Antibiotic Stewardship in the Long Term Care Setting. Lisa Venditti, R.Ph., FASCP, Founder and CEO Long Term Solutions Inc LTSRX.

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Antibiotic Stewardship in the Long Term Care Setting Lisa Venditti, R.Ph., FASCP, Founder and CEO Long Term Solutions Inc. 845.208.3328 LTSRX.com 1

Resistant Bacteria Crisis The Centers for Medicare & Medicaid Services (CMS) proposed a rule requiring all long term care facilities to establish an antibiotic stewardship program, including antibiotic use protocols and antibiotic monitoring The CDC charged pharmaceutical companies with inventing 10 new antibiotics by 2020 in an effort to get ahead of the crisis. 2

Strategies for an effective program Preauthorization Syndrome specific interventions Rapid diagnostic testing 3

Antimicrobial Use in Nursing Homes Primary indications for antibiotics: Urinary tract infections Respiratory tract infections Skin and soft tissue infections Fluoroquinolone ( Levaquin, Avelox, Cipro) use is common 25% to 75% of antibiotic use deemed inappropriate Nicolle LE, et al; ICHE 2000 21:537-45 Van Buul LW, et al; JAMDA 2012; 13: 568.e1-568e13 Benoit et al. JAGS 2008; 56: 2039-2044 4

Some Common Situations Where Antibiotics are Used and Rarely Necessary 1. Positive urine culture in asymptomatic resident 2. U/A and culture for cloudy or malodorous urine 3. Non specific symptoms not referable to the urinary tract 4. Suspected or proven influenza with no secondary infection 5. Skin wound without cellulitis, sepsis, osteomyelitis 5

Challenges in Clinical Decision to Initiate Antibiotics in the Nursing Home Family pressure Medical staff not available to perform an evaluation of the resident Low nurse to patient ratio and poor communication and assessment skills Diagnostic tests less readily available Colonization is common 6

Overuse of Antibiotics Adverse drug effects: Antibiotic related side effects Interaction with other drugs Antibiotic Resistance: Increase opportunities for transmission to other patients C. difficile infections Older adults are at higher risk of infections 7

SHEA and JAMDA Guidelines Minimum Criteria for Initiation of Antibiotics Algorithms for Treatment of Common Infections in LTCF Surveillance Definitions of Infections for Nursing Homes Full Guidelines available free on www.idsociety.org and www.shea-online.org 8

URINARY TRACT INFECTIONS 9

Urinary Tract Infections in Nursing Homes Most common indication for antibiotic use Accounts for 32-66% of prescriptions UTI is most common condition associated with inappropriate treatment secondary to asymptomatic bacteriuria 10

Asymptomatic Bacteriuria is Common Women less than 60 years 3-5% Prevalence Elderly in Community Setting Women Men Elderly in Nursing Homes Women Men 11-16% 15-40% 25-50% 14-40% Patients with Indwelling Catheters 100% Nicolle LE, Clinical Infectious Diseases 2005;40(5): 643 54 11

UTI versus Asymptomatic Bacteriuria Bacteria in Urine Urinary Symptoms NO Asymptomatic Bacteriuria Yes UTI 12

Specific Urinary Tract Symptoms Symptoms Dysuria Urgency Flank Pain Incontinence Frequency Hematuria Suprapubic Pain * For residents without indwelling catheter NOT Symptoms New Onset Delirium* Mental Status Changes* Acting Funny Weakness Fatigue Decrease oral intake Falls/gait disturbances Foul Smelling /Cloudy Urine 13

What to do in resident with Advanced Dementia? A patient with advanced dementia may be unable to report urinary symptoms, in this situation, it is reasonable to obtain a urine culture if there are signs of systemic infection such as fever, (increase in temperature 2o F from baseline), leukocytosis, or chills, in the absence of additional symptoms (e.g. new cough) to suggest an alternative source of infection 14

When to Treat UTI Microbiologic criteria Symptom criteria No indwelling catheter Positive urinalysis (WBC 10/HPF) and Positive urine culture ( 105 cfu/ml in voided specimen 102 cfu/ml if in and out cath) Acute dysuria --OR-- Fever* + at least 1 of following (new or worsening):* If no fever, 2 of the following (new or worsening) Urinary urgency Frequency Suprapubic pain Gross hematuria Urinary incontinence Indwelling catheter Positive urinalysis (WBC 10/HPF) and Positive urine culture ( 103 cfu/ml) At least 1 of the following (new or worsening): Fever* Rigors (shaking chills) Delirium Flank pain (back, side pain) pelvic discomfort Acute hematuria *Fever: A single oral temperature 100o F(37.8oC); or repeated oral t 99oF (37.2oC); or Persistent rectal t 99.5oF (37.5oC); or an increase in t of > 2o F (1.1oC) over the baseline temperature Loeb M. BMJ 2005;331:669 15

How to set up an Antibiotic Stewardship Program Review the Core Elements of Antibiotic Stewardship from CDC Infection Control Committee members include clinical pharmacist and lab Antibiograms analyzed : See AHRQ Website Protocols on treating common infections developed 16

Antibiogram Antibiograms aggregate information about susceptibility patterns of organisms to commonly prescribed antibiotics. Antibiograms display the organisms present in clinical specimens for laboratory testing as well as the susceptibility of each organism to an array of antibiotics. Antibiograms are routinely prepared by hospital laboratories, over a period of months or years, but antibiograms are not routine in the nursing home setting. 17

MANAGEMENT OF UTI 18

UTI definitions Uncomplicated UTI infection in a structurally/functionally normal urinary tract. Includes women post menopausal and with controlled diabetes Complicated UTI patients with a structural or functional abnormality of the urinary tract. Includes men and any patient with structural urinary abnormalities Lower UTI UTI without involvement of the kidneys (whether complicated or uncomplicated) Upper UTI/pyelonephritis infection of the kidney 19

Cystitis/Lower UTI (Complicated or Uncomplicated) Agent Notes Nitrofurantoin Most active agent against E. coli Avoid if CrCl < 30 ml/min Avoid if systemic signs of infection/suspicion of pyelonephritis or prostatitis Does not cover Proteus 1st line TMP-SMX Drug-drug interactions with warfarin Monitor potassium level if concomitant use of spironolactone, angiotensinconverting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) Renal dose adjustments, avoid if CrCl < 15 ml/min 2nd line Cephalexin Active against E. coli, Proteus, and Klebsiella 20

Pyelonephritis/ Upper UTI 1st line Agent TMP-SMX Notes Patient should receive 1 dose of IV/IM ceftriaxone prior to starting oral therapy 2nd line Ciprofloxacin If patient unable to tolerate TMP/SMX 3rd line Beta-lactams Data suggests that oral beta- lactams are inferior to TMP/SMX or fluoroquinolones for pyelonephritis Initial dose of IV/IM ceftriaxone and longer treatment duration of 10-14 days are recommended 21

Severely ill patients (high fever, shaking chills, hypotension, etc.) Agent Notes 1st line Ceftriaxone Can be used safely in patients with mild penicillin allergy (i.e. rash), crossreactivity very low 2nd line Gentamicin ONLY in patients who need parenteral therapy and have severe IgE mediated penicillin allergy Significant nephrotoxicity/ototoxicity concerns 22

UTI Treatment Duration UTI Location Agent Duration Uncomplicated UTI TMP/SMX Quinolones 3 days Complicated UTI Any Agent 5 days Pyelonephritis Catheter Related UTI Quinolones TMP/SMX B-Lactams 5-7 days 10-14 days 7 days if rapid improvement 10-14 days if delayed response Hooten, TM, et al. Clinical Infectious Diseases 2010; 50:625 663 Gupta et al. Clinical Infectious Diseases 2011;52(5):e103 e120 Grigoryan L, et al. JAMA 2014;312(16):1677-1684 Schaeffer AJ, et al. N Engl J Med 2016;374:562-71 Mody, L, et al JAMA. 2014;311(8):844-854 23

RESPIRATORY INFECTIONS 24

Respiratory Tract Infections Signs and symptoms Antibiotics Upper Respiratory Tract infection (URTI) Runny nose Sore throat cervical lymphadenopathy Dry cough X Influenza like illness Fever with increased cough, headache, myalgia, sore throat X Bronchitis No COPD New or worsening cough Sputum production X COPD exacerbation New or worsening cough and sputum production Pneumonia (bacterial) New or worsening cough, sputum production, shortness of breath pleuritic chest pain, HR > 125/min RR> 24/min, fever, O2 saturation <94% and + CXR 25

Nursing Home Pneumonia Community Acquired PNA Nursing Home Associated PNA Healthcare Associated PNA 26

Healthcare Associated Pneumonia (HCAP) HCAP: is defined as pneumonia that occurs in a non-hospitalized patient with extensive healthcare contact, as defined by one or more of the following: Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days Residence in a nursing home or other long-term care facility Hospitalization in an acute care hospital for two or more days within the prior 90 days Attendance at a hospital or hemodialysis clinic within the prior 30 days 27

Suggested Pneumonia Treatment 1st line Agents Dosing Mild Azithromycin or 500mg PO for 3 days Moderate Moderate to severe 2nd line Doxycycline Amoxicillin Cefuroxime Cefpodoxime Amoxicillin/Clavulanate Ceftriaxone Levofloxacin Moxifloxacin 100mg PO twice a day x 7d 1 gm PO 3 times a day x 7d 500mg PO twice daily x 7 d 200mg or 400mg PO BID x 7d 2 gm twice daily x 7d 1gm IM q day (switch to oral when improved, afebrile, can take oral meds) 500-750mg PO Q24H x 7d 400mg PO Q24H x 7d 28 Mandel L, et al. IDSA/ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27 72

Skin and Soft Tissue Infections 29

Suspected Skin and Soft Tissue Infections New or increasing purulent drainage at a wound, skin, or soft-tissue site or Fever (100oF] or a 2.4oF increase above baseline temperature) Redness Tenderness Warmth New or increasing swelling 30

Colonization Versus Infection Colonization: When an organism lives on your skin but not causing disease Infection: When the organisms on your skin invade though a break in your skin, multiply and cause disease 31

Is it Cellulitis? 32

Purulent and Non purulent Cellulitis 33

34

Treatment for Cellulitis Drug Regimen Indication Amoxicillin Dicloxacillin Cephalexin TMX/SMZ Clindamycin 500mg PO TID Dose Adjustment: CrCl 10-30 = 500mg BID CrCl <10 = 500mg Q Day 500mg PO q6h Dose Adjustment: None 500mg PO q6h Dose Adjustment: CrCl 10-50 = 500mg q8-12h CrCl <10 = 250mg 500mg q12-24h 1-2 DS tab PO BID Dose Adjustment: CrCl 15-30 = 50% of dose CrCl <15 = do not use 450mg PO TID Use for Strep Infections Good for Strep or MSSA Can use to treat Strep or MSSA Use for MRSA (if susceptible) Not a good option for Strep infections! Use for Strep or MRSA (some strep resistant) Caution: High risk of C. Diff. Only use if not other 35 options available

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C. DIFFICILE INFECTIONS 37

23% Developed CDI without recent healthcare exposure 95% received antibiotics 51% 26% Developed CDI during hospitalization Developed CDI within 30 days post discharge from the hospital 68% were in sub-acute care 80% received antibiotics during hospitalization 58% were still receiving antibiotics at the time of transfer JAGS 61:122 125, 2013

Antibiotics C. difficile Infection Risk Frequent associated Fluoroquinolones Clindamycin Cephalosporins (broad spectrum) Penicillins Occasionally associated macrolides TMP/SMZ Rarely associated Aminoglycosies Tetracylines Metronidazole Vancomycin 39

Treatment for C. difficile Infections Initial Episode Mild disease Metronidazole 500 mg 3 times daily or 250 mg 4 times daily Moderate Disease Severe Disease First relapse Second relapse Subsequent relapse Vancomycin 125 mg 4 times daily Hospitalization As initial or fidaxomicin 200 mg twice daily Vancomycin taper over 6 weeks Or fidaxomicin 200 mg twice daily fidaxomicin 200 mg twice daily Fecal microbiota transplant ModifiedfromLefflerDA,LamontJT.NEnglJMed2015;372:1539-1548.

Fidaxomycin Vs. Vancomycin LouieTJetal.N EnglJ Med2011;364:422-431.

Probiotics Many strains and combinations exist Initial studies evaluating the use of probiotics for control of antibiotic-associated diarrhea were underpowered for the detection of protection against C. difficile infection. More recent studies have shown mixed results At present, probiotics have an uncertain effect on the prevention of C. difficile infection

Questions? 43