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Massimo Antonelli, MD Dept. of Intensive Care & Anesthesiology Universit Cattolica del Sacro Cuore Rome - Italy Antibiotics: The old and the new

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Major sites of infection in medical ICU n= 13,592 Richards MJ, et al. Infect Control Hosp Epidemiol 2000; 21: 510-515

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Facts Multi-resistant germs are common Antimicrobial resistance increases over time Inadequate therapy is associated with Mortality Can we adopt specific strategies to decrease resistance ?

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Most Frequently Reported Pathogens from ICU Patients with Nosocomial Pneumonia 1. Pseudomonas aeruginosa 2. Staphylococcus aureus 3. Enterobacter spp. 4. Klebsiella pneumoniae 5. Acinetobacter spp. Richards MJ et al. Crit Care Med 1999; 887-892.

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S. aureus The Most Frequent Isolate in EPIC Study Vincent JL, et al. JAMA 1995;274:639-644. Vincent JL. Int Care Med 2000;26:S3-S8.

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MRSA Pneumonia: Infection-Related Mortality

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Multiresistant bacteria are a problem in VAP 7.7S. pneumoniae % of all isolatesOrganism 3.1MSSA 8.4H. influenzae 11.8A. baumannii 11.8MRSA 31.7P. aeruginosa Rello J. Am J Respir Crit Care Med 1999; 160:608-613. (n = 321 isolates from 290 episodes)

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Acinetobacter baumannii Resistance in 118 ICUs of 5 European Countries 16%5%9% Imipenem 81%75%78% Ciprofloxacin 51%10%36% Amikacin 58%75%44% Pip/taz 76%81%70% Ceftazidime Spain PortugalFranceAntibiotic Pip/taz=piperacillin/tazobactam Hanberger H et al. JAMA 1999;281:67-71.

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Variables indipendently associated with VAP caused by Potentially Resistant bacteria *.0251.2-14.24.12Broad-spectrum antibiotics (Y/N).00033.3-55.013.46Prior antibiotic use (Y/N).0091.6-23.16.01Duration of MV before VAP episode 7 d (Y/N) p Value95% CIOdds Ratio Variable Trouillet JL., et al. AM J RESPIR CRIT CARE MED 1998; 157: 531-539 * Discriminant value (AUC) = 0.89

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Facts Multi-resistant germs are common Antimicrobial resistance increases over time Inadequate therapy is associated with Mortality We may adopt specific strategies to decrease resistance: antibiotic rotation ?

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ICU Patients Non-ICU Patients Source: NNIS Data. Clin Chest Med. 20:303-315. Antimicrobial Resistance in Nosocomial Infections Gram-Negative Pathogens

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ICU Patients Non-ICU Patients Source: NNIS data. Clin Chest Med. 20:303-315. Antimicrobial Resistance of Nosocomial Infections Gram-Positive Pathogens

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Facts Multi-resistant germs are common Antimicrobial resistance increases over time Inadequate therapy is associated with Mortality We may adopt specific strategies to decrease resistance: antibiotic rotation ?

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Mortality Associated With Initial Inadequate Therapy In Critically Ill Patients With Serious Infections in the ICU 0%20%40%60%80%100 % Luna, 1997 Ibrahim, 2000 Kollef, 1998 Kollef, 1999 Rello, 1997 Alvarez-Lerma,1996 Initial appropriate therapy Initial inadequate therapy *Mortality refers to crude or infection-related mortality Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394. Ibrahim EH et al. Chest 2000;118L146-155. Kollef MH et al. Chest 1999; 115:462-474 Kollef MH et al. Chest 1998;113:412-420. Luna CM et al. Chest 1997;111:676-685. Rello J et al. Am J Resp Crit Care Med 1997;156:196-200. Mortality*

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Reducing Inadequate Therapy Antibiotic Management Through Practice Guidelines 0 2 4 6 8 10 12 14 16 18 Duration of Antibiotic Therapy Length of ICU Stay ICU Admission to Discharge Total Length of Stay Number of Days Computer-Generated Regimen Physician-Generated Regimen *P

Risk Factors for Resistance in VAP Use of antibiotics within 15 days 1 Duration of hospitalization 2 Duration of mechanical ventilation > 7 days 1 1 Trouillet J-L et al. Am J Respir Crit Care Med 1998;157:531-539. 2 Lautenbach E et al. Clin Infect Dis 2001;32:1162-1171.

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Facts Multi-resistant germs are common Antimicrobial resistance increases over time Inadequate therapy is associated with Mortality We may adopt specific strategies to decrease resistance: antibiotic rotation ?

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Antimicrobial Resistance: Key Prevention Strategies Optimize Use Prevent Transmission Prevent Infection Effective Diagnosis & Treatment Pathogen Antimicrobial-Resistant Pathogen Antimicrobi al Resistance Antimicrobial Use Infection Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Susceptible Pathogen

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Key Prevention Strategies Prevent infection Diagnose and treat infection effectively Use antimicrobials wisely Prevent transmission Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Clinicians hold the solution!

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12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 1.Vaccinate 2.Get the catheters out 3.Target the pathogen 4.Access the experts 5.Practice antimicrobial control 6.Use local data 7.Treat infection, not contamination 8.Treat infection, not colonization 9.Know when to say no to vanco 10.Stop treatment when infection is cured or unlikely 11.Isolate the pathogen 12. Break the chain of contagion Diagnose and Treat Infection Effectively Prevent Infection Use Antimicrobials Wisely Prevent Transmission 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults

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Use Antimicrobials Wisely Step 6: Use local data Fact: The prevalence of resistance can vary by local, patient population, hospital unit, and length of stay. Actions: know your local antibiogram know your patient population Link to: NCCLS Proposed Guidance for Antibiogram DevelopmentNCCLS Proposed Guidance for Antibiogram Development 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults

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Risk factors for Early Onset Pneumonia Incidence % 14,6 30 41,7 19 29,2 25 13,6 30,6 14,7 8,7 26,9 46,7 8,2 33,3 Age 65 Males Females Multiple trauma Head trauma Pulmonary contusion No pulmonary contusion AIS 1^ AIS 2 AIS 3 MV > 24 h MV