05a Doernberg Antimicrobial › 2020 › MDM20K01 › slides › 05a...Gilbert DN et al. The Sanford...

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Antibiotic stewardship

Sarah Doernberg, MD, MASAssociate Professor, Division of Infectious DiseasesMedical Director of Adult Antimicrobial Stewardship

Disclosures

Consultant: Genentech, Basilea Pharmaceutica


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.pdfBaggs 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


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 or

nonbacterial 33%

Colonization or

contamination16%

Duration too long34%

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


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


What is antibiotic stewardship?

Improve patient outcomes

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?

AccountabilityResources Expertise

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

Action Tracking/reporting Education


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 durationappropriate for the syndrome?

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


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 of ceftriaxone

A. 14 days

B. 10 days

C. 7 days

D. 5 days

E. 3 days


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

Sho

rt c

ours

e • Stabilized• Source control• Predictable

response

Long

er c

ours

e • Slow response• Inadequate

source control• Very resistant

organism• +/- compromised

host


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 materialAguilar-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 15Sutton JD et al. Open Forum Infect Dis. 2018 Apr 21;5(5):ofy087. doi: 10.1093/ofid/ofy087Wald-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 15Sutton 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


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 foleyadmitted 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.130042Gilbert 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


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

Fav

ors

switc

h

Do not sw

itch

Most syndromes can be treated with POs

Pneumonia

Cellulitis

Abscess

UTI


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 sensisKlebsiella ↓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: 43-50Pullucku 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 LOSNo 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


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):848-50Zhao 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/NEJMoa1808312Iverson 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 ▲ mortality16d ↓LOS


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

Continue IV

Switch to PO

< 7d IV abx>70 days abxPOmore 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

↓LOSMD 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/ofy087Willekens 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


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 2014Macy JACI 2014

Rolensky JACI Practice 2015Blumenthal CID 2015

> 90% are not PCN-allergic

Inpatients with reported PCN allergy

Longer Stays10% more days in the hospital

30% more drug-resistant infections23% more C diff, 14% more MRSA, 30% more VRE

10-15% of patients report PCN allergy

Slide courtesy of Iris Otani, MD


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.

His

tory • What

happened?• Subsequent

beta-lactam receipt

Gra

ded

chal

leng

e • Pts unlikely to be allergic

• Low-risk history or low-risk for cross reactivity

• 2 doses• Can perform

on the wardS

kin

test

ing • If high-risk

history and want to use same/similar medication

• Follow-up with test dose

Des

ensi

tizat

ion • 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:


THANK YOU!

History is crucial

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

05a Doernberg Antimicrobial › 2020 › MDM20K01 › slides › 05a...Gilbert DN et al. The Sanford...

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