Considerations for minimizing Considerations for minimizing antibiotic resistance:antibiotic resistance:

Analyzing current practice in the context of Analyzing current practice in the context of Pseudomonas aeruginosaPseudomonas aeruginosa resistance patterns resistance patterns

Becky CarlsonBecky CarlsonAdvisor - Professor FahringerAdvisor - Professor Fahringer

Presentation outlinePresentation outline

Review of mechanisms of resistanceReview of mechanisms of resistance Consequences of antimicrobial resistanceConsequences of antimicrobial resistance Analysis of current recommendations for Analysis of current recommendations for

decreasing antimicrobial resistancedecreasing antimicrobial resistance Implications for the clinicianImplications for the clinician Available resourcesAvailable resources

Review of resistance mechanismsReview of resistance mechanisms

Definition:Definition:

Organism Mutated Organism

Hostile

Environm

ent

Review of resistance mechanismsReview of resistance mechanisms

Bacterial catabolism of antibioticBacterial catabolism of antibiotic Loss of enzymeLoss of enzyme Loss of receptor sensitivityLoss of receptor sensitivity Efflux pumpsEfflux pumps Defensive outer surface structuresDefensive outer surface structures

Antimicrobial resistance consequencesAntimicrobial resistance consequences

Empirical treatment impaired

Limited resources

No Resources

Antimicrobial resistance consequencesAntimicrobial resistance consequences

Limited resourcesLimited resources1999 Brazilian study of polymyxin use 1999 Brazilian study of polymyxin use

- - IV colistin treatmentIV colistin treatment

- 58% of patients responded (25% of those with - 58% of patients responded (25% of those with nosocomial pneumonia)nosocomial pneumonia)

- 27% of patients developed renal insufficiency- 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 RecommendationsCurrent Recommendations

Infection preventionInfection prevention

- Ventilator use educational program - Ventilator use educational program

- 73% reduction in ventilator associated - 73% reduction in ventilator associated pneumonia with a cycling programpneumonia with a cycling program

- 57% reduction in VAP without the cycling - 57% reduction in VAP without the cycling programprogram

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 RecommendationsCurrent Recommendations

Initial effective treatmentInitial effective treatment

- - MIC vs MLC – benefits and disadvantagesMIC vs MLC – benefits and disadvantages

- More research on direct relationship - More research on direct relationship between between failed treatment and resistance failed treatment and resistance developmentdevelopment

Current RecommendationsCurrent Recommendations

Antibiotic controlAntibiotic control

- Cycling programs - Cycling programs

- Self-resistance- Self-resistance

Demonstrated correlations between use of Demonstrated correlations between use of beta-lactams and fluoroquinolones and beta-lactams and fluoroquinolones and

development of resistancedevelopment 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 RecommendationsCurrent Recommendations

Antibiotic control, continuedAntibiotic control, continued

- Cross-resistance- Cross-resistance

Fluoroquinolones Fluoroquinolones gentamicin, gentamicin, ceftazidime, imipenem, amikacinceftazidime, imipenem, amikacin11

Imipenem Imipenem ceftazidime, piperacillin- ceftazidime, piperacillin-tazobactamtazobactam22

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.

Current RecommendationsCurrent Recommendations

Transmission preventionTransmission prevention

http://www.cdc.gov/drugresistance/healthcare/ha/12steps-HA.htmhttp://www.cdc.gov/drugresistance/healthcare/ha/12steps-HA.htm

Implications for the ClinicianImplications for the Clinician

Be selectiveBe selective Consider the broader consequencesConsider the broader consequences Consider this as a current problem, not Consider this as a current problem, not

merely a future problemmerely a future problem Pay attention to local surveillance dataPay attention to local surveillance data

ResourcesResources

CDCCDC Infectious Diseases Society of America Infectious Diseases Society of America

http://www.journals.uchicago.edu/IDSA/guidelines/http://www.journals.uchicago.edu/IDSA/guidelines/

Owens RC, Ambrose PG, Nightingale CH, Owens RC, Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts editors. Antibiotic optimization: concepts and strategies in clinical practice. New and strategies in clinical practice. New York: Marcus Dekker; 2005. York: Marcus Dekker; 2005.

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