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Published in: Critical Care 4/2008

01-05-2008 | Review

Gram-negative antibiotic resistance: there is a price to pay

Author: Thomas G Slama

Published in: Critical Care | Special Issue 4/2008

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Abstract

Resistance rates are increasing among several problematic Gram-negative pathogens that are often responsible for serious nosocomial infections, including Acinetobacter spp., Pseudomonas aeruginosa, and (because of their production of extended-spectrum β-lactamase) Enterobacteriaceae. The presence of multiresistant strains of these organisms has been associated with prolonged hospital stays, higher health care costs, and increased mortality, particularly when initial antibiotic therapy does not provide coverage of the causative pathogen. Conversely, with high rates of appropriate initial antibiotic therapy, infections caused by multiresistant Gram-negative pathogens do not negatively influence patient outcomes or costs. Taken together, these observations underscore the importance of a 'hit hard and hit fast' approach to treating serious nosocomial infections, particularly when it is suspected that multiresistant pathogens are responsible. They also point to the need for a multidisciplinary effort to combat resistance, which should include improved antimicrobial stewardship, increased resources for infection control, and development of new antimicrobial agents with activity against multiresistant Gram-negative pathogens.
Literature
1.
go back to reference Bhavnani SM, Ambrose PG, Craig WA, Dudley MN, Jones RN, SENTRY Antimicrobial Surveillance Program: Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis. 2006, 54: 231-236. 10.1016/j.diagmicrobio.2005.09.011.CrossRefPubMed Bhavnani SM, Ambrose PG, Craig WA, Dudley MN, Jones RN, SENTRY Antimicrobial Surveillance Program: Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis. 2006, 54: 231-236. 10.1016/j.diagmicrobio.2005.09.011.CrossRefPubMed
2.
go back to reference Kang CI, Kim SH, Kim DM, Park WB, Lee KD, Kim HB, Oh MD, Kim EC, Choe KW: Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2004, 25: 860-867. 10.1086/502310.CrossRefPubMed Kang CI, Kim SH, Kim DM, Park WB, Lee KD, Kim HB, Oh MD, Kim EC, Choe KW: Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2004, 25: 860-867. 10.1086/502310.CrossRefPubMed
3.
go back to reference Talbot GH, Bradley J, Edwards JE, Gilbert D, Scheld M, Barlett JG, Antimicrobial vailability Task Force of the Infectious Diseases Society of America: Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006, 42: 657-668. 10.1086/499819.CrossRefPubMed Talbot GH, Bradley J, Edwards JE, Gilbert D, Scheld M, Barlett JG, Antimicrobial vailability Task Force of the Infectious Diseases Society of America: Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006, 42: 657-668. 10.1086/499819.CrossRefPubMed
4.
go back to reference McGowan JE: Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Am J Med. 2006, 119: S29-S36. 10.1016/j.amjmed.2006.03.014.CrossRefPubMed McGowan JE: Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Am J Med. 2006, 119: S29-S36. 10.1016/j.amjmed.2006.03.014.CrossRefPubMed
5.
go back to reference Davis KA, Moran KA, McAllister CK, Grey PJ: Multidrug-resistant Acinetobacter extremity infections in soldiers. Emerg Infect Dis. 2005, 11: 1218-1224.CrossRefPubMed Davis KA, Moran KA, McAllister CK, Grey PJ: Multidrug-resistant Acinetobacter extremity infections in soldiers. Emerg Infect Dis. 2005, 11: 1218-1224.CrossRefPubMed
6.
go back to reference Garzoni C, Emonet S, Legout L, Benedict R, Hoffmeyer P, Bernard L, Garbino J: Atypical infections in tsunami survivors. Emerg Infect Dis. 2005, 11: 1591-1593.CrossRefPubMed Garzoni C, Emonet S, Legout L, Benedict R, Hoffmeyer P, Bernard L, Garbino J: Atypical infections in tsunami survivors. Emerg Infect Dis. 2005, 11: 1591-1593.CrossRefPubMed
7.
go back to reference Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Ecker DJ, Massire C, Eshoo MW, Sampath R, Thomson JM, Rather PN, Craft DW, Fishbain JT, Ewell AJ, Jacobs MR, Paterson DL, Bonomo RA: Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother. 2006, 50: 4114-4123. 10.1128/AAC.00778-06.CrossRefPubMed Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Ecker DJ, Massire C, Eshoo MW, Sampath R, Thomson JM, Rather PN, Craft DW, Fishbain JT, Ewell AJ, Jacobs MR, Paterson DL, Bonomo RA: Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother. 2006, 50: 4114-4123. 10.1128/AAC.00778-06.CrossRefPubMed
8.
go back to reference Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System: Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005, 41: 848-854. 10.1086/432803.CrossRefPubMed Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System: Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005, 41: 848-854. 10.1086/432803.CrossRefPubMed
9.
go back to reference Gales AC, Jones RN, Forward KR, Linares J, Sader HS, Verhoef J: Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997–1999). Clin Infect Dis. 2001, 32 (suppl 2): S104-S113. 10.1086/320183.CrossRefPubMed Gales AC, Jones RN, Forward KR, Linares J, Sader HS, Verhoef J: Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997–1999). Clin Infect Dis. 2001, 32 (suppl 2): S104-S113. 10.1086/320183.CrossRefPubMed
10.
go back to reference Bonomo RA, Szabo D: Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis. 2006, 43 (suppl 2): S49-S56. 10.1086/504477.CrossRefPubMed Bonomo RA, Szabo D: Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis. 2006, 43 (suppl 2): S49-S56. 10.1086/504477.CrossRefPubMed
11.
go back to reference Landman D, Quale JM, Mayorga D, Adedeji A, Vangala K, Ravishankar J, Flores C, Brooks S: Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned. Arch Intern Med. 2002, 162: 1515-1520. 10.1001/archinte.162.13.1515.CrossRefPubMed Landman D, Quale JM, Mayorga D, Adedeji A, Vangala K, Ravishankar J, Flores C, Brooks S: Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned. Arch Intern Med. 2002, 162: 1515-1520. 10.1001/archinte.162.13.1515.CrossRefPubMed
12.
go back to reference Kwon KT, Oh WS, Song J-H, Chang HH, Jung SI, Kim SW, Ryu SY, Heo ST, Jung DS, Rhee JY, Shin SY, Ko KS, Peck KR, Lee NY: Impact of imipenem resistance on mortality in patients with Acinetobacter bacteremia. J Antimicrob Chemother. 2007, 59: 525-530. 10.1093/jac/dkl499.CrossRefPubMed Kwon KT, Oh WS, Song J-H, Chang HH, Jung SI, Kim SW, Ryu SY, Heo ST, Jung DS, Rhee JY, Shin SY, Ko KS, Peck KR, Lee NY: Impact of imipenem resistance on mortality in patients with Acinetobacter bacteremia. J Antimicrob Chemother. 2007, 59: 525-530. 10.1093/jac/dkl499.CrossRefPubMed
13.
go back to reference Jacoby GA, Munoz-Price LS: The new β-lactamases. N Engl J Med. 2005, 352: 380-391. 10.1056/NEJMra041359.CrossRefPubMed Jacoby GA, Munoz-Price LS: The new β-lactamases. N Engl J Med. 2005, 352: 380-391. 10.1056/NEJMra041359.CrossRefPubMed
14.
go back to reference Biedenbach DJ, Moet GJ, Jones RN: Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997–2002). Diagn Microbiol Infect Dis. 2004, 50: 59-69. 10.1016/j.diagmicrobio.2004.05.003.CrossRefPubMed Biedenbach DJ, Moet GJ, Jones RN: Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997–2002). Diagn Microbiol Infect Dis. 2004, 50: 59-69. 10.1016/j.diagmicrobio.2004.05.003.CrossRefPubMed
15.
go back to reference Streit JM, Jones RN, Sader HS, Fritsche TR: Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents. 2004, 24: 111-118. 10.1016/j.ijantimicag.2003.12.019.CrossRefPubMed Streit JM, Jones RN, Sader HS, Fritsche TR: Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents. 2004, 24: 111-118. 10.1016/j.ijantimicag.2003.12.019.CrossRefPubMed
16.
go back to reference Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J: Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 β-lactamases in New York City. Clin Infect Dis. 2004, 39: 55-60. 10.1086/421495.CrossRefPubMed Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J: Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 β-lactamases in New York City. Clin Infect Dis. 2004, 39: 55-60. 10.1086/421495.CrossRefPubMed
17.
go back to reference Lee SY, Kotapati S, Kuti JL, Nightingale CH, Nicolau DP: Impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol. 2006, 27: 1226-1232. 10.1086/507962.CrossRefPubMed Lee SY, Kotapati S, Kuti JL, Nightingale CH, Nicolau DP: Impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol. 2006, 27: 1226-1232. 10.1086/507962.CrossRefPubMed
18.
go back to reference Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO: Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis. 2001, 32: 1162-1171. 10.1086/319757.CrossRefPubMed Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO: Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis. 2001, 32: 1162-1171. 10.1086/319757.CrossRefPubMed
19.
go back to reference Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y: Clinical and economic impact of bacteremia with extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006, 50: 1257-1262. 10.1128/AAC.50.4.1257-1262.2006.CrossRefPubMed Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y: Clinical and economic impact of bacteremia with extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006, 50: 1257-1262. 10.1128/AAC.50.4.1257-1262.2006.CrossRefPubMed
20.
go back to reference Paterson DL, Ko W-C, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Watener MM, McCormack JG, Yu VL: Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum β-lactamases. Clin Infect Dis. 2004, 39: 31-37. 10.1086/420816.CrossRefPubMed Paterson DL, Ko W-C, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Watener MM, McCormack JG, Yu VL: Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum β-lactamases. Clin Infect Dis. 2004, 39: 31-37. 10.1086/420816.CrossRefPubMed
21.
go back to reference Lambert PA: Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. J Roy Soc Med. 2002, 95 (suppl 41): 22-26.PubMed Lambert PA: Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. J Roy Soc Med. 2002, 95 (suppl 41): 22-26.PubMed
22.
go back to reference NNIS System: National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 through June issued October 2004. Am J Infect Control. 2004, 32: 470-485. 10.1016/j.ajic.2004.10.001.CrossRef NNIS System: National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 through June issued October 2004. Am J Infect Control. 2004, 32: 470-485. 10.1016/j.ajic.2004.10.001.CrossRef
23.
go back to reference Tacconelli E, Tumbarello M, Bertagnolio S, Citton R, Spanu T, Fadda G, Cauda R: Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: analysis of trends in prevalence and epidemiology [letter]. Emerg Infect Dis. 2002, 8: 220-221.CrossRefPubMed Tacconelli E, Tumbarello M, Bertagnolio S, Citton R, Spanu T, Fadda G, Cauda R: Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: analysis of trends in prevalence and epidemiology [letter]. Emerg Infect Dis. 2002, 8: 220-221.CrossRefPubMed
24.
go back to reference Harris A, Torres-Viera C, Venkataraman L, DeGirolami P, Samore M, Carmeli Y: Epidemiology and clinical outcomes of patient with multiresistant Pseudomonas aeruginosa. Clin Infect Dis. 1999, 28: 1128-1133. 10.1086/514760.CrossRefPubMed Harris A, Torres-Viera C, Venkataraman L, DeGirolami P, Samore M, Carmeli Y: Epidemiology and clinical outcomes of patient with multiresistant Pseudomonas aeruginosa. Clin Infect Dis. 1999, 28: 1128-1133. 10.1086/514760.CrossRefPubMed
25.
go back to reference Carmeli Y, Troillet N, Karchmer AW, Samore MH: Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa. Arch Intern Med. 1999, 159: 1127-1132. 10.1001/archinte.159.10.1127.CrossRefPubMed Carmeli Y, Troillet N, Karchmer AW, Samore MH: Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa. Arch Intern Med. 1999, 159: 1127-1132. 10.1001/archinte.159.10.1127.CrossRefPubMed
26.
go back to reference Cosgrove SE, Kaye KS, Eliopoulous GM, Carmeli Y: Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med. 2002, 162: 185-190. 10.1001/archinte.162.2.185.CrossRefPubMed Cosgrove SE, Kaye KS, Eliopoulous GM, Carmeli Y: Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med. 2002, 162: 185-190. 10.1001/archinte.162.2.185.CrossRefPubMed
27.
go back to reference Blot S, Vandewoude K, De Bacquer D, Colardyn F: Nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in critically ill patients: clinical outcome and length of hospitalization. Clin Infect Dis. 2002, 34: 1600-1606. 10.1086/340616.CrossRefPubMed Blot S, Vandewoude K, De Bacquer D, Colardyn F: Nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in critically ill patients: clinical outcome and length of hospitalization. Clin Infect Dis. 2002, 34: 1600-1606. 10.1086/340616.CrossRefPubMed
28.
go back to reference Evans HL, Lefrak SN, Lyman J, Smith RL, Chong TW, McElearney ST, Schulman AR, Hughes MG, Raymond DP, Pruett TL, Sawyer RG: Cost of gram-negative resistance. Crit Care Med. 2007, 35: 89-95. 10.1097/01.CCM.0000251496.61520.75.CrossRefPubMed Evans HL, Lefrak SN, Lyman J, Smith RL, Chong TW, McElearney ST, Schulman AR, Hughes MG, Raymond DP, Pruett TL, Sawyer RG: Cost of gram-negative resistance. Crit Care Med. 2007, 35: 89-95. 10.1097/01.CCM.0000251496.61520.75.CrossRefPubMed
Metadata
Title
Gram-negative antibiotic resistance: there is a price to pay
Author
Thomas G Slama
Publication date
01-05-2008
Publisher
BioMed Central
Published in
Critical Care / Issue Special Issue 4/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc6820

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