Golden Nuggets: Bugs, Drugs and Antibiotic Stewardship · The Sanford Guide to Antimicrobial...

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Golden Nuggets: Bugs, Drugs and Antibiotic Stewardship

Please logon to: www.ascp.com/qa and find the session title to submit your questions.

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Pharmacist Learning Objectives • Discuss methods for prevention, treatment of infection with best in

class/new therapies, and prevention of drug resistance for use in the older adult.• Identify novel strategies for therapeutics for infectious conditions

and antibiotic stewardship.• Describe medication strategies for prevention of bacterial resistance

and best practices in antibiotic stewardship.• List practice models for antibiotic stewardship and prevention of drug

resistance in senior care practice settings.

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http://www.ascp.com/qa

10/18/19

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Pharmacy Technician Learning Objectives• List best in class and new therapies for use in the

older adult.• Identify novel therapeutic strategies for infectious

conditions.•Describe best practices in antibiotic stewardship for

older adults.

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Chair and Moderator

• Dr. Deborah Milito

• Disclosure: I have no actual or potential conflict of interest to this presentation. I have no financial relationships with regard to this presentation to disclose.

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Topics and Speakers (Each talk is 15 minutes)1. Bugs & Drugs for the Older Adult—Spencer Durham2. AnNbioNc Adverse Drug Events: Improving PaNent Assessment and Management—Joshua

Chou3. New and Future AnNbioNcs in the Pipeline—Jonathan Cho

15 minute Q&A Session with first 3 speakers

4. OpNmizing The Use Of Clinical Laboratory Values In AnNmicrobial Stewardship—Nicholas Ladikos

5. Clostridioides difficile InfecNon in the Older Adult—Elias B. Chahine6. MulN-Drug Resistant Organisms—Eddie Grace

15 minute Q&A Session with second 3 speakers

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Bugs & Drugs for the

Older AdultSpencer H. Durham, Pharm.D., BCPS, BCIDP

Associate Clinical Professor of Pharmacy PracticeDirector, Alumni & Professional Affairs

Auburn University Harrison School of Pharmacy

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Disclosure

I have no conflicts of interest to disclose.

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Introduction

• “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.”

- Sir Alexander Fleming

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Introduction

• Multidrug-resistant organisms (MDROs) are increasing at an alarming rate• 2 million illnesses and 23,000 deaths associated with antibiotic-resistant

bacteria annually• Misuse of antimicrobial agents is the major contributing factor to

disseminated resistance• Up to 50% of antimicrobials prescribed in the outpatient, emergency, and

acute care settings are unnecessary or inappropriate• Up to 75% of antimicrobials in the long-term care setting are prescribed

inappropriately

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Introduction

• Older adults are at a high risk of infection with MDROs• Immune system naturally weakens over time

• Immunosenescence

• Have likely been exposed to many courses of antibiotics over time• Comorbidities may predispose to acquiring certain infections

• Examples: diabetes, COPD

• May be at higher risk for adverse effects associated with antimicrobial treatment• C.difficile infection

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Introduction

• Antimicrobial therapy crosses into most, if not all, areas of pharmacy practice• Many antibiotics are either unnecessary, or prescribed

inappropriately, all of which may contribute to antimicrobial resistance• No indication for antibiotic therapy• Incorrect antibiotic for the disease• Incorrect dose, frequency or duration

• Limited development of new antibiotics, particularly novel antibiotics

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Goals of Antimicrobial Therapy

• In general, ultimate goal is to eradicate the causative organism of infection• Treat infection appropriately

• Empiric therapy: target most likely pathogens for the disease state• Definitive therapy: use the least broad-spectrum, yet most appropriate,

therapy to target the known pathogen

• Minimize the development of antimicrobial resistance• Use most narrow-spectrum, effective agent possible• Judicious overall use of antimicrobials

• Example: Abx use for infections likely due to viral causes

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Antimicrobial Considerations

• Empiric therapy• Broad-spectrum agent(s) with reliable coverage against the most likely

causative pathogens

• Definitive therapy• Can generally only be done after obtaining culture and sensitivity results• May use other tests to guide therapy, such as PCRs

• Duration of treatment• Not well-defined, usually based on experience rather than evidence• Generally, 7-14 days for most infections

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Antimicrobial Stewardship

• SNAP approach to antimicrobial stewardship• Safety, Need, Adequacy, Prudence• Step-by-step process to assess antimicrobial therapy when antibiotics

have already been prescribed• If initially recommending an antibiotic, change to the NAPS approach

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• “S” – Safety• Ask “is it safe for this patient to be receiving this antimicrobial?”• Assessment of allergies• Assess for likelihood of potential adverse drug reactions

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• “N” – Need• Ask “Does this paNent need anNmicrobial therapy?

• Does the paNent actually have an infecNon?• Is the infecNon likely to be:

• Bacterial?• Viral?• Fungal?

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• “A” – Adequacy• Ask “Is the prescribed antimicrobial treating, or likely to treat, the

infection?”• Is the antimicrobial a guideline recommended therapy?• Does the antimicrobial provide appropriate coverage against the pathogens

most likely causing the infection?• Will the antimicrobial reach the site of infection?

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• “P” – Prudence• Ask “Is this the most prudent drug to use for this infection?”

• Is the drug the most-narrow spectrum agent that will adequately treat this infection?

• This often cannot be fully assessed unless culture and susceptibility results are available

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Self-Assessment Question #1

• D.B. is a 67-year-old male, permanent resident of a LTCF, who is admitted to the hospital for evaluation of difficulty breathing, 3 day history of fever, productive cough, night sweats, and chills• Allergies: NKDA• PMH: T2DM, HTN, dyslipidemia• Meds: Metformin, glypizide, atorvastatin, lisinopril, HCTZ• PE: BP-130/82; HR-90; RR-28; Temp 103.5°F• Chest x-ray reveals bilateral infiltrates

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What is the best recommendation for D.B. at this time?A. Begin oral azithromycin 500 mg PO on day 1, then 250 mg on days

2-5B. Do not begin antibiotics, infection is likely viral; supportive care

onlyC. Begin ciprofloxacin 500 mg IV BIDD. Begin ceftriaxone 2 grams IV once daily plus azithromycin 500 mg

IV once daily

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What is the best recommendation for D.B. at this time?A. Begin oral azithromycin 500 mg PO on day 1, then 250 mg on days

2-5B. Do not begin antibiotics, infection is likely viral; supportive care

onlyC. Begin ciprofloxacin 500 mg IV BIDD. Begin ceftriaxone 2 grams IV once daily plus azithromycin 500 mg

IV once daily

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References

• Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of America and the society for healthcare epidemiology of America. Clin Infect Dis. 2016;62(10):1197-202.

• Cunha CB, Cunha BA. Antibiotic essentials. 15 ed. London, England: JaypeeBrothers Medical Publishing; 2017.

• Gallagher JC, Macdougall C. Antibiotics simplified. 4 ed. Burlington, MA: Jones & Bartlett Learning; 2018.

• Gilbert DN, Chambers HF, Eliopoulos GM, et al. The Sanford Guide to Antimicrobial Therapy. 48 ed. Sperryville, VA: Antimicrobial Therapy, Inc; 2018.

• The core elements of antibiotic stewardship for nursing homes. Available from: https://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html. Accessed August 25, 2019.

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https://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html

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Bugs & Drugs for the

Older AdultSpencer H. Durham, Pharm.D., BCPS, BCIDP

Associate Clinical Professor of Pharmacy PracticeDirector, Alumni & Professional Affairs

Auburn University Harrison School of Pharmacy

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Antibiotic Adverse Drug Events: Improving

Patient Assessment and Management

Joshua Chou, PharmD

Geriatric Pharmacotherapy FellowPeter Lamy Center on Drug Therapy and Aging

University of Maryland School of Pharmacy

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Disclosure• I have no actual or potentially relevant financial relationship to

disclose and no conflict of interest in relation to this activity.

• This work was supported by a Cooperative Agreement funded by the Centers for Disease Control and Prevention in collaboration with the Maryland Department of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Centers for Disease Control and Prevention of the Department of Health and Human Services.

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Why Focus on Antibiotic Adverse Drug Events (AADEs)?

• Protect the resident from future exposure to the AADEs• Communicate findings with other health care clinicians to avoid

future occurrences • Comply with standards of practice• Adhere to regulatory and accreditation guidance

• Centers for Disease Control (CDC) Core Principles of Antibiotic Stewardship• State Operations Manual: Appendix PP

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https://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html

https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/GuidanceforLawsAndRegulations/Downloads/Appendix-PP-State-Operations-Manual.pdf

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Tracking: Monitoring Antibiotic Prescribing, Use, and Resistance

Does your facility monitor one or more outcomes of antibiotic use?

− Rates of C. difficile infection− Rates of antibiotic resistant

organisms− Rates of adverse drug events due

to antibiotics

Adverse events due to use of medications in skilled nursing homes accounted for nearly 40% of harms identified in a

recent report.1 Antibiotics are among the most frequently

prescribed medications in LTCFs and have a high rate of adverse

drug events.2,3

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Antibiotic Adverse Drug Events4

20% of hospitalized adults have at least 1 adverse drug event (ADE)

Every 10 days of antibiotic therapy confers a 3% increased risk of ADE

GI (42%), Renal (24%), Blood (15%), Liver (7%), Neurologic (7%)

RATE

RISK

TYPE

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Antibiotic ADE: GI Event4

• Diarrhea: > 3 loose stools per day; absence of laxatives

• Nausea and/or vomiting; nausea and vomiting associated with antibiotic; no other explanation

• Prevalence: 42%• Median time to

occurrence: 5 days (2 – 9)

Nausea and vomitingassociated with

antibiotic administration

Possible Gastrointestinal Adverse Event

Contact Prescriber. Evaluate whether antibiotic can be

taken with food to decrease

nausea/vomiting.

Non-infectious diarrhea,

i.e., not C. difficile PCR positive

Contact Prescriber. Obtain C. difficile PCR if not already known. Evaluate whether probiotic/ prebiotic can be

taken at least 2 hours prior to antibiotic to decrease diarrhea.

Antibiotics Implicated

Ampicillin Amoxicillin-clavulanateAmpicillin-sulbactam OxacillinPiperacillin-tazobactam CeftriaxoneCefpodoxime CefepimeTrimethoprim-Sulfamethoxazole

ErtapenemMeropenem

AzithromycinClindamycinDoxycycline

FluoroquinolonesMetronidazole

Vancomycin

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ADE: Renal Event4

• Increase in SCr to > 1.5 times baseline; absence of precipitating renal factors (i.e. sepsis, other nephrotoxic drugs)

• Prevalence: 24%

• Median time to occurrence: 5 days (2 – 10)

Increase in SCr to > 1.5 times baseline value

Possible Renal Event

Contact Prescriber.Evaluate other possible causes

of renal impairment, i.e. sepsis, contrast dye

Antibiotics ImplicatedAminoglycosidesTrimethoprim-

SulfamethoxazoleVancomycin IV

Ampicillin-sulbactamCephalosporins

Ampicillin

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ADE: Blood Disorder4

• Anemia (hgb < 10 g/dL); Leukopenia (WBC < 4500 cells/μL); thrombocytopenia (platelets < 150 x 103/μL; no bleeding or myelosuppressive therapy

• Prevalence: 15%• Median time to occurrence:

12 days (6 – 24)

Decrease in Hgb to < 10 g/dL; and/orDecrease in WBC to < 4,500 cells/μL;

Decrease in platelets to < 150 x 103/μLto below baseline, in absence of

bleeding or myelosuppressive therapy

Possible Blood Disorder Event

Contact Prescriber. Evaluate other possible causes of decreased blood

counts. Consider discontinuing likely-implicated antibiotic.

Most Likely Antibiotics ImplicatedAmpicillin OxacillinPiperacillin-tazobactam CefazolinCeftriaxone CefepimeMacrolides MeropenemFluoroquinolones Trimethoprim-Sulfamethoxazole

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ADE: Cardiac Event - Arrhythmia4-5

• QTc > 440 ms in females

• QTc > 460 ms in males on two or more EKGs; absence of pre-existing arrhythmias

• Prevalence: 1%• Median time to

occurrence: 11 days (4-18)

áQTc interval by 60 msover baseline or

áto > 440 ms in males;á to > 460 ms in females

áPossible Arrhythmia

áEvaluate HR and rhythm.áIf HR > 140 or tachyarrhythmia,áHOLD ANTIBIOTIC & CONTACT

PRESCRIBER

Anti-infective ImplicatedAzithromycinCiprofloxacinErythromycinFluconazoleLevofloxacinMoxifloxacinKetoconazoleItraconazole;

Determine if other risk factors for Torsades de Pointes exist

Evaluate need for emergency

triage, and potassium and

magnesium replacement.

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Longer Term Antibiotic ADEs – up to 90 days4

C. Difficile Infection – Infectious Diarrhea

• Prevalence: • 3.9 cases per 10,000 person

days • 4% of study patients

• Median time to occurrence: 15 days (4 – 34)

• Implicated antibiotics: 3rd generation cephalosporins, cefepime, and fluoroquinolones

Infection with Multi-drug Resistant Organisms (MDROs)

• Prevalence: • 6.1 cases per 10,000 person days• 6% of study patients

• Median time to occurrence: within 90 days

• Gram positive resistance (4.8/10,000 person days): VRE (67%)

• Gram negative resistance (1.7/10,000 person days): extended spectrum β-lactamase production

C. difficile and MDROs infections comprised 43% of all antibiotic-associated ADEs

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Where: EHR=electronic health record

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Self-Assessment Question

Which of the following are reasons why documenting antibiotic adverse drug events are important?

A. Avoid future exposure to the antibiotic that caused the antibiotic adverse drug event

B. Communicate findings with other healthcare professionals to reduce future occurrences

C. To increase Medicare reimbursementD. A and B

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Which of the following are reasons why documenting antibiotic adverse drug events are important?

A. Avoid future exposure to the antibiotic that caused the antibiotic adverse drug event

B. Communicate findings with other healthcare professionals to reduce future occurrences

C. To increase Medicare reimbursementD. A and B

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Golden Nuggets

• Monitoring and documenting antibiotic adverse drug events (AADEs) is critical in reducing future AADEs.• Increasing ongoing surveillance of potential and actual AADEs needs

to be integrated into workflow.• Reducing AADEs requires an interprofessional collaborative effort

championed by the pharmacy team.

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References1. Office of the Inspector General. Adverse Events in Skilled Nursing Facilities:

National Incidence Among Medicare Beneficiaries (OEI-06-11-00370), February 2014.

2. Nicolle LE, Bentley D, Garibaldi R, et al. Antimicrobial use in long-term care facilities. Infect Control Hosp Epidemiol 2000; 21:537–45.

3. Gurwitz JH, Field TS, Avorn J et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med. 2000;109:87–94.

4. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med.2017;177(9):1308–1315.

5. Woosley RL, Heise CW , Gallo T, Tate J, Woosley D and Romero KA, www.CredibleMeds.org, QTdrugs List, Accessed August 27, 2019.

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Antibiotic Adverse Drug Events: Improving

Patient Assessment and Management

Joshua Chou, PharmD

Geriatric Pharmacotherapy FellowPeter Lamy Center on Drug Therapy and Aging

University of Maryland School of Pharmacy

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New and Future Antibiotics in the Pipeline

Jonathan Cho, PharmD, MBA, BCIDP, BCPS

Clinical Associate ProfessorThe University of Texas at Tyler Fisch College of Pharmacy

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Disclosure

Jonathan Cho serves on the speakers’ bureau for Allergan.

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Antimicrobial Drug Approval

0

2

4

6

8

10

12

14

16

18

198 3-87 198 8-92 199 3-97 199 8-20 02 200 3-07 200 8-12 201 3-18

Adapted from Spellberg B, et al. Clin Infect Dis. 2011;52:S397-S428

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Which of the following antimicrobials works against vancomycin-resistant Enterococcus sp.?

A. Meropenem/vaborbactamB. PlazomicinC. OmadacyclineD. None of the above

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Which of the following antimicrobials works against vancomycin-resistant Enterococcus sp.?

A. Meropenem/vaborbactamB. PlazomicinC. OmadacyclineD. None of the above

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Delafloxacin (Baxdela®)

• Studies compared delafloxacin vs. vancomycin/aztreonam (V/A)• IV delafloxacin to V/A: 78.2% vs. 80.9% in intent-to-treat (ITT) analysis• PO delafloxacin to V/A: 83.7% vs. 80.6% in ITT analysis

• Pooled safety analysis showed no association of adverse reactions seen with other fluoroquinolones

Approval Date Indications Spectrum of Activity Dosing Clinical Pearls

June 2017 ABSSSI MRSA, P. aeruginosa 450mg PO BID or300mg IV daily

- No phototoxic effects or QTc prolongation seen

O’Riordan W, et al. Clin Infect Dis. 2018 Aug 16;67(5):657-666.Pullman J, et al. J Antimicrob Chemother. 2017 Dec 1;72(12):3471-3480.Bassetti M, et al. Clin Infect Dis. 2019 Apr 8;68(Supplement_3):S233-S240.

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Meropenem/vaborbactam (Vabomere®)

• Phase 3 study compared meropenem/vaborbactam vs. piperacillin/tazobactam with optional PO levofloxacin switch• Overall success: 98.4% vs. 94%• Microbial eradication in ITT population: 66.7% vs. 57.7%

• What about CRE? à evaluated against best available therapy • Associated with ↑ clinical cure, ↓ mortality, and ↓ nephrotoxicity


August 2017 cUTI ESBL, CRE 4g (2/2g) IV q8h infused over 3 hrs

- No additional benefit against A. baumannii, P. aeruginosa

Kaye KS, et al. JAMA. 2018 Feb 27;319(8):788-799.Wunderink RG, et al. Infect Dis Ther. 2018 Dec;7(4):439-455.

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Plazomicin (ZemdriTM)

• Phase 3 study compared plazomicin vs. meropenem• Composite cure rate at day 5: 88% vs. 91.4% • Composite cure rate at test-of-cure (TOC): 81.7% vs. 70.1% • Fewer recurrence: 3.7% vs. 8.1%• Fewer clinical relapse: 1.6% vs. 7.1%• Increase in serum creatinine levels ≥0.5mg/dL: 7% vs 4%


June 2018 cUTI ESBL, CRE, MRSA 15mg/kg IV daily - Same adverse reactions seen with other aminoglycosides

Wagenlehner FME, et al. N Engl J Med. 2019 Feb 21;380(8):729-740.

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Eravacycline (XeravaTM)

• Phase 3 study compared eravacycline vs. meropenem • Clinical cure rates at TOC: 90.8% vs. 91.2%• Clinical cure rates in modified-ITT: 92.4% vs. 91.6%• Clinical cure rates in clinically evaluable population: 96.9% vs. 96.1%• Clinical cure in patients with ESBL-producing Enterobacteriaceae: 87.5%

(14/16) vs. 84.6% (11/13)


August 2018 cIAI MRSA, VRE, ESBL, CRE, A. baumannii

1mg/kg IV q12h - Same adverse reactions seen with other tetracyclines

Solomkin JS, et al. Clin Infect Dis. 2018 Dec 18. doi: 10.1093/cid/ciy1029. [Epub ahead of print]

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Omadacycline (NuzyraTM)

• Two phase 3 studies compared omadacycline vs. linezolid• Oasis-1: initiated on IV with option to transition to PO after day 3

• Modified-ITT early clinical response: 84.8% vs. 85.5%• Oasis-2: PO only study

• Modified-ITT early clinical response: 88% vs. 83%• Gastrointestinal adverse events were most common


October 2018 CABP, ABSSSI

MRSA, VRE, ESBL, ±CRE, A. baumannii

LD then 100mg IV or 300mg PO daily

- Same adverse reactions seen with other tetracyclines

O’Riordan W, et al. Lancet Infect Dis. 2019 Aug 29. pii: S1473-3099(19)30275-0.O’Riordan W, et al. N Engl J Med. 2019 Feb 7;380(6):528-538.

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Imipenem/cilastatin/relebactam (RecarbrioTM)

• Phase 3 study compared imipenem/cilastatin/relebactam vs. colistin + imipenem/cilastatin for HAP/VAP, cIAI, or cUTI due to imipenem non-susceptible pathogens• Favorable overall response: 71% vs. 70%• Day 28 clinical response: 71% vs. 40%• 28-day mortality: 10% vs. 30%• Serious adverse events: 10% vs. 31%; drug-related: 16% vs. 31%


July 2019 cUTI, cIAI ESBL, CRE, P. aeruginosa

1.25g (500 / 500 / 250mg) IV q6h

- Similar adverse effect profile as imipenem/cilastatin

Motsch J, et al. Clin Infect Dis. 2019 Aug 10. pii: ciz530. doi: 10.1093/cid/ciz530. [Epub ahead of print]

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Lefamulin (XenletaTM)

• LEAP-1: 7 days of IV to PO lefamulin vs. moxifloxacin (±) linezolid for moderate-severe CABP• Early clinical response: 87.3% vs. 90.2%• Modified-ITT clinical response: 81.7% vs. 84.2%• Clinically evaluable: 86.9% vs. 89.4%

• LEAP-2: 5 days of PO lefamulin vs. 7 days of moxifloxacin for moderate CABP• Similar results were found


August 2019 CABP MRSA, VRE, Atypicals, MDR-N. gonorrhoeae

150mg IV BID or 600mg PO BID

- First pleuromutilin systemically- Potential for QTc prolongation and fetal harm

File T MJr, et al. Clin Infect Dis. 2019 Feb 4. doi: 10.1093/cid/ciz090. [Epub ahead of print]

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Summary of Approved AntibioticsMRSA VRE ESBL CRE CR-

PseudomonasMDR-

Acinetobacter

Delafloxacin

Meropenem / vaborbactam

Plazomicin

Eravacycline

Omadacycline

Imipenem / relebactam

Lefamulin

Great activityModerate activityLow/no activity

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Cefiderocol

• Siderophore cephalosporin• Enhanced stability to β-lactamases (AmpC, ESBL, carbapenemases)

• Currently being studied in phase 3 trials as 2g IV q8h as 3-hr infusion• Spectrum of activity is mainly targeted against gram-negatives

• ESBL, CRE, MDR-A. baumannii, MDR-P. aeruginosa, S. maltophilia

• Phase 2 study compared cefiderocol vs. imipenem/cilastatin for cUTI• Clinical response and microbiological response at TOC: 73% vs. 55%• Adverse events: 41% vs. 51% with gastrointestinal being the most common

Portsmouth S, et al. Lancet Infect Dis. 2018 Dec;18(12):1319-1328.

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Iclaprim

• Dihydrofolate reductase inhibitor • Designed to overcome trimethoprim resistance without sulphonamide use

• Spectrum of activity is mainly targeted against gram-positives• MRSA, vancomycin-resistant strains

• Two phase 3 trials were conducted (REVIVE-1 and REVIVE-2) comparing iclaprim vs. vancomycin for ABSSSI• ≥20% reduction in lesion size: 79.6% vs. 78.8%• Adverse reactions were same except for ↑ incidence of SCr with vancomycin

• FDA requested additional data to evaluate risk for liver toxicity

Huang DB, et al. Int J Antimicrob Agents. 2018 Aug;52(2):233-240.

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Zoliflodacin

• Spiropyrimidinetrione against bacterial type II topoisomerases• FDA awarded fast track status as PO option for gonococcal infections• Phase 2 study compared zoliflodacin 2g or 3g PO x1 dose vs.

ceftriaxone 500mg IM x1 dose for uncomplicated or untreated urogenital gonorrhea• Microbiologic cure in the micro-ITT: 96% vs. 96% vs. 100%• All rectal patients were cured in all 3 groups• Pharyngeal infections: 50% vs. 82% vs. 100%• Most adverse reactions with zoliflodacin were gastrointestinal

Taylor SN, et al. N Engl J Med. 2018 Nov 8;379(19):1835-1845.

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Ridinilazole

• Demonstrates rapid bactericidal activity for C. difficile infection (CDI) • Diminish production of C. difficile toxins

• Preclinical studies show negligible systemic exposure• Phase 2 study compared ridinilazole vs. vancomycin x 10 days

• Sustained clinical response: 66.7% vs. 42.4%, showing superiority• Largely due to reduced CDI 30-day recurrence rates

• Adverse effect profile was similar to vancomycin, most being gastrointestinal

• Lower propensity for collateral damage to gut microbiome compared with vancomycin

Vickers RJ, et al. Lancet Infect Dis. 2017 Jul;17(7):735-744.

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Fosfomycin

• Works against many gram-positive and gram-negatives• MRSA, VRE, ESBL, CRE• Does not work against Pseudomonas and Acinetobacter sp.

• Phase 2/3 study evaluated IV fosfomycin vs. piperacillin/tazobactam for treatment of cUTI• Overall success: 64.7% vs. 54.5%• Clinical cure at TOC: 90.8% vs. 91.6%• Adverse reactions include hypokalemia, hypernatremia, ↑ AST/ALT

• FDA rejected approval due to manufacturing issues

Kaye KS, et al. Clin Infect Dis. 2019 Mar 6. pii: ciz181. doi: 10.1093/cid/ciz181. [Epub ahead of print]

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New and Future Antibiotics in the Pipeline

Jonathan Cho, PharmD, MBA, BCIDP, BCPS

Clinical Associate ProfessorThe University of Texas at Tyler Fisch College of Pharmacy

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Q&A Session 1 – 15 min

Moderated by Dr. Milito

1. Bugs & Drugs for the Older Adult—Spencer Durham2. Antibiotic Adverse Drug Events: Improving Patient Assessment and

Management—Joshua Chou3. New and Future Antibiotics in the Pipeline—Jonathan Cho


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Golden Nuggets: Bugs, Drugs and Antibiotic Stewardship:

2nd Hour

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Optimizing The Use of Clinical Laboratory Values in Antimicrobial Stewardship

Nicholas Ladikos, PharmD, BCPS, BCGP, BCIDPClinical Coordinator

Antimicrobial Stewardship Program Lead PharmacistInvestigational Drug Program Lead PharmacistJohns Hopkins Medicine | Suburban Hospital

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Speaker Information–Bio• Committee member for ASCP,

SIDP, ACCP, SHEA, and MSHP• Additional degrees in

Biochemistry, Finance, and International Business

• LEAN/Six Sigma Certification• Recipient of The Johns Hopkins

Patient Safety Award (twice)

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Disclosure – Nicholas Ladikos, PharmDBCPS, BCGP, BCIDP• I have no actual or potentially relevant financial relationship to

disclose and no conflict of interest in relation to this activity

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Learning Objectives

At the end of this presentation, attendees will be able to understand:

• The effects of immunosenescence on laboratory values• The complexities of penicillin allergy skin testing and procalcitonin

values• The limitations of current clinical laboratory instrumentation

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Historical Context: Hippocrates (c. 425 BC)

• Separated medicine from superstition and religion and made it a science• The original uroscopist:

Advocated examination of urine to diagnose disease• “Understand the patient as an

individual”

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Clinical Laboratory Values

• 13 billion tests performed annually in the U.S.• Acute (baseline) and chronic changes (trends)• Initiate medication regimens, then adjust based on new information• Order tests only when necessary

• Will you take action on the results?

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Is a Laboratory Value “WNL” Really Normal?

• Population norms can be established for any physiologic parameter and its laboratory measurement

•Normal lab value = Mean ± 2 SD of healthy people

-i.e., 95% of results

•Thus, 5% of results are classified as "abnormal," even though they represent variability within a normal population

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Immunosenescence

• Multifactorial, progressive decline in immune function with increasing age• Low-grade chronic inflammation

(“inflamm-aging”)• Increased incidence and severity

of infections• Attenuates the host’s capacity to

respond to infections• Difference in clinical presentation

of infections

Infe

ctio

nSC

r/GFR

/CrC

l

ESR

Bloo

d Gl

ucos

eFe

ver/

Chills

?

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“All that is gold does not glitter, not all who wander are lost, and not all laboratory values are legitimate.”

Clinical Suspicion

Bacterial infection

Aspergillosis

Syphilis

Instrument False Positive/False Negative

Sample contamination or inadequate smear preparation

False-positive if concomitant piperacillin-tazobactam

False-positive screen in patients with lupus

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Microbiology Laboratory—Your [New] BFF!

• Institutional/Facility antibiograms• Feeder hospital’s antibiograms

• Rapid/POC tests• Turnaround time from preliminary/final cultures and susceptibilities

to regimen change• Strategic suppression and/or displaying of susceptibilities

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Medical Team: “Patient is fine, but the urine…”Urinalysis in Asymptomatic Bacteriuria (ASB)

Screen/Treat• Patients undergoing endo-urologic surgery

(1 or 2 doses)• Renal transplant patients within one

month of transplant• Pregnant women (4-7 days)

Do NOT Screen/Treat• Elderly persons living independently or in

a long-term care facility• Patients with indwelling urinary catheters

of any duration• Patients with diabetes• Patients with spinal cord injury• Healthy non-pregnant women of any age

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Patient: “I’m Allergic to Penicillin…”

• ~10% of US population self-identifies as allergic to penicillin• <0.05%-1% have an IgE-mediated penicillin allergy

• 1/100,000 experience anaphylaxis

• 1%-2% cross-allergy to carbapenems/select cephalosporins

• Do your due diligence—Investigate, interpret, ask questions!• Beta-lactams often first-line therapy• Penicillin allergy skin testing (NPV ~98%)

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Which is the Penicillin Allergy?

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Procalcitonin

The Good…• Serum biomarker that rises in

response to bacterial infections• Approved for CAP and sepsis

• Bacterial versus viral/atypical• 95% NPV

• Known kinetics (follow trends)

The Bad…• Not for viral/atypical infections• Many other causes of systemic

inflammation• Not perfect

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The Future…

• Cell-free DNA• 16s (bacteria)• 18s (fungi)

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Which of the following is true?

A. The normal value for a laboratory measurement is usually defined as its mean value ± 3 SD.

B. Infections manifest with typical signs or symptoms characterizing disease the same for adults of all ages.

C. ~1% of the U.S. population self-identifies as having an allergy to penicillin.

D. Patients with indwelling catheters should always be treated with antibiotics.

E. Hippocrates advocated to understand the patient as an individual.

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Which of the following is true?

A. The normal value for a laboratory measurement is usually defined as its mean value ± 3 SD.

B. Infections manifest with typical signs or symptoms characterizing disease the same for adults of all ages.

C. ~1% of the U.S. population self-identifies as having an allergy to penicillin.

D. Patients with indwelling catheters should always be treated with antibiotics.

E. Hippocrates advocated to understand the patient as an individual.

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Golden Nuggets

• Don’t interpret the patient based on the test• Interpret the test based on the patient

• Understand the limitations and timing of tests• Partner with your clinical laboratory staff and other infection

prevention specialists!

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Optimizing The Use of Clinical Laboratory Values in Antimicrobial Stewardship

Nicholas LadikosPharmD, BCPS, BCGP, BCIDP

Thank you!

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Clostridioides difficile Infection in the Older Adult

Elias B. Chahine, PharmD, FCCP, FFSHP, BCPS, BCIDPProfessor of Pharmacy Practice

Gregory School of PharmacyPalm Beach Atlantic University

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Conflicts of Interest

• Speakers’ bureau of Merck & Co, Inc.• Speaker’s bureau of Paratek Pharmaceuticals, Inc.

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Outline

• Epidemiology

• Clinical presentation

• Risk factors

• Treatment

• Prevention

https://www.cdc.gov/cdiff/what-is.html

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Epidemiology

Leffler DA. N Engl J Med. 2015;372:1539-48

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Epidemiology

www.cdc.gov/vitalsigns/HAI/index.html

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Epidemiology

Chopra T et al. Pharmacotherapy. 2016;36:1281-9

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Epidemiology

Clements AC et al. Lancet Infect Dis. 2010;10:395-404

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Question

•Which statement is true?

• A) CDI cases are decreasing in frequency and severity.

• B) C. difficile is more likely to cause disease in children than older adults.

• C) More than 50% of healthy adults are carriers of C. difficile in their stool.

• D) The NAP1/BI/027 and 078 ribotypes of C. difficile are very virulent.

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Clinical Presentation• Asymptomatic carrier

• Offensive-smelling acute watery diarrhea and fever

• Pseudomembranous colitis with adherent plaques

• Toxic megacolon and systemic toxicity

• Fulminant colitis, sepsis, and paralytic ileus

• Recurrent infections

Grace E et al. Sr Care Pharm. 2019;34:29-42

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Clinical Presentation

Definitions Supportive data

Initial episode, non-severe WBC count <15,000 cells/mLAND

SCr <1.5 mg/dL

Initial episode, severe WBC count ≥15,000 cells/mLOR

SCr ≥1.5 mg/dL

Initial episode, fulminant Hypotension or shock, ileus, megacolon

McDonald LC et al. Clin Infect Dis. 2018;31:431-55

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Question

• Which patient would be classified under the category of severe infection according to the IDSA/SHEA guidelines?

• A) A 65-year-old man with a WBC count of 10,100 cells/mL and a SCr of 1.1 mg/dL

• B) A 70-year-old man with a WBC count of 12,200 cells/mL and a SCr of 1.2 mg/dL

• C) A 75-year-old woman with a WBC count of 16,300 cells/mL and a SCr of 1.6 mg/dL

• D) A 79-year-old woman with a WBC count of 10,000 cells/mL and a SCr of 1.4 mg/dL

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Risk Factors• Drug-induced:

• Antibiotic exposure

• Broad-spectrum antibiotics

• Multiple antibiotics

• Long-term antibiotics

• Proton pump inhibitors

• Histamine-2 receptor blockers

• Chemotherapy agents

• Non drug-induced:

• Advanced age

• Female gender

• Caucasian ethnicity

• Severe underlying disease

• Immunocompromising conditions

• Manipulation of the GI tract

• Hospitalization or ICU admission

Grace E et al. Sr Care Pharm. 2019;34:29-42

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Risk Factors

Low risk Medium risk High risk

Aminoglycosides Penicillins Clindamycin

Tetracyclines Trimethoprim/ sulfamethoxazole

Ampicillin

Rifampin Macrolides Amoxicillin

Metronidazole Cephalosporins

Vancomycin Fluoroquinolones

Leffler DA. N Engl J Med. 2015;372:1539-48

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Question

•Which antibiotic is the LEAST likely to cause CDI?

• A) Ampicillin

• B) Ceftriaxone

• C) Gentamicin

• D) Levofloxacin

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Treatment

• Stop offending antibiotics when possible

• Replace fluid and electrolytes

• Avoid antimotility agents

• Consider surgical interventions in severe cases

• Treat for 10 days


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TreatmentDefinitions Supportive data Recommended treatment

Initial episode, non-severe

WBC <15,000 cells/mLANDSCr <1.5 mg/dL

Vancomycin 125 mg PO every 6 hrs for 10 daysFidaxomicin 200 mg PO every 12 hrs for 10 daysMetronidazole 500 mg PO every 8 hrs for days if no access to first-line options

Initial episode, severe WBC ≥15,000 cells/mLORSCr ≥1.5 mg/dL

Vancomycin 125 mg PO every 6 hrs for 10 daysFidaxomicin 200 mg PO every 12 hrs for 10 days

Initial episode, fulminant

Hypotension or shock, ileus, megacolon

Vancomycin 500 mg PO/NG every 6 hrs+ Metronidazole 500 mg IV every 8 hrs± Vancomycin via rectal instillation


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TreatmentDefinitions Recommended treatment

First recurrence Vancomycin 125 mg PO every 6 hrs for 10 days if metronidazole was used initiallyVancomycin 125 mg PO every 6 hrs for 10 to 14 days, every 12 hrs for a week, every 24 hrs for a week, and then every 2 or 3 days for 2 to 8 weeks (tapered and pulsed regimen)Fidaxomicin 200 mg PO every 12 hours for 10 days if vancomycin was used initially

Second or subsequent recurrence

Vancomycin 125 mg PO every 6 hrs for 10 to 14 days, every 12 hrs for a week, every 24 hrs for a week, and then every 2 or 3 days for 2 to 8 weeks (tapered and pulsed regimen)Vancomycin 125 mg PO every 6 hrs for 10 days followed by rifaximin 400 mg PO every 8 hours for 20 days (rifaximin chaser)Fidaxomicin 200 mg PO every 12 hours for 10 daysFecal microbiota transplantation


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Bezlotoxumab

Wilcox MH et al. N Engl J Med. 2017;376:305-17

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Case Vignette

• M.F., a 71-year-old man, was transferred from the nursing home to the hospital for the management of HAP. • He is receiving cefepime and ciprofloxacin.• On day 8, his lungs are clear, and he is no longer complaining of

shortness of breath.• However, he is now complaining of foul-smelling diarrhea and is

diagnosed with CDI.• WBC 22,000 cells/mm3; SCr 2 mg/dL; Alb 2.4 g/dL. • All: penicillin (itching).

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Question

• What is the best recommendation for M.F.?

• A) Start vancomycin 125 mg PO every 6 hours and continue cefepime and ciprofloxacin

• B) Start vancomycin 125 mg PO every 6 hours and discontinue cefepime and ciprofloxacin

• C) Start vancomycin 1000 mg IV every 12 hours and continue cefepime and ciprofloxacin

• D) Start vancomycin 1000 mg IV every 12 hours and discontinue cefepime and ciprofloxacin

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Prevention

• Implement institution-based infection control programs

• Isolate affected patients in single rooms

• Use barrier precautions such as gloves and gowns

• Emphasize hygiene particularly hand washing

• Implement antimicrobial stewardship programs

• Discontinue unnecessary gastric acid suppression

Marshall LL et al. Consult Pharm. 2017;32:24-41

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Key References and Readings

• McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America. Clin Infect Dis. 2018;66:987-994.

• Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372:1539-48.

• Grace E, Chahine EB. Updates on Clostridioides (Clostridium) difficileinfection with emphasis on long-term care. Sr Care Pharm. 2019;34:29-42.

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Clostridioides difficile Infection in the Older Adult

Elias B. Chahine, PharmD, FCCP, FFSHP, BCPS, BCIDPProfessor of Pharmacy Practice

Gregory School of PharmacyPalm Beach Atlantic University

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Multi-Drug Resistant Organisms

Eddie Grace, Pharm.D., BCIDP, AAHIVP, FIDSA

President & Chief Infectious Diseases Consultant Sovereign Medical Consulting, LLC

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Speaker Information –Bio

• Board-Certified Infectious Diseases Pharmacist • Fellow of the Infectious Diseases Society of America (IDSA)• American Academy of HIV Medicine Certified HIV

Pharmacist • ASCP Antimicrobial Stewardship and Infection Control

Committee • Current Chair of ACCP HIV PRN (2018-19)

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Disclosure – Eddie Grace, Pharm.D., BCIDP, AAHIVP, FIDSA• None to disclose

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Gram-negative MDROsEvolution of Resistance • Extended-Spectrum Beta-Lactamase (ESBL):

• Enzymes able to hydrolyze third and fourth generation cephalosporins and monobactams.

• Inhibited by CLA, TZB, and SLB• Resistance genes acquired through plasmids (not chromosomally present)

• Carbapenem-Resistant Enterobacteriaceae (CRE)/ Carbapenemase Producing Enterobacteriaceae (CPE)• Enzymes able to hydrolyze penicillins, cephalosporins, most ß-lactams, most

ß-lactamase inhibitors (±TZB), and carbapenems

J of Chemother 2017;29(S1): 2-9

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Gram-Negative MDROsEvolution of Resistance

1940s 1950s 1960s 1970s 1980s 1990s 2000-2010 2010-Now

1941: Penicillin

introduced

1940: Penicillinase Identified in E. coli

1965: TEM-1 Identified in

E. coli

1976: ß-lactamase inhibitors

introduced

1981: 3rd

Generation Cephalosporins

introduced

1983: SHV-2 Identified First ESBL

1985: Imipenem introduced

1989: ampC(CMY-1) & ESBL (CTX-

M) identified

1991: CRE identified(MBL and

OXA-1)

2001: KPC-1 identified

(NC, USA)

1968: SHV-1 Identified

J of Chemother 2017;29(S1): 2-9J Basic Microbiol 2017;57:460-70Infect Dis Clin N Am 2016:30:347-75Annu Rev Microbiol 2011;65:455-78

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Gram-Negative MDROsEvolution of Resistance

Infect Dis Clin N Am 2016;30:347-75Annu Rev Microbiol 2011;65:455-78

• CTX-M has become the dominant ESBL with a prevalence of 35-45% of all E. coli related UTIs and BSIs

• Currently >5 subtypes have been identified • E. coli CTX-M has been identified as E. coli Sequence Type 131 (ST131)• Also known as phylogenetic type B2 or serotype 025:H4• Resistance to CLA and TZB• Resistance to fluoroquinolones (especially ciprofloxacin) is common • Co-resistance to aminoglycosides and TMP/SMX also common

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Gram-negative MDROs Evolution of Resistance

J Basic Microbiol 2017;57:460-70

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Gram-negative MDROs Evolution of Resistance

J of Chemother 2017;29(S1): 2-9

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Gram-Negative MDROsE. coli • Gram-negative rod• Facultative anaerobe• Lactose and D-glucose fermenter• Member of the Enterobacteriaceae family • Most common organism in the small intestines• Wild-type E. coli is typically susceptible to most antibiotic classes:

• penicillins, aminopenicillins, cephalosporins, fluoroquinolones, sulfonamides, carbapenems, aminoglycosides, nitrofurantoin, fosfomycin, ß-lactam/ß-lactamase inhibitors

Curr Opin Infect Dis 2010;23:320-6Infect Dis Clin N Am 2016;30:347-75

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MDRO E. coli Colonization in NH-patients (42.6%)

E. coli resistant antibiotics Prevalence among E. coli ST131 isolates

3-drug resistance (88.4% of all MDRO E. coli)

Ciprofloxacin, extended-spectrum penicillins, and gentamicin

74.4% of all

Ciprofloxacin, extended spectrum penicillin, and extended-spectrum cephalosporins

23.2%

4-drug resistance (10.5% of all MDRO E. coli)

Ciprofloxacin, extended-spectrum penicillins, extended-spectrum cephalosporins, and gentamicin

100%

Gram-negative MDROs E. Coli –Resistance

Infect Control Hosp Epidemiol 2015;36(8):930-935

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Gram-negative MDROs E. Coli –Resistance • E. coli resistance patterns:

• ESBL E. coli • Resistance to one or more of the following:

• Penicillins • Cephalosporins • ß-lactam ß-lactamase inhibitor combinations• Fluoroquinolones • Aminoglycosides • TMP/SMX• Monobactams • Carbapenems (≥1 agent)

• CR-E. coli• Resistance to all the following:

• Carbapenems (ALL)• Cephalosporins (ALL)

Emerg Infect Dis 2015;21(9):1611-16Infect Dis Clin N Am 2016;30:347-75

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Gram-negative MDROs E. Coli –CipREc• Ciprofloxacin-Resistant E. coli (CipREc)

• 2011 study 34% of NH-residents colonized with CipREc• Risk factor for colonization was use of medical devices (HR 1.93)

• 2014 study showed a prevalence among colonized NH-residents of 47.5% (57 of 120)• Time to colonization positive averaged 46 days (IQR 21-296 days)• Risk factors for CR-EC acquisition included:

• Fecal incontinence (HR 1.78, 95%CI 1.04-3.06, p=0.04)• Amoxicillin-clavulanate receipt within 12-months (HR 6.48, 95%CI 1.43-29.4, p=0.02)• Urinary catheter use (HR 3.81, 95%CI 1.06-13.8, p=0.04)

Infect Control Hosp Epidemiol 2011;32:177-80J Infect Dis 2014;209:420-425

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Gram-negative MDROs E. Coli –CipREc• 2016 study in high-risk NH-residents (urinary-catheter or enteral

nutrition tubes or both)• 15% of all NH-residents were colonized with CipREc with an increase of

7.7%/year • 62.2% of CipREc were identified as ST131 (ESBL+)• All residents with CipREc had urinary-catheters• 63.2% of non-colonized residents had urinary-catheters

• Risk of CipREc was higher with suprapubic-catheter vs ureteral- catheters (22.6% vs 12.3%, respectively)

• Interestingly, residents with enteral nutrition tubes were less likely to have CipREc colonization (28.3% vs 49.2%)


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Gram-negative MDROs E. Coli –ESBL/ST131• Nosocomial colonization rate in the US:

• 7.8% in 2010 and 18.3% in 2014

• In NH-residents the mean ESBL colonization rate is ~17% (data from 2016) with a range from 8-28%• Risk factors for colonization:

• MDRO history (OR 4.1, 95%CI 1.6-10.4, p=0.003)• Bed-bound status (OR 2.6, 95%CI 1.3-5.4, p=0.008)• Urinary/fecal incontinence (OR 8.86, p<0.001)• Presence of urinary catheter (OR 8.57, P<0.001)

Infect Gen Evol 2018;61:185-8Med Sci Monit 2013;19:317-326

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Gram-negative MDROs E. Coli –ESBL/ST131• NH-residents are at increased risk of E.coli ST131 infections and

resulting bacteremia • 2014 study showed that being a resident of a LTCF increased the risk of

hospital-onset ESBL bacteremia by 5.1-fold (95%CI 2.2-11.9, p<0.01) in residents without antibiotic use in the past 30 days and without history of ESBL • Odds ratio increased to 6.9 with antibiotic use in prior 30 days• Odds ratio increased by 1.8 if resident had history of ESBL infections (95%CI 1.3-2.7,

p<0.01)• The risk remained elevated even after 48-hours of hospitalization (OR 3.4, 95%CI 1.3-9.0,

p=0.01)


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Gram-negative MDROs ESBL E. Coli –Treatment

Antibiotic/Class Place in therapy Indications Comments

Carbapenems Drugs of choice All Consider Etrapenem when pseudomonas and Acinetobacter not suspected Consider extended infusions

Piperacillin-tazobactam Alternative All Debatable whether it should be used in ESBL + infections. Latest study in 2018 supports its use

Fosfomycin Alternative UTI (mild-moderate High resistance threshold to ESBLs but use based on C&S results

Nitrofurantoin Alternative UTI (mild-moderate)

Infect Dis Clin N Am 2016;30:347-75

Polymyxin E/B Drugs of choice for severe infections with evidence of resistance to carbapenems

All Use in combination with other agents (never use monotherapy)

Aminoglycosides Alternative UTI Can be used in the treatment of UTIs is shown susceptible. Do not use monotherapy for severe invasive infections

Cephalosporins AVOID High likelihood of resistance

Fluoroquinolones AVOID

TMP/SMX AVOID

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• Carbapenem-Resistant Enterobacteriaceae are resistant to carbapenems and most other antibiotic classes previous mentioned • CRE are encoded by one or more of the following genes: NDM, OXA, VIM,

and IMP• 4.6% of NH-residents admitted to hospitals are colonized with a

carbapenem-resistant GN• Approximately 25% are colonized with CR-E. coli

• CRE (including E. coli) infections account for 4.2% of all infections in the US (2011)• Increase from 1.2% of infections in 2001

• E. coli accounts for 10% of all CRE-related infections

Gram-negative MDROs E. Coli –CRE

Emerg Infect Dis 2015;21(9):1611-1616Am J Infect Control 2016;44:126-30

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Which of the following antibiotics would be considered an appropriate agent for the empiric treatment of a suspected ESBL E. coli (ST131) bacteremia secondary to a UTI of the same organism?

A. Tobramycin B. Colistin C. ErtapenemD. Levofloxacin

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Which of the following antibiotics would be considered an appropriate agent for the empiric treatment of a suspected ESBL E. coli (ST131) bacteremia secondary to a UTI of the same organism?

A. Tobramycin B. Colistin C. ErtapenemD. Levofloxacin

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References• Han JH, Maslow J, Han X, et al. Risk factors for the development of gastrointestinal colonization with

fluoroquinolone-resistant Escherichia coli in residents of long-term care facilities. J Infect Dis. 2014 Feb 1;209(3):420-5.

• Dommeti P, Wang L, Flannery EL, et al. Patterns of ciprofloxacin-resistant gram-negative bacteria colonization in nursing home residents. Infect Control Hosp Epidemiol. 2011 Feb;32(2):177-80.

• Chong Y, Shimoda S, Shimono N. Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Infect Genet Evol. 2018 Jul;61:185-188

• Pobiega M, Wojkowska-Mach J, Chmielarczyk A, et al. Molecular characterization and drug resistance of Escherichia coli strains isolated from urine from long-term care facility residents in Cracow, Poland. Med Sci Monit. 2013 May 1;19:317-26.

• Venkatachalam I, Yang HL, Fisher D, et al. Multidrug-resistant gram-negative bloodstream infections among residents of long-term care facilities. Infect Control Hosp Epidemiol. 2014 May;35(5):519-26

• Cunha CB, Kassakian SZ, Chan T, et al. Screening of nursing home residents for colonization with carbapenem-resistant Enterobacteriaceae admitted to acute care hospitals: Incidence and risk factors. Am J Infect Control. 2016 Feb;44(2):126-30

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References• Mazzariol A, Bazaj A, Cornaglia G. Multi-drug-resistant Gram-negative bacteria causing urinary tract infections: a

review. J Chemother. 2017 Dec;29(sup1):2-9• Adler A, Katz DE, Marchaim D. The Continuing Plague of Extended-spectrum β-lactamase-producing

Enterobacteriaceae Infections. Infect Dis Clin North Am. 2016 Jun;30(2):347-375• Bush K, Fisher JF. Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases

from gram-negative bacteria. Annu Rev Microbiol. 2011;65:455-78• Padmini N, Ajilda AAK, Sivakumar N,et al. Extended spectrum β-lactamase producing Escherichia coli and

Klebsiella pneumoniae: critical tools for antibiotic resistance pattern. J Basic Microbiol. 2017 Jun;57(6):460-470.• Oteo J, Pérez-Vázquez M, Campos J. Extended-spectrum [beta]-lactamase producing Escherichia coli: changing

epidemiology and clinical impact. Curr Opin Infect Dis. 2010 Aug;23(4):320-6.• D'Agata EM, Habtemariam D, Mitchell S. Multidrug-Resistant Gram-Negative Bacteria: Inter- and

Intradissemination Among Nursing Homes of Residents With Advanced Dementia. Infect Control Hosp Epidemiol. 2015 Aug;36(8):930-5

• Chea N, Bulens SN, Kongphet T, et al. Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae. Emerg Infect Dis. 2015 Sep;21(9):1611-6

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Multi-Drug Resistant Organisms

Eddie Grace, Pharm.D., BCIDP, AAHIVP, FIDSA

President & Chief Infectious Diseases Consultant Sovereign Medical Consulting, LLC

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Q&A Session 2 – 15 min

Moderated by Dr. Milito

4. OpNmizing The Use Of Clinical Laboratory Values In AnNmicrobial Stewardship—Nicholas Ladikos

5. Clostridioides difficile InfecNon in the Older Adult—Elias B. Chahine 6. MulN-Drug Resistant Organisms—Eddie Grace


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Golden Nuggets: Bugs, Drugs and Antibiotic Stewardship

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