Improving drug use to enhance infection prevention: antibiotic stewardship and beyond

1. Improving drug use to enhance infection prevention: antibiotic stewardship and beyond CDI Prevention Partnership Collaborative Audio Conference Call April 25, 2012 www.macoalition.org

2. Program Overview Conference call:  April 25th noon-1:30PM   • Overview of antibiotic stewardship and steps you can take in your facility • Appropriate use of PPIs in acute and long term care: who needs to be on them, who doesn’t? Morning workshop: April 30th 8AM-Noon Newton MA (repeated May 16 in Sturbridge) • Appropriate diagnosis and treatment of UTI in acute and long term care • Communication about antibiotic treatment inside and across facilities: working with with residents/ families, colleagues, and transferring facilities ALL programs grant CME / CEUs for physicians, nurses, pharmacists and long term care administrators

3. Today’s Agenda Shira Doron, MD Assistant Professor of Medicine Division of Geographic Medicine and Infectious Diseases Tufts Medical Center Erica Tenholder, PharmD, BCPS Clinical pharmacy specialist, antimicrobial stewardship, Baystate Medical Center David B. Goldwater R.Ph Clinical Consultant Pharmacist Partners Pharmacy Massachusetts Terrence A. O’Malley, MD, CMD Medical Director, Non-Acute Care Services Partners HealthCare System, Inc. Overview of antibiotic stewardship and the long term care opportunity Appropriate use of Proton pump inhibitors (PPIs) • In the acute care setting • PPI reduction strategies • PPIs across a transition of care

4. Upcoming Events April 30th or May 16 Morning Workshops register now! • April 30th 8AM-Noon, Newton MA • Repeated May 16 8AM-Noon, Sturbridge MA • Ask the expert • Focus on Diagnosis and Treating UTI • Communication strategies to promote appropriate medication use June 22nd C. Difficile PreventionPartnership Collaborative Learning and Sharing Workshop • Learn additional strategies for C. diff prevention from local and national experts, and your Massachusetts colleagues Contact Fiona Roberts froberts@macoalition.org

5. Continuing Education Disclosures • The speakers on today’s call have no financial interests or relationships to disclose.

6. Overview of antibiotic stewardship and the long term care opportunity Shira Doron, MD Assistant Professor of Medicine Division of Geographic Medicine and Infectious Diseases Tufts Medical Center Boston, MA

7. Antibiotics in Long Term Care:why do we care? • Antibiotics are among the most commonly prescribed classes of medications in long-term care facilities • Up to 70% of residents in long-term care facilities per year receive an antibiotic • It is estimated that between $38 million and $137 million are spent each year on antibiotics for long-term care residents

8. The importance of prudent use of antibiotics

9. Bad Bugs No Drugs

10. The drug development pipeline for antibacterials

11. The burden of infection in long term care • 12 studies in North America: • 1.8-13.5 infections per 1000 resident-care days • Rate of death from infection 0.04-0.71 per 1000 resident-care days Strausbaugh et al. Infection Control and Hospital Epidemiology 2000, 21(10), p. 674-679

13. The burden of resistance in long term care • Rogers et al: • Over 3000 LTCFs • One year (2003) • Incidence of new infection caused by an antibiotic-resistant organism was 12.7 per 1000 patients Rogers et al. Journal of Infection Control 2008, Volume 36, Issue 7, Pages 472-475

16. Antimicrobial Therapy Unnecessary Antibiotics, adverse patient outcomes and increased cost Appropriate initial antibiotic while improving patient outcomes and healthcare A Balancing Act

17. Why focus on long term care? • Many long-term care residents are colonized with bacteria that live in an on the patient without causing harm • Protocols are not readily available or consistently used to distinguish between colonization and true infection • So, patients are regularly treated for infection when they have none • 30-50% of elderly long-term care residents have a positive urine culture in the absence of infection

18. Why focus on long term care? • When patients are transferred from acute to long-term care, potential for miscommunication can lead to inappropriate antibiotic use • Elderly or debilitated long-term care residents are at particularly high risk for complications due to the adverse effects of antibiotics, including Clostridium difficile infection

19. Common long-term care scenarios in which antibiotics are not needed • Positive urine culture in the absence of symptoms (cloudy or smelly urine should not be considered symptoms) • Upper respiratory infection (common cold with or without fever, bronchitis, sinusitis not meeting clinical criteria for antibiotics) • Abnormal chest x-ray without signs/symptoms of respiratory infection • Positive wound culture in the absence of cellulitis, abscess or necrosis • Diarrhea in the absence of positive C. diff toxin assay

20. Case 1 • The nurse notes that an 82-year-old long-term care resident has cloudy urine • She sends a culture which grows >100,000 CFU of E. coli • The patient is started on ciprofloxacin and given a 2-week course • By the end of treatment the patient has diarrhea and C. diff toxin assay is positive

21. What could have been done differently? • Urine changes have many causes • In the absence of symptoms of UTI, no need to culture urine • A urinalysis should be sent with the urine culture • If the urinalysis doesn’t have white blood cells, there is no inflammation in the bladder and therefore NO UTI (regardless of symptoms) • Ciprofloxacin and the other quinolone antibiotics (levofloxacin, moxifloxacin) are known to promote the development of C. diff.

22. Colonized or Infected:What is the Difference? • People who carry bacteria without evidence of infection are colonized • If an infection develops, it is usually from bacteria that colonize patients • Bacteria that colonize patients can be transmitted from one patient to another by the hands of healthcare workers • There is no need to treat for colonization

23. Infected Colonized The Iceberg Effect

24. Clostridium difficile–Associated Disease (CDAD) • Most common cause of nosocomial infectious diarrhea in adults1 • Significant associated morbidity2 • Antibiotic use is strongly associated with CDAD1,3 • Highest association with clindamycin, penicillins, cephalosporins, quinolones4,5 • Judicious antibiotic use decreases incidence of CDAD3 1. Settle CD, et al. Aliment Pharmacol Ther. 1998;12:1217-1223. 2. Anand A, et al. Am J Gastroenterol. 1994;89:519-523. 3. Kelly CP, et al. Annu Rev Med. 1998;49:375-390 4. KellyCP, et al. Annu Rev Med. 1998;49:375-390. 5. McCusker ME, et al. Emerg Infect Dis. 2003;9:730-733..

25. Clostridium difficile: New Issues • INCREASING INCIDENCE • Estimated >400,000 hospital cases annually in US • EPIDEMIC STRAIN • A common resistant epidemic C. difficile strain called NAP-1 has been found in the US, Canada, and Europe. • MORE SEVERE • Higher mortality and higher rates of colectomy

26. C. Diff rates in the US Courtesy CDC

27. Pathogenesis of CDAD Antibiotic therapy Alteration of colonic microflora C. difficile exposure and colonization Release of toxin A and toxinB (and in some strains, binary toxin) Colonic mucosal injury and inflammation Reprinted from Kelly CP, et al. Annu Rev Med. 1998;49:375-390.

29. Case 2 • A 72 year old man is sent back to his long-term care facility after a brief stay at an acute care hospital • On transfer, he is on intravenous vancomycin for “bloodstream infection” • This is continued for 4 weeks, at which point the patient develops a brain bleed • When his labs are checked he is found to have severely low platelets, presumably a side effect of the vancomycin • The blood culture results had been incomplete at the acute care hospital at the time of transfer. As it turned out, when the organism was finally identified, it was one typically associated with blood culture contamination rather than infection, and the patient did not need any antibiotics.

30. What could have been done differently? • Improve communication and coordination • Acute care hospital could have communicated to long-term care facility the plan re duration of antibiotics and the pending lab result • A system could be in place for the hospital to follow up on the culture results of a longer in their care and communicate with the long term care facility.

31. Case 3 • A 49 year old long term care resident develops respiratory symptoms, and chest xray is consistent with pneumonia, so he is started on the broad-spectrum antibiotic piperacillin-tazobactam to cover resistant organisms • 2 days later the sputum culture grows Strep pneumoniae • No one narrows the antibiotic, and the patient gets better quickly, completing a 10-day course • One month later the patient develops urosepsis with Pseudomonas highly resistant to all antibiotics tested including piperacillin-tazobactam

32. What could have been done differently? • Use of a narrower agent rather than a broad-spectrum antibiotic • Shorter, appropriate course of treatment • Adjust antibiotic based on culture results

33. Long term facilities can* • Establish multidisciplinary teams to address antibiotic stewardship and optimal drug use • Have protocols that outline the appropriate circumstances for use of antibiotics • Review antibiotic culture data for trends suggesting a worsening resistance problem • Have protocols ensuring that cultures are checked and antibiotics adjusted according to culture results • Establish programs for periodic review of antibiotic utilization *Centers for Disease Control

34. Long term facility providers should* • Obtain cultures whenever available when starting antibiotics, and check results, adjusting antibiotics appropriately to the narrowest spectrum agent possible • Avoid the use of antibiotics for colonization or viral infections, and keep the duration as short as possible • Take care to effectively communicate with the transferring facility re pending lab results and plan for antibiotics and follow-up *Centers for Disease Control

35. Nurses Can • Be familiar with current protocols for testing and treatment of urinary tract infection • Educate families and residents that many respiratory infections are caused by viruses and do not require antibiotics • Identify advanced directives for limited treatment • Follow up with referring facility regarding pending lab results

36. Physicians / NPs can • Obtain cultures whenever available when starting antibiotics, and check results, adjusting antibiotics appropriately to the narrowest spectrum agent possible • Avoid the use of antibiotics for colonization or viral infections, and keep the duration as short as possible • Encourage use of screening tools and protocols to decrease the use of unnecessary antibiotics. • Educate fellow clinicians, staff and family members on appropriate use of antibiotics • Implement measures to reduce the need for treating with antibiotics (avoidance of indwelling urinary catheters, maximizing immunization levels, decubitus ulcers, etc. • Take care to effectively communicate with the transferring facility re pending lab results and plan for antibiotics and follow-up

37. Pharmacists can • Get more involved with infection control issues in each facility serviced, particularly antibiotic treatment of symptomatic versus asymptomatic UTIs. • Review antibiotic utilization and, where possible, appropriateness; identify opportunities for improved prescribing to discuss at quarterly QI meetings. • Educate physicians and nursing staff about targeted antibiotic use, using a narrow spectrum antibiotic based on culture results. • Prepare updated and easily accessible protocols for certain antibiotics; monitor vancomycin trough levels and focus on monitoring for appropriate vancomycin doses, dosing intervals and duration of therapy • Avoid simultaneous administration of “heavy metal” drugs (containing Fe, Ca, Zn, Mg, etc) with Quinolones. Either temporarily hold or administer these drugs AT LEAST Six (6) hours BEFORE or Two (2) hours AFTER the Quinolones.

38. What facilities can do together • Develop communication tools to share critical information between acute and long term facilities when patients are transferred • Culture results • Pending results • Treatments initiated (what, when, indication, stop date) • Precautions • Immunizations • History of C. difficile • Ensure contact information is provided for follow up on patient history and pending test results. • Establish cross-facility teams to address infection prevention and antibiotic stewardship.

39. Proton-pump inhibitors in the Acute Care Setting Erica Tenholder, PharmD, BCPS Clinical pharmacy specialist, antimicrobial stewardship Baystate Medical Center April, 2012

40. Objectives Summarize adverse effects associated with acid suppression medications Evaluate appropriate indications for the use of proton-pump inhibitors Discuss practical approaches to decrease unnecessary use

41. Adverse Effects: proton-pump inhibitors Increased risk • C. difficile-associated diarrhea • Health-care associated • Community acquired • Recurrence • Pneumonia Decreased absorption • Calcium • Osteoporosis • Magnesium • Annualized cost of the inpatient and outpatient costs of inappropriate stress ulcer prophylaxis estimated at $111,7911

42. How do PPIs increase risk? • Non-antibiotic disruption of normal flora • Mechanism not completely understood • ↓ gastric acidity • Allows survival of vegetative cells • Associated with colonization of upper GI tract – alters normal flora • Effects on host immune function • Effects on organism toxin production

43. Proton-pump inhibitors are associated with Community-Acquired CDI2 3-fold ↑ risk Hospital-Acquired CDI3 1.7-fold ↑ if taken daily 2.4-fold ↑ if taken > daily Recurrence of CDI4 1.7-fold ↑ after antibiotics 1.3-fold ↑ w/o antibiotics H2 receptor antagonists are associated with 2-fold ↑ risk of Community-Acquired CDI2 *Detailed slides with evidence and references at end of presentation Risk of C. difficile Infection (CDI)*

44. Increased risk of C. diff infection Antibiotic PPI Increased risk of colonization Antibiotic PPI H2RA New study assessing risk factors for C. difficile infection or colonization5

45. And if that doesn’t convince you…

46. Appropriate Indications in Acute Care • Patient has active GERD • Try to limit use to 4 weeks • H. pylori eradication • Recommended duration: 10-14 days • High dose NSAIDs • Stress Ulcer Prophylaxis • Mechanical Ventilation/ ICU • Coagulopathy • INR > 1.5 • Platelets < 50,000 • 2+ Risk Factors

47. Stress Ulcer Prophylaxis • Incidence of clinically significant gastrointestinal bleeding ranges <1% to 6% in ICU patients • Variability due to definition of clinical significance • Increased mortality • 57% in patients with endoscopic evidence of ulcers, bleeding, or both within 18 hours of ICU admission • 24% in patients with either a normal mucosa, only non-hemorrhagic erosions, or petechial changes • Conflicting data regarding superiority of PPIs • PPIs are at least as effective as H2RAs for SUP • H2RAs may cause development of tolerance within 5 days (some patients within 24 hours)

48. Risk Factors for Stress Ulcers • Risk factors independently predictive of clinically significant bleeding: • Mechanical ventilation >48 hours • Coagulopathy (plt <50,000 or INR >1.5) • Other risk factors • Sepsis • Renal Failure • Hepatic Failure • Hypotension • Trauma • Bleeding significantly lower with prophylaxis only if ≥ 2 RF • Major non-ICU risk of GI bleed is anticoagulation • Not affected by SUP • Severe Burns • Myocardial Infarction • Multiple Organ Failure • Ileus • High Dose Corticosteroids • Major Surgery

49. Discontinuation in acute care • Stop PPI or H2RA once extubated (or other indications have resolved) • Taper • duration > 28 days • present at admission

50. Steps taken at Baystate Multi-factorial approach • Didactic sessions to educate prescribers on the clinical indications • Internal medicine attending physicians, third year medical residents, first year medical interns, and fourth year medical students • Repeated quarterly • Pharmacy students are trained to intervene on PPI orders when rounding • Appropriate indications • Patient was taking PPI prior to admission • Validate GERD history • ID pharmacist reviews all patient profiles if positive C. difficile • Reviews indication for PPI • Contacts prescribers directly • A computerized alert was designed to fire a message to the prescriber to prevent discharge on a PPI for stress ulcer prophylaxis • Medication reconciliation is performed both at admission and discharge. • If a patient is being discharged on a PPI and was not on a PPI at admission, an automated message will alert the physician that the patient is newly on a PPI • This message also outlines the indications and adverse effects of PPIs • At that point, the prescriber may choose to continue with the order or cancel the PPI