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Abstract

Antibiotic resistance is increasingly recognised as a major threat to global health, with few new antimicrobial agents in development. The intensive care unit provides a unique environment for the growth and spread of drug-resistant organisms. Knowledge of the pathogenesis and mechanisms of resistance of drug-resistant organisms provides a conceptual framework which underpins the clinical manifestation of infections caused by these organisms, and is crucial for the intensivist to understand. Particular importance lies in the prevention of infection and the control of drug-resistant pathogens. The major resistance mechanisms of these organisms will be highlighted, focusing on specific gram-positive (meticillin-resistant Staphylococcus aureus and glycopeptide-resistant Enterococci), gram-negative (Pseudomonas aeruginosa, Acinetobacter baumannii and multi-drug resistant Enterobacteriaceae) organisms, and then placed in historical and clinical context.

Keywords

antibiotic resistance intensive care

References

Rammelkamp

Maxon

. Resistance of Staphylococcus aureus to the action of penicillin. Proc Royal Soc Exper Biol Med. 1942;51: 386–89.

D'Costa

King

Kalan

. Antibiotic resistance is ancient. Nature 2011;477: 451–61.

Boucher

Talbot

Bradley

. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America? Clin Infect Dis 2009; 48: 1–12.

Fridkin

. Increasing prevalence of antimicrobial resistance in intensive care units. Crit Care Med 2001;29(4 Suppl):N64–68.

Hawkey

. The origins and molecular basis of antibiotic resistance. BMJ 1998;317: 657–60.

Spratt

. Resistance to antibiotics mediated by target alterations. Science 1994;264: 388–93.

Jacoby

. Mechanisms of resistance to quinolones. Clin Infect Dis 2005;15: 41 Suppl 2:S120–26.

Van Bambeke

Michot

J-M

Van Eldere

. Quinolones in 2005: an update. Clin Microbiol Infect 2005;11: 256–80.

Poole

. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 2005;56: 20–51.

10.

Kaye

Engemann

Fraimow

Abrutyn

. Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms and clinical management. Infect Dis Clin N Am 2004;18: 467–511.

11.

Vincent

Rello

Marshall

. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302: 2323–29.

12.

Esposito

Leone

. Antimicrobial treatment for intensive care unit (ICU) infections including the role of the infectious disease specialist. Int J Antimicrob Agents 2007;29: 494–500.

13.

Stone

Pogorzelska

Kunches

Hirschhorn

. Hospital staffing and health care-associated infections: a systematic review of the literature. Clin Infect Dis 2008;47: 937–44.

14.

Fridkin

Pear

Williamson

. The role of understaffing in central venous catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 1996;17: 150–58.

15.

Haley

Bergman

. The role of understaffing and overcrowding in recurrent outbreaks of staphylococcal infections in a neonatal special-care unit. J Infect Dis 1982;145: 875–85.

16.

Maragakis

Perl

. Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin Infect Dis 2008;46: 1254–63.

17.

Willems

Bonten

. Glycopeptide-resistant enterococci: Deciphering virulence, resistance and epidemicity. Curr Opin Infect Dis 2007;20: 384–90.

18.

Hawkey

. The growing burden of antimicrobial resistance. J Antimicrob Chemother 2008;62 Suppl 1:i1–9.

19.

Patrick

Hutchinson

. Antibiotic use and population ecology: how you can reduce your “resistance footprint”. CMAJ 2009;180: 416–21.

20.

Kaki

Elligsen

Walker

. Impact of antimicrobial stewardship in critical care: a systematic review. J Antimicrob Chemother 2011;66: 1223–30.

21.

Kluytmans

Van Belkum

Verbrugh

. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms and associated risks. Clin Microbiol Rev 1997;10: 505–20.

22.

Barber

. Methiciliin-resistant staphylococci. J Clin Pathol 1961;14: 385–93.

23.

Nair

Kourbatova

Poole

. Molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) among patients admitted to adult intensive care units: the STAR*ICU trial. Infect Control Hosp Epidemiol 2011;32: 1057–63.

24.

National Nosocomial Infections Surveillance (NNIS) System Report, Data Summary from January 1992-June 2001, issued August 2001. Am J Infect Control 2001;29404–21.

25.

Clark

Hershberger

Zervosc

. Antimicrobial resistance among gram-positive organisms in the intensive care unit. Curr Opin Crit Care 2003;9: 403–12.

26.

Smith

Pearson

Wilcox

. Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group. N Engl J Med 1999;340: 493–501.

27.

Bartley

. First case of VRSA identified in Michigan. Infect Control Hosp Epidemiol 2002;23: 480.

28.

Noble

Virani

Cree

. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992;72: 195–98.

29.

Centres for Disease Control and Prevention. CDC reminds clinical laboratories and infection preventionists of their role in the search and containment of vancomycin-resistant Staphlococcus aureus (VRSA). http://www.cdc.gov/HAI/settings/lab/vrsa_lab_search_containment.html. Accessed May 2012.

30.

Fisher

Phillips

. The ecology, epidemiology and virulence of Enterococcus. Microbiology 2009;155: 1749–57.

31.

Murray

. The life and times of the Enterococcus. Clin Microbiol Rev 1990;3: 46–65.

32.

Grayson

Eliopoulos

Wennersten

. Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution. Antimicrob Agents Chemother 1991;35: 2180–84.

33.

Uttley

Collins

Naidoo

. Vancomycin-resistant enterococci. Lancet 1988 2–9;1: 57–58.

34.

Werner

Coque

Hammerum

. Emergence and spread of vancomycin resistance among enterococci in Europe. Euro Surveill 2008;13 (47):1–11.

35.

Ippolito

Leone

Lauria

. Meticillin-resistant Staphylococcus aureus: the superbug. Int J Infect Dis 2010;14 Suppl 4:S7–11.

36.

Livermore

. Has the era of untreatable infections arrived? J Antimicrob Chemother. 2009 Sep;64 Suppl 1:i29–36.

37.

Mesaros

Nordmann

Piésiat

. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 2007;13: 560–78.

38.

Vaisvila

Morgan

Posfai

Raleigh

. Discovery and distribution of super-integrons among pseudomonads. Mol Microbiol 2001;42: 587–601.

39.

Giamarellou

. Prescribing guidelines for severe Pseudomonas infections. J Antimicrob Chemother 2002;49: 229–33.

40.

Cunha

. Ventilator-associated pneumonia: monotherapy is optimal if chosen wisely. Crit Care 2006;10: 141.

41.

Paul

Benuri-Silbiger

Soares-Weiser

Leibovici

. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004;328: 668.

42.

Rello

Diaz

Rodriguez

. Advances in the management of pneumonia in the intensive care unit: review of current thinking? Clin Microbiol Infect 2005; 11 (Suppl 5):30–38.

43.

Moya

Zamorano

Carlos

. Activity of a new cephalosporin, CXA-101 (FR264205), against beta-lactam-resistant P. aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit patients. Antimicrob Agents Chemother 2010;54: 1213–17.

44.

Peleg

Seifert

Paterson

. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008;21: 538–82.

45.

Calhoun

Murray

Manring

. Multidrug-resistant organisms in military wounds from Iraq and Afghanistan. Clin Orthop Relat Res 2008;466: 1356–62.

46.

Fournier

Richet

. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 2006;42: 692–99.

47.

Zavascki

Carvalhaes

Picao

Gales

. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy. Expert Rev Anti Infect Ther 2010;8: 71–93.

48.

Neonakis

Spandidos

Petinaki

. Confronting multidrug-resistant Acinetobacter baumannii: a review. Int J Antimicrob Agents 2011;37: 102–109.

49.

Perez

Hujer

. Global Challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2007;51: 3471–84.

50.

Vila

Marti

Sanchez-Cespedes

. Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J Antimicrob Chemother 2007;59: 1210–15.

51.

Coyne

Courvalin

Perichon

. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 2011;55: 947–53.

52.

Perez

Hujer

. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2007;51: 3471–84.

53.

Fournier

Richet

. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 2006;42: 692–99.

54.

Falagas

Karveli

Siempos

Vardakas

. Acinetobacter infections: a growing threat for critically ill patients. Epidemiol Infect 2008;136: 1009–19.

55.

Falagas

Rafailidis

Ioannidou

. Colistin therapy for microbiologically documented multidrug-resistant gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents 2010;35: 194–99.

56.

Neonakis

Spandidos

Petinaki

. Confronting multidrug-resistant A.baumannii: a review. Int J Antimicrob Agents 2011;37: 102–09.

57.

Wolinsky

Hines

. Neurotoxic and nephrotoxic effects of colistin in patients with renal disease. N Engl J Med 1962;266: 759–62.

58.

Koch-Weser

Sidel

Federman

. Adverse effects of sodium colistimethate. Manifestations and specific reaction ratesduring 317 courses of therapy. Ann Intern Med 1970;72: 857–68.

59.

Markogiannakis

Fildisis

Tsiplakou

. Cross-transmission of multidrug-resistant Acinetobacter baumannii clonal strains causing episodes of sepsis in a trauma intensive care unit. Infect Control Hosp Epidemiol. 2008;29: 410–17.

60.

Rupp

Fey

. Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment. Drugs 2003;63: 353–65.

61.

Ambler

. The structure of beta-lactamases. Phil Trans R Soc London Series B 1980;289: 321–331.

62.

Bush

Jacoby

Medeiros

. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39: 1211–33.

63.

Bradford

. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001;14: 933–51.

64.

Hawkey

Jones

. The changing epidemiology of resistance? J Antimicrob Chemother 2009; 64(Suppl 1):i3–i10.

65.

Schwaber

Carmeli

. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 2007;60: 913–20.

66.

Bush

Fisher

. Epidemiological expansion and clinical challenges of new beta-lactamases. Ann Rev Microbiol 2011;65: 455–78.

67.

Falagas

Karageorgopoulos

. Extended-spectrum beta-lactamase-producing organisms. J Hosp Infect 2009;73: 345–54.

68.

Livermore

Paterson

. Infection with ESBL producers: risk factors and treatment. In: Pocket guide to extended-spectrum beta-lactamases in resistance. 1st ed.

Current Medicine Group Ltd

2006: 34–42.

69.

Paterson

. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamases. Clin Infect Dis 2004;39: 31–37.

70.

Marsik

Nambiar

. Review of carbapenemases and ampC-beta lactamases. Pediatr Infect Dis J 2011;30: 1094–95.

71.

Hobson

MacKenzie

Gould

. An outbreak of multiply-resistant Klebsiella pneumoniae in the Grampian region of Scotland. J Hosp Infect 1996;33: 249–62.

72.

Goddard

Muller

. The efficacy of infection control interventions in reducing the incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae. Am J Infect Control 2011;39: 599–601.

Antibiotic Resistance Mechanisms in the Intensive Care Unit

Abstract

Keywords

References