Considerations for minimizing antibiotic resistance:

1. Considerations for minimizing antibiotic resistance: Analyzing current practice in the context of Pseudomonas aeruginosa resistance patterns Becky Carlson Advisor - Professor Fahringer

2. Presentation outline • Review of mechanisms of resistance • Consequences of antimicrobial resistance • Analysis of current recommendations for decreasing antimicrobial resistance • Implications for the clinician • Available resources

3. Review of resistance mechanisms • Definition: Hostile Environment Organism Mutated Organism

4. Review of resistance mechanisms • Bacterial catabolism of antibiotic • Loss of enzyme • Loss of receptor sensitivity • Efflux pumps • Defensive outer surface structures

5. Antimicrobial resistance consequences Empiricaltreatment impaired Limited resources NoResources

6. Antimicrobial resistance consequences • 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.

7. Current Recommendations • 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.

8. Current Recommendations • Initial effective treatment - MIC vs MLC – benefits and disadvantages - More research on direct relationship between failed treatment and resistance development

9. Current Recommendations • 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.

10. Current Recommendations • Antibiotic control, continued - Cross-resistance Fluoroquinolones  gentamicin, ceftazidime, imipenem, amikacin1 Imipenem  ceftazidime, piperacillin- tazobactam2 1. Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, and Quinn JP. Antibiotic resistance among Gram-negative 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.

11. Current Recommendations • Transmission prevention http://www.cdc.gov/drugresistance/healthcare/ha/12steps-HA.htm

12. Implications for the Clinician • Be selective • Consider the broader consequences • Consider this as a current problem, not merely a future problem • Pay attention to local surveillance data

13. Resources • CDC • Infectious Diseases Society of America http://www.journals.uchicago.edu/IDSA/guidelines/ • Owens RC, Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcus Dekker; 2005.

14. Bibliography • 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. 54-59, 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: 1-92. • 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. • Kiska DL, Gilligan PH. Pseudomonas. In: Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, editors. Manual of clinical microbiology. Washington DC: ASM Press; 1999. p. 517-525. • Kollef MK. Why appropriate antimicrobial selection is important: focus on outcomes. In: Owens RC Jr., Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcel Dekker; 2005. p. 41-57. • Lederman MM. Antimicrobial therapy. In: Andreoli TE, Carpenter CCJ, Griggs RC, Loscalzo J, editors. Cecil essentials of medicine. 6th ed. Philadelphia: Saunders; 2004. p. 815-819. • 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. • Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, and Quinn JP. Antibiotic resistance among Gram-negative bacilli in US intensive care units. JAMA. 2003, Feb 19; 289(7): 885-888. • Obritsch MD, Fish DN, MacLaren R, and Jung R. National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patient from 1993 to 2002. Antimicrob Agents Chemother. 2004, Dec; 48: 4606-4610. • Owens RC, Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcus Dekker; 2005. p. v. • Quinn JP. Pseudomonas aeruginosa infections in the intensive care unit. Seminars in respiratory and critical care medicine. 2003; 24(1): 61-68. • Rossolini GM, and Mantengol E. Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa. Clin Microbiol Infect. 2005; 11 (Suppl. 4): 17-32. • Steinke D, Davey P. Association between antibiotic resistance and community prescribing: a critical review of bias and confounding in published studies. Clin Infect Dis. 2001; 33(S3): S193-S205. • Stratton CW. Molecular mechanisms of action for antimicrobial agents: general principles and mechanisms for selected classes of antibiotics. In: Lorian V, editor. Antibiotics in laboratory medicine, 5th ed. New York: Lippincott, Williams & Wilkins; 2005. p. 532-563. • Valenti AJ. The role of infection control and hospital epidemiology in the optimization of antibiotic use. In: Owens RC, Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcel Dekker; 2005. p. 209-259. • 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. • Weber JT. The public health action plan to combat antimicrobial resistance and the prevention of antimicrobial resistance in health care settings. In: Owens RC Jr., Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcel Dekker; 2005. p. 21-37.