Updates in Antimicrobial Stewardship

Transcription

1 Updates in Antimicrobial Stewardship Meghan Brett, MD Medical Director, Antimicrobial Stewardship Program UNMH Hospital Epidemiologist Assistant Professor, Infectious Diseases APIC NM Meeting

2 None Disclosures

3 Objectives Describe key/informative articles and topics regarding antimicrobial stewardship which also tie into infection control Discuss the implications of increasing antimicrobial resistance for antimicrobial stewardship and infection preventionists Learn about how infection preventionists and antimicrobial stewardship team members can support each other/combine forces

4 Highlights from 2017 Clostridium difficile Guidelines McDonald LC et al. CID

5 What s Different? Testing Recommendations Clinicians + Lab agree to not submit specimens for patients on laxatives AND only specimens with unexplained, new onset 3 unformed stools in 24 hours for CDI testing No Yes Stool toxin test as part of multiple step algorithm* (specific) NAAT alone OR Stool toxin test as part of multiple step algorithm* (sensitive) No repeat testing in 7d Note: Yield ~2% more cases NPV of NAAT or tiered algorithm > 99%) *GDH + toxin arbitrated by NAAT or NAAT + toxin

6 What s Different? Definitions & Associated Treatment Classification of C difficile infections Initial episode then recurrences Initial episode: severe, non-severe, vs. fulminant* infection First vs. second/subsequent recurrences Antibiotic recommendations for initial and recurrent episodes *Hypotension or shock, ileus, or megacolon

7 Treatment - It s Mostly Vanco Clinical Definition Initial, non-severe Initial, severe Initial, fulminant Rx Vanco 4x/d for 10d, OR FDX 2x/d for 10d Alt: metronidazole Vanco 4x/d for 10d, OR FDX 2x/d for 10d Vanco 4x/d (oral/ngt) plus Metro IV q8 hours If +ileus, consider rectal instillation Rec Strength/ Quality of Evidence Strong/High Strong/High Weak/High Strong/High Strong/High Strong/Mod Weak/Low Why? Additional RCTs suggest better cure rates with vanco >> metro and lower risk of C diff recurrence as well.

8 Treatment - It s Mostly Vanco Clinical Definition Rx Rec Strength/ Quality of Evidence Vanco 4x/d for 10d if metro for 1 st episode, OR Weak/Low First recurrence Second/subsequent recurrence Prolonged tapered/pulsed regimen with vanco if vanco for 1 st episode, OR FDX 2x/d for 10d if vanco for 1 st episode Prolonged tapered/pulsed regimen with vanco, OR Vanco x 10d then rifaxamin 3x/d for 20d, OR FDX 2x/d for 10d, OR Fecal microbiota transplantation* Weak/Low Weak/Mod Weak/Low Weak/Low Weak/Low Strong/Mod

9 ASP s Role in C difficile?

10 C diff and PPIs? Probiotics? Proton pump inhibitors (PPIs) Although linked, insufficient evidence for discontinuation Probiotics for 1 o prevention? Insufficient data (no recommendation)

11 For a patient with C diff still on ABX? No recommendations to extend length of C diff treatment OR empiric restarts of C diff therapy while on other ABX

12 Highlights from 2017 Clostridium difficile Guidelines Many other recommendations for infection control in these guidelines

13 Other Notable ASP Literature for IPs and Pharmacists

14 Shorter is More Common The Antibiotic Course has had its Day from BMJ July 2017 Stopping early does NOT increase resistance What increases/causes resistance? Inadequate dosing Monotherapy where multiple drugs are required Collateral selection Where did the idea of completing the full prescription for ABX come from?

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16 Few Controlled Trials What s Too Short of a Course? Fear of undertreatment persists

17 Take Away Points About Shorter Antimicrobial Courses Some infections require long treatment Endocarditis, osteomyelitis, TB However most common infections have limited data regarding outcomes for varying lengths of antibiotic courses

18 Antibiotic Selection and SSI Prevention Evaluation of patients undergoing surgery at 1 hospital THA, TKA, hysterectomy, colon surgery, and CABG 4 year period: 8385 pts with 9004 procedures 11% (922) reported PCN allergy 2.7% (241) had an SSI AOR of 1.51 for developing an SSI Why? Use of non-beta-lactam antibiotics such as vanco, clinda, gent, FQs and metro Vancomycin challenges with infusion preincision >90% of patients tested will not have a true allergy challenge is sorting this out in clinical practice Blumenthal KG et al. CID 2018.

19 Antibiotics Increase Risk of Sepsis? Risk of sepsis assessed within 90d of discharge after previous hospital stay From large national database, identified a hospitalized cohort (516 hospitals), 7 year period Exposure: antibiotics more strongly associated with clinically important microbiome disruption Assessed subsequent hospitalization for discharge diagnosis of severe sepsis or septic shock 0.17% patients developed sepsis Higher risk for pts whose index visit related to infection (0.3% vs. 0.13%) or CDI (1.0% vs. 0.16%) Greater risk for pts exposed to high-risk ABX during index visit Baggs J et al. CID Prescott HC et al. Am J Respir Crit Care Med 2015.

20 Antibiotic Risk for Microbiome Disruption High Risk Low Risk Control Exposures 3 rd /4 th generation cephalosporin 1 st /2 nd generation cephalosporins Aminoglycoside Fluoroquinolones Macrolide Penicillin Lincosamides Tetracycline IV vancomycin β-lactam/β-lactamase inhibitors Oral vancomycin Carbapenems Metronidazole Sulfa (No high risk ABX) (No high or low risk ABX) Baggs J et al. CID 2018.

21 Baggs J et al. CID 2018.

22 Why Does Gut Microbiome Disruption Change Sepsis Risk? Hypothesis 1: loss of colonization resistance against more virulent/pathogen microbes Hypothesis 2: impacting the immune-regulatory dampening functions of the gut microbiome Hypothesis 3: loss of gut mucosal barrier function (lose microbes reduce short chain fatty acids impact health of large intestinal enterocytes integrity impacted)

23 Antibiotic Exposure Matters Encourage Antimicrobial Stewardship to Save Patient s Microbiome!!!

24 Antibiotic Pressure and Generation of Antibiotic Resistance Jernberg C et al. Microbiology 2010

25 How Frequent Are Adverse Effects from Antibiotics? Retrospective cohort of ~1,500 adult inpatients Admitted to general medicine wards Single academic medical center Reviews for adverse drug event (ADE) 30d after at least 24 hours of any parenteral or oral ABX GI, derm, MSK, heme, hepatobiliary, renal, cardiac and neurologic 90d follow-up: C difficile or new MDR infection Findings 20% experienced at least 1 ADE Of these ~300 patients, 56 (20%) were not clinically indicated Every additional 10d of ABX had a 3% increased risk for ADE GI (42%), renal (24%), and hematologic (15%) were most common Notable differences for ADEs associated with specific ABX Tamma PD et al. JAMA Internal Medicine 2017.

26 Increased Risk of AKI with Pip/Tazo 3 studies to date: (Zosyn) + Vancomycin? Metanalysis: aor 3.11 for AKI with combo 1 Incidence with Vanco + Zosyn (21.4%) vs. with Vanco + cefepime (12.5%) 2 AKI incidence with Vanco + Zosyn (16.3%) vs. 8.1% with Vanco alone 3 1 Hammond DA, et al. Clin Infect Dis. 2017; 64: Rutter WC, et al. Antimicrob Agents Chemother. 2017; 61:e Burgess DL, et al. Pharmacother. 2014;34:

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28 Health Consequences of Microbiome Disruption Across a Lifetime Langdon A, Crook N, Dantas G. Genome Medicine 2016.

29 Vanco for VAPs Not Always Needed Assess likelihood that patients with negative MRSA nasal swabs develop subsequent MRSA infection Bacteremia, +sputum cx with signs/sx pneumonia, CSF or intraabdominal fluid, skin/bone/joints Secondary Goal: assess avoidable vancomycin days 6 ICUs in tertiary care hospital, ~1.5y period 11,441 patients with negative nasal swabs Low overall number of MRSA infections Subsequent MRSA infection 0.22% Rates of MRSA infection with and without MRSA nasal colonization were 27.4% vs. 22.7% Note: 31% of patients did not have nasal swabs upon admission NPV 99.4% Vancomycin use in patients with negative nasal swabs amounted to 7,364 vancomycin days Chotiprasitsakul D et al. ICHE 2018.

30 Cochrane Review of Procalcitonin for Acute Respiratory Tract Infections (ARIs) Procalcitonin Marker for bacterial infections FDA approved for sepsis but has utility for antibiotic deescalation (ARIs) Update from 2012 analysis 18 new trials with 32 trials overall Data pooled from 26 trials Mortality: 8.6% for PCT-guided participants vs. 10.0% in controls (AOR 0.83, 95% CI 0.70 to 0.99, P = 0.037) Treatment failure: not significantly lower (23.0% PCT vs. 24.9% controls, P =0.068) Antibiotic exposure: 2.4 day reduction (5.7 vs. 8.1 days) Length of stay or ICU stay: no impact Scheutz P et al. Cochrane 2017.

31 Antibiotic Are Needed Not only for treatment of common infections Pneumonia UTIs Gonorrhea But also to support other advances in healthcare Chemotherapy for cancer Increasing immunosuppression for autoimmune diseases Solid organ and stem cell transplantation Complex surgeries Patients on dialysis/end stage renal disease

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33 New Antibiotics Ceftazidime/avibactam (Avycaz) Ceftolozane/tazobactam (Zerbaxa) Meropenem/vaborbactam (Vabomere) Delafloxacin (Baxdela)

34 A Review of the Pipeline Sept drugs listed 38% would have activity against drug-resistant gramnegatives (ESKAPE) 25% might impact treatment of various carpabenemresistant organisms (CRE, CRPA or CRAB) Note: only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trials) will be approved for patients

35 Worldwide Antibiotic Consumption by Country Income Classification Klein EY et al. PNAS 2018.

36 Projected Total Antibiotic Consumption Klein EY et al. PNAS 2018.

37 Source: Dr. Brad Spellberg

38 A Few Words About Antibiotic Resistant Organisms

39 Links between ABX and IC IV ABX HC equipment HC environment

40 Antibiotic-Resistant Organisms Gram-Positives MRSA (Methicillin-resistant Staphylococcus aureus) VISA (Vancomycin-intermediate S.aureus) VRSA (Vancomycin-resistant S. aureus) VRE (Vancomycin-resistant enterococci) MRSP (Multidrug-resistant Streptococcus pneumoniae) Gram-Negatives MDROs (Multidrug-resistant organisms) AmpC-producing SPACE bacteria ESBL (extended spectrum betalactamase)-producing bacteria CRE (Carbapenem-resistant Enterobacteriaceae) MDR/XDR Pseudomonas aeruginosa or Acinetobacter baumanii

41 Antibiotic Susceptibility Report for CRE E. coli Antibiotic Name MIC (µg/ml) Interpretation Aztreonam > 16 Resistant Cefoxitin > 32 Resistant Ceftriaxone > 32 Resistant Ceftazidime > 16 Resistant Tobramycin > 8 Resistant Ciprofloxacin > 2 Resistant Ertapenem > 4 Resistant Imipenem > 8 Resistant Meropenem > 8 Resistant Pip/tazo > 64/4 Resistant SMX/TMP > 2/38 Resistant Ahmed-Bentley J, et al. Antimicrob Agents Chemother

42 CP CRE (KPC) 2001 Source: CDC

43 CP CRE (KPC) 2013 Source: CDC

44 No one is safe from CRE (KPC)

45 And NDMs are Closing in

46 Uncharacterized Transmission Events for CRE Denver, Janelle SJ et al. MMWR 2016.

47 MMWR 2018 (Vital Signs). Trends of CRE vs. ESBLs, US

48 Synergies of ASP pharmacists and IPs

49 Combating C. difficile Infections (CDI) Hospital-onset CDI (Community-onset healthcare facility associated [HCFA]) Sharing data about rates Joining forces Prioritizing hospital-level interventions Combined case reviews by pharmacists and infection preventionists to glean local factors

50 Antibiotic Resistant Organisms Sharing data regarding trends (IPs) or unusual clusters (pharmacists) Alerting each other to more highly drugresistant organisms Are prescribers using most appropriate antibiotics? (pharmacists) Are providers/nursing following infection control practice? (IPs) If carbapenem-resistant Enterobacteriaceae, reported the patient s case to NM DOH? (IPs)

51 Surgical Site Infections (SSIs) Antibiotic prophylaxis for surgical site infections Appropriate antibiotic use Limiting antibiotic overuse (stop at time of incision) Managing penicillin allergies Limiting high risk antibiotics Sharing data regarding surgical site infections and consider case reviews Developing a clinical pathway for management of specific surgical site infections (SSIs) and assess impact on outcomes

52 Summary Much opportunity exists for ASPs and IPs to work together Data sharing Case reviews Prioritized interventions for preventing healthcare associated infections and limiting antibiotic resistant infections among our patients

53 A Pitch for Antimicrobial Stewardship ECHO Clinic

54 Antimicrobial Stewardship ECHO ECHO is telementoring instead of telemedicine Improve networks of providers and provide real-time feedback/education Started in June 2017 Great collaboration between NM DOH and UNM SOM/COP and the entire ASP ECHO community Acute care hospitals in New Mexico (focus) Pharmacists and IP participation CPE and CME available Interested in joining?

55 QUESTIONS?

56 THANK YOU!