Antibiotics the root cause for resistance Darwinism Alexander Flemming Louis Weinstein Native American wisdom

2. Antibiotics = the root cause for resistance Darwinism Alexander Flemming Louis Weinstein Native American wisdom

3. Goal of Antibiotic Stewardship Attack the root cause by fine tuning antibiotic use Condense clinical infectious disease, ad absurdum Create mini-ID specialists, by recipe Practicality?

4. Agenda Basics (theory) Specifics (practice) Physician/administration approval Physician response Measurement/reporting Cost implications BREAK Clinical vignettes Summary/Implementation Questions/Discussion

5. What is Antibiotic Stewardship? A program that encourages judicious (vs injudicious) use of antibiotics.

6. Antibiotics are relatively so effective, non-toxic and inexpensive�so easy to use�that they are prone to misuse When the diagnosis is uncertain, antibiotics are often prescribed, viewed as a medical necessity (drugs of fear�); but they�re not benign� We need a paradigm shift

7. Man has an inborn craving for medicine�the desire to take medicine is one feature which distinguishes man, the animal, from his fellow creatures. Sir William Osler: Teaching and Thinking, in Aequanimitas

8. Risk Perception and Inappropriate Antimicrobial Use: Yes, It can Hurt Powers. Clin Infect Dis 2009;48:1350-3

9. Emergency Department Visits for Adverse Drug Reactions Fix with CID articleFix with CID article

10. Stewardship strives to fine tune antibiotic Rx in regards to Efficacy/Toxicity Resistance-induction/C. difficile Cost Appropriate discontinuation

11. What are its Limitations? It�s difficult� dangerous� outrageous� to practice clinical infectious diseases with limited information Select cases very carefully Primum non nocere Practicality?

12. Does it work?

13. Outcomes of the University of Pennsylvania Hospital�s Antibiotic Stewardship Program 772 bed tertiary care medical center compared 96 patients cared for by the ASP vs 96 patients taken care of by ID fellows772 bed tertiary care medical center compared 96 patients cared for by the ASP vs 96 patients taken care of by ID fellows

14. MRSA and C. difficille Rates After Implementation of an Antibiotic Stewardship Program UK study of 6129 elderly ICU patients. UK study of 6129 elderly ICU patients.

15. Effect of an Antibiotic Stewardship Program on the Rate of Resistant Enterobacter Infections Carney Hospital (Boston University and Tufts school of medicine). VRE rates decreased to 6% despite increased patient acuity (decrease = 0.001 compared with NNIS averages).Carney Hospital (Boston University and Tufts school of medicine). VRE rates decreased to 6% despite increased patient acuity (decrease = 0.001 compared with NNIS averages).

16. Recommended by Collaborative Drs. Perl, Bratzler, CW IDSA Dellit et al. Clin Infect Dis 2007; 44: 159-77 CDC Tattevin et al. Emerg Infect Dis 2009; 15: 953-5 Practiced regularly

17. How does it work? A pharmacist, par excellence, or someone else� reviews patients on antibiotics and makes recommendations, prn; overseen by a PHYSICIAN CHAMPION, an ID-trained physician, when available� Training� Contact the prescribing physician Telephone call� Announce; non-threatening�; don�t interrupt (leave message) Chart notation� Rx change implemented Physician Pharmacist, verbal order

18. Common Interventions Allergies, interactions Dosing IV-to-po switch Redundancy Cost Empiric Rx, then Streamlining, (de-escalation) When not to use antibiotics in the first place Discontinuation

19. Common InterventionsSome are so evident that they should be/are automatic Allergy, e.g. PCN; PCN-cephalosporin cross-reactivity Drug-drug interactions, e.g. Vanco-gentamicin synergistic toxicity Rifampin�s effect on hepatic drug metabolism Coumadin Address toxicities, e.g. Renal Aminoglycosides Hepatic

20. Dosing Cefazolin: q8h Ceftriaxone: q24h Aminoglycosides: q24h Levels Aminoglycosides Vancomycin

21. Vancomycin Dosing MRSA epidemic MIC creep Dosing reviewed Traditional: 1gm q12 h New recommendation: 15mg/kg q12 h (ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416) Nomogram for renal impairment

23. IV-to-po Switch Criteria Afebrile, WBC normalized Maybe the patient doesn�t need any further antibiotics in the first place� Intact GI tract, i.e. no N/V/D Oral bioavailability, e.g. quinolones Patient can often go home, on po AB, without further in-hospital observation* *Ramirez et al. Arch Intern Med 2001; 161:848�50 270 cap article270 cap article

24. IV removal = #1 defense vs BSI Requirement for hospitalization �intensity of care� criterion Leave in place �just in case�� �what if�?�

25. Antibiotic Redundancy vs Anaerobes: PCN/pcn-ase inhibitor (e.g. Zosyn, Unasyn) or carbapenem (e.g. Primaxin) +Flagyl vs C. diff: po Flagyl + po vanco Etc.

26. Promoting use of less costly alternatives:Cascade reporting

27. Cost Issues:Therapeutic Substitutions When the efficacy and safety profiles are [almost] identical, use the less expensive alternative Quinolones Cephalosporins Cabapenems Echinocandins

29. Empiric broad-spectrum antibiotic Rx,then streamline Empiric, i.e before the diagnosis is determined Must acknowledge the MDRO epidemic vs gpc, gnr, anaerobes, fungi Then, streamline (a.k.a. de-escalate) based on C&S

30. When to Not Use in the First Place or When to Discontinue Antibiotics Altogether? Asymptomatic UTI Viral URI Exacerbation of COPD? CHF, misdiagnosed as pneumonia CoNS bacteremia, when contamination more likely than true infection Duration?: criteria to d/c

31. Asymptomatic UTINicolle et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54 Definition: pyuria/bacteriuria, without Sx, with normal temperature and WBC Common

32. Asymptomatic UTI

33. Asymptomatic UTI Make one slide to show outcomesMake one slide to show outcomes

35. Practitioners do not feel comfortable ignoring bacteriuria once they are aware of its presence. Encourage physicians not to screen for asymptomatic bacteriuria U.S. Preventive Services Task Force. Screening for asymptomatic bacteriuria in adults: U.S. Preventive Services reaffirmation recommendation statement. Ann Intern Med 2008;149:43-7

36. Increase adherence to non-treatment guidelines Gross, Patel. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria. Clin Infect Dis 2007;45:1335-7

37. Asymtomatic UTI:Is it applicable to catheter- associated bacteriuria? Yes� Cope et al. Inappropriate Treatment of Catheter-Associated Asymtomatic Bacteriuria in a Tertiary Care Hospital. Clin Infect Dis. 2009;48:1182-88 Kunin. Editorial Commentary: Catheter-Associated UTIs: A Syllogism Compounded by a Questionable Dichotomy. Ibid: 1189-90

38. Viral URI Review of Acute Rhinosinusitis. JAMA. 2009;301(17):1798-1807 How do you know it�s viral and not bacterial? Physical exam: non-specific Temperature `` WBC `` Prevailing attitude of physicians and patients: Take an antibiotic, just in case� what if� Changing paradigm, because of MDROs Side effects C. diff Other Recommendation: Withhold AB for the first 10 days�

39. Antibiotics for Treatment of Acute Maxillary Sinusitis

40. Cdc rx

41. Cdc return to school letter Make Order form slideMake Order form slide

42. Materials order form http://www.cid.gov/ncidod/dbmd/antibiotic resistance/educatio.htm

43. Exacerbation of COPD?Van Der Valk et al. Clin Inf Dis 2004;39: 980-6 How do you know if it�s bacterial? Tough question, not adequately answered in the literature Antibiotics not unreasonable. 5 days should suffice� W will add criteriaW will add criteria

44. CHF, misdiagnosed as pneumonia How do you distinguish one from the other? H&P, temperature, WBC, CXR, BNP, BioZ, cultures (sputum and blood), pneumococcal urine antigen� The patient could have both�

45. Community-Acquired Pneumonia: When to Begin Antibiotics? The 2-4-6-8 hour rules IDSA/ATS Guidelines for CAP in Adults. Clin Infect Dis 2007; 44: S27-72. CMS Specifications Manual For National Inpatient Quality Measures

46. Timing of antibiotics for CAP:Controversy Earlier better than later Intuitive Data Embraced by CMS IDSA/ATS response Rebuts the data Points out the negative consequences of injudicious antibiotics� Present state of affairs:

47. IDSA/ATS Guidelines � A problem of internal consistency is also present, because, in both studies [109, 264], patients who received antibiotics in the first 2 h after presentation actually did worse than those who received antibiotics 2�4 h after presentation�

48. For these and other reasons, the committee did not feel that a specific time window for delivery of the first antibiotic dose should be recommended. However, the committee does feel that therapy should be administered as soon as possible after the diagnosis is considered likely.

49. Conversely, a delay in antibiotic therapy has adverse consequences in many infections. For critically ill, hemodynamically unstable patients, early antibiotic therapy should be encouraged, although no prospective data support this recommendation.

50. Delay in beginning antibiotic treatment during the transition from the ED is not uncommon. Especially with the frequent use of once-daily antibiotics for CAP, timing and communication issues may result in patients not receiving antibiotics for 18 h after hospital admission. The committee felt that the best and most practical resolution to this issue was that the initial dose be given in the ED.

52. If antibiotics started, and patient doesn�t have pneumonia� discontinue them At once; If continued, 5 days should suffice Dunbar et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis 2003; 37:752�60. Etc.

53. VAP: Duration of Rx Shorter than longer� Chastre et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290:2588�98.

54. CoNS bacteremia How do you know if it�s real or contamination? Real Hospitalized, IV (phlebitis), fever, leukocytosis, multiple positive cultures Contamination Present on admission/no IV, no fever, no leukocytosis, few positive cultures/denominator

56. Additional recommendations SCIP C.difficile Pneumonia CAP HAP

57. Surgical Care Improvement Project (SCIP) Antibiotics for surgical prophylaxis (Bratzler et al. Clin Infect Dis. 2004 Jun 15;38(12):1706-15) Which agent? Function of most common pathogen(s) Staph. aureus First generation cephalosporin If PCN-allergic� If high prevalence of MRSA� Anaerobes Cefoxitin When to start? 1 hour pre-op� When to stop? 1 dose only� Within 24 hours

60. HAP

61. Duration: Criteria to d/c antibiotics By the numbers, e.g. 5, 7, 10, 14 days� no! Empiric discontinuation, once temperature and WBC have normalized Notable exceptions Endocarditis Osteomyelitis Community-acquired pneumonia: 5 days� Healthcare-acquired pneumonia: abbreviate� Uncomplicated UTI: 3 days Clin Infect Dis 1999;29:745�58 W will findW will find

63. Physician/administration approval and notification Medical Executive Committee Physician champion Physicians

64. Sample letter to physicians Dear Colleague, In an attempt to confront the MDRO (multi-drug resistant organism, e.g. MRSA) and C. difficile epidemics, our Hospital is initiating an Antibiotic Stewardship Program. Our goal is to promote judicious antibiotic use. Implementation will be through review of patients on antibiotics, then physician notification to consider Rx modifications. This has been approved by the Medical Executive Committee.

65. Physician Response Bell-shaped curve� Dr. D Dr. S Dr. C Dr. O Antibiotics viewed as �drugs of fear� Fear of omission Law suits� Fear of commission Law suits�

67. Outcomes: Measure Interventions # patients reviewed # interventions recommended Divided by # patients of reviewed = % # interventions accomplished Divided by # recommended = % Change to avoid allergic reaction: % Drug-drug interactions addressed: % Change to different antibiotic based on C&S: % Change dose: % IV-to-po switch: % Redundancy addressed: % Antibiotics discontinued altogether: %

68. Outcomes: Measure Interventions # patients reviewed ~ 500 # interventions recommended = 45 Divided by # patients of reviewed = 9% # interventions accomplished = 38 Divided by # recommended = 84% Change to avoid allergic reaction: 0% Drug-drug interactions addressed: 0% Change to different antibiotic based on C&S: 8% Change dose: 0% IV-to-po switch: 24% Redundancy addressed: 0% Antibiotics discontinued altogether: 68 %

69. Outcomes:Rates C. difficile MDRO MRSA VRE GNR ESBL CRE

70. Outcomes:Negative Consequences Keep a close eye out for any patient who suffers because of an antibiotic stewardship intervention, viz. relapse of infection from �antibiotic deficiency�

71. Reporting the Outcomes Hospital P&T Committee Infection Control Committee Medical Executive Committee MRSA Collaborative Federal Agencies JCAHO CMS Public relations Local newspaper

72. Cost Implications It�s the right thing to do, regardless of cost issues Antibiotic costs: savings predicted/proven Administration happy Personnel needs to be recognized/compensated Pharmacist ID or other MD oversight Self-perpetuating

73. Results of an Antibiotic Intervention Program in a University-Affiliated Teaching Hospital

74. 2008 Antibiotic Cost Per MonthMidwest Regional Medical Center Make 2007 bar for average monthly expenseMake 2007 bar for average monthly expense

75. BREAK

76. Vignettes Asymptomatic UTI Viral URI Exacerbation of COPD Pneumonia vs CHF Immunocompromised host with fever Antibiotic duration C. difficile SCIP

77. Asymtomatic UTI An 83 yo woman suffers from dementia and resides in a nursing home. The NH staff is concerned about her increased confusion and decides to send her to the local ER. VS: BP 140/90, P 90, RR 16, T 98.6. PE WNL except for mild confusion. No Foley. WBC 10.1. U/A 5-10 WBC/hpf. Dx: �UTI.� Rx Avelox. The following day her urine culture returns with E.coli, >100K. Avelox is continued x 1 wk. She becomes more confused. And she develops C.diff antibiotic-associated colitis�

78. Comments: On occasion, �sepsis� can present with normal or low temperature and WBC, and with confusion� However, she wasn�t septic based on the normal BP and P� An asymptomatic UTI does not need Rx. Avelox is not indicated for UTI. Quinolones can cause CNS problems� All antibiotics can cause C.diff AAC. The elderly and NH residents are predisposed

79. Antibiotic Stewardship:Asymptomatic bacteriuria This patient appears to have asymptomatic bacteriuria which does not merit antibiotic Rx. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults Clin Infect Dis 2005; 40: 643�54

80. Viral URI A 72 yo diabetic man developed nasal congestion and cough productive of purulent sputum. He went to his local ER where the evaluation was noteworthy for a temperature of 99.6, normal respirations, mild tenderness to palpation and percussion over his sinuses, clear lungs, a WBC of 7.8 with 6% eosinophils and CXR showing �chronic scarring.� His blood sugar was 311. He was admitted. After a sputum was obtained for C&S, he was started on Rocephin and Zithromax for �possible community-acquired pneumonia.� The sputum had >25 epithelial cells and was rejected. The symptoms persisted for another 3 days. Levaquin was added. He developed C.diff antibiotic-associated colitis, his fifth episode.

81. Comments: Great respect and extra attention must be given to immunocompromised hosts, e.g. diabetics. Yet even immunocompromised hosts can catch otherwise benign, self-limiting viral URIs for which antibiotics are not indicated. 99.6 isn�t fever� A reasonable clinical approach would be to d/c antibiotics and follow clinically, re-thinking their indication if the patient develops symptoms of a bacterial superinfection, e.g. fever.

82. Antibiotic Stewardship:Viral URI This patient appears to have a viral URI which does not merit antibiotic Rx Review of Acute Rhinosinusitis. JAMA. 2009;301(17)1798-1807

83. Exacerbation of COPD It�s February, and a 60 yo smoker with COPD developed worsening of his chronic cough and SOB. His sputum has become more copious, thicker, discolored and foul-smelling, and he has noted a fleck of blood. He has not had any chills or fever. On physical exam, he is receiving O2 through nasal prongs. His respiratory rate is 24/min and slightly labored. His temperature is 99.1, BP 95/70, pulse 120. His breath sounds are distant and there are scattered ronchi and wheezes. The WBC is 11.1. A CXR shows emphysema and a faint haze at the bases interpreted as �cannot rule out pneumonia.�

84. Although influenza and RSV has been reported in the community, rapid tests for influenza A&B and RSV are negative.There are many PMNs and mixed flora on the sputum gram stain. It ultimately grows H. influenza and the pneumococcus (PCN MIC 1.0). He is admitted to hospital and is treated with Cipro.

85. Comments: Since it�s respiratory virus season, this is a good bet. Rapid tests have variable sensitivity. Go with the epidemiology� Give an anti-influenza agent�, ASAP While the H.flu and pneumococcus could represent otherwise benign colonization, either could be playing a pathogenic role. And colonization is the first step to infection, so why wait? He�s too fragile to risk withholding antibiotics. Use a respiratory quinolone, i.e. not cipro-, but rather levo- or moxi- Make sure he has received influenza and pneumococcal vaccines

86. Antibiotic Stewardship:COPD exacerbation Recommendations: Tamiflu Change from Cipro to Levaquin

87. Pneumonia vs CHF A 90 yo with a h/o CHF has become more short of breath over the past few days. There have been no fevers or chills. On physical exam the temperature is 97, RR 24, BP 160/100 and pulse 80. Bibasilar rales are noted on auscultation. There�s a cardiac gallop. The CXR shows cardiomegaly and pulmonary congestion consistent with CHF, �cannot rule out early pneumonia.� The BNP is 1567. BioZ says CHF. He receives Lasix and improves. Rocephin and Zithromax were also started in the ER, for possible pneumonia.

88. Comments: CHF seems readily apparent. While pneumonia isn�t entirely impossible�and he could have both�the potential side-effect of antibiotics don�t seem worth the risk in this case. Blame the ER for having started them ER: Hospital�s front door, EMTALA Dx often uncertain ABs used liberally ABs can/should be d/c�d promptly, once ID unlikely

89. Antibiotic Stewardship: Pneumonia vs CHF Recommendation: CHF is apparent, and pneumonia seems unlikely, so consider d/c antibiotics.

90. Immunocompromised Patient with Fever A 45 yo woman has fever complicating her metastatic breast cancer and its chemotherapy. She presents with chills and shortness of breath. Her temperature is 105, RR 32, BP 90/70, pulse 130. Her lungs are clear. The WBC is 0.3. There are bilateral infiltrates on the CXR. She is started on Fortaz, Vancomycin, Zithromax, Diflucan and Zovirax.

91. Comments: Too complex to intervene.

92. Antibiotic Duration? A 92 yo nursing home resident (where C. diff has been epidemic) is transferred to the hospital for decreased mentation and poor intake. Her BMs are normal. On admission her temperature is 101 and the physical exam non-diagnostic. She has a 16K WBC and her creatinine is 3.1. There are 5-10 WBC in the U/A and the CXR reads �cannot R/O pneumonia.� She is treated empirically with Rocephin, Levaquin and vancomycin. Cultures of urine and blood remain negative. There is no diarrhea to suspect C. diff. A repeat CXR shows �no change.� She promptly defervesces and her WBC has normalized when repeated at 48 hours.

93. Comments: The diagnosis is uncertain: presumably infected�, but source (i.e. site and pathogen) not defined. Whether she improved from the empiric antibiotics or not is also uncertain. Pneumonia: the CXR often remains abnormal several weeks after the clinical syndrome has resolved Injudicious to continue ABs until CXR resolution She is at considerable risk for C. diff and other AB-associated problems. So: it wouldn�t be unreasonable to d/c antibiotics.

94. Antibiotic Stewardship:Antibiotic Duration Recommendation: Consider d/c�ing antibiotics, as the temperature and WBC have normalized.

95. C. difficile An 85 yo WF is admitted from the NH with C. difficile. Her temperature is 102 and her WBC is 65,000. She receives Vanco IV and po, Flagyl I V and po, Immodium, probiotics and Rocephin.

96. Comments: Refer to the C. diff guidelines Continue po Flagyl d/c other antibiotics d/c Immodium

97. SCIP An 85 yo WM is admitted to the hospital for a hip fracture. He undergoes ORIF and receives peri-operative antibiotics. These are continued indefinitely. His wound is clean and he has a normal temperature and WBC.

98. Comments: Refer to SCIP guidelines Recommend d/c antibiotics post-op

100. Antibiotic Stewardship:Summary/Implementation Decide if you want to do it. Decide who�s going to do it. **Must have a PHYSICIAN CHAMPION** Seek approval from the Medical Executive Committee. Decide upon form of communication: phone call vs notation in chart. Send an introductory/explanatory letter to the Medical Staff. Do it. Measure the results. Present and discuss results. Review and improve.

103. Questions/Discussion