Appropriate Antibiotic Prescribing: Making Good Choices for Bad Bugs. Disclosure 4/22/17

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1 Appropriate Antibiotic Prescribing: Making Good Choices for Bad Bugs Elizabeth O. Hand, Pharm.D., BCPS Pediatric Infectious Disease Pharmacist University Health System Clinical Assistant Professor The University of Texas at Austin College of Pharmacy Disclosure I have nothing to disclose regarding the content of this presentation. Antibiotics are the only medication in which use in one patient can affect outcomes in another. 1

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3 Infections More Deadly Than Cancer?! This image cannot currently be Objectives Describe recent trends in antimicrobial resistance in the United States List three common bacterial pathogens seen in the primary care setting and available treatment options Explain unintentional consequences of inappropriate antibiotic prescribing Identify ways to improve appropriate antibiotic prescribing in clinical practice By The Numbers million antibiotic prescriptions annually 30-50% inappropriate >60% of expenditures in outpatient setting 80-90% of antibiotic volume in humans Most common antibiotics Azithromycin and amoxicillin 3

4 U.S. Outpatient Antibiotic Prescribing This image cannot currently be NEJM 2013; 368(15) What is Appropriate Antibiotic Prescribing? Using antibiotics to treat a bacterial infection Using the narrowest spectrum agent(s) needed to cover possible or known pathogens Using antibiotics for the shortest time possible Backed by the highest level of efficacy data available to treat the infection in question ANYTHING ELSE IS INAPPROPRIATE Adapted from slide presentation by Dr. Brad Spellberg, SIDP Presentation, Boston, MA 2016 What Are YOUR Biggest Challenges? This image cannot currently be 4

5 Challenges in the Outpatient Setting Lack of culture-driven therapy Viral vs. bacterial Fully susceptible vs. fully resistant Lack of knowledge or misconceptions about resistance Majority of providers unable to describe local trends Limited oral antibiotic options Perception antibiotics are benign Antibiotic Resistance Threats in the United States, CDC 2013 Report This image cannot currently be 1. Drug-resistant Streptococcus pneumoniae 2. Extended-spectrum beta lactamase producing Enterobacteriaceae (ESBLs) a. E.coli 3. MRSA Antibiotic Resistance Porin Deletion Altered Binding Site This image cannot currently be Efflux Enzymatic Breakdown 5

6 Most Common Reasons for Antibiotics Respiratory tract infections Urinary tract infections Skin/soft tissue infections Principles of Empiric Antibiotic Prescribing Presumed activity against >90% of isolates Most benign side effect profile Supported by clinical evidence Affordable for patient *Balancing potential risks vs. potential benefit* Most Common Reasons for Antibiotics Respiratory tract infections Pathogen of concern: Streptococcus pneumoniae Urinary tract infections Pathogen of concern: E.coli Skin/soft tissue infections Pathogen of concern: Staphylococcus aureus 6

7 Bacterial Respiratory Tract Infections Pharyngitis due to Streptococcus pyogenes (Group A streptococcus) Sometimes bacterial Community acquired pneumonia (CAP) Acute bacterial rhinosinusitis Acute otitis media (AOM) NOT BRONCHITIS Epidemiology of CAP This image cannot currently be 2% Jain S et al. NEJM 2015; 373: Streptococcus pneumoniae 4 million infections 22,000 deaths annually Most common bacterial cause of CAP Meningitis AOM? Immunization WORKS This image cannot currently be CDC, Antibiotic Resistance Threats in the United States,

8 Pneumococcal Conjugate Vaccine Impact PCV13 contains polysaccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F Efficacy Rates Evaluation of 3232 visits for suspected pneumonia or invasive disease 46% for first episode of vaccine-type CAP This image 75% for cannot vaccine-type currently be invasive disease N Engl J Med 2015;372: Pneumococcal Conjugate Vaccine Impact in Pediatrics This image cannot currently be This image cannot currently be J Pediatric Infect Dis Soc Feb 22. ACIP Recommendations for PCV13 Children Four dose series at 2, 4, 6 and months Adults >65 years Single dose followed by PPSV23 Adults >19 with immunocompromising conditions Single dose followed by PPSV23 8

9 Risk Factors For Pneumonia Smoking Poor oral hygiene or prosthesis Malnutrition Dust exposure in work place Oropharyngeal dysphagia Contact with children Nonvaccination against S.pneumoniae PPSV23 vs. PCV13 Clin Pulm Med 2016; 23: Guideline Recommended Regimens for CAP Previously healthy, no antibiotics in prior 3 months Macrolide (à azithromycin) Doxycycline Significant comorbidities (DM, alcoholism, malignancy, asplenia, etc), use of antibiotics in prior 3 months Respiratory fluoroquinolone (levo, moxi) Beta lactam (amoxicillin) plus a macrolide Clin Infect Dis 2007; 44: S Macrolides Azithromycin Oral 100% bioavailable Once daily dosing Fairly benign side effect profile Active against atypical pathogens, some S.pneumoniae A wolf in sheep s clothing? Driver of penicillin resistance in S.pneumoniae Concern for increased risk of sudden cardiac death NEJM 2012; 366: Clin Infect Dis 2011;53(7):

10 FDA Drug Safety Communication: Fluoroquinlones Health care professionals should not prescribe systemic fluoroquinolones to patients who have other treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections because the risks outweigh the benefits in these patients. FDA Drug Safety Communication, Safety Announcement, July Reliable Antibiotics for S.pneumoniae in CAP First line Penicillin, amoxicillin Amoxicillin-clavulanic acid Second line Cefdinir Cefuroxime Third line Respiratory fluoroquinolones Sinusitis: Treatment This image cannot currently be IDSA Clinical Practice Guidelines for Acute Bacterial Rhinos inus itis in Children and Adults. Clin Infect Dis

11 This Acute image Sinusitis: cannot currently Treatment be AZITHROMYCIN NOT RECOMMENDED FOR SINUSITIS DUE TO HIGH LEVELS OF RESISTANCE IN STREPTOCOCCUS PNEUMONIAE IDSA Clinical Practice Guidelines for Acute Bacterial Rhinos inus itis in Children and Adults. Clin Infect Dis Respiratory Infections: Take Home Points Most are viral Sick contacts are a clue If bacterial, mostly Streptococcus pneumoniae Macrolide resistance is increasing High dose amoxicillin is the most reliable option Fluoroquinolones as a last resort Most Common Reasons for Antibiotics Respiratory tract infections Pathogen of concern: Streptococcus pneumoniae Urinary tract infections Pathogen of concern: E.coli Skin/soft tissue infections Pathogen of concern: Staphylococcus aureus 11

12 E.coli Major cause of uncomplicated urinary tract infections and pyelonephritis Highly susceptible to multi-drug resistant Godzilla bug Antibiotic therapy should use a combination of the antibiogram and past antibiotic exposure This image cannot currently be Have You Recently Traveled to India? E.coli 83% resistance to ceftriaxone 84% resistance to fluoroquinolones 11% resistance to carbapenems CCEDP Resistance Map, This image cannot currently be 12

13 E.Coli in San Antonio % susceptible Amoxicillin 44 Ampicillin-sulbactam 54 Cefazolin 83 Cefpodoxime 84 SMX/TMP 65 Ciprofloxacin 75 Nitrofurantoin 93 Susceptible based on ability to clear a systemic infection Oral Empiric Options for E.coli Nitrofurantoin Only uncomplicated cystitis Sulfamethoxazole/tri methopri m Ciprofloxacin, levofloxacin Oral third generation cephalosporins Cefpodoxime, cefdinir $$$ Fosfomycin 3 gram single dose (aka the Fosfo bomb ) $$$ Which Agent is Best? This image cannot currently be Possibly algorithm First uncomplicated UTI? Nitrofurantoin First complicated UTI Send for culture Ciprofloxacin Repeat UTIs Send for culture JAMA 2014;312(16): Early clinical and bacterial cure >~90% for most regimens 13

14 Beware Asymptomatic Bactiuria Diagnosis of UTI Symptoms (aka dysuria) + positive culture Symptoms + positive urinalysis Discharge + dysuria? Don t forget sexually transmitted diseases Only treat asymptomatic bactiuria in SPECIFIC populations Pregnant women, those underlying GI/GU surgery, immunosuppressed patients (+/-) Urinary Tract Infections: Take Home Points E.coli is a problem Resistance increasing with no signs of slowing down MDR pathogens becoming more common in the community Reserve broader spectrum agents for second UTI or more complicated cases Nitrofurantoin preferred first line Send for culture, even though results are delayed Most Common Reasons for Antibiotics Respiratory tract infections Pathogen of concern: Streptococcus pneumoniae Urinary tract infections Pathogen of concern: E.coli Skin/soft tissue infections Pathogen of concern: Staphylococcus aureus 14

15 Staphylococcus aureus Gram positive cocci Three flavors Penicillin susceptible Methicillin susceptible (MSSA) Methicillin resistant (MRSA) Varying mechanisms of resistance Penicillin susceptible à penicillin resistant Beta lactamase production Methicillin susceptible à methicillin resistant Alteration in binding site MRSA aka THE KING Colonizes ~ 30% of US populations >80,000 invasive infections annually Bacteremia, endocarditis, pneumonia, bone and joint infections >11,000 deaths Why is MRSA so much worse? This image cannot currently Clin Microbiol Rev 2015; 28(3): How We Got Here 1960 First MRSA isolate identified 1981 MRSA outbreak amongst IVDU in Detroit fold increase in rate of hospitalizatio ns due to MRSA in patients with no risk factors MRSA infections in US academic centers double Increase in ED visits due to MRSA SSTIs from 1.2 to 3.4 million University of Chicago MRSA Research Center a-researc h-center.bsd. uchicag o.ed u/tim eline. ht ml 15

16 70 The Emergence of MRSA Prevalence All pts ICU UH Inpts UH Outpts Ann Clin Microbiol Antimicrob 2006 UHS Antibiograms MRSA in Recent Years Significant reductions in MRSA bacteremia since % reduction in hospital-associated MRSA infections Possible slight reduction in MRSA skin/soft tissue infections in the last decade Morbidity and mortality remain high Where Are We Now? Community onset MRSA ~40-45% of all S.aureus infections Common cause of skin/soft tissue infections Rare cause of community-acquired pneumonia <1% Can affect anyone, certain risk factors do exist IVDU, hemodialysis, FQ use? 16

17 MRSA by Age This image cannot currently be Guidelines for SSTI Management This image cannot currently be IDSA Guidelines for Management of SSTIs, MRSA Management Vancomycin Preferred agent for severe, invasive infections requiring intravenous therapy Oral antibiotic options Sulfamethoxazole/trimethoprim Doxycyline Minocycline Clindamycin Linezolid 17

18 Oral Options for MRSA Highly active in vitro (>95%) Sulfamethoxazole/trimethoprim Sulfa allergy, rash, hyperkalemia Linezolid Drug interactions (SSRIs), peripheral and optic neuropathy, bone marrow suppression, wallet toxicity Doxycyline, minocycline GI upset, binding of divalent cations Modest activity (60-70%) Clindamycin C.difficile associated diarrhea New Kids on the Block Dalbavancin, oritavancin Intravenous agents with activity against MRSA Approved in 2014 for acute bacterial skin/skin structure infections Half lives range from days 1 to 2 dose regimens $$$$$ Jury still out on clinical utility This image cannot currently be Nothing Kills like a Beta Lactam IDSA Guidelines for Management of SSTIs,

19 Avoidable Antibiotic Exposure in SSTIs Retrospective cohort study in Colorado 364 cases (pediatric and adult) 155 cellulitis, 168 abscess 139 cases of drained abscesses Antibiotics given in 80% of cases Average 7 day duration Overall 46% of all antibiotic use was deemed AVOIDABLE Am J Med 2013; 126(12) Skin Soft Tissue Infections: Take Home Points Purulence? à think Staphylococcus aureus IF an antibiotic is needed, cover for MRSA SMX/TMP, doxycycline, linezolid Non-purulent Cephalexin Clindamycin Five days is enough Tips on Picking the Right Drug DRUG BUG Interaction evaluated in the microbiology lab Effect of drug on bug at a set concentration Static interaction ONE PIECE OF THE PUZZLE 19

20 DRUG BUG DOUG Wrapping Up Antibiotics are a shared resource Most antibiotic prescribing occurring in the outpatient setting Limited development in new antibiotics Knowing your resistant pathogens and treatment options is key CDC 12 Steps to Reducing Antibiotic Resistance 1. Vaccinate 2. Get the catheters out 3. Target the pathogen 4. Access the experts 5. Practice antimicrobial control 6. Use local data 7. Treat infection, not contamination 8. Treat infection, not colonization 9. Know when to say no to vanco 10. Stop treatment when infection is cured or unlikely 11. Isolate the pathogen 12. Contain the contagion 20

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