Antimicrobial Stewardship and PRIME

Steven Park, MD/PhD

Associate Professor of Clinical Medicine

Director, Antimicrobial Stewardship Program

Director, Fellowship Program

Division of Infectious Diseases

UCI Medical Center

Public Hospital Redesign and Incentives in Medi-Cal (PRIME)

• Part of the California Medicaid 2020 Waiver • Successor program to DSRIP • Incentive payments will be based on pre-defined

metrics reporting and performance improvement (total of ~55 metrics across 9 projects)

• Program duration is 5 years (January 1st, 2016 – December 31st, 2020)

• 5-year Project Plan was approved May 31st, 2016 • Antibiotic Stewardship Metric chosen for participation • Each stewardship metric worth 465,000 dollars

3.1.1 - Avoidance of Antibiotic Treatment in Adults with Acute Bronchitis

3.1.4 - Prophylactic antibiotics discontinued at time of surgical closure for all clean and clean-contaminated procedures (reporting but turns to performance July 2018)

3.1.5 - Reduction in Hospital Acquired Clostridium Difficile Infections (performance)

PRIME ANTIBIOTIC STEWARDSHIP METRICS

3.1.3 - National Healthcare Safety Network Antimicrobial Use Measure (reporting but turns to performance July 2018) • Anti-MRSA and anti-pseudomonal b-lactams • Pay for performance July 1, 2018

3.1.3 - National Healthcare Safety Network Antimicrobial Use Measure • Anti-MRSA drugs and anti-pseudomonal b-lactams • UCI rate was 0.25 days of therapy per patient day

How to meet? • Cellulitis • Healthcare associated pneumonia

Streptococci believed to be involved in 75-90% of cases based on serologic and immunofluorescence studies

Blood cultures are mainly streptococci Punch biopsies and needle aspirations however show mainly S.

aureus IDSA guidelines based on studies of empirical coverage of

cellulitis

Randomized, double blind, multi-center trial with 146 patients

½ got Keflex and placebo or Keflex and Bactrim Clinical cure in 82% of Keflex and 85% of Keflex/Bactrim No impact of MRSA colonization

Management of Skin/Soft Tissue Infection IDSA Practice Guidelines 2014

Skin and Soft Tissue Infections: Proposal

No vancomycin for cases of cellulitis given: • No purulent drainage • No evidence of abscess by exam • If unsure of exam, ask ED to do ultrasound • Remember do not use Zosyn since ceftriaxone is first

line for streptococcus

Healthcare Associated Pneumonia

Overly broad and HCAP removed from 2016 IDSA practice guidelines for HAP AND VAP

May be addressed in new CAP guidelines this summer

50 yo male with htn admitted 2 months ago for 2 days for rule out MI presents with pneumonia

85 yo female with dementia, PEG and tracheostomy, long time SNF resident, frequent admissions to UCI, on IV ceftriaxone 1 month ago for pyelonephritis admitted for pneumonia

Spectrum of HCAP

How do you predict who will have MDRO’s? DRIP score (Antibiotic use previous 60 days, long term

care facility, tube feeding, prior infection with MDRO within last year)

Has not been validated widely

Does MRSA colonization in the nares predict MRSA Pneumonia?

22 studies reviewed comprising 5163 patients For all pneumonias:

Positive predictive value: 44.8% Negative predictive value: 96.5%

For CAP and HCAP, negative predictive value: 98.1%

Healthcare Associated Pneumonia: Proposal for Vancomycin

All HCAP cases get sputum culture All HCAP cases get procalcitonin HCAP cases do not receive vancomycin unless there is

history of MRSA infection or culture (nares) in the past If nares comes back positive for MRSA (1-2 days) and

patient not responding to therapy, then consider adding vancomycin

If sputum comes back with MRSA and patient not responding to therapy, then consider adding vancomycin

ICU not included

What about Zosyn?

Healthcare Associated Pneumonia: The case against empiric Zosyn

If patient empirically started on Zosyn and patient responds, what do you discharge them on?

If patient empirically responds to ceftriaxone or levofloxacin, then can confidently discharge on oral antibiotics

True resistant gram negative pneumonia is still fairly uncommon even at our hospital (<5%)

Number needed to treat is then minimum of 20. Is it worth it?

HCAP: Zosyn use

Will have to be decided case by case by physician If started, de-escalate once sputum cultures back Do you always have to be right initially? Can you safely escalate?

Empiric Antibiotic Choice: Do you have to always be right at the beginning? There is time to broaden

Growing data in non-ICU patients - no harm in delay

No difference in mortality when appropriate antibiotics for high risk MDROs is delayed1

Empiric use of narrow spectrum antibiotics can result in similar

outcomes when compared to broad spectrum2

1Kang, C et al. Antimicr Agents and Chem Dec, 2004, 4574-4581 2Queen, MA et al. Pediatrics 2014, 133(1): e23-29

HCAP Broad-Spectrum Treatment and Mortality

Retrospective cohort VA study - 15,071 HCAP patients in >150 hospitals

Compared 30-day mortality in non-ICU patients treated with (2005) guideline-concordant (GC)-HCAP or GC-CAP therapy

Attridge, Russell T., et al. "Guideline-concordant therapy and outcomes in healthcare-associated pneumonia." European Respiratory Journal 38.4 (2011): 878-887

HCAP Broad-Spectrum Treatment and Mortality

No difference in pathogen between GC and non-GC HCAP

MRSA rates not available but pseudomonas rates 14.4%

In non-critically ill HCAP patients, receiving broad vs narrow antibiotics – No difference in 30-day mortality – No difference hospital LOS

Attridge, Russell T., et al. "Guideline-concordant therapy and outcomes in healthcare-associated pneumonia." European Respiratory Journal 38.4 (2011): 878-887

Delay in Active Antimicrobials and Mortality in Bacteremia

Retrospective cohort - mono-microbial bacteremia at a large urban US hospital (2001 to 2006)

Assessed impact of delayed active antibiotics on mortality − N=1,523 − 64.5% received active antimicrobial agent <24h, 35.5% delayed

In non-ICU patients with ANC >100, delay not associated with

higher mortality

Lin, Michael Y., Robert A. Weinstein, and Bala Hota. "Delay of active antimicrobial therapy and mortality among patients with bacteremia: impact of severe neutropenia." Antimicrobial agents and chemotherapy 52.9 (2008): 3188-3194.

Cochrane Review

“Lower use of antibiotics probably does not increase mortality and likely reduces length of stay. “

Davey, P., et al. "Interventions to improve antibiotic prescribing practices for hospital inpatients." Cochrane Database of Systematic Reviews. 2017 2:CD003543.

Procalcitonin in respiratory tract infections

Cochrane review looked at 14 randomized controlled trials looking at procalcitonin algorithms in antibiotic decision making for acute respiratory infections

Lowered antibiotic use by 65% in primary care, 35% in ED, and 30% in ICU

Decreased antibiotic exposure in hospital by 3.5 days No difference in treatment failure or mortality at 30 days No firm conclusions on cost-effectiveness

Schuetz P et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Review. 2012.

UCI Procalcitonin Algorithm1: Respiratory tract infections

PCT value

Antibiotic Recommendation

<0.1 mg/ml >0.24 mg/ml 0.1-0.24 mg/ml

Antibiotics strongly discouraged

Antibiotics discouraged

Antibiotics encouraged

PCT to initiate antibiotics

Consider viral infection Consider non-infectious cause

Repeat q2-3 days to consider stopping antibiotics See Algorithm 2

UCI Procalcitonin Algorithm2: Respiratory tract infections

PCT value

Antibiotic Recommendation

<0.1 mg/ml >0.24 mg/ml

Strongly recommend antibiotics be stopped

Recommend continuation of antibiotics

PCT to stop antibiotics

Make sure there is appropriate clinical response

If PCT rising or not decreasing, consider broadening coverage and/or ID consult

0.1-0.24 mg/ml

Recommend antibiotics be stopped

Summary

• No vancomycin or Zosyn in pure cellulitis cases coming from the community. Use ceftriaxone. If unsure of abscess, ask ED for US.

• No vancomycin empirically for HCAP unless patient has history of MRSA infection or culture

• Can add vancomycin if nares or sputum cultures come back with MRSA and patient not responding to initial therapy

• Decision to use Zosyn for HCAP should be individualized based on risk factors

• Remember that starting with narrower agent makes discharge easier

• Escalating in HCAP does not make difference in mortality or LOS

KEEP UP THE GOOD WORK ON ANTIBIOTIC USE!