Antibiotic stewardship Sarah Doernberg, MD, MAS Associate - - PDF document

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Antibiotic stewardship Sarah Doernberg, MD, MAS Associate - - PDF document

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Antibiotic stewardship Sarah Doernberg, MD, MAS Associate Professor, Division of Infectious Diseases Medical Director of Adult Antimicrobial Stewardship Disclosures Consultant: Genentech, Basilea Pharmaceutica 1 | [footer text here]

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Antibiotic stewardship

Sarah Doernberg, MD, MAS Associate Professor, Division of Infectious Diseases Medical Director of Adult Antimicrobial Stewardship

Disclosures

  • Consultant: Genentech, Basilea Pharmaceutica
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Outline

  • Introduction to stewardship
  • 4 moments of antibiotic decision-making
  • Quick takes:
  • How long should I treat…?
  • Can I switch to oral therapy for…?
  • My patient has an allergy!
  • Wrap-up

Antibiotic use in the hospital is extensive

https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf Baggs J et al. JAMA Intern Med. 2016 Nov 1;176(11):1639-1648. doi: 10.1001/jamainternmed.2016.5651.

Average DOT/1000 pt-days: 754.8

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Hecker MT et al. Arch Intern Med. 2003;163:972-978.

30% of inpatient antibiotic use is unnecessary

  • 58% received ≥ 1 day of unnecessary antibiotics

Noninfectious

  • r

nonbacterial 33% Colonization

  • r

contamination 16% Duration too long 34% Adjustment not made 3% Redundant coverage 10% Spectrum not indicated 4%

Antibiotic use selects for resistance and causes harm

Tamma PD et al. JAMA Intern Med. 2017 Sep 1;177(9):1308-1315. doi: 10.1001/jamainternmed.2017.1938.

1488 inpatients receiving antibiotics 138 (9%) got CDI or MDRO infection within 90 days 324 (22%) had an antibiotic-associated adverse drug effect within 30 days

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http://chicago-mosaic.medill.northwestern.edu/antibiotic-resistance-superbugs/

Antimicrobial resistance threatens human health 35,900 annual deaths >2.8 million illnesses

https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

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What is antibiotic stewardship?

Improve patient

  • utcomes

Decrease antibiotic resistance, AE, costs Interventions designed to optimize the appropriate use of antimicrobials

MacDougall C and Polk RE. Clin Microbiol Rev. 2005;18:638-56.

But what exactly does that mean?

Accountability Resources Expertise

https://www.cdc.gov/antibiotic-use/healthcare/implementation/core-elements.html

Action Tracking/reporting Education

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Does it work?

MDRO incidence rate w/ ASP: 0.49 (0.35-0.68) CDI incidence rate w/ ASP: 0.68 (0.53-0.88)

Baur D et al. Lancet Infect Dis. 2017 Sep;17(9):990-1001. doi: 10.1016/S1473-3099(17)30325-0.

What steps can you take now?

4 moments of antibiotic prescribing

Treatment initiation

Based on the available clinical information, does the patient have an infection that requires antibiotics?

Initial assessment and cultures

Were appropriate empirical antibiotics started based on the suspected syndrome?

Time-out

Were antibiotics modified or stopped appropriately?

Definitive Rx

Is the duration appropriate for the syndrome?

Tamma PD et al. JAMA. 2018 Dec 27. doi: 10.1001/jama.2018.19509

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Outline

 Introduction to stewardship

  • Quick takes:
  • How long should I treat…?
  • Can I switch to oral therapy for…?
  • Wrap-up

How long would you treat? 76 y/o M with cholangitis and E. coli bacteremia now afebrile and stable on day 2

  • f ceftriaxone

A.

14 days

B.

10 days

C.

7 days

D.

5 days

E.

3 days

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How long would you treat? 46 year-old M with DM and obesity admitted with LLE cellulitis, improving on day 3 of cefazolin

A.

14 days

B.

10 days

C.

7 days

D.

5 days

E.

3 days

General principles of shorter-course antibiotics

Short course

  • Stabilized
  • Source control
  • Predictable

response

Longer course

  • Slow response
  • Inadequate

source control

  • Very resistant
  • rganism
  • +/- compromised

host

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How long should I treat?

Yadav K et al. Open Forum Infect Dis. 2018 Dec 3;6(1):ofy319. doi: 10.1093/ofid/ofy319. eCollection 2019 Jan. Supplementary material Aguilar-Guisado et al. Lancet Haematol. 2017 Dec;4(12):e573-e583 Yahav D et al. Clin Infect Dis. 2018 Dec 11. doi: 10.1093/cid/ciy1054. Havey TC et al. Crit Care. 2011;15(6):R267. doi: 10.1186/cc10545. Epub 2011 Nov 15 Sutton JD et al. Open Forum Infect Dis. 2018 Apr 21;5(5):ofy087. doi: 10.1093/ofid/ofy087 Wald-Dickler N and Spellberg B. Clinical Infectious Diseases, ciy1134, https://doi.org/10.1093/cid/ciy1134

Syndrome Duration (days) Comments CAP 5 Not studied in ICU/intubated pts HAP/VAP 7 Includes intubated pts Intra-abdominal infection 4 Assuming source control Cellulitis 5 If responds to initial treatment Complicated UTI 5-7 Remove foley Febrile neutropenia 48-72h post-fever Even if neutropenia persists Enteric GNR BSI 7 Stable after 48h Pneumococcal BSI in CAP 5-7 Extrapolation from RCT subgroups

Areas of uncertainty for short duration

Havey TC et al. Crit Care. 2011;15(6):R267. doi: 10.1186/cc10545. Epub 2011 Nov 15 Sutton JD et al. Open Forum Infect Dis. 2018 Apr 21;5(5):ofy087. doi: 10.1093/ofid/ofy087

Maybe

  • Other strep

BSIs

  • Non-enteric

GNR BSIs No-go

  • Endocarditis
  • Staphylococcus

aureus

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Is there an oral option?

  • 71 year-old F with recurrent UTIs admitted with cystitis due to

ceftriaxone-resistant E. coli

  • 34 year-old M with primary biliary cirrhosis admitted with

Klebsiella bacteremia from cholangitis

  • 59 year-old F with Group A Strep cellulitis with positive blood

cultures

  • 69 year-old M with complex urological history and chronic foley

admitted with VRE bacteremia in the setting of a suspected UTI

Bioavailability

Cyriac JM and James E. J Pharmacol Pharmacother. 2014 Apr-Jun; 5(2): 83–87.doi: 10.4103/0976-500X.130042 Gilbert DN et al. The Sanford Guide to Antimicrobial Therapy. 45th Ed.

Drug % absorption Amoxicillin 80 Amoxicillin-clavulanic acid 80/30 Cephalexin 90 Ciprofloxacin 70 Clindamycin 90 Levofloxacin 99 Linezolid 100 Metronidazole 100 Moxifloxacin 89 PCN VK 60-73 TMP/SMX 85

Drug exposure also

  • matters. Intolerance may

limit doses equivalent to IV being given PO

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General rules for switching

Clinical stability Afebrile Working GI tract Good bioavailability Meningitis, other deep- seated infections GI dysfunction Cannot take PO Poor PO options Critically ill

Favors switch Do not switch

Most syndromes can be treated with POs

  • Pneumonia
  • Cellulitis
  • Abscess
  • UTI
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Oral options for ESBL infections

Drug Urine Non-urine Comments Fluoroquinolone X X ↓Susceptbility TMP/SMX X X ↓Susceptbility Nitrofurantoin Cystitis No CrCl≥60 only Fosfomycin Cystitis Not PO Send-out sensis Klebsiella ↓susc Amox-clav Cystitis No Esp if MIC ≤ 8 Cefpodoxime+amox-clav X Unknown Hard to schedule

Sorlozano Puerto A. Diagn Microbiol Infect Dis 2006; 54: 135-139. Livermore DM, et al. Clin Microbiol Infect 2008; 14 S1: 189-193; Rodriguez-Bano J, et al. Arch Intern Med 2008; 168: 1897-1902 Falagas ME, et al. Lancet ID 2010; 10: 43-50 Pullucku H, et al. Int J Antimicrob Agents 2007; 29: 62-65

  • Most serious infections will require IV carbapenems

Can PO antibiotics be used for enteric GNR BSI?

Pts with GNR BSI &

  • Source control
  • Pitt score ≤ 1 by d5
  • Taking POs
  • PO option

(70% FQ, 13% tmp/smx, 16% β-lactam) PO switch ≤ day 5 (med 3d) (N = 739) IV rx > 5 days (med 14d) (N = 739)

Propensity score matched

30d mortality

13.1% 13.4%

↓hospital LOS No diff in recurrent BSI

7-14 days of antibiotics allowed

Tamma TD et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6226

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Can PO antibiotics be used for streptococcal bacteremias?

Disease PO antibiotic switch? Comments CAP w/ pneumococcal bacteremia Yes Small studies VRE bacteremias Yes (LZD) Group A Strep bacteremia Likely Lack of data Amp-susceptible enterococcus Likely (amox or LZD) Lack of data

Ramirez JA and Bordon J. Arch Intern Med. 2001 Mar 26;161(6):848-50 Zhao M,, et al. Int J Antimicrob Agents 2016; 48:231–8

  • Open-label RCT
  • Noninferiority (10%)
  • All Danish ♥ centers
  • L-sided NVE or PVE
  • Gram-positive only
  • Stable

Continue IV Switch to PO ≥ 10 dd IV abx ≥ 10 dd abx left

(mean 17) (mean 19 days) (mean 17 days)

Iverson K et al. New Engl J Med 2018; DOI: 10.1056/NEJMoa1808312 Iverson K et al. Am Heart J. 2013 Feb;165(2):116-22. doi: 10.1016/j.ahj.2012.11.006

12.1% 9.0%

Diff: -3.1% (-3.4 to 9.6%)

Failure

No ▲ mortality 16d ↓LOS

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  • Open-label RCT
  • Native osteomyelitis
  • Native joint infection
  • PJI
  • Fixation device ifxn
  • Vertebral osteo

Continue IV Switch to PO < 7d IV abx >70 days abx POmore rif

OK step-down to PO

Li H-K et al. N Engl J Med 2019; 380:425-436. DOI: 10.1056/NEJMoa1710926

14.6% 13.2%

Diff: -1.4% (−5.6 to 2.9)

1y failure

↓LOS

MD discretion

Areas of uncertainty for PO antibiotics

Sutton JD et al. Open Forum Infect Dis. 2018 Apr 21;5(5):ofy087. doi: 10.1093/ofid/ofy087 Willekens R, et al. Clin Infect Dis. 2018 Oct 23. DOI: 10.1093/cid/ciy916. [Epub ahead of print]

Staph aureus bacteremias Non-enteric GNR bacteremias Strep bacteremias

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73 year-old F coming onto your service with suspected CAP . You’d like to start ceftriaxone and azithromycin but note that she has an allergy to penicillin, listed as hives. What should you do next?

A.

Treat with levofloxacin

B.

Start levofloxacin and refer to Allergy clinic for penicillin skin testing

C.

Start levofloxacin and give a graded challenge of ceftriaxone

D.

Desensitize to ceftriaxone

Albin AAP 2014 Macy JACI 2014 Rolensky JACI Practice 2015 Blumenthal CID 2015

> 90% are not PCN-allergic

Inpatients with reported PCN allergy Longer Stays

10% more days in the hospital

30% more drug-resistant infections

23% more C diff, 14% more MRSA, 30% more VRE

10-15% of patients report PCN allergy

Slide courtesy of Iris Otani, MD

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What can you do when your patient reports an allergy?

Shenoy ES et al. JAMA. 2019 Jan 15;321(2):188-199. doi: 10.1001/jama.2018.19283.

History

  • What

happened?

  • Subsequent

beta-lactam receipt

Graded challenge

  • Pts unlikely

to be allergic

  • Low-risk

history or low-risk for cross reactivity

  • 2 doses
  • Can perform
  • n the ward

Skin testing

  • If high-risk

history and want to use same/similar medication

  • Follow-up

with test dose

Desensitization

  • High-risk

with positive skin test but clear beta- lactam indication

  • High-risk

and beta- lactam required right away

  • ICU

https://idmp.ucsf.edu/sites/idmp.ucsf.edu/files/wysiwyg/beta-lactam%20pathway%201.10.2019.pdf

How can you use this in your practice?

  • You can steward use of antibiotics with a checklist
  • Shorter courses of antibiotics are safe and effective for most

indications

  • Oral antibiotics can be used for most infections, as initial

therapy or step-down

  • Great set of tools:
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THANK YOU!

History is crucial

https://idmp.ucsf.edu/sites/idmp.ucsf.edu/files/wysiwyg/beta-lactam%20pathway%201.10.2019.pdf