Infectious Disease 101: Helping the Consultant Pharmacist with Stewardship Principles

Infectious Disease 101: Helping the Consultant Pharmacist with Stewardship Principles Conflicts of Interest None at this time May be discussing off-label indications KALIN M. CLIFFORD, PHARM.D., BCPS, BCGP ASSISTANT PROFESSOR, GERIATRICS DIVISION TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER SCHOOL OF PHARMACY JANUARY 27, 2018 Objectives Why should we care? Discuss the most common long-term care pathogens and the antibiotics most effective in treating them Evaluate antibiogram accessibility and applicability to the long-term care environment Identify 3 items a consultant pharmacist can monitor easily during a monthly medication review to make an impact on antimicrobial stewardship Provide recommendations to facility leadership with regard to interventions necessary to improve antimicrobial stewardship Increasing colonization rates in nursing homes Organism Healthcare-associated infections increasing among older adults in long-term care facilities 11.5% prevalence > 85 years of age Colonization Rates Vancomycin-Resistant Enterococcus (VRE) 33% Clostridium difficile 4-30% Methicillin-resistant S. aureus (MRSA) 30% Multidrug resistant Enterobacteriaceae spp. (Klebsiella spp., Proteus spp., etc.) 20% Why should we care? Antibiotics contribute to approximately 20% of adverse drug events 40% of hospice patients on antibiotics in last 2 weeks of life May not have appropriate symptoms Associated with decreased comfort What are potential limitations in geriatric care settings? Access to lab and microbiology reports Nursing staff to administer appropriate antibiotics Funding Time Difficulty with diagnosing infections Lack of geriatrics training in medical education 1

Specific Infectious Diseases Pneumonia Clostridium difficile Urinary Tract Infections Skin and Soft-Tissue infections Cellulitis Osteomyelitis Urinary Tract Infection Common Pathogens: Escherichia coli - still #1 likely pathogen Proteus mirabilis Klebsiella oxytoca Not as common: Staphylococcus spp. Enterococcus spp Pseudomonas aeruginosa Urinary Tract Infection Where is the infection? Cystitis vs. Pyelonephritis Uncomplicated vs. Complicated Catheter vs. No catheter Symptoms vs. No symptoms Unfortunately these questions play into treatment decisions and durations Urinary Tract Infection Uncomplicated Cystitis Nitrofurantoin 100 mg BID x 5 days Trimethoprim/Sulfamethoxazole DS BID x 3 days Fosfomycin 3 g x 1 dose Amoxicillin-clavulanate 875/125 (or 500/125) mg PO BID x 7 days Uncomplicated Pyelonephritis Ciprofloxacin 500 mg PO BID x 7 days (can also do IV) Trimethoprim/sulfamethoxazole DS BID x 14 days Maybe: Tobramycin (weight based) IV daily Maybe: Ceftriaxone 1 gram IV daily Complicated: use the same drugs but treat between 7 14 days (most likely 10-14 days) Fluoroquinolones should not be as relied upon unless needed Other Treatment Pearls Pneumonia Nitrofurantoin Great for E. coli coverage, but not P. mirabilis Sulfamethoxazole/Trimethoprim Great for patients with a history of gramnegative infections Remember to tailor antibiotics once susceptibilities are known Duration: still similar depending on if the infection is complicated or uncomplicated Likely to receive longer courses of antibiotic treatment Common Pathogens: Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Mycoplasma pneumoniae Chlamydiophila pneumoniae Staphylococcus aureus Likely may not even get cultures due to inaccuracy of sputum Infect Drug Resist. 2013;7:1-7 2

Pneumonia Risk Factors for Drug Resistance Drug Resistant Strep. Pneumoniae Prior antibiotic therapy Alcoholism Immunosuppres sion Multiple Comorbidities Atypical Pathogens Increased age (over 65 years) LTCF residency Pseudomonas aeruginosa Severe COPD Oral corticosteroids Alcoholism Recent antibiotic use Diabetes mellitus??? Pneumonia - CAP Setting Outpatient Inpatient (non-icu) Inpatient (ICU) Pseudomonas CA-MRSA Treatment No use of antibiotics in past 90 days: Macrolide or doxycycline Comorbidities or use of antibiotics: Respiratory fluoroquinolone or Beta-lactam plus macrolide Respiratory fluoroquinolone Beta-lactam plus macrolide Beta-lactam plus macrolide Respiratory fluoroquinolone Antipneumococcal and Antipseudomonal Beta-lactam PLUS ciprofloxacin or levofloxacin (750 mg dose) or aminoglycoside + macrolide Add vancomycin or linezolid May also need to consider clindamycin if treating orally (Due to presence of PVL) CID. 2007;44:S27-S72 What secret code words did I just say? Respiratory fluoroquinolone: levofloxacin or moxifloxacin Macrolide: Azithromycin Beta-lactam: amoxicillin-clavulanate, cephalosporins (cephalexin, ceftriaxone, etc) Aminoglycoside: gentamicin or tobramycin Antipneumoccal: drugs that cover S. pneumo Antipseudomonal: drugs that cover P. aeruginosa Pneumonia - HAP Not at High Risk of Mortality or MRSA Piperacillin-Tazobactam 4.5 grams IV q 6 Cefepime 2 g IV q8 Levofloxacin 750 mg IV daily *Imipenem 500 mg IV q6 *Meropenem 1 gram IV q8 Risk Factors for MRSA Piperacillin-Tazobactam 4.5 grams IV q 6 Cefepime 2 g IV q8 Levofloxacin 750 mg IV daily Ciprofloxacin 400mg IV q8 *Imipenem 500 mg IV q6 *Meropenem 1 gram IV q8 Aztreonam 2 g IV q8 PLUS: Vancomycin 15mg/kg (may need to load) OR Linezolid 600 mg IV q12 Increased Mortality or recent IV antibiotics Piperacillin-Tazobactam 4.5 grams IV q 6 Cefepime 2 g IV q8 Levofloxacin 750 mg IV daily Ciprofloxacin 400mg IV q8 *Imipenem 500 mg IV q6 *Meropenem 1 gram IV q8 Aztreonam 2 g IV q8 Gentamicin/Tobramycin 5-7 mg/kg daily; or Amikacin 15-20 mg/kg daily PLUS: Vancomycin 15mg/kg (may need to load) OR Linezolid 600 mg IV q12 CID. 2016; 63(5):e61-111. Pneumonia treatment pearls HCAP no longer covered in guidelines New CAP guidelines in Spring 2018 Daptomycin should not be used for treatment of pneumonia even if the pathogen is MRSA, VRE, etc. Duration: HAP 7 days CAP 5 days If afebrile 48-72 + no CAP sign of instability: STOP Monotherapy with macrolide not recommended for older adults Aspiration: may need to add clindamycin Clostridium difficile New guidelines any day No more metronidazole therapy for treatment Fidaxomicin (Dificid ) should be included for recurrent C. diff Bezlotoxumab (Zinplava 0 likely not going to be included in new update Mainstay of therapy: Oral vancomycin x 10-14 days 125 mg Depends on severity White count elevation Serum Creatinine Caution with probiotics 3

Skin and Soft-Tissue Infections Skin and Soft-Tissue Infections Common pathogen: Staphylococcus spp. Streptococcos spp. Pseudomonas aeruginosa Diabetic patients Wounds increase risk of resistant pathogens Also increase risk of bacteremia Not as common of infections in nursing homes, but growing especially in rehab and LTACs Many times will be continuing treatment from the hospital Often still on IV therapy Do not treat older adults differently Be cautious with cultures Purulent wounds are more likely to get an accurate cultures (abscess) Blood cultures more beneficial Durations: Cellulitis: 5-7 days Abscess: One time: may not even need antibiotics Recurrent: 5-10 days Osteomyelitis: 6 weeks Chronic osteomyelitis: 12 weeks (lack of literature) CID. 2014; 59(2):e10-52. CID. 2014; 59(2):e10-52. Skin and Soft-Tissue Infections Lots of antibiotic choices Non MRSA/MSSA MSSA MRSA Dicloxacillin 250 mg Cephalexin 250 mg Erythromycin 250 mg Clindamycin 300 450 Amoxicllin-clavulanate 875/125 BID Nafcillin 1-2 g IV q4 Cefazolin 1g q8 Clindamycin 600 mg IV q8 Dicloxacillin 500 mg Cephalexin 500 mg Sulfamethoxazoletrimethoprim DS 1-2 tabs BID Vancomycin (weight based/renal function) Linezolid 600 mg IV/PO BID Clindamycin 600 mg IV q8 Daptomycin 4mg/kg IV qday Ceftaroline 600 mg IV BID Sulfamethoxazoletrimethoprim DS 1-2 tabs BID Self-Assessment Question #1 Which of the following pathogens is the most common in urinary tract infections? A. Escherichia coli B. Moraxella catarrhalis C. Pseudomonas aeruginosa D. Staphylococcus aureus CID. 2014; 59(2):e10-52. Self-Assessment Question #1 Which of the following pathogens is the most common in urinary tract infections? A. Escherichia coli B. Moraxella catarrhalis C. Pseudomonas aeruginosa D. Staphylococcus aureus Using an antibiogram What is an antibiogram? Overall profile of antimicrobial susceptibility testing results of a specific microorganism to a battery of antimicrobial drugs How is it developed? Performed annually At least 30 isolates required for inclusion in analysis Isolates from diagnostic testing Do not include MRSA screenings or colonizers Include antibiotics that are routinely tested Use only a first isolate from a patient Evaluating percentage susceptible Indian J Med Microbiol. 2010;28(4):277-80 4

Here s what it could look like CIP LEV IMP MER NTF SMX/TMP TOB E. coli 28% 58% 100% 100% 95% 86% 96% P. mirabilis 36% 68% 95% 97% 98% 82% 99% K. oxytoca 48% 41% 90% 92% 92% 84% 95% Presentation and Utility of Antibiograms Gram-positive and gram-negative species should be split into their own tables Remember different antibiotics cover different pathogens Make them available Reporting on different levels of care within institution ICUs: 5-25% more resistant organisms compared to other units Monitoring of antibiotic resistance rates Establish facility-specific empiric antibiotic recommendations Indian J Med Microbiol. 2010;28(4):277-80 Infect Control Hosp Epidemiol. 2006;27:682-7 Effectiveness of Antibiogram Antibiogram Approach Antibiotics chosen: Cystitis Pyelonephritis Education session after creating ED-specific antibiogram for UTI therapy Primary outcome: adherence to recommendations based on local resistance rates Nitrofurantoin 100 mg q12 x 5 days IV: Ceftriaxone 1 gram, tobramycin or gentamicin 5-7 mg/kg (Pharmacy to Dose) Cephalexin 500 mg q12 x 7 days PO: Ciprofloxacin 250 mg q12 x 7 days or Levofloxacin 250 mg q24 x 5 days SMX-TMP 800/160 mg q12 x 3 days SMX-TMP 800/160 mg q12 x 14 days Ciprofloxacin 250 mg q12 or Levofloxacin 250 mg q24 x 3 days Cephalexin 500 mg q6 x 14 days Am J Emerg Med. 2015;33(9):1129-33. Am J Emerg Med. 2015;33(9):1129-33. Antibiogram Approach Isolate susceptible Cystitis Pyelonephritis P-Value Pre- Post- Education Education N=106 (%) N=149 (%) Pre- Education N=68 (%) Post- Education N=27 (%) 74% 89% 90% 76% 0.05 / 0.23 Cephalexin 1 (0.9) 2 (1.3) 0 1 (18.5) 0.77 / 0.11 Fluoroquinolones 35 (33) 16 (12.8) 32 (47) 19 (70.4) <0.001 / 0.04 Nitrofurantoin 13 (12.3) 119 (79.9) 7 (10) 5 (18.5) <0.001 / 0.28 Antibiogram Approach Choice of empiric therapy: 44.8% Pre vs. 83% Post (P<0.001) Lowest rate of adherence was duration of therapy 16% Pre vs. 25.5% Post (P=0.029) Follow up care within 30 days: 4.6% Pre vs. 7.4% Post (P=0.27) Strengths First study to evaluate use of antibiograms in ED Strong outcomes by utilizing education Limitations Single-center observational study Follow-up care may have occurred at a different facility Misclassification as abstractor was not fully blinded SMX-TMP 56 (52.8) 8 (5.4) 29 (43) 2 (7.4) <0.001/0.001 Am J Emerg Med. 2015;33(9):1129-33. Am J Emerg Med. 2015;33(9):1129-33. 5

Let s Practice What did we find out? Instructions: On your table there should be some pages of culture and susceptibility reports from the lab. Break into groups at your table, and I ll assign you a couple of antibiotics to specific calculate the % susceptibility After 3-5 minutes, will discuss our findings and fill in the antibiogram E. coli Amk Amp A/S Am A/C Cip Ert Gen Lev Mer P/T T/S Tob Other Antibiogram Studies in Nursing Homes Furuno, et.al Antibiogram in SNF Appropriate antibiotic prescribing increased from 32% - 45% Prior to antibiogram: 85% of all prescriptions were empiric Kindschuh, et al Hospital antibiogram vs. LTCF Proved antibiotic resistance worse in LTCF Seen in both gram-positive and gram-negative pathogens Need to create facility specific antibiogram do not rely on your local hospital Self-Assessment Question #2 How many isolates are needed in order to create an antibiogram with a specific pathogen? A. 15 B. 30 C. 45 D. 60 Infect Control Hosp Epidemiol. 2014;35 Suppl 3:S56-61 Self-Assessment Question #2 Now it s time to ask How many isolates are needed in order to create an antibiogram with a specific pathogen? A. 15 B.30 C. 45 D. 60 6

Everyone is requiring it Joint Commission Centers for Disease Control and Prevention Agency for Healthcare Research and Quality Centers for Medicare and Medicaid Services Long Term Care Institute White House, and on and on CDC s Specific Tasks Facility-specific interventions Communication tools for infection Algorithms for assessing residents with infections Facility-specific antibiograms Pharmacy-specific interventions Drug regimen review (DRR) of antibiotics Review microbiology results Infection-specific interventions Reduce antibiotics in asymptomatic bacteriuria Optimize pneumonia care in nursing home patients But how does this work in LTC? Who is going to pay for it? How much more time is it? Where do I even start??????? This question is just now starting to be answered Where did my facility start? Duration of Therapy Is there a documented start date or stop date pre-specified? Incorporated this into chart review First recommendation was: when do you want the antibiotic to stop? Could match indication to anticipated duration Paid attention to antibiotic orders that were active > 14 days Put in hard stops in computer system Utilized 7 days, then drug would fall off Stop dates written in order Where did my facility start? Reviewed cultures as part of chart review Started with is there one there? Then reviewed was empiric therapy correct and effective Communicated with my team that I have some ID background and to contact me before calling the ID pharmacist Performed pharmacokinetics/renal dose adjustments on IV antibiotics What else have I done/planning to do? Education sessions with providers Antibiotics discussed twice yearly goal quarterly New Guidelines Pneumonia and Urinary Tract Infections Created hand outs for nursing staff Use of Antibiogram Disperse antibiogram Review # times our empiric treatment was effective Updating materials as antibiogram data renewed 7

What else have I done/planning to do? What are my struggles? Daily Discharge Huddle Interdisciplinary Started bringing up culture results IV antibiotic duration/use C.diff discussions Great thing to send students to Quality Improvement Projects Been able to be more successful at looking at data Documentation and discussion Getting support to perform these tasks on top of additional duties Student support Another pharmacist? Updating Scope of Practice/Collaborative Practice Agreements How to get administrator buy-in? Get in touch with MDS team, DON, etc Each activity for your program should line up with one of the 7 elements Pharmacists can help with 5 right off the bat Rehab facilities do worry about LOS Survey visit CDC s Core Elements Leadership Commitment Accountability Drug Expertise Action Tracking Reporting Education New: AMDA has released a stewardship policy for nursing home administrators to implement Where do we fit things in? Leadership Commitment Accountability Drug Expertise Action Tracking Reporting Monthly medication reviews Evaluating stop dates Keeping record of C. difficile infections Antibiotic Adverse Drug Events Talking with providers regarding what you have tracked Follow up from the chart review Education Inservices Summary Majority of antibiotic durations should be less than 2 weeks. If you see an antibiotic on for more than 14 days, there needs to be a documented indication Antibiograms can provide useful information, but it needs to be used wisely. Getting support to perform stewardship will be challenging, but the more that we can do, even small steps, we can start moving in the right direction 8

Infectious Disease 101: Helping the Consultant Pharmacist with Stewardship Principles KALIN M. CLIFFORD, PHARM.D., BCPS, BCGP ASSISTANT PROFESSOR, GERIATRICS DIVISION TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER SCHOOL OF PHARMACY JANUARY 27, 2018 9