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

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]

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 Average DOT/1000 pt-days: 754.8 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. 2 | [footer text here]

30% of inpatient antibiotic use is unnecessary  58% received ≥ 1 day of unnecessary antibiotics Redundant Spectrum coverage not indicated Noninfectious 10% 4% or nonbacterial Adjustment 33% not made 3% Colonization or Duration too contamination long 34% 16% Hecker MT et al . Arch Intern Med. 2003;163:972-978. Antibiotic use selects for resistance and causes harm 324 (22%) had an antibiotic-associated adverse drug effect within 30 days 138 (9%) got CDI or 1488 inpatients MDRO infection receiving antibiotics within 90 days Tamma PD et al. JAMA Intern Med. 2017 Sep 1;177(9):1308-1315. doi: 10.1001/jamainternmed.2017.1938. 3 | [footer text here]

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 4 | [footer text here]

What is antibiotic stewardship? Interventions designed to optimize the appropriate use of antimicrobials Improve patient outcomes Decrease antibiotic resistance, AE, costs MacDougall C and Polk RE. Clin Microbiol Rev. 2005;18:638-56. But what exactly does that mean? Expertise Resources Accountability Action Tracking/reporting Education https://www.cdc.gov/antibiotic-use/healthcare/implementation/core-elements.html 5 | [footer text here]

Does it work? CDI incidence rate w/ ASP: MDRO incidence rate w/ ASP: 0.68 (0.53-0.88) 0.49 (0.35-0.68) 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 Initial assessment and cultures Based on the Time-out available clinical Were information, Definitive Rx appropriate does the Were antibiotics empirical patient have an modified or antibiotics infection that Is the duration stopped started based on appropriate for requires appropriately? the suspected the syndrome? antibiotics? syndrome? Tamma PD et al. JAMA. 2018 Dec 27. doi: 10.1001/jama.2018.19509 6 | [footer text here]

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 14 days A. 10 days B. 7 days C. 5 days D. 3 days E. 7 | [footer text here]

How long would you treat? 46 year-old M with DM and obesity admitted with LLE cellulitis, improving on day 3 of cefazolin 14 days A. 10 days B. 7 days C. 5 days D. 3 days E. General principles of shorter-course antibiotics • Stabilized • Slow response Short course Longer course • Source control • Inadequate source control • Predictable response • Very resistant organism • +/- compromised host 8 | [footer text here]

How long should I treat? 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 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 Areas of uncertainty for short duration Maybe No-go • Other strep • Endocarditis BSIs • Staphylococcus • Non-enteric aureus GNR BSIs 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 9 | [footer text here]

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 Drug % absorption Bioavailability Amoxicillin 80 Amoxicillin-clavulanic acid 80/30  Drug exposure also Cephalexin 90 matters. Intolerance may Ciprofloxacin 70 limit doses equivalent to Clindamycin 90 IV being given PO Levofloxacin 99 Linezolid 100 Metronidazole 100 Moxifloxacin 89 PCN VK 60-73 TMP/SMX 85 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. 45 th Ed. 10 | [footer text here]

General rules for switching Favors switch Clinical stability Meningitis, other deep- seated infections Afebrile GI dysfunction Working GI tract Cannot take PO Do not switch Good bioavailability Poor PO options Critically ill Most syndromes can be treated with POs  Pneumonia  Cellulitis  Abscess  UTI 11 | [footer text here]

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 • Most serious infections will require IV carbapenems Sorlozano Puerto A. Diagn Microbiol Infect Dis 2006; 54: 135-139. Falagas ME, et al. Lancet ID 2010; 10: 43-50 Livermore DM, et al. Clin Microbiol Infect 2008; 14 S1: 189-193; Pullucku H, et al. Int J Antimicrob Agents 2007; 29: 62-65 Rodriguez-Bano J, et al. Arch Intern Med 2008; 168: 1897-1902 Can PO antibiotics be used for enteric GNR BSI? 7-14 days of antibiotics allowed 30d mortality PO switch ≤ day 5 (med 3d) 13.1% (N = 739) Pts with GNR BSI & • Source control Propensity ↓ hospital LOS • Pitt score ≤ 1 by d5 score matched No diff in recurrent BSI • Taking POs • PO option IV rx > 5 days (med 14d) 13.4% (70% FQ, 13% tmp/smx, (N = 739) 16% β -lactam) Tamma TD et al. JAMA Intern Med. 2019 Jan 22. doi: 10.1001/jamainternmed.2018.6226 12 | [footer text here]

Can PO antibiotics be used for streptococcal bacteremias? Disease PO antibiotic switch? Comments CAP w/ pneumococcal Yes Small studies bacteremia VRE bacteremias Yes (LZD) Group A Strep Likely Lack of data bacteremia Amp-susceptible Likely (amox or LZD) Lack of data enterococcus 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 Failure Continue IV 12.1% ≥ 10 dd IV abx (mean 19 days) (mean 17) • Open-label RCT Diff: -3.1% (-3.4 to 9.6%) ≥ 10 dd abx left • Noninferiority (10%) Switch to PO • All Danish ♥ centers 9.0% • L-sided NVE or PVE (mean 17 days) No ▲ mortality • Gram-positive only 16d ↓ LOS • Stable 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 13 | [footer text here]

1y failure Continue IV 14.6% OK step-down to PO < 7d IV abx >70 days abx • Open-label RCT Diff: -1.4% ( − 5.6 to 2.9) PO  more rif • Native osteomyelitis Switch to PO • Native joint infection 13.2% • PJI MD discretion ↓ LOS • Fixation device ifxn • Vertebral osteo Li H-K et al. N Engl J Med 2019; 380:425-436. DOI: 10.1056/NEJMoa1710926 Areas of uncertainty for PO antibiotics Non-enteric Staph GNR aureus bacteremias bacteremias Strep bacteremias 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] 14 | [footer text here]