Il rischio infettivo Controllo delle farmaco-resistenze

1. 37 ° Congresso Nazionale ANMDO Bologna, 8-11 giugno 2011 Il rischio infettivo Controllo delle farmaco-resistenze Pierluigi Viale Clinica di Malattie Infettive Policlinico S. Orsola – Malpighi Bologna

2. The Vanco-MIC creep of S. aureus The stabilized ESBL endemia The troubling outbreaks of KPC The ominous epidemiology of MDR Acinetobacter The long walk of MDR P. aeruginosa Antibiotic resistance is a well recognized problem facing modern medicine and it is undeniable that in the last few years, levels of resistance have reached a tipping point

3. The vicious circle of antibiotic resistance Environment control HCWs behavior ATB stewardship Bed side ATB choice Bed site ATB use ATB stewardship

4. Antimicrobial Stewardship: DEFINITIONS Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship Dellit TH et al, Clin Infect Dis 2007; 44:159–77 An activity that optimizes antimicrobial management and includes selection, dosing, route and duration of antimicrobial therapy. A marriage of infection control (Epidemiologist) and antimicrobial management (Infectious Diseases specialist) finalized to share the principles of the optimized treatment between the bench to bed side point of view and the hospital-wide vision

5. “The desire to ingest medicines is one of the principal features which distinguish man from the animals” Osler W. Aequanimitas, 1920 “To Prescribe an antibiotic is easier and faster than think about its usefulness” Anonymous 2010

6. A marriage of infection control (Epidemiologist) and antimicrobial management (Infectious Diseases specialist) finalized to share the principles of the optimized treatment between the bench to bed side point of view and the hospital-wide vision MINIMIZING UNINTENDED CONSEQUENCES OF ANTIMICROBIAL USE, INCLUDING TOXICITY, THE SELECTION OF PATHOGENIC ORGANISMS AND THE EMERGENCE OF RESISTANCE. TO REDUCE HEALTH CARE COSTS WITHOUT ADVERSELY IMPACTING QUALITY OF CARE.

7. A marriage of infection control (Epidemiologist) and antimicrobial management (Infectious Diseases specialist) finalized to share the principles of the optimized treatment between the bench to bed side point of view and the hospital-wide vision A CORRECT ANTIMICROBIAL THERAPY IS MANDATORY IN ALL THESE PATIENTS TO GUARANTEE THE BEST CLINICAL OUTCOME A NEW DEAL IN ANTIMICROBIALS MANGEMENT ?

8. WHAT DOES IT MEAN • “CORRECT ANTIBIOTIC THERAPY”? • The microorganism point of view • A GOOD MICROBIOLOGICAL / EPIDEMIOLOGICAL CHOICE • The drug point of view • A CORRECT PHARMACOKINETICAL CHOICE and ADMINISTRATION • liphophilic vs hydrophilic drugs • time dependent vs concentration dependent drugs • The patient point of view • A TARGETED PHYSIOPHATOLOGICAL DAILY SCHEDULA • illness severity grading • physio-pathological conditions affecting distribution Viale P & Pea F Crit Care Med 2006

9. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship Dellit TH et al, Clin Infect Dis 2007; 44:159–77 A comprehensive evidence-based stewardship program to combat antimicrobial resistance includes elements chosen from several recommendations based on local antimicrobial use and resistance problems and on available resources that may differ, depending on the size of the institution or clinical setting.

10. Antibiotic stewardship: overcoming implementation barriers Bala AM and Gould IM Curr Op Infect Dis 2011;24 Antimicrobial stewardship needs high-level executive commitment. Infection control and antimicrobial stewardship teams need to work closely together Antibiotic care bundles should be implemented. Antimicrobial stewardship must be seen as part of patient care and not a management-led cost-saving exercise Antimicrobial de-escalation has been largely ignored as an important operational component and should earn its rightful place alongside guidelines and clinical pathways.

11. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship Dellit TH et al, Clin Infect Dis 2007; 44:159–77 6. There are 2 core strategies, both proactive, that provide the foundation for an antimicrobial stewardship program. These strategies are not mutually exclusive. A.Prospective audit with intervention and feedback. Prospective audit of antimicrobial use with direct interaction and feedback to the prescriber, performed by either an infectious diseases physician or a clinical pharmacist with infectious diseases training, can result in reduced inappropriate use of antimicrobials (A-I). B. Formulary restriction and preauthorization. Formulary restriction and preauthorization requirements can lead to immediate and significant reductions in antimicrobial use and cost (A-II) and may be beneficial as part of a multifaceted response to a nosocomial outbreak of infection (B-II). The use of preauthorization requirements as a means of controlling antimicrobial resistance is less clear, because a long-term beneficial impact on resistance has not been established, and in some circumstances, use may simply shift to an alternative agent with resulting increased resistance (B-II). In institutions that use preauthorization to limit the use of selected antimicrobials, monitoring overall trends in antimicrobial use is necessary to assess and respond to such shifts in use (B-III).

12. ANTIMICROBIAL ORDER FORMS. Antimicrobial order forms can be an effective component of antimicrobial stewardship (B-II) and can facilitate implementation of practice guidelines.

13. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. Rahal JJ, et al. JAMA 1998; 280:1233–7 In response to an increasing incidence of cephalosporin- resistant Klebsiella spp, a preapproval policy was implemented for cephalosporins. 200 141 150 100 69 50 ceph use caz-R Klebsiella caz-R Klebsiella in UTI 0 imip use imip-R P.aeruginosa -50 -44 -77% -80 -100

14. FROM A ZEALOT VISION OF THE FORMULARY TOWARD A TRUE USEFUL FORMULARY • NO RESTRICTEDDRUGS • SHAREDINDICATIONSOFPRESCRIPTIONBYLOCALEXPERTS • GRADINGOF THE INDICATIONS TO THE PRESCRIPTION • - GRADINGOF THE RESPONSABILITYOF THE PRESCRIPTION

15. FROM A ZEALOT VISION OF THE FORMULARY TOWARD A TRUE USEFUL FORMULARY • GRADINGOF THE INDICATIONS TO THE PRESCRIPTION • FREE PRESCRIPTION • PRESCRIPTION INSIDE A HOSPITAL PROTOCOL • PAYATTENTION – CONSIDERALTERNATIVES • ON ID SPECIALISTPRESCRIPTION • AVOID IT IF POSSIBLE !

16. GUIDELINES AND CLINICAL PATHWAYS. Multidisciplinary development of evidence-based practice guidelines incorporating local microbiology and resistance patterns can improve antimicrobial utilization (A-I). Guideline implementation can be facilitated through provider education and feedback on antimicrobial use and patient outcomes (A-III).

17. Epidemiology and outcomes of HCAP: results form a large US database of culture-positive pneumonia Koleff M et al., Chest 2005;128:3854-62

18. Outcomes of patients hospitalized with CAP, HCAP, HAP Venditti M et al, Ann Intern Med 2009;150:19-26 362 patientshospitalizedwith pneumonia duringtwo 1-week surveillanceperiods 61.6% had CAP, 24.9% hadHCAP, and 13.5% hadHAP HCAP = HAP

19. Low incidenceofmultidrug-resistantorganisms in patientswithhealthcare-associated pneumonia requiringhospitalizationGarcia-Vidal C et al, ClinMicrobiolInfect. 2011 Feb 1 A total of 2245 patients with pneumonia were hospitalized, of whom 577 (25.7%) had HCAP Group 1: received any intravenous therapy at home; received wound care or specialized nursing care through a healthcare agency, family, or friends; or had self-administered intravenous medical therapy in the 30 days before pneumonia (patients whose only home therapy was oxygen were excluded). Group 2: attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the 30 days before pneumonia. Group 3: admitted to an acute-care hospital for two or more days in the 90 days before pneumonia. Group 4: resided in a nursing home or long-term-care facility.

20. Low incidenceofmultidrug-resistantorganisms in patientswithhealthcare-associated pneumonia requiringhospitalizationGarcia-Vidal C et al, ClinMicrobiolInfect. 2011 Feb 1 A total of 2245 patients with pneumonia were hospitalized, of whom 577 (25.7%) had HCAP HCAP = CAP

21. Impact of guideline-consistent therapy on outcome of patients with HCAP and CAP Grenier C et al, J Antimicrob Chemother Advance Access published May 17, 2011 Methods: A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and 2008. Characteristics of patients with CAP versus HCAP

22. Impact of guideline-consistent therapy on outcome of patients with HCAP and CAP Grenier C et al, J Antimicrob Chemother Advance Access published May 17, 2011 Distribution of bacterial pathogens For CAP cases, compliance with guidelines was independently associated with lower mortality and shorter hospital stay For HCAP cases, non-concordance of the initial empirical regimen with guidelines was not a risk factor for mortality.

23. The vicious circle within the hospital-acquired pneumonia and health-care-associated pneumonia guidelines Yu V Lancet Infect Dis 2011; 11: 248–52

24. HCAP = HAP ? Linezolid + Carbapenem + Quinolone / Aminoglycosides Critically ill / ICU admitted HCAP = CAP ? Amoxi-clav + Macrolide Non Critically ill / Medical Ward admitted

25. COMBINATION THERAPY There are insufficient data to recommend the routine use of combination therapy to prevent the emergence of resistance (C-II). Combination therapy does have a role in certain clinical contexts, including use for empirical therapy for critically ill patients at risk of infection with multidrug-resistant pathogens, to increase the breadth of coverage and the likelihood of adequate initial therapy (A-II).

26. Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study Kett DH et al, Lancet Infect Dis 2011; 11: 181–89 A performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes was implemented. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28; 303 Patients in ICU, at risk for MDR pneumonia and treated empirically were included.

27. Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study Kett DH et al, Lancet Infect Dis 2011; 11: 181–89 Guideline-compliant empirical treatment outcomes for 28-day mortality Reasons for non-compliance were failure to use a secondary anti-Gram-negative drug –mainly AG - (154 patients) or, less commonly, failure to use either a primary anti-Gram negative drug (24 patients) or anti-MRSA drug (24 patients).

28. A stewardship program about the COMBINATION USE COMBINATION routinely against selected microorganisms, clinical conditions and patients NARROW THE ANTIMICROBIAL SPECTRUM AS SOON AS POSSIBLE using sensitivity data and clinical outcome AVOID COMBINATION using drugs with overlapping spectrum CHOOSE FOR THE COMBINATION different antibiotic classes USING A COMBINATION don’t reduce the daily dose of singular drugs CHOOSE FOR COMBINATION Drugs with the best evidence AVOID THE ROUTINELY USE OF COMBINATION REGIMENS based on traditions, compulsivity, poor evidence

29. EDUCATION Education is considered to be an essential element of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies (A-III). However, education alone, without incorporation of active intervention, is only marginally effective in changing antimicrobial prescribing practices and has not demonstrated a sustained impact (B-II).

30. Would you like to easily improve your antimicrobial stewardship ? Go to the market and … Buy a skilled infectivologist And give him the change to work