Considerations for minimizing
antibiotic resistance:
Analyzing current practice in the context of
Pseudomonas aeruginosa resistance patterns
Becky Carlson
Advisor - Professor Fahringer
Presentation outline
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Review of mechanisms of resistance
Consequences of antimicrobial resistance
Analysis of current recommendations for
decreasing antimicrobial resistance
Implications for the clinician
Available resources
Review of resistance mechanisms
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Definition:
Mutated Organism
Hostile
Environment
Organism
Review of resistance mechanisms
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Bacterial catabolism of antibiotic
Loss of enzyme
Loss of receptor sensitivity
Efflux pumps
Defensive outer surface structures
Antimicrobial resistance consequences
Empirical treatment impaired
Limited resources
No Resources
Antimicrobial resistance consequences
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Limited resources
1999 Brazilian study of polymyxin use
- IV colistin treatment
- 58% of patients responded (25% of those with
nosocomial pneumonia)
- 27% of patients developed renal insufficiency
Quinn JP. Pseudomonas aeruginosa infections in the intensive care unit. Seminars in respiratory and critical care medicine.
2003; 24(1): 61-68.
Current Recommendations
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Infection prevention
- Ventilator use educational program
- 73% reduction in ventilator associated
pneumonia with a cycling program
- 57% reduction in VAP without the cycling
program
Warren DK, Hill HA, Merz LR, Kollef MH, Hayden MK, Fraser VJ, and Fridkin SK. Cycling empirical antimicrobial agents to
prevent emergence of antimicrobial resistant Gram-negative bacteria among intensive care unit patients. Crit Care Med.
2004, Dec; 32(12): 2450-2456.
Current Recommendations
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Initial effective treatment
- MIC vs MLC – benefits and disadvantages
- More research on direct relationship between
failed treatment and resistance development
Current Recommendations
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Antibiotic control
- Cycling programs
- Self-resistance
Demonstrated correlations between use of
beta-lactams and fluoroquinolones and
development of resistance
Quinn JP. Pseudomonas aeruginosa infections in the intensive care unit. Seminars in respiratory and critical care medicine.
2003; 24(1): 61-68, Lepper PM, Grusa E, Reichl H, Hogel J, Trautmann M. Consumption of imipenem correlates with
B-lactam resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2002; 46(9): 2920-2925, Karlowsky JA,
Draghi DC, Jones ME, Thornsberry C, Friedland IR, and Sahm DF. Surveillance for antimicrobial susceptibility
among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United
States, 1998 to 2001. Antimicrob Agents Chemother. 2003, May; 47(5): 1681-1688.
Current Recommendations
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Antibiotic control, continued
- Cross-resistance
Fluoroquinolones  gentamicin,
ceftazidime, imipenem, amikacin1
Imipenem  ceftazidime, piperacillintazobactam2
1. Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, and Quinn JP. Antibiotic resistance among Gramnegative bacilli in US intensive care units. JAMA. 2003, Feb 19; 289(7): 885-888 2. Lepper PM, Grusa E, Reichl H,
Hogel J, Trautmann M. Consumption of imipenem correlates with B-lactam resistance in Pseudomonas aeruginosa.
Antimicrob Agents Chemother. 2002; 46(9): 2920-2925.
Current Recommendations
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Transmission prevention
http://www.cdc.gov/drugresistance/healthcare/ha/12steps-HA.htm
Implications for the Clinician
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Be selective
Consider the broader consequences
Consider this as a current problem, not
merely a future problem
Pay attention to local surveillance data
Resources
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CDC
Infectious Diseases Society of America
http://www.journals.uchicago.edu/IDSA/guidelines/
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Owens RC, Ambrose PG, Nightingale CH,
editors. Antibiotic optimization: concepts
and strategies in clinical practice. New
York: Marcus Dekker; 2005.
Bibliography
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Barcenilla F, Gasco E, Rello J, Alvarez-Rocha L. Antibacterial treatment of
invasive mechanical ventilation-associated pneumonia. Drugs & Aging.
2001; 18(3): 189-200.
Center for Disease Control and Prevention. Campaign to prevent
antimicrobial resistance in healthcare settings: 12 steps to prevent
antimicrobial resistance among hospitalized adults. Dec 5, 2003. Available
at: http://www.cdc.gov/drugresistance/healthcare/ha/12steps_HA.htm.
Accessed on Nov 29, 2005.
Conte JE, Jr. Manual of antibiotics and infectious diseases: treatment and
prevention. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 5459, 171-173
Craig CR, Stitzel RE. Modern pharmacology with clinical applications. 6th
ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p.538-554.
Davey P, Brown E, Fenelon L, Finch R, Gould I, Hartman G, Holmes A,
Ramsay C, Taylor E,Wilcox M, Wiffen P. Interventions to improve antibiotic
prescribing practices for hospital inpatients. The Cochrane Database of
Systematic Reviews. 2005, October; Issue 4. Art No. CD003543.pub2: 192.
Franklin TJ, Snow GA. Biochemistry and molecular biology of antimicrobial
drug action. 6th ed. New York: Springer; 2005. p.136-149.
Karlowsky JA, Draghi DC, Jones ME, Thornsberry C, Friedland IR, and
Sahm DF. Surveillance for antimicrobial susceptibility among clinical
isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from
hospitalized patients in the United States, 1998 to 2001. Antimicrob Agents
Chemother. 2003, May; 47(5): 1681-1688.