Antimicrobial Stewardship: Strategies for Appropriate Antimicrobial Use

Transcription

1 Antimicrobial Stewardship: Strategies for Appropriate Antimicrobial Use Thomas M. File, Jr, MD, MSc, MACP Chair, Infectious Disease Division Summa Health System; Professor of Internal Medicine, Master Teacher, Chair ID Section NEOMED

2 No. of new antimicrobials IDSA Call-to-Action: Bad Bugs, No Drugs As resistance increases... number of new antimicrobials diminishes IDSA. Infectious Diseases Soc. Of Am. Bad Bugs, No Drugs. Available at:

3 Antibiotics Should Be Assigned to a Special Drug Class to Preserve Their Power, Says Alliance for the Prudent Use of Antibiotics S. Levy 2010 Antimicrobial Clin Infect resistance Dis is a major public health crisis. Clin Infect Dis 2011 Drug resistance follows the drug like a faithful shadow. Paul Erhlich It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them.there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant. Alexander Fleming Nobel Prize lecture Dec 11, 1945

4 The Impact of Antimicrobial Resistance Affects clinical outcomes Associated with higher mortality Results in higher healthcare costs Leads to prolonged hospitalization Increase challenge for appropriate management Empiric therapy Directed therapy File TM, Jr. Chest. 1999;115(suppl):3S-8S.

5 Clinical Practice Guidelines "Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances" (Institute of Medicine, 1990). Bringing scientific evidence into daily clinical routines Evidence-based IDSA > 50 guidelines ( guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment (IDSA guidelines)

6 From Pirates of the Caribbean Curse of the Black Pearl 2003 Jack Sparrow: I thought you were supposed to keep to the code (referring to the pirates code that Any man that falls behind stays behind when the Black Pearl waits for him to escape) Mr. Gibb: We figured they were more like guidelines rather than actual rules

7 CMS Measures and Stewardship Core Measures--Effort to improve care of patients 1 Based on Process of care recommendations (within control of HCP) or outcomes Should be complementary to Stewardship Unintended consequences Effects reimbursement Stewardship Strategies Avoid Antimicrobials if not warranted Appropriate agent (based on susceptibility) Stop in not warranted Stop MRSA therapy if no MRSA Avoid discordant therapy De-escalation Switch to oral Reduce Duration Dose Optimization ID consult 1. File TM Jr. et al. Clin Infect Dis. 2011; 53: S15-S22 2. File TM Jr, Gross PA. Clin Infect Dis. 2007;44: ;

8 Link Between Evidence-based Guidelines, Core Measures, & Outcomes CORE MEASURES & GUIDELINES Reduce variance Improve care Actual Practice GAP Individual factors justify variance of care Ideal Practice

9 Reasons to Target Antimicrobials Increased rates of bacterial resistance result in part from antimicrobial drug use 50% antimicrobial use is inappropriate Improvements in antimicrobial use have been shown to improve patient outcomes and reduce rates of resistance Pt with resistant infection is 15% more likely to die Stimulus for Antimicrobial Stewardship The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms (such as Clostridium difficile), and the emergence of resistance..effective antimicrobial stewardship programs can be financially self-supporting and improve patient care.. Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship: Dellit T et al. Clin Infect Dis. 2007;44:159-77

10 Appropriate antimicrobial usage: For optimal outcomes and reduce resistance Antimicrobial Avoidance when not indicated 3 Ds Right DRUG Guidelines Local resistance patterns Patient risk stratification Right DOSE Pharmacokinetics/Pharmacodynamics (PK/PD) Right DURATION Compliance

11 Who of the following patients are likely to warrant antibacterial therapy? year old afebrile, non-smoking male with mild nasal congestion and non-productive cough for three days year old afebrile college student with nonexudative acute sore throat year old afebrile female with signs of acute sinusitis of three days duration year old smoking male with diabetes and acute fever cough and localised rhonchi 5. All of the above

12 1 MacKay DN. J Gen Inter Med. 1996;11: Bent S, et al. Am J Med. 1999;107: Smith et al. Cochrane Systematic Review 2012 Antibiotics and Acute Bronchitis 9 studies reviewed (placebo versus ATMB) 1 Antibiotics had no benefit Albuterol better than antibiotics (2 studies) Treating a condition that is largely viral in origin with antibiotics promotes resistance Meta-analysis, 8 studies 2 Small benefit (? clinically significant) As the benefit must be weighed against the risk of side effects and the societal cost of increasing antibiotic resistance, we believe that the use of antibiotics is not justified in these patients Cochrane systematic review (2012) 3 the current update provides clearer evidence on the lack of effectiveness of antibiotics for acute bronchitis.

13 Acute Bronchitis Clinical Cough (50% scant sputum; often green or yellow); occasional wheezing, chest wall discomfort; assoc with common cold Procalcitonin-low if viral Etiology 90% viral; 10%-Mycoplasma, Chlamydophila; B. pertussis CXR-negative Therapy No antimicrobials for viral Antimicrobial only if bacterial (Pertussis > 3 wks cough; treatment to reduce transmission, not for acute resolution) Symptomatic NSAIDS, Aspirin, Ipratroprium (Atrovent ) Delayed prescription File TM Jr. Up-To-Date 2012

14 Procalcitonin for Antimicrobial Stewardship for RTIs PCT < 0.1 ug/ml Bacterial Infection VERY UNLIKELY NO ANTIMICROBIALS Consider repeat 6-24hrs based on clinical status PCT ug/ml Bacterial infection UNLIKELY NO ANTIMICROBIALS Use of ABX based on clinical status ( unstable ) & judgment PCT > ug/ml Bacterial infection LIKELY YES ANTIMICROBIALS Repeat PCT day 3, 5, 7 (for Duration) PCT > 0.5 ug/ml Bacterial infection VERY LIKELY YES ANTIMICROBIALS CONSIDER STOP ABX when 80=90% decrease; if PCT remains high consdier treatment failure File TM Jr. Clin Cherst Med. 2011; modified from Schuetz P. et al. Eur Respir J 2011;37(2):

15 NQF PERFORMANCE MEASURE: ACUTE BRONCHITIS NQF=National Quality Forum

16 Acute respiratory infection Case: 40-year-old male with non-productive cough x 4 days; non-smoker; no comorbidity Exam: Afebrile; P-72; R-20; lungs no localized findings Survey of PCPs: No Yes Should antibiotics be used? 90% 10% Would antibiotics be used? 12% 88%

17 Antimicrobials for Colds Why? Patient pressures Patient satisfaction correlates with quality of patient-doctor intervention, not prescription 1 Prevent bacterial superinfection Several controlled studies showed no benefit for URI/colds 2 1 Hamm RM, et al. J Fam Pract. 1996;43: Rosenstein N, et al. Pediatrics. 1998;101:

18 Overuse of antibiotics Receiving an antibiotic reinforces the patients belief that antibiotics are warranted when a similar situation arises Patients may continue to consult for acute RTIs and expect antibiotics to be prescribed Doctors may also prescribe antibiotics rather than educate patients Most patients and many doctors view unnecessary antibiotic prescribing as a neutral intervention that is, one that cannot harm but may help File T. Curr Opin Infect Dis. 2002;15:149 50

19 Reduce use by reducing demand Primary care: acute bronchitis (> 200 patients) Antibiotics used by: Prescription alone (no leaflet) 62% (P = 0.04) Prescription plus explanatory leaflet 47% Macfarlane et al. BMJ 2002; 324:1 6 Primary care: acute bronchitis (> 2,000 patients) Decline in antibiotic use associated with education of patient and prescriber (74% to 48%, P = 0.003) Gonzales et al. JAMA 1999; 281:

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21 Restricting antibiotics reduces resistance Finland reduced erythromycin use led to reduced Streptococcus pyogenes resistance 1 Iceland reduced antibiotic use led to reduced penicillin-nonsusceptible S. pneumoniae 2 Alaska reduced antibiotic use led to reduced penicillin-resistant S. pneumoniae 3 1 Seppala et al. N Engl J Med. 1997; 337: Arason et al. BMJ 1996; 313: Petersen et al. 37th IDSA Meeting 1999 [Abstract 62]

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24 Hospital Antimicrobial Stewardship: Definition An ongoing effort to optimize antimicrobial use in order to improve patient outcomes, ensure costeffective therapy, and reduce adverse sequelae of antimicrobial use (including antimicrobial resistance) Dellit T, et al. Clin Infect Dis. 2007;44:

25 Common interventions in pilot programs at SUMMA Avoid Antimicrobials if not warranted Appropriate agent (based on susceptibility) Avoid discordant therapy Dose Optimization Based on renal function, weight, MIC De-escalation Stop if no antimicrobial warranted Stop MRSA therapy if no MRSA Reduce duration Switch to oral

26 What is appropriate therapy for a 55 year old asymptomatic diabetic female with >10 5 E. coli in urine culture? a. Trimethoprim/Sulfamethoxazole (e.g. Septra, Bactrim) three DS tablets as a single dose b. Ciprofloxacin (Cipro) 250 mg po b.i.d. for 6 doses c. Nitrofurantoin (e.g. Macrobid) 100 mg po b.i.d. for three days d. None of the above; no therapy is required

27 ASYMPTOMATIC BACTERIURIA SCREENING AND TREATMENT NOT INDICATED Premenopausal, Nonpregnant or Diabetic Women 1 Older persons whether living in Nursing Homes or in the community 2 Spinal cord Injury 2 Catheterized patients 2 1 ACOG Bulletin #91. Obstet Gynecol 2008;111:785 2 Nicolle et al. IDSA Guidelines. Clin Infect Dis 2005;40:

28 ASYMPTOMATIC BACTERIURIA DEFINITION Single Catheter Specimen with > 10 5 Bacteria Women: 2 CCU Specimens with same Bacteria (> 10 5 ) Men: Single CCU specimen with > 10 5 Bacteria SCREENING AND TREATMENT INDICATED Urologic Surgery (Including TURP) Pregnancy Nicolle et al. IDSA Guidelines. Clin Infect Dis 2005;40:643-50

29 Prevalence of Asymptomatic Bacteriuria Population Prevalence Healthy premenopausal women 1-5% Pregnant women 2-10% Postmenopausal women (50-70) 3-9% Diabetic women/men 9-27/4-19% Elderly (>70) in community: W/M 25-50/15-40% Spinal cord injuries 23-90% Indwelling catheters short term 9-23% Long term 100% Nicolle L et al. Clin Infect Dis 2005; 40: (IDSA Guidelines for asymptomatic bacteriuria in adults)

30 ASYMPTOMATIC BACTERIURIA Cai T et al. Clin Infect Dis 2012; early access July in Young Women RCT of 673 young women (18-40) No therapy vs antimicrobial (based on culture) RESULT: Recurrence: No therapy 13% vs Therapy 47% (p< 0.001) CONCLUSION: No benefit to treat. AB should not be treated in young women and it may play a protective role in preventing symptomatic recurrence

31 82 y/o female transferred from LTCF with chest pain; has acute MI. Has foley catheter. Afebrile; + pyuria; Culture: 10 5 Klebsiella pneumoniae Course of action? A. Start antimicrobial B. Await susceptibility test and chose most cost effective agent for therapy C. No antimicrobial therapy warranted D. Methenamine

32 UTI in LTCF CULTURE SHOULD NOT BE PERFORMED FOR ASYMPTOMATIC RESIDENTS!!!!![A-I] % or residents have >10 5 cfu/ml Prospective studies have shown no benefit to treat In catheterized patients, reserve U/A and culture for those with symptoms [A-II] 1 Pyuria or positive dipstick for leukocyte esterase not helpful unless negative Methenamine not recommended in patients with longterm catheterization 2 1. High K. et al. Clin Infect dis. 2009; 48: ; can access via 2. Hooton et al. Clin Infect Dis. 2010

33 82 y/o female transferred from LTCF with fever, decrease mental status; WBC-15,000. Exam unremarkable. Has long-term foley catheter: + pyuria; Treated initially with ciprofloxacin. Day #3 lab reports culture with > 100,000 E. coli resistant to ciprofloxacin but susceptible to all other agents tested. What is the appropriate choice now? Stop ciprofloxacin and start: A. Cefepime B. Ampicillin C. Piperacillin/tazobactam D. Imipenem

34 De-escalation Susceptibility results used to more specifically target microbiological results; narrowing the antibiotic spectrum by changing from a broad spectrum agent to a narrow spectrum agent or by eliminating a drug from combination therapy. Should ideally occur as soon as possible, but within 48 hours of the availability of culture results. Benefits include reduced bacterial resistance, decreased incidence of bacterial, viral, and fungal superinfections, limited exposure to unnecessary drug therapy and the associated risks decreased costs.

35 Case Study: Nososcomial Pneumonia CXR courtesy of T File 52 y/o male in ICU; 5 days post abdominal surgery Develops fever, pulmonary infiltrates, purulent sputum, leukocytosis Principles: Nosocomial Pneumonia* Recognise variability in bacteriology from hospital to hospital, and customise therapy to local data Avoid untreated or inadequately treated patients by using prompt and appropriate therapy Avoid the overuse of antibiotics: accurate diagnosis, tailor therapy to culture data, shorten duration of therapy as much as possible (7-8 days unless Pseudomonas) De-escalation * ATS/IDSA Guidelines Am J Resp Crit Care Med. 2005

36 VAP: Empiric Treatment Patient at Risk for MDR* Potential Pathogens Combination Therapy Core pathogens + Antipseudomonal cephalosporin (cefepime, ceftazidime) MDR pathogens or P. aeruginosa Antipseudomonal carbapenem (imipenem, meropenem) ESBL or Acinetobacter spp Piperacillin-tazobactam MRSA PLUS Antipseudomonal fluoroquinolone Legionella (levofloxacin, ciprofloxacin) or aminoglycoside PLUS linezolid or vancomycin (if MRSA risk) *Multidrug Resistance; Adapt to local patterns of resistance. American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171:

37 Case Study: Patient Initially Treated with Cefepime and Vancomycin. Day #3 Patient Improved and ETA culture reveals Klebsiella sp. (pan susceptible). What therapy? 1. Continue present therapy 2. Continue cefepime; stop vancomycin 3. Continue cefepime; add gentamicin 4. De-escalate to cefazolin or ceftriaxone ETA: endotracheal aspirate.

38 Strategy for Optimization: De-escalation De-escalation in ICU 1 20 ICUs; 398 pts with VAP (MRSA, Pseudomonas most frequent pathogens) Mortality No De-escalation (62%): 24% Escalation 43% DE-ESCALATION 17% (P=0.001) De-escalation for VAP in Surgical ICU 2 Retrospective evaluation 138 of 1596 patients (8.7%) developed VAP Mortality De-escalation: 35.1; No de-escalation: 42.1% (P=0.324) IMPORTANCE OF CULTURE 1. Kollef MH et al. Chest. 2006;129: Eachempati SR et al. J Trauma. 2009;66:

39 VAP: Case Study, Senerio 2 CXR Courtesy of T File 72 y/o male in ICU on ventilator; New Fever, Purulent ET secretions, Leukocytosis Endotracheal aspirate culture reveals: MRSA (vancomycin MIC 1.5 μg/ml by E-test) and Acinetobacter: Gentamicin-R; Amikacin-R; Cipro-R; Cefepime-R; Amp/Sulb- R;Pip/tazob-R Ertapenem-R; Meropenem-R; Doripenem-R

40 Resistant Gram Negative Infections: Treatment Options Optimize PK/PD Extended infusion; Continuous Infusion; Higher doses for Beta-lactams (e.g., Cefepime, Amp/sulb) 1-3 Use of old drugs: colistin IV New drugs: (tigecycline; doripenem) Combination therapy Variable combinations (colistin, carbapenems, tigecycline, rifampin.) Aerosolized drugs (aminoglycosides, colistin) 4 1.Lodise TP Jr et al. Clin Infect Dis. 2007;44: Chastre J et al. Crit Care Med. 2008;36: ; 4 Betrosian AP et al. Scand J Infect Dis. 2007;39(1):38-43 ; 4 Palmer L. Curr Opin Crit Care 2009

41 Concentration (mg/l) Slide courtesy of D Nicolau Optimizing Beta-lactam Therapy: Maximizing Percent T>MIC Increased duration of infusion Prolonged infusion Same dose and dosing interval, ml, however, change duration of infusion (0.5 hr 3-4hr) MIC Time Since Start of Infusion (h)

42 Summa Health System Pharmacodynamic Dose Optimization for Pip/tazob Empiric Therapy CrCl > 40 ml/min Piperacillin/tazobactam 4.5 g IV over 3 hrs every 6 hrs CrCl ml/min Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) Piperacillin/tazobactam 2.25 g IV over 3 hrs every 6 hrs CRRT patients (ie. CVVHD) Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs MIC 32 MIC <16 MIC 8** MIC < 4** ** Only If no IV access for extended infusion CrCl > 40 ml/min Piperacillin/tazobactam 4.5 g IV over 3 hrs every 6 hrs CrCl ml/min Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) Piperacillin/tazobactam 2.25 g IV over 3 hrs every 6 hrs CRRT patients (ie. CVVHD) Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs CrCl > 20 ml/min Piperacillin/tazobactam g IV over 4 hrs every 8 hrs CrCl < 20 (inc. intermittent HD) Piperacillin/tazobactam g IV over 4 hrs every 12 hrs CRRT patients (i.e. CVVHD) Piperacillin/tazobactam g IV over 4 hrs every 8 hrs CrCl > 40 ml/min Piperacillin/tazobactam 4.5 g IV over 30 min every 6 hrs CrCl ml/min Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) Piperacillin/tazobactam 2.25 g IV over 30 min every 6 hrs CRRT patients (ie. CVVHD) Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs CrCl > 20 ml/min Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) Piperacillin/tazobactam 2.25 g IV over 30 min every 6 hrs CRRT patients (ie. CVVHD) Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs 8/2010 Ref: Shea KM, et al. Annals of Pharmacother 2009;43: Kim A, et al. Pharmacother 2007;27:

43 Case Study SENARIO 2a: Pt on Cefepime, Vancomycin, gentamicin. ETA culture reveals Heavy growth MSSA. You D/C cefepime and gentamicin. Choice of therapy for MSSA? 1. Vancomycin 15 mg/kg q 8-12 h 2. Vancomycin + rifampin 3. Linezolid 4. Nafcillin

44 Outcomes in MSSA Bacteremia Nafcillin vs Vancomycin Prospective Observational Study With 6 Months Follow-up Nafcillin (n=18) Vancomycin (n=70) Persistent >3 but 7 Days Persistent >7 Days Relapse Bacteriologic Failure Chang et al. Medicine (Baltimore). 2003;82:

45 Duration: 8 vs 15 days of ABX for VAP Prospective, R,D-B RCT in 51 French ICUs 401 pts diagnosed by quant culture results Results Mortality: 8 vs 15 no difference (18.8% vs 17.2%) Recurrent infections: No difference (28.9% vs 26.0%) Antibiotic-free days less with 8 d; Resistance LESS NO difference in # ventilator-days, Organ dysfunction Infection caused by non-fermenting GNR had higher pulminfection-recurrence Conclusion: Comparable clinical effectiveness against VAP was obtained. Reduction in days of antibiotics could help control costs and contain the emergence of resistance Chastre et al. JAMA Med 2003; 290:

46 2013 Measures and Timing: 20 Measures for FFY 2013 Experience of Care Measures Encompassing 8 Key Topics Communication with nurses Communication with doctors Responsiveness of staff Pain management Communication about meds Cleanliness and quietness of hospital environment Discharge information Overall rating of hospital Weighted 30% Weighted 70% 17 Clinical Process Measures Acute Myocardial Infection Heart Failure Pneumonia SCIP (SCIP 1,2,3 and 4 considered HAI) FFY, Federal Fiscal Year. Medicare Program; Hospital Inpatient Value-Based Purchasing Program. Available at: Accessed June 5, 2012.