScholarPubMed
20.Jacobs, C, Huang, LJ, Bartowsky, E, Normark, S, Park, JT. Bacterial cell wall recycling provides cytosolic muropeptides as effectors for β-lactamase induction. EMBO J 1994;13(19):46844694.CrossRefGoogle ScholarPubMed
21.Jacobs, C, Joris, B, Jamin, M, 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.Google Scholar
22.Sanders, CC, Sanders, WE JrGoering, RV. In vitro antagonism of β-lactam antibiotics by cefoxitin. Antimicrob Agents Chemother 1982;21:968975.Google Scholar
23.Schmidtke, AJ, Hanson, ND. Role of ampD homologs in overproduction of AmpC in clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2008;52(11):39223927.Google Scholar
24.Chambers, HF. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 1997;10(4):781791.CrossRefGoogle ScholarPubMed
25.Rice, LB, Carias, LL, Rudin, S, 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.CrossRefGoogle Scholar
26.Strahilevitz, J, Jacoby, GA, Hooper, DC, Robicsek, A. Plasmid-mediated quinolone resistance: a multifaceted threat. Clin Microbiol Rev 2009;22(4):664689.Google Scholar
27.Hernandez-Alles, S, Alberti, S, Alvarez, D, et al.Porin expression in clinical isolates of Klebsiella pneumoniae. Microbiology 1999;145(3):673679.Google Scholar
28.Lewis, K. Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol 2008;322:107131.Google Scholar
29.Brook, I. The role of beta-lactamase-producing-bacteria in mixed infections. BMC Infect Dis 2009;9:202.CrossRefGoogle ScholarPubMed
30.Yim, G, Wang, HH, Davies, J. Antibiotics as signalling molecules. Philos Trans R Soc Lond B Biol Sci 2007;362(1483):11951200.CrossRefGoogle ScholarPubMed
31.Projan, SJ, Shlaes, DM. Antibacterial drug discovery: is it all downhill from here? Clin Microbiol Infect 2004;10(Suppl 4):1822.Google Scholar
32.Boucher, HW, Talbot, GH, Bradley, JS, et al.Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48(1):112.Google Scholar