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What intervention on the use or dosing of antibiotics work to decrease resistance ?

What intervention on the use or dosing of antibiotics work to decrease resistance ?. Jan. 18, 2007 Sung-Ching Pan. Antibiotics control strategies. Agriculture use. Mutation prevention dose. Combination therapy. Conan MacDougall and Ron E. Polk, CLINICAL MICROBIOLOGY REVIEWS, 2005.

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What intervention on the use or dosing of antibiotics work to decrease resistance ?

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  1. What intervention on the use or dosingof antibioticswork to decrease resistance? Jan. 18, 2007 Sung-Ching Pan

  2. Antibiotics control strategies Agriculture use Mutation prevention dose Combination therapy Conan MacDougall and Ron E. Polk, CLINICAL MICROBIOLOGY REVIEWS, 2005

  3. Antibiotics control • Relationship between antibiotics usage and resistance • Ecological study • Penicillin use and penicillin resistant S. pneumononas (PRSP) • Antibiotics use (3rd cephalosporin, macrolide and fluroquilolone) and MRSA

  4. Antibiotics control • Relationship between antibiotics usage and resistance • Individual study Leibovici et al. J Antimicrob Chem, 2001

  5. Antibiotics control • Relationship between antibiotics usage and resistance- Temporal sequence? • Intervention-change • Discontinue intervention-reverse

  6. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  7. Education campaignHELENA SEPPALA, et al. NEJM 1997 Intervention In the end1991 *Physicians were reached mainly through the Finnish Medical Journal and lectures at national and local meetings for general practitioners.

  8. Limitations • Ecological study, hard to control confounding • After the intervention stop, what will happen? • The problem of this strategy: Decrease use of macrolide, but increase use of other antibiotics, other resistance? • “the total rate of use of antimicrobial agents remained unchanged”

  9. Education campaign (hospital/individual level) • Some researches study the behavior change of antibiotics prescription after education campaign • Education campaign- antibiotics resistance? • Publication bias? • Combination with other infection control strategies

  10. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  11. Restriction of usageWhite AC, CID, 1997 • Prior authorization • Ben Taub General Hospital is a 575-bed urban teaching hospital in Houston. • Enforcement of the prior-authorization requirement began on 1 January 1994. • Intravenous amikacin, ceftazidime, ciprofloxacin, fluconazole, ofloxacin, and ticarcillin/clavulanate. • Faculty of the Infectious Diseases Service, Department of Medicine, were available 24 hours a day to provide antibiotic approval

  12. Restriction of usageWhite AC, CID, 1997

  13. Restriction of usageWhite AC, CID, 1997 • Limitation: • Before –after study • Other intervention? in-service programs for surgical ICU staff on hand washing in November 1993 and July and August 1994. • Need staffs support

  14. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  15. Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997 • Switch of empirical for nosocomial pneumonia in ICU from ceftazidime to ciproxin • Primary outcome: • incidence of ventilator-associated pneumonia (VAP) • nosocomial bacteremia • Study design: • before(6 months) Vs. after (6 months)

  16. Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997

  17. Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997 • Before-after design • Ceftazidime related drug resistance change did not clarified • Ceftazidime resistant P. aeruginosa • ESBL K. pneumonia or E.coli • Problem with this strategy: • How about drug resistance to ciproxin?

  18. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  19. Routine cyclingRaymond DP, et al. Crit Care Med 2001

  20. Routine cycling

  21. Routine cycling Resistance Agent A Agent B Agent A Agent B Agent A Agent B Time Ciproxin Tazocin carbapenem cefepime • Limitation: • Short follow up time • Different patients population in the before-after setting

  22. Routine cycling

  23. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  24. Combination therapy • β-lactams+ aminoglycoside: • Pseudomonas • Carbapemen+aminoglycoside • MDR Acinectobacter baumanii • Work for therapeutic goal, but for resistance?

  25. Combination therapy El Amari EB, et al. CID 2001 • Case-control study • Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates • piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides

  26. Combination therapy (meta-analysis of RCT)Bliziotis IA, CID 2005

  27. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Mutation prevention dose • Control use in agriculture

  28. Concentration dependent Vs. Time dependent

  29. The emergence of resistance

  30. Mutation prevention concentration • Describes the antibacterial concentration that inhibits the growth of the least-susceptible, single step mutant; • The MIC of the least susceptible organism • There is a low likelihood for spontaneous mutant formation at or above the MPC.

  31. Mutation prevention concentration • Limitation on clinical use • MPCs differ among the various fluoroquinolones against different pathogens • the MPC for each antibacterial agent is dependent on the genotypic profile of the organism. KD2138: parC KD2139: gyrA

  32. Antibiotics control • Education campaign • Restriction of usage • Single switch/ antibiotics cycling • Combination therapy • Pk/Pd, Mutation prevention dose • Control use in agriculture

  33. Agriculture use regulation Antibiotics Animal pathogen Human pathogen resistance

  34. Study designRamsay CE, J. Antimicrob. Chemother, 2003 • Review of 306 studies of interventions to improve antimicrobial prescribing in hospitals, 70% did not meet the minimum criteria of the Cochrane Collaboration’s Effective Practice and Organization of Care Group. • The most commonly excluded studies were those using uncontrolled before- and-after designs (46%) or inadequate interrupted time series analysis (24%).

  35. Study design • Interrupted time series with segmented regression: a method of analysis applied to before-and-after quasi-experimental study designs

  36. Study design • Mathematic modeling: • While a long-term follow up is needed for before-and-after quasi-experimental study designs • Control confounding

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