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1、ANTIBIOTIC RESISTANT PATHOGENS: IMPACT AND CONTROL,David Jay Weber, M.D., M.P.H. Professor of Medicine, Pediatrics & Epidemiology University of North Carolina at Chapel Hill, USA,SOURCES OF SLIDES,Thanks are given to the following persons who provided slides for this lecture William Jarvis, CDC Mari
2、n Kollef, Washington Universitiy, St. Louis Christopher Ohl, Wake Forest University Jan Patterson, University of Texas, San Antonio Michael Pfaller, University of Iowa Louis Rice, VA Medical Center, Cleveland,IMPACT OF NOSOCOMIAL INFECTIONS,IMPACT OF NOSOCOMIAL INFECTIONS,Incidence = 5-10% Incidence
3、 rising with time 2,000,000 patients develop a healthcare-associated infection each year Healthcare-associated infections result in 90,000 death Cost estimated at $4.5 to $5.7 billion dollars per year,NOSOCOMIAL INFECTIONS IN THE UNITED STATES,Burke JP. NEJM 2003;348:651,PREVALENCE: ICU (EUROPE),Stu
4、dy design: Point prevalence rate 17 countries, 1447 ICUs, 10,038 patients Frequency of infections: 4,501 (44.8%) Community-acquired: 1,876 (13.7%) Hospital-acquired: 975 (9.7%) ICU-acquired: 2,064 (20.6%)Pneumonia: 967 (46.9%)Other lower respiratory tract: 368 (17.8%)Urinary tract: 363 (17.6%)Bloods
5、tream: 247 (12.0%),Vincent J-L, et al. JAMA 1995;274:639,CHALLENGES IN THE PREVENTION AND MANAGEMENT OF HEALTHCARE-ASSOCIATED INFECTIONS,Changing population of hospital patients Increased severity of illness Increased numbers of immunocompromised patients Shorter duration of hospitalization More and
6、 larger intensive care units Growing frequency of antimicrobial-resistant pathogens Importation of antimicrobial-resistant pathogens from the community into the hospital Lack of compliance with hand hygiene Reduced infection control resources nationwide Future: Prion diseases, bioterrorism agents, g
7、ene therapy, xenotransplantation,HEALTHCARE SYSTEM OF THE PAST,Home Care,Acute Care Facility,Outpatient/ Ambulatory Facility,Long Term Care Facility,CURRENT HEALTHCARE SYSTEM,Home Care,Acute Care Facility,Outpatient/ Ambulatory Facility,Long Term Care Facility,CURRENT STATE OF HEALTHCARE EPIDEMIOLOG
8、Y IN ACUTE CARE HOSPITALS,Fewer hospitals Smaller hospitals More and larger intensive care units Greater patient severity of illness More immunocompromised patients Shorter stays Fewer nurses? Fewer infection control personnel?,MECHANISMS OF ANTIBIOTIC RESISTANCE,Intrinsic resistance Acquired resist
9、ance Antibiotic modifying enzymes (e.g., penicillin resistance in S. aureus) Target site alteration (e.g., methicillin resistance in S. aureus) Permeability barriers (e.g., vancomycin tolerance in VISA) Efflux pumps (e.g., erythromycin resistance in S. pneumoniae),Mechanisms of Resistance,Eliopoulos
10、. Infectious Diseases. 1992.,IMPACT OF DRUG RESISTANT PATHOGENS,Inappropriate therapy with worse outcome Prolonged hospitalization Increased difficulty with placement in an extended care facility Need of isolation precautions (may negatively impact on quality of patient care) Increased cost Higher m
11、ortality,EMERGING DRUG RESISTANCE IN COMMUNITY PATHOGENS,EMERGING RESISTANT PATHOGENS: COMMUNITY,HIV: Multiple agents Pneumococcus: Penicillin/cephalosporins, erythromycin Group A streptococcus: Erythromycin Mycobacterium tuberculosis: INH, rifampin Neisseria gonorrhoeae: Penicillin, quinolones Stap
12、hyloccus aureus: Oxacillin Plasmodium falciparum: Chloroquine, mefloquine, others,VA,Feedlots,Foreign,Daycare,Community Hospitals,Tertiary Hospitals,Nursing Homes,Community,Homecare,Environments Where Antibiotic Resistance Develops and Their Relationships,Adapted from B. Murray,S. PNEUMONIAE: INCIDE
13、NCE, US,Meningitis: 3,000 cases Bacteremia: 50,000 cases Pneumonia: 500,000 cases Otitis media: 7 million casesDeaths: 20,000 Source: Centers for Disease Control. MMWR 1997;46(RR-8),% of Isolates Resistant to Penicillin,Year,Breiman RF, et al. JAMA. 1994;271:1831-1835. Doern GV, et al. AAC. 1996;40:
14、1208-1213. Thornsberry C, et al. DMID. 1997;29:249-257. Thornsberry C, et al. JAC. 1999;44:749-759. Thornsberry C, et al. CID 2002;34(S1):S4-S16. Karlowsky, et al. CID. 2003;36:963-970. Sahm, et al. IDSA 2003, abstract 201. Data on file, Ortho-McNeil Pharmaceutical, Inc. In vitro activity does not n
15、ecessarily correlate with clinical results.,Trend for Penicillin-Resistant (MIC 2 mg/ml) S. pneumoniae in the US (1988-2002),PENICILLIN SUSCEPTIBILITY,CLINICAL SYNDROMES: STAPHYLOCOCCUS AUREUS,Skin Primary pyodermas: Impetigo, folliculitis, furuncles, carbuncles, paronychia, cellulitis Toxin mediate
16、d syndromes: Toxic shock syndrome (TSS), scalded skin syndrome (SSS) Systemic: Sepsis, bacteremia, endocarditis Organ system: Meningitis, osteomyelitis, septic arthritis, paratitis, myositis,Evolution of Antimicrobial Resistance in Gram-positive Cocci,CLASSIFICATION OF S. AUREUS RESISTANCE,ORSA: Prevalence of co-resistance to other drugs, U.S., 1997-1999:,MRSA with Co-Resistance,Diekema DJ et al. CID. 2001;32:S114-S132.,ORSA strains showed resistance to mean 3.5 (median 3) additional drug classes,
