Antimicrobial Stewardship The Adventure Continues… IM R-1 Orientation

1. Antimicrobial StewardshipThe Adventure Continues…IM R-1 Orientation Paul Pottinger, MD, FIDSA June 27, 2019 https://occam.uwmedicine.org or search “UW OCCAM” in app store

2. Abx in the Hospital • OBJECTIVE • Increase your confidence in Prescribing Antibiotics • Understand your role in Antimicrobial Stewardship • FORMAT • Case-based & interactive • CONTENT • Cases you will work up as an R-1 • SLIDES • Available on the web

3. A Question…. What’s the susceptibility rate for P.aeruginosa at UWMC (non-CF)

4. GET HELP if you are unsure what’s best… You are NOT alone!

5. Stewardship Resources • Stewardship Teams at UWMC & HMC • OCCAM (in your pocket, on your phone, online) • Service Pharmacists • ID Consult Service UW ID Fellows 2018-2019

6. Stewards at Your Service VA Kanishka Garvin MD & Jonathan Casavant PharmD UWMC Paul Pottinger MD & Rupali Jain PharmD HMC SCCA Catherine Liu MD & Ania Sweet PharmD Chloe Bryson-Cahn MD & Jeannie Chan PharmD

7. RESISTANCE is a problem here… YOUR problem (sorry)

8. https://occam.uwmedicine.org • or search “UW OCCAM” in app store

9. Got Sepsis? Type SOS!(Sepsis Order Set) Use Disease-Specific Abx PowerPlans

10. Be a Steward! Specify Antibiotic Indications!

12. Case • A 68 y/o woman with type-2 DM & HTN recently Rx’d for CAP with cefotaxime • Now admitted for major CVA • Febrile → Ceftazidime started • BCx & foley cath urine grew K.pneumoniae • Two days later: Fever persists, and she becomes less responsive…. Switch to Levo or Cipro Switch to Ceftriaxone Switch to Cefepime Switch to Meropenem Everything’s groovy, make no change Switch to Levo or Cipro Switch to Ceftriaxone Switch to Cefepime Switch to Meropenem Everything’s groovy, make no change

13. Emerging Resistance: ESBL • Extended Spectrum ß-Lactamases • Mutant TEM-1, SHV-1, CTX-M, or OXA ß-lactamase • Enzymes hydrolyze oxyimino-ß-lactams (includes 3rd Gen Cephalosporins) • Usually in Klebsiella spp. and E.coli • Consider in all nosocomial infections with these organisms • Risk Factor = Previous ß-lactam use • Overall prevalence may > 10%

14. ESBL • Worry if resistance “skips a generation” • Confirm with  3-fold decrease in MIC with ß–lacatmase inhibitor • Rx of choice: • Carbapenem • Variable success: • FQ • Aminoglycoside • TMP/SMX, Nitro, Fosfo

15. BROAD SPECTRUM abx will select resistant mutants

16. Catheter-Associated UTI: CAUTI Pathogenesis • Colonization (universal): Endogenous flora ascends peri-catheter space or lumen • Infection (rare): Systemic inflammatory response to adherent or invasive bugs Confirm Diagnosis • U/A and reflexive quantitative UCx

17. Diagnostic Options: UTI • Leukocyte esterase: • If >105 cfu/ml, then: • sensitivity 68-98% specificity 59-96% • Nitrite: • If >105 cfu/ml, then: • sensitivity 19-45% specificity 95-98% • False negatives common. • Enterobacteriaceae reduce nitrate to nitrite, but Pseudomonas, S. saprophyticus, & Enterococcus do not reduce nitrate. • False positive tests uncommon. + LE poorly predictive of real UTI in foley patients! Tom Hawn, MD-PhD

18. Diagnostic Options: UTI • Microscopic analysis • Pyuria: Majority of symptomatic UTIs have pyuria… but lower PPV among catheterized pts • Gram stain for bacteria: >1 organism per hpf on uncentrifuged urine is >105 on culture • Culture • Method: collect from sterilized tube port, not bag • Inoculate 1 to 10 l onto agar plate • Criteria for Enterobacteriaceae UTI if NO foley • Symptomatic women • 102: sensitivity 95%, specificity 85% for cystitis • Asymptomatic women • 105: used in high risk clinical settings & research + WBC poorly predictive in foley patients!

19. Diagnostic Options: UTI • Summary • Test judiciously! (Death, Taxes, and Foley Colonization) • If NOT immunosuppressed: Order “UA with reflexive culture.” • Immunosuppressed: Order both UA and UCx.

20. Treatment Options: CAUTI Empiric coverage depends on gram stain: GNR’s: Ceftazidime (vs. Meropenem if MDRO hx or heavy recent cephalosporin exposure) GPC’s: add Vancomycin (cover Staph) Total Length of Therapy: Usually 7 days; longer may be needed for pyelo Definitive Treatment: Focus spectrum based on C&S results…

21. CAUTI Other Management • Change or remove the catheter if UTI detected • Colonization virtually universal… No need for routine surveillance cultures! • Appreciate difference between asymptomatic bacteriuria and UTI!

22. CAUTI Prevention • Use foley only when necessary! • Aseptic insertion technique • Maintain securely, proper bag placement • Know who has a Foley • Condom caths when feasible • Pull them ASAP

23. TIME + TUBE = TROUBLE Disinvade your pt ASAP

25. Case • A 58 y/o man in MVC 9 days ago sustained CHI → remains comatose, intubated to protect airway. New onset fever, WBC, rising FiO2 requirements. • Unresponsive w/o sedation, on vent, febrile, HR 112, BP fine, POX 92% on 40% FiO2. B/L ronchi. • CXR: Working Diagnosis Ventilator-Associated Pneumonia B/L Infiltrates

26. Case: VAP • A 58 y/o man in MVC 9 days ago sustained CHI → remains comatose, intubated to protect airway. New onset fever, WBC, rising FiO2 requirements. • Unresponsive w/o sedation, on vent, febrile, HR 112, POX 92% on 40% FiO2. B/L ronchi. • CXR: B/L Infiltrates Meropenem + Gent + Linezolid Ceftazidime + Ertapenem + Cipro Pip/Tazo + Cipro + Tigecycline Cefepime + Gent + Daptomycin Cefepime + Vancomycin Meropenem + Gent + Linezolid Ceftazidime + Ertapenem + Cipro Pip/Tazo + Cipro + Tigecycline Cefepime + Gent + Daptomycin Cefepime + Vancomycin

27. ATS/IDSA Guidelines Case: VAP • MDR Pathogen Risks • Hospitalized ≥ 5 days • Abx in last 90 days • High ward MDR prevalence • SNF resident • Contact with MDR patient • Chronic Dialysis • Chronic Infusions • Immunosuppressed

28. ATS/IDSA Guidelines Case: VAP • Anti-Pseudomonal cephalosporin • (Ceftaz, Cefepime) or • Anti-Pseudomonal carbapenem • (Meropenem, Imipenem) or • -lactam with lactamase inhibitor • (Piperacillin/tazobactam) • + • Anti-Pseudomonal FQ • (Cipro, Levo) or • Aminoglycoside • (Gent, tobra) • + • Linezolid or Vancomycin OUR APPROACH: Second GNR Agent (cipro or tobra) NOT routinely recommended at HMC or UWMC • MDR Pathogen Risks • Hospitalized ≥ 5 days • Abx in last 90 days • High ward MDR prevalence • SNF resident • Contact with MDR patient • Chronic Dialysis • Chronic Infusions • Immunosuppressed • Pseudomonas aeruginosa • Burkholderia • Stenotrophomonas • Klebsiella • Citrobacter • Acinetobacter • MRSA

29. Case: VAP Zosyn: Too Much of a Good Thing? • Only Vanco used more often by IM. • Covers PsA, enterobacteriaciae, strep, anaerobes. • Concern: Heavy use → Resistance. • Solutions: • Seek Empiric Alternatives… Use OCCAM! • Establish a Diagnosis (BAL or “mini-BAL”) and de-escalate ASAP. • Prolonged Infusion +

30. VANCOMYCIN

31. Case: VAP MRSA VAP: Vancomycin Levels? Patient Outcomes Study Design • Methods - Retrospective analysis 1999-2005 - University Hospital (Washington U) - N =102 Adults - Nosocomial MRSA pneumonia - MRSA established by BAL - Monotherapy with vancomycin > 72 hrs • Measurements - Vancomycin trough levels - Clinical outcome From: Isakow W, et al. ICAAC 2006. DHS/PP

32. MRSA: Vancomycin MIC Creep? • Not all VSSA created alike. • Published reports of rising vanco MIC’s in last 5 years. • Presumed MOR: increased cell wall thickness. • Retrospective case series: higher MIC’s associated with higher liklihood of clinical failure on vanco. Soriano CID 2008

33. MRSA: Vancomycin MIC Creep? • MIC ≤ 2 still considered susceptible (VSSA)… Concern: clinical failures with vanco. • If pt fails to clear bacteremia or clinically improve after 7 days of therapy things may not be going well. • Consider switch to alternative agent if MIC = 2, and if pt is failing vanco.

34. MRSA: Vancomycin MIC Creep? What, pray tell, shall I use instead of “Vitamin V?” • “Consider” switch to alternative agent if MIC = 2, and if pt is failing vanco.

35. Abx Stewardship: Linezolid • “It’s An Anti-Depressant!” • Oxazolidinone, targets gram-positive ribosomes (no GNR coverage) • IV or PO • Bacteriostatic, but inhibits toxin production • Toxicities: Neuropathy, myelo-suppression, serotonin syndrome, cost

36. Round One: VAP Vancomycin vs. Linezolid Clinical Cure Study Design • Methods - Retrospective analysis of 2 prospective, randomized, case-control studies - N =1019 Adults - Nosocomial pneumonia - Suspected gram-positive pneumonia - 339 with documented S. aureus - 160 with documented MRSA • Regimens - Vancomycin + Aztreonam - Linezolid + Aztreonam P = 0.182 P = 0.009 From: Wunderink RG, et al. Chest 2003;124:1789-97. DHS/PP Wunderink et al. CHEST / 124 (5) 2003

37. Round Two: VAP Vancomycin vs. Linezolid Outcomes Study Design • Methods - Blinded, Randomized prospective non-inferiority trial of pneumonia - Nosocomial pneumonia - N =1225 Adults Randomized - 339 with documented MRSA - Well-matched… except 9% more ventilated pts in vanco arm • Regimens - Vancomycin 15mg/kg IV Q 12 H - Linezolid 600mg IV Q 12 H - Both arms treated 7-14 days P = 0.042 CI = 0.5-21.6 “Not significantly different” From: Chastre J et al, 2010 IDSA Conference and CID January 2012

39. Round Two: VAP Vancomycin vs. Linezolid • Jury Still Out.. At least for me • Trend to survival benefit with Linezolid in meta-analysis • Trend to better “clinical response” in large prospective trial sponsored by industry… no mortality difference • Adverse events comparable • Many intensivists now favor linezolid for MRSA VAP… at UW we start with vanco

40. For empiric MRSA VAP coverage… Linezolid Vancomycin Newer, Fancier, Pricier ≠ Better!

41. Case: VAP How Long to Treat? (Less is More) Study Design Results • Methods (N = 401) - Microbiologically-Proven VAP* - Received initial appropriate therapy - Randomized, double-blinded - Performed 1999-2002 • Regimens* - 8 days of therapy - 15 days of therapy * All patients had quantitative cultures from bronchoscopy From: Chastre J, et al. JAMA 2003;290:2588-98. DHS/PP

42. Prevention: VAP What Works? “VAP Bundle!” • Elevate head of bed to 30° • Sterile technique with hand hygiene & ETT suctioning. Oral care. • Daily sedation holiday… • Get the tube out ASAP!! • Small added benefit: Silver tube or continuous suction

44. Apparent Paradox

45. MAKE A DIAGNOSIS whenever you can… Be ready to react to results

46. START BROAD, BUT DE-ESCALATE ASAP (based on micro)

47. I WANT YOU… To keep MDR bugs under control! P2

48. Prevent Infection • “Clean Your *&^%@! Hands” • Hand Hygiene Remains Cornerstone of IC • Biggest Cost:Benefit Ratio Around • Patients Will Thank (or Chastise) You! • Obey Precaution Placards Ignac Philipp Semmelweis (1818-65)

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