1. ??????????? ??? ???? ???

2. CHANGING PATTERN OF PATHOGENS CAUSING NOSOCOMIAL INFECTIONS, NTUH, 1981- 2008

6. Bacterial Resistance Associated with Use of Antibiotics Selective pressures Low therapeutic index

7. ?????????? True Pathogen or Colonization Treat Underlying Disease Reduce Nosocomial Procedure Prudent use of Antibiotics Vigorous Infection Control

10. ?????????? ?????????(????,????..). ????: ??????????? ???????????????? ????????bronchial washing?biopsy????? ??X??????????,???????? ?????: ?????????????105??/ml? ????????????? ???????WBC esterase?nitrate??,???(>10 WBC/HPF)???????????>102??/ml? ????: ?????????????,??????????????????

11. ?????? Coagulase-negative staphylocci Staphylococcus epidermidis Viridans streptococci Micrococci Bacillus species Corynebacterium species Neisseria species (?N. gonorrheae?N. meningitidis) Nonfermentative gram-negative bacilli Acaligenes, Flavobacterium, Sphingomonas...

13. ??susceptible hosts: ???????????? Age, underlying diseases, cancer therapy.. Invasive procedures: Removing them as soon as possible Dedicate usage of antibiotics Breaking colonization resistance Selective pressure Discharge from hospital (or ICU) early Host-Factor

14. Risk Factors for Getting MDRAB ??????????????? ?????????? ??????????? ??????????? ???????????? ??????????????

15. Treatment for MRSA Bacteremia 30% complicated with metastatic lesions Duration of antimicrobial therapy: At least 4 – 6 weeks for those with Infective endocarditis Metastatic foci 14-day duration only if No endocarditis, no implanted prosthesis F/U B/C within 2 – 4 days are negative No metastatic foci Defervescence within 72 hours after effective Tx

16. Principles: Use of antibiotics

17. Vancomycin Therapeutic Guidelines 2009, IDSA, ASAHP, SIDP Recommend Loading : 25-30 mg/kg Achieve rapid target concentration Maintain : 15-20 mg/kg, q8~12h, if MIC < 1 mg/L Trough : 15-20 mg/L Achieve AUC/MIC >400, if MIC < 1 mg/L Infusion period : 1.5 ~ 2h, or continuous infusion Alternative therapy considered if MIC ? 2 mg/L

20. Drug Penetration: % Tissue/Serum

23. ????????????????? ??????????(2000. 3. 11) Drug of choice Alternative Asymptomatic bacteriuria non-pregnant* - - pregnant 1o or 2o cepha Amoxicillin (for enterococci) Acute bacterial cystitis non-pregnant TMP/SMZ, dolcol FQ, amoxicillin pregnant 1o or 2o cepha amoxicillin Acute pyelonephritis (APN) 1o or 2o cepha Ampicillin, AG Acute prostatitis 3ocepha or FQ TMP/SMZ

26. Enterococci or pneumococci Penicillin + GM Vancomycin + GM or rifampin VRE (daptomycin or linezolid) MRSA Vancomycin (or Teicoplanain ) + GM or RIF Daptomycin + GM or RIF Linezolid + GM or RIF

27. for Pseudomonas, MDR- E. coli, KP… Anti-pseudomonal b-lactams/carbapenem + GM/AMK or FQs for MDR- Acinetobacter baumannii Meropenem (or imipenem) + sulbactam or amikacin Tigecycline + colistin

28. De-Escalation Therapy (????) ?????????????????

33. Rotating (cycling) antibiotics

34. Antibiotic Cycling vs. Diversity Cycling (Rotation) Diversity Models and clinical trials shown that heterogeneous antibiotic use is a potential way of reducing the selection pressure that leads to antibiotic resistance Slide 34. Cycling or rotation is the scheduled substitution of a class of antibiotics (or a specific member of a class) with a different class (or a specific member of that class) that exhibits a comparable spectrum of activity. This substitution may be followed after a fixed interval by a third, fourth, or, indeed, any number of substitutions, but the ‘cycle’ must be repeated, with reintroduction of the original class/drug. Cycling/rotation should not be confused with scheduled changes or restrictions of antibiotic regimens without repeating the process (a common occurrence among both investigators and reviewers). The duration of each cycle is based on either local susceptibility patterns or a predetermined time period.1 [Brown, p.6] In contrast, mixing refers to an antibiotic program where each targeted patient receives one of several drug classes used simultaneously in the unit or hospital.3 [Bergstrom, p.13286] References Brown EM, Nathwani D. Antibiotic cycling or rotation: a systematic review of the evidence of efficacy. J Antimicrob Chemother. 2005;55:6-9. Fridkin SK. Routine cycling of antimicrobial agents as an infection-control measure. Clin Infect Dis. 2003:36:1438-1444. Bergstrom CT, Lo M, Lipsitch M. Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci USA. 2004;101:13285-13290. Bonhoeffer S, Lipsitch M, Levin B. Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci U S A. 1997;94:12106-12111. Bonten MJM, Austin DJ, Lipsitch M. Understanding the spread of antibiotic resistant pathogens in hospitals: mathematical models as tools for control. Clin Infect Dis. 2001;33:1739-1746. Sandiumenge A, Diaz E, Rodriguez A, et al. Impact of diversity of antibiotic use on the development of antimicrobial resistance. J Antimicrob Chemother. 2006;57:1197-1204.Slide 34. Cycling or rotation is the scheduled substitution of a class of antibiotics (or a specific member of a class) with a different class (or a specific member of that class) that exhibits a comparable spectrum of activity. This substitution may be followed after a fixed interval by a third, fourth, or, indeed, any number of substitutions, but the ‘cycle’ must be repeated, with reintroduction of the original class/drug. Cycling/rotation should not be confused with scheduled changes or restrictions of antibiotic regimens without repeating the process (a common occurrence among both investigators and reviewers). The duration of each cycle is based on either local susceptibility patterns or a predetermined time period.1 [Brown, p.6] In contrast, mixing refers to an antibiotic program where each targeted patient receives one of several drug classes used simultaneously in the unit or hospital.3 [Bergstrom, p.13286] References Brown EM, Nathwani D. Antibiotic cycling or rotation: a systematic review of the evidence of efficacy. J Antimicrob Chemother. 2005;55:6-9. Fridkin SK. Routine cycling of antimicrobial agents as an infection-control measure. Clin Infect Dis. 2003:36:1438-1444. Bergstrom CT, Lo M, Lipsitch M. Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci USA. 2004;101:13285-13290. Bonhoeffer S, Lipsitch M, Levin B. Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci U S A. 1997;94:12106-12111. Bonten MJM, Austin DJ, Lipsitch M. Understanding the spread of antibiotic resistant pathogens in hospitals: mathematical models as tools for control. Clin Infect Dis. 2001;33:1739-1746. Sandiumenge A, Diaz E, Rodriguez A, et al. Impact of diversity of antibiotic use on the development of antimicrobial resistance. J Antimicrob Chemother. 2006;57:1197-1204.

35. Cycling vs. Mixing and Selective Pressure on a Bacterial Clone Slide 28. Bergstrom and colleagues developed a mathematical model of antimicrobial cycling in a hospital setting, revealing that cycling is unlikely to reduce rates of resistance carriage relative to alternative drug-use programs. [Bergstrom, p.13285A] This figure illustrates the time course of a single clone in a hospital setting. Each square represents a patient in a hospital bed; gray squares receive treatment with drug 1, whereas white squares receive treatment with drug 2. In a ward where drugs are mixed, the fractions of patients receiving drug 1 and drug 2 do not change appreciably over time. In a ward with cycling, the fractions receiving each drug change considerably over time. At any given time, however, each individual bacterial clone faces a selective regime defined by the drug used by a single patient, not by the ward average. Thus, in the course of patient-to-patient transfer, a bacterial clone actually faces more rapid environmental fluctuations in the mixing ward. [Bergstrom, p.13288B & p.13288C] For example, the clone on the left (mixing), tracked by the solid line, faces a new drug five times during the span of the diagram. By contrast, the clone tracked on the right (cycling) faces a new drug only once, during the mass switch-over from drug 1 to drug 2. [Bergstrom, p.13288B & p.13288C] Thus, mixing provides a more heterogeneous environment than does cycling at the single-patient scale, despite its constancy in treatment protocol at the scale of the ward. [Bergstrom, p.13288C] Reference Bergstrom CT, Lo M, Lipsitch M. Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci. 2004;101:13285-13290.Slide 28. Bergstrom and colleagues developed a mathematical model of antimicrobial cycling in a hospital setting, revealing that cycling is unlikely to reduce rates of resistance carriage relative to alternative drug-use programs. [Bergstrom, p.13285A] This figure illustrates the time course of a single clone in a hospital setting. Each square represents a patient in a hospital bed; gray squares receive treatment with drug 1, whereas white squares receive treatment with drug 2. In a ward where drugs are mixed, the fractions of patients receiving drug 1 and drug 2 do not change appreciably over time. In a ward with cycling, the fractions receiving each drug change considerably over time. At any given time, however, each individual bacterial clone faces a selective regime defined by the drug used by a single patient, not by the ward average. Thus, in the course of patient-to-patient transfer, a bacterial clone actually faces more rapid environmental fluctuations in the mixing ward. [Bergstrom, p.13288B & p.13288C] For example, the clone on the left (mixing), tracked by the solid line, faces a new drug five times during the span of the diagram. By contrast, the clone tracked on the right (cycling) faces a new drug only once, during the mass switch-over from drug 1 to drug 2. [Bergstrom, p.13288B & p.13288C] Thus, mixing provides a more heterogeneous environment than does cycling at the single-patient scale, despite its constancy in treatment protocol at the scale of the ward. [Bergstrom, p.13288C] Reference Bergstrom CT, Lo M, Lipsitch M. Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci. 2004;101:13285-13290.

36. Restriction use of 3rd-cephalosporin ESBL-K. pneumoniae outbreak at ICU Associated with 3rd cephem use Restriction use of 3rd ceph., substitute to imipenem Decrease ESBL-KP, but lead to IMP-R Acinetobacter (metallo-b-lactamase) and P. aeruginosa (loss porins) Pena, et al. AAC 1998;42:53-7. Impact of cephalosporin restriction 44% reduction of ESBL K. pneumoniae 68% increased IMP-resistant P. aeruginosa Rahal, et al. JAMA 1998;280:1233-7.

37. Infection Control to Prevent MDR-bacterial infection

40. ????????“?????”?? Universal Precaution (?????) ??????????? (?????????) ?????????!

41. ????????? ???? ???? ?????? ?????? ?????????? ???(??????) ??????(??????):?????????,???????? ????????? ????(0.5% )

42. ???? ?? ??????????????????????? ????????? ?????????? ??????????,?????????? ?? ????????????? ????????????? ??/??/??? ?????????????(?CPR)??? ?????? ????

44.

49. Summary Appropriate antibiotic use and effective infection control reduce outbreak of MDR-pathogens Antibiotic heterogeneity Short-course antibiotic treatment De-escalating antibiotic regimens Isolation precautions Handwash and contact isolation precautions Active surveillance Education