Antimicrobial Stewardship 101...Antimicrobial Stewardship 101: Tips and Tricks for Changing Your...
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Antimicrobial Stewardship 101: Tips and Tricks for Changing Your Practice Annie Wirtz, PharmD, BCPPS Clinical Pharmacy Specialist Infectious Diseases and Antimicrobial Stewardship October 4, 2019 Nothing to Disclose
Antimicrobial Stewardship 101...Antimicrobial Stewardship 101: Tips and Tricks for Changing Your Practice Annie Wirtz, PharmD, BCPPS Clinical Pharmacy Specialist Infectious Diseases
Antimicrobial Stewardship 101: Tips and Tricks for Changing Your Practice
Annie Wirtz, PharmD, BCPPS
Clinical Pharmacy Specialist
Infectious Diseases and Antimicrobial Stewardship
October 4, 2019
Nothing to Disclose
Objectives
• Report increased knowledge of how antimicrobial stewardship improves outcomes
• Identify a role for advanced practice providers (APP) within antimicrobial stewardship
• Optimize personal antibiotic prescribing within the four moments of antibiotic decision making
Presenter
Presentation Notes
Outcomes in patients improved through antimicrobial stewardship efforts Role of advanced practice providers within stewardship including ways to optimize prescribing within 4 moments of antibiotic decision making, which we will discuss
Stewardship is “the responsible overseeing and protection of something considered worth caring for and preserving.”
How does this apply to antimicrobials?
Dictionary.com
Presenter
Presentation Notes
-When thinking about antimicrobial stewardship, important to review what the actual definition of stewardship is -Stewarding resources, managing one’s resources carefully and responsibly to preserve them for future use -(click) throughout this presentation – thinking about how this applies to antimicrobials, meaning antibiotics, antifungals, and antivirals
History of Antimicrobials
• Penicillin discovered in 1928
• Improvement in survival and advances in modern medicine
• 1/3 of antibiotics are prescribed inappropriately• Wrong agent, dose, duration, frequency, or indication• Large percentage of pediatric antibiotics
ACS.comZetts RM, Stoesz A, Smith BA, Hyun DY. Pediatrics. 2018;141(6)1-10.
Presenter
Presentation Notes
-The first antibiotics were discovered back in the 20s -Great advancements in survival from previously fatal infections, development of new antibiotics for multiple type of bacteria -However, with great advances also come consequences, not always used in the right population -1/3 antibiotics prescribed inappropriately (wrong dose, drug, too long or too short duration; or used for a virus) -Antibiotics most prescribed medication in pediatrics – large percentage being inappropriate
Consequences of Inappropriate Antimicrobial Use
Patient• Resistance• Adverse Effects• Limited treatment options• Hospital acquired conditions• Cost burden• Missed days at work or school• Prolonged hospital admissions
Healthcare System• Cost burden• Waste of antimicrobials• Drug shortages• Infection control concerns
Community• Resistance• Cost burden
Presenter
Presentation Notes
-Inappropriate use of antibiotics can lead to significant consequences for the patient, healthcare system, and community -I will discuss these more in depth over the next few slides, but inappropriate antibiotic use can effect all financially, influence antibiotic choices, and cause additional negative outcomes
Antimicrobial Resistance
• Antimicrobials = “community resource”• Effectiveness decreases overtime and with overuse
Image Source: CDC
Presenter
Presentation Notes
-Antimicrobial resistance is the most publicized consequence of inappropriate antibiotic use -Antimicrobials can be referred to as a community resource. What this means is that they are the one class of drugs where they lose effectiveness overtime and with continued use, so the more they are used the less effective they become -This is unique to this medication class and also can be a huge issue -Live in a world now where multidrug resistant bacteria exist with treatment options and result in morbidity and mortality -So called “Superbugs” include carbapenem resistant exterobacteriacae, extended spectrum beta latamases, MRSA, VRE – limited treatment options
Bad Drugs, Few New Drugs
• ~50 antibiotics in development• Limited dosing or safety
information in pediatric patients
Image Source: Economist, IDSA
Presenter
Presentation Notes
-Problem because number of new antibiotic approvals has dwendelled – large drop after the 80s with no new antiiotics -Development is expensive and usually not incredibly lucrative – resistance develops quickly, making new discoveries minute -To encourage drug companies to develop antibiotics – 10x20 initiative as created (crated 10 new antibiotics by the year 2020). -New discoveries – pediatrics usually the last to be studied, limited dosing info in pediatrics and for pediatric infections
Patient Case
• Presented with signs and symptoms of pyelonephritis
• Urine culture with >100K of E. coli
• 14 days of IV antibiotics + inpatient admission
• Age of this patient???
Presenter
Presentation Notes
Resistance is hard to relate with unless you are working in infectious disease or microbiology and seeing resistant isolates or have a loved one who has been affected by this -patient with positive urine culture for Ecoli and signs/symptoms of pyelo -Susceptibility results showed only susceptible to carbapenems, amikacin, nitrofurantoin; no PO options nitrofurantoin cannot be used for pyelonephritis – required 14 days of IV antibiotics inpatient -Based on these susceptibilities 1) 65 year old male with multiple comorbid conditions; 2) 9 year old with multiple antibiotic courses 3) 9 month old patient no past medical history; Was a 9 month old with no PMH; parents do not work in the medical field; no prior hospitalizations – shows the impact resistance has on the community
Antimicrobial Resistance in Pediatrics
• Increasing both nationally and globally• Staphylococcus aureus
• Increase in clindamycin resistance for both MSSA and MRSA• Guidelines recommend avoid if resistance rates >10% for certain
MSSA= methicillin susceptible S. aureus; MRSA = methicillin resistant S. aureusLiu C, et al. Clin Infect Dis. 2011;52(3):e18–e55.
Medernach RL, et al. Dis Clin North Am. 2018;32(1):1-17.
Presenter
Presentation Notes
-Used to be thought of as not a pediatric problem -Although resistance is less frequent than in adults, there has been an increase in antibiotic resistance in pediatrics on both a national, global, and local level -S. aureus – frequent cause of SSTI in pediatrics – observed increases in frequently used medications for staph including Bactrim and clindamycin -Specifically locally, increasing clinda resistance for MSSA and MRSA -Susceptibility rates at Childrens Mercy over the years – 2013 MSSA 85% strains susceptible – last year 77% susceptible (>20% resistant), not the best empiric choice for MSSA -MRSA 88% susceptible in 2013; decrease to where around 20% of strains are resistant -Interesting as MRSA guidelines for IDSA recommend avoiding clindamycin use empirically for certain MRSA infections (pneumonia, serious SSTI, osteomyelitis) if resistance is > 10%
“Super Bugs” in Pediatrics
• Extended-spectrum beta-lactamases (ESBLs)
• Resistance to most beta-lactam antibiotics
0
2
4
6
8
10
2016 2017 2018 2019
CM Carbapenem Resistant Isolates
01020304050607080
2013 2014 2015 2016 2017 2018
CM Extended-Spectrum Beta-Lactamases
• Carbapenem-resistant Enterobacteriaceae (CRE)
• Resistance to carbapenem antibiotics (e.g. meropenem)
Medernach RL, et al. Dis Clin North Am. 2018;32(1):1-17.
Presenter
Presentation Notes
-Starting to see a rise in superbugs in pediatrics -ESBLs – limit treatment to usually carbapenems, occasionally other antibiotics susceptible – number cases has doubled at children’s mercy since 2013 -Carbapenem resistant organisms – resistant to our strongest antibiotics (meropenem, ertapenem) – very few treatment options, often higher toxicity profiles; vast increase in the last few years -Additionally, increase in vancomycin resistant enterococci (VRE) – natonally 53 cases/million to 120 cases per million in children
Cost Burden of Resistance
• $20,000 = average cost for treatment of multidrug resistant infection
• Amounts to $20 billion nationally
• Additional costs:• Additional microbiology tests to determine treatment options• Prolonged hospital stay• Missed days of work or school• Additional tests, admissions, and treatments for adverse drug reactions
Ventola CL. PT. 2015; 40(4):277-83.
Presenter
Presentation Notes
-In addition to limiting antibiotic treatment options, resistance is also a large financial burden on the patient, institution, and the healthcare system -Patient costs around $20K management of a multidrug resistant infection - $20 billion nationally -Require additional microbiology tests to help teams figure out treatment options (Panel sent to Mayo to determine presence of a cRE gene = $1000) -Hospital stays often result in missed days of school or work which aren’t accounted for usually in cost -Adverse drug reactons can amount to additional costs -
Patient Safety with Antimicrobials
Image Sources: Klancir et al. (2017). Acta Dermatovenerol. CroatSolensky et al. (2018). Up To Date
Presenter
Presentation Notes
Antibiotics are one of most common causes of adverse reactions Plenty of reports in the media outlining risks and patient safety issues Familiar with rash -Stevens Johnson syndrome – significant reaction to antibiotics -Fluoroquinolones – addition of multiple new FDA warnings for neurological adverse effects and aortic dissection, in addition to tendon rupture; we have stopped therapy in patients who have experienced psychotic like symptoms or worsening dpersssion -Antifungals associated with phototoxicity carrying a melanoma risk -More recently published out of my institution, use of Bactrim and development of severe respiratory failure leading to ECMO in patients receiving Bactrim for normal diagnoses, acne and urinary tract infections
Patient Safety with Antimicrobials
• 5-year review ED visits for antibiotic adverse drugs events (ADE)
• ~70,000 visits/year• 46.2% of ED visits for drug-
related ADE
• 40.7% in children ≤ 2 years
ED= Emergency Department Lovegrove MC, et al. J Pediatric Infect Dis Soc. 2018 [epub ahead of print].
Presenter
Presentation Notes
-Recent study examined emergency department visits for antibiotic adverse drug events -~70K visits per year over a 5 year period; made up about half of overall visits for drug-related ADE -most common in < 2 years was amoxicillin (pink bar); older children Bactrim (pink bar) -Overall most ADE visits for antibiotics occurred in children < 2 years – thought to be that the antibiotic prescribing rate is 2x higher in this population, although viruses more commonly found
Conserving for the Right Patients
• Significant amount of antimicrobial waste hospital-wide
• Inappropriate use• Doses prepared, but not
administered (i.e. discontinued or discharged)
• $250,000/year• 50 wasted doses/day
Presenter
Presentation Notes
-Antibiotics associated with resistance and Adverse effects – important to have them available when necessary as beneficial -Conserving for the right patients – eliminating waste -Significant amount of waste hospital wide not only from inappropriate use, but also doses prepared and not administered; also includes outpatient prescriptions dispensed and not taken -Graph shows waste alone from doses prepared and not administered (either patient was discharged or order discontinued or another reason) @ CMH -Amounts to about $250,000 year – antibotics rather cheap – 50 wasted doses/day -Doesn’t include waste of bags, syringes, needles, time to prepare these
Conserving for the Right Patients
• Significant antimicrobial drug shortages• Recent antibiotic shortages:
• Important role of stewardship in conservation and allocation
Presenter
Presentation Notes
-Impact of not discontinuing the antibiotic order or extending the duration for a longer period of time -Plagued by antimicrobial drug shortages in the past years -All listed have been on shortage, impacting multiple hospitals, additional oral agents on shortage too -2nd line agents – for example, cefotaxime shortage for years, discontinued; agent of choice for neonates unable to receive CRO due to bilirubin displacement and calcium precipitation. Use broader agent ceftazidime for these patiens; some institutions using CRO in ages younger than what is approved -Other side of stewardship in conserving for healthcare system and allocating to appropriate patients -esp frontline staff -
Consequences of Inappropriate Antimicrobial Use
Patient• Resistance• Adverse Effects• Limited treatment options• Hospital acquired conditions• Cost burden• Missed days at work or school• Prolonged hospital admissions
Healthcare System• Cost burden• Waste of antimicrobials• Drug shortages• Infection control concerns
Community• Resistance• Cost burden
Presenter
Presentation Notes
-Consequences of inappropriate use impct on patient, community, and healthcare system – how do we control?
Antimicrobial Stewardship Program (ASP) Requirements
Presenter
Presentation Notes
-Concerns reached a national and global level – multiple initiatives and regulations incorporating antimicrobial stewardship programs (ASPs) into different healthcare settings including inptaient, outpatient, long term care, critical access, hospitals and so forth -2014 – executive order signed by president Obama creating a national action plan to combat antibiotic resistance -Led to the development of the CDC core elements of antibiotic stewardship – structure of ASP and components – will discuss -Joint commission required all accediated hospitals and nursing care centers to have a stewardship program as of Jan 1, 2017, requirements to what that includings Right next door Missouri Senate Bill No. 579 – one of two states mandating all hospitals have an ASP – after a senator had a relative with a MDR infection he Centers for Medicare and Medicaid Services’ new rule requiring hospitals participating in its programs as of 9/26 to to establish antibiotic stewardship programs
Antimicrobial Stewardship
“Optimizing clinical outcomes while minimizing unintended
consequences of antimicrobial use, including toxicity, selection of pathogenic organisms, and the emergence of resistance.”
Presenter
Presentation Notes
-The concern of Antimicrobial stewardship is really focused around…. -Focuse on the term optimize. Many think all about stopping antibiotics; associated antimicrobial stewardship activities as the antibiotic police and removal of provider autonomy -Goal is to really find ways to optimize
Stewardship StoriesA patient presented with an intraabdominal infection after a bowel
perforation. The patient was receiving a lower dose of an antibiotic at a twice daily frequency. ASP recommending increasing the antibiotic dose and administering it once daily, thereby minimizing line entries and CLABSI risk.
ASP reviewed a patient receiving IV antibiotics for a urinary tract infection. The team was planning to discharge the patient on a broad-spectrum
antibiotic associated with many side effects. ASP recommended transitioning the patient to a more narrow-spectrum, well-tolerated oral antibiotic administered once daily. The patient was discharged on this antibiotic.
Presenter
Presentation Notes
-Two examples – consolidating line entries based on the dosing and decrese CLABSI risk -Narrow to a better tolerated antibiotic
Antimicrobial Stewardship Interventions
• Selecting the right antibiotic at the right dose for the rightindication and duration
Stewardship Interventions
Optimize therapy (IV to PO, dosing)Modify therapy (duration, broaden/narrow coverage)
Discontinue therapyID Specialist Consultation
Clinical practice guideline implementationAntimicrobial restriction
Quality and cost utilization analysesEducation and resource development
Appropriate testing
Presenter
Presentation Notes
Simple terms – selecting the right antibiotic right dose indication and duration -Examples of recommendations, roles and responsibilities that inolve ASP practices (including quality improvement projects, education, and guideline development) -Picture of my team
Children’s Mercy ASP
• Review of inpatient antibiotic orders at 48 hours• Antibiotic “time-outs”• Nursing antibiotic engagement tool• Guideline development• Quality improvement projects pharyngitis and otitis media• Outpatient Handbook
• Children’s Mercy Evidence Based Practice Website à Care Process Models à Acute Otitis Media à Outpatient Antibiotic Handbook
• Penicillin allergy clarification and testing
Presenter
Presentation Notes
Brief overview of CM ASP – inpatient and outpatient initiatives -Review all inpatient broad-spectrum antibiotic orders at 48 hours after drug started – provide recommendations to prescriber; can choose to accept (like on previous slide) -Timeout procedure; at 48 hours after antibiotic started when you have more cultures and data; alert that encourages pharmacists to discuss with teams whether the antibiotic should continue or should be modified -Nursing antibiotic engagement tool help nurses identify and bring up antibiotic related issues -Guidelines; quality improvement projects focused on GAS testing and otitis media treatment -Outpatient handbook – discuss later -Implemented penicillin allergy clarification and allegy testing to confirm and delabel inappropriate allergies Happy to serve as resource
Multidisciplinary Approach to
ASP
Presenter
Presentation Notes
-ASP involves multiple disciplines beyond just pharmacists -Nursing (cultures, IV to PO), microbiology (cultures), infection control (prevent spread of organisms), data analyst -Advanced practice providers as prescribers (appropriate antibiotics, reassess these, and provide education to families and patients)
APPs and ASP
Large contributor to outpatient prescribing• >189,000 Nurse practitioners (NPs) in the United States• 23% of outpatient antibiotic prescriptions (and increasing)
Perceptions about antimicrobial stewardship• Single-center survey of 58 NPs
• Unfamiliar with antimicrobial stewardship program• Aware and concerned about antibiotic overuse and consequences• Would like more education and feedback on antibiotic prescribing
Manning ML. J Am Assoc Nurse Pract. 2014;26(8):411-3.Zetts RM, Stoesz A, Smith BA, Hyun DY. Pediatrics. 2018;141(6)1-10.
Abbo L, et al. Journal for Nurse Practitioners. 2012;8(5):370-6
Presenter
Presentation Notes
When looking at outpatient prescribing in general, nurse practitioners prescribe a large portion of mediations in the United states given the large sheer number of nurse practitioners across all areas -As of 2014 there were189K nurse practitioners in the United states and likely more now. As well as other types of APPs -APPs Prescribe 23% of antibiotic prescriptions and this number has increased by 64% since 2011 -Despite this, paucity of data about nurse practitioners and antimicrobial stewardship. Handful of articles examining overall prescribing likely increasing. -When looking at nurse practitioners perceptions and attitudes towards antimicrobial stewardship, single center survey published by a tertiary hospital which was part of a larger university hospital system. Sent a survey and got responses from 58 nurse practitioners. specifically -Looked at attitudes and influences when selecting antibiotics, perceptions about antibiotics and resistance, education and overall antibiotic knowledge -Found that majority of nurse practitioners were unaware of ASP at this institution, unaware of ASP as an education resource yet most were concerned about resistance and antibiotic over use. Most aware that inappropriate use can cause harm and resistance -Most wanted to see more education and feedback on their personal prescribing patterns
Call to Action: APPs in ASP
• Key role for APPs• Majority with prescriptive authority• Frequent prescribing of antibiotics• Experience with patient care
Advance your knowledge
Optimize your antibiotic prescribing
performance and practice
Advocate for adoption of at least one ASP
recommended action in your practice setting
Reach out and connect with APPs in
your local region
NP ASP Action Items
Manning ML. J Am Assoc Nurse Pract. 2014;26(8):411-3.
Presenter
Presentation Notes
-More recently call to action was published highlighting the important role of APPs in ASP because most have prescriptive authority and write approximately 19 scripts/day, frequently antibiotics -Additionally NP have experience with patient care both from a nursing perspective and prescriber perspective with is an extremely valuable combination -Within this call to action there were 4 action items: -Advancing knowledge: last survey, NPs wanted to learn more. Identifying educational opportunities to advance antibiotic knowledge and update on newest guidelines/literature. Journal club with ASP topics -Optimize antibiotic prescribing: take care and thought when prescribing, clearly identify dose, duration, indication when prescribing. Knowledgeable about local resistance. Frequent audits of personal prescribing practices -Adopt 1 ASP recommended action into practice setting: stewardship looks many different ways; identify something that works for your specific area and go with it; avoid adopting too many interventions at once. Work closely with colleagues or other institutions. We are always happy to provide expertise and guidance -Connect with other NPs: identify strategies to overcome barriers; serve as a support system; smaller groups can develop partnerships and collaborations -All these areas, identify one and focus on this. CM focused on these first two areas with a study performed in 2017
Education and Antibiotic Prescribing
• Education for NPs in urgent cares
• Antibiotic use in common pediatric infections
• Decrease in inappropriate antibiotic prescribing for session attendees (9% to 6%; p <0.01)
Weddle G, Goldman J, Myers A, Newland N. J Pediatr Health Care. 2017. 31(2):184-188.
Presenter
Presentation Notes
-Education provided to nurse practitioners in 4 urgent care settings on antibiotic choices (whats first line) for common pediatric infections including GAS pharyngitis, UTI, SSTI, sinusitis, otitis media. -Of those nurse practitioners that attended, significant decrease in inappropriate prescribing overall and for certain areas. Graphical depiction (maroon color inappropriate; decrease esp with UTI after the intervention -No difference was observed with those who didn’t attend the sessions -Showing that education can be effective and impact prescribing; usually combined with practice change to make this sustainable
4 Moments of Antibiotic Prescribing
• Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use
• Opportunities for optimizationMoment 1• Does this patient have an infection that
requires antibiotics?
Moment 2• Have I ordered appropriate cultures
before antibiotics? What empirical antibiotic therapy should I initiate?
Moment 3• A day or more has passed. Can I stop
antibiotics? Can I narrow therapy? Can I change from IV to PO?
Moment 4• What duration of antibiotic therapy is
needed?
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.
Presenter
Presentation Notes
Hope for the rest of this presentation, provide some stewardship related education that can motivate you to make a practice change in your area of work -Realize work in a variety of different areas, not all tips and tricks will be applicable to all -A paper just came out discussing Including in the agency for healthcare research and quality safety program for improving antibiotic use – 4 moments of antibiotic prescribing -Perfect impact all all who prescribe antibiotics, potentially at different timepoints and on different levels depending on practice location – as these have to do with the 4 moments of decision making within antibiotics -Bringing it back to optimization focus of ASP – how can you optimize your prescribing within these 4 moments Happens before prescribing – asking does this patient need antibiotics Determine yes, gotten cultures if possible before antibiotics, completed diagnostic workup; thinking about what influences empirical choice Time has passed. This is more of the antibiotic timeout portion. Time to think and reassess whether you really need antibiotics or how things could be modified. May not alwaysexperience this if you work in the outpatient setting, but potentially situations like culture call back or watchful waiting Moment 4 thinking about what is the optimal duration -Walk through some of the components of these decisions – common stewardship interventions, helpful resources, questions to ask yourself
1. Does this patient have an infection that requires antibiotics?
• Initiation of antibiotics for a variety of reasons:
• Isolated symptom (e.g. fever) vs. constellation of symptoms
• Provider discomfort• Lack of knowledge or understanding• Parental/patient request or
expectation
What other processes are going on with this patient?
Does this patient meet diagnostic criteria?
Could this be non-infectious or non-bacterial?
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.
Presenter
Presentation Notes
First moment goes into does the patient need antibiotics in general? Prescribed for a variety of reasons – isolated symptom (fever in ICU patient or increasing WBC count) vs group of symptoms Provider concerned of missing something; or patient really sick Lack of knowledge whats going on with the patient or the added benefit the antibiotic is really going to give you Prescriber concern parent/patient request or expections Clarifying questions to ask: how can I synthesize all the different things going on in this patient, all the labs, signs, symptoms and put them together? Do they fit an infection? Consider the whole picture Does this patient meet the diagnostic criteria if that exists? Hard in patients? No consolidation on Cxray probably not a bacterial pneumonia Could this be noninfectious? Frequently on ASP find where there might be fever or vital sign changes explained by some other process (withdrawal, drug fever) -Examples within the three of these
1. Does this patient have an infection that requires antibiotics?• Acute otitis media (AOM)
• >50% resolve without antibiotics
• Consider “watchful waiting” for patients with mild symptoms:• ≥ 6 months with unilateral AOM without otorrhea • ≥ 2 years with bilateral AOM without otorrhea
• “Safety net antibiotic prescription” if no improvement in 48-72 hours
• Cost-effective and 65% reduction in antibiotic use
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Lieberthal AS, Carroll AE, Chomaitree T et al. Pediatrics. 2013;131:e964-e999.
Presenter
Presentation Notes
-Otitis media – disease state with diagnostic uncertainty; often overtreatment of patients not fitting diagnostic criteria or not a true bacterial cause -In studies some say that greater than 50% of patients will have resolution of otitis media even with out antibiotics -To aid in reducing unnecessary antibiotic use – concept watchful waiting; hold on antibiotics in certain populations with mild symptoms listed on the slide -No observed harm or complications when done appropriately with close follow up -Concerns that follow up may not happen; safety net antibiotic Rx – script with instructions to fill if no improvement by X date -Showed to be cost effective and overall reduce antibiotic use by 65%
1. Does this patient have an infection that requires antibiotics?
• Aspiration pneumonia• Consider non-infectious diagnoses and waiting to initiate treatment
• Asymptomatic bacteriuria• No benefit observed with treatment• No harm observed with avoiding treatment
Aspiration Pneumonia Aspiration PneumonitisMechanism Infection after aspiration event Irritation/inflammation from sterile gastric contents
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Nicolle LE. Clin Infect Dis. 2019;68(10):1611-15
Marik P. N Engl J Med. 2001;344(9):665-671.
Presenter
Presentation Notes
-Aspiration pneumonia – disease state hard to diagnose. Often confused for aspiration pneumonitis -Similar signs and symptoms; aspiration pneumonitis – more shortly after an aspiration event; sterile doesn’t require antibiotics -aspiration pneumonia, infectious, few days to weeks later – does require treatment -Often see providers initiate treatment immediately after aspiration event – consideration of noninfectious diagnoses this one – waiting to initiate antibiotics may not be harmful but may reduce overall use -Lastly diagnoses where often see inappropriate treatment in patients not meeting diagnostic criteria for UTI. Not symptomatic , but have bacteria positive on culture -New 2019 guidelines do not recommend treating these patients limited benefit seen, often continued bacteruria and development of resistance; no harm seen in terms of renal scarring
1. Does this patient have an infection that requires antibiotics?
• Group A Streptococcus (GAS) Pharyngitis• 70% outpatients with sore throat receive antibiotics
• 20-30% actually have GAS pharyngitis• Significantly lower < 3 years à testing is not routinely indicated
• Rapid testing cannot distinguish between colonization and carriage• 25% of healthy children are colonized• Consider colonization vs. actual infection
• 0% resistance for GAS for amoxicillin
Kimberlin DW, et al. American Academy of Pediatrics 2018; 748-762.Shulman ST, et al. Clinical Infectious Diseases 2012; 55(10): 86-102.
Presenter
Presentation Notes
As you can see, the majority of patients with sore throats presenting in the outpatient setting are prescribed antibiotics, while a minority actually have GAS pharyngitis (most viral) Up to 25% of children asymptomatically carry GAS and testing with RADTs cannot differentiate between colonization and true disease In addition, several potential consequences of over-diagnosing 2 National guidelines (IDSA and AAP) state that testing for GAS pharyngitis is not recommended in patients < 3 years of age or in those with viral features (rhinorrhea, cough, oral ulcers, or hoarseness) Patients < 3 years of age are less likely to have GAS pharyngitis and have higher rates of asymptomatic colonization If viral symptoms, more likely to be a viral infection (70-80% of infections are viral) RADTs have good specificity (95%) but don’t differentiate Mom that has saying that amoxicillin has failed – they need cefdinir – may be just colonization
Speaking with Families
• Inaccurate prescriber perception that parents demand antibiotics
• 109 parent interviews demonstrated:• None planned to ask for antibiotics• Seeking reassurance and guidance regarding child’s condition• Wary about using antibiotics, concerned about adverse effects
• Opportunities for tailoring communication• Explain why antibiotics are not needed• Positive treatment recommendations• Contingency plan
Fleming Dutra KE, et al. Am Fam Physician. 2016 Aug 1;94(3):200-202.Symczak J, et al. JPIDS. 2018;7(4):303–9.
Mangione-Smith R, et al. Am Fam Med. 2015;13(3):221-7.
Presenter
Presentation Notes
Always the question of if I choose not to prescribe antibiotics parents or patients will be upset or disappointed -Evaluated more recently found that this is really for the most part an inaccurate perception -109 parent survey performed; none admitted to planning to ask for antibiotics; really just wanted to know that this wasn’t something more serious and how can they make their child feel better -Worried about antibiotics especially with adverse effects, including stomach upset. -Resistance wasn’t really a large worry, most parents thought this was driven more by other parents wanting antibiotics consistently actually, not necessarily themselves -Group out of seattle done work regarding how to speak to families when you are not going to prescribe them antibiotics – would encourage you to take a look -Explain why antibiotics aren’t needed – cold is caused by a virus antibiotics wont help -Positive treatment recs – ibuprofen and plenty of sleep will make your child feel better -Contingency plan gives comfort – not better in 5 days, call again and we can reassess for antibiotics
2. What empirical antibiotic therapy should I initiate?
• What are the most common pathogens for this infection and this patient?• Clinical practice guidelines or tertiary resources• Consideration of patient factors (e.g., MRSA history, immunocompromised)• Utilization of antibiogram (if available)
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.
Presenter
Presentation Notes
-Determined they need antibiotics, gotten cultures and workup, how do you determine what to start -First question: what are the most common pathogens for this infection and this patient? -Intraabdominal- gram negative anaerobes; pneumonia – S. pneumo – clinical practice guidelines often give a really nice overview iwhtin the text of common organisms; tertitary resources – Sandford or Hopkins guide, uptodate also are useful as well -Patient factors – MRSA history (recent paper about MRSA nasal colonization impacts therapy); vaccinated or not; immunocompromised – think about more gram negatives; recent antbiotic treatment -Apply this to local antibiogram if possible – perentage susceptible – odds of covering a certain organism with antibiotic -Best example, my institution clinda 77% MSSA compared with oxacillin 100% - if I am worried about MSSA – better choice would be oxacillin vs clindamycin -Copuled with rapid diagnostic testing; useful tool to have if you have this at your institution; limitation not ptient specific; institution specific
2. What empirical antibiotic therapy should I initiate?
• What resistance mechanisms does this bacteria carry?• Pathogen-specific
Decreased affinity for penicillin binding proteins Beta-lactamase (30%) Beta-lactamase (100%)
Treatment High-dose ampicillin or amoxicillin Ampicillin/sulbactamAmoxicillin/clavulanate
Ampicillin/sulbactamAmoxicillin/clavulanate
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Bradley JS, Byington CL, Shah SS, et al. Clin Infect Dis. 2011;53(7):e25-e76.
Presenter
Presentation Notes
-After thinking about what bacteria to cover, coupled with what resistance mechanisms does this carry if this is known to you. -Pathogen specific – general ones, S. aureus – Methicillin resistance or inducible clindamycin resistance with stpah or strep good to know may influence choice -Classic one is in peditrric pneumonia, sinusitis, otitis media between these three bacteria -Common misconceptions about what you gain in coverage when you use amoxicillin or ampicillin vs amp/sulb or amox/clav or augmentin -Most common resistance mechanism with Strep pneumoniae is decreased affinity for penicillin binding proteins where amoxicillin or ampicillin work -Overcome by increasing the dose – do not gain ANY strep pneumo coverge by adding sulbactam or clavulanate -These beta lactamase inhibitors are useful if you want to have coverage against less common organisms such as H flu or M cat as these produce a beta lactamase that is inhibited by clavanate or sulbactam. -Important more GI effects with clavulanate or sulbactam; also unnecessarily broad coverage
2. What empirical antibiotic therapy should I initiate?
• Will the antibiotic reach the site of infection?• Difficult to penetrate = central nervous system, bone/joint, lung,
abscess or vegetation
• Utilize Lexi-Comp or Micromedex or clinical practice guidelines
• Urinary tract infections• Cefdinir: 12-18% excreted in urine• Cephalexin: >90% excreted in urine• Cefixime: 50% excreted in urine
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Lexi-comp.
Presenter
Presentation Notes
-Once you know what you want to cover, think about does it get to the site of the infection -Common intervention on stewardship, people treating infections with antibiotics that do not get to that actual site, urine or brain -parts hard to penetrate, but often you can look this information up if you do not have a pharmacist on staff -Lexicomp/Micromedex/uptodate – pharmcoknetics/dynamics section that only pharmacists look at -Distribution and exrcretion great to look at esp for urine penetration -Classic example cefdinir – always thought to be a great UTI drug; not really because it penetrates the urine very poorly compared to alternatives – do not recommend this for UTIs
2. What empirical antibiotic therapy should I initiate?
• What allergies does this patient have?• 10% report penicillin allergies; 1% truly allergic
• 26% increased C. difficile risk and 69% increased MRSA risk
• Consider challenging low-risk patients in controlled setting or allergy referral
• Low risk of cross-reactivity between penicillins and cephalosporins• Similar side chains = higher likelihood of reaction
Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. BMJ. 2018;361:k2400.Vyles D, Chiu A, Routes J, et al Pediatrics. 2018;14(5):e20173466.
Eaddy Norton A, Konvinse K, Phillips EJ, Dioun Broyles A. Pediatrics. 2018;141(5):e20172497.
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Finally, patient allergies should be taken into consideration. Encourage you to take the time to clarify allergy. Cant tell you how many patients I see that have amoxicillin as an allergy with no documentation of what happened – avoid it, ends up being more of a side effect like stomach upset -Only 1% of the population is truly allergic; 80% will outgrow allergies -Recent study shows a 26% increased risk of Cdiff and 69% increased risk of MRSA with those labeled with a penicillin allegy b/c more likely to receive non betalactam antibiotics (macrolides, fluoroquinolones); vanco was given because of a cephalosporin allergy not clarified – MSSA surgical site infection -Significant harm if not clarified; surgery – -Look for buzz words of a true allergy – hives, immediate reaction, wheezing – CDC has nice documents; generally rash not consistent with a true IgE mediated reaction -If you feel comfortable, controlled setting, low risk ptients could receive an oral dose with monitoring under provider watch; consider allergy referral to undergo a formal delableing process -Recently started doing oral amoxicillin challenges and penicillin skin tests within our infectious diseases clinic at childrens Mercy -Just because they have a penicillin allergy doesn’t mean all beta lactams should be avoided also – low rate of cross reactivity; most likely to have an allergic reaction if has a similar side chain to the offending agent.
Beta-lactam Cross Reactivity
DePestel D, et al. J Am Pharm Association. 2008;48:530-540.
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Great resources and charts where cross tables show the similar side chains – amoxicillin and cephalexin similar side chains at bothe the 6/7 position but cefixime doesn’t so potentially an option to try if the patient is low risk.
3. Can I narrow antibiotics?
• Opportunity to decrease broad-spectrum antibiotic use
• How to I utilize susceptibility results?• Minimum inhibitory concentration (MIC) and
interpretation• Common misconceptions
• MICs can be compared• Lowest = best
• Specific for each antibiotic and bacteria combination
• Consider what’s susceptible + infection and patient factors
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Image Source: KhanAcademy.
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-Once selected antibiotic, 48-72 hours later important to take a timeout to either assess diagnostic findings and susceptibilities if in a more acute setting or even in the outpatient setting to review any cultures you have and determine whether any antibiotic changes need to be made. -Opportunity to optimize antibiotics and decrease broadspectrum use -Most common queston is how do I interpret susceptibility results – all practice levels, confusion -Keep this simple as I realize most may not have these results always available in their practice setting, but it is a valuable skill. -Susceptibility results – Minimum inhibitory concentration – minimum concentration required to inhibit bacterial growth in the body – number figured out from dilutions in the microlab with that bacteria growing on culture – compare that number to a set of guidelines put out by international bodies that determine where that MIC number fits in terms of susceptible (S), intermediate (I), resistant (R) categories; susceptible – can use to treat; intermediate – maybe should avoid but could overcome potentially with a higher dose; resistant – avoid wont work -Common misconceptions – compare these numbers – number and what falls into S, I, R categories bacteria-antibiotic specific pair; lowest doesn’t mean better; cant go through and say I will pick this because its 0.5 and linezolid is 2- different for those bacteria –antibiotic specific pairs -Can consider generally what is susceptile, whats the infection and what gets to the site of infection, patient specific factors (allergy, interations so forth)
3. Can I switch from IV to PO?• Which antibiotic is my patient receiving?
• Certain antibiotics: IV = PO (e.g., ciprofloxacin, SMX/TMP, metronidazole)
• What is the indication?• Prolonged IV course required for certain infections (e.g., endocarditis,
central line infections, meningitis)• IV to PO for infant UTI, gram negative bacteremia
• Is my patient improving?• Minimize line entries, potentially reduce cost and length of stay• IV to PO transition policy
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Brady PW, et al. Pediatrics. 2010;126:196-203.
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-Another intervention at this point IV to PO switch -Important some antibiotics should always be given oral; 100% bioavailable = IV = PO if patient normally absorbing -Bacteria doesn’t know how the antibiotic gets there -Certain infections require prolonged course – endocarditis, meningitis -Although newer data is coming out to suggest oral theapy transition even in severe infections- new papers for infant UTI gram negative bactereia where switch to oral hasn’t resulted in engative outcomes -patient improving, make the switch – beneficial reduce clabsi risk, potentially cost and length of stya -Some institutions hve implemented IV to PO policies, often including pharmacists to help transition patients as soon as possible
4. What duration of antibiotic therapy is needed?• Variability in prescribed antibiotic durations
• Late-career physicians more likely to prescribe >8-day durations• Mean durations = 7-8 days
• New practice trend = shorter is better
Tamma PD, Miller MA, Cosgrove SE. JAMA. 2019;321(2):139-140.Fernandez-Lazaro CI, Brown KA, Langford BJ, et al Clin Infec Dis. 2019;XX(XX):1-9.
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-Final moment – what duration is required -Historically duartions framed around days of the week – Constantine units – 7 days, 14 days, 21 days – 5 fingers, 10 fingers, or 7 calendar days -More recently studies have been published blooking at shorter durations -Hard for those been in practice longer to adapt – recent study looking at antibiotic durations showed wide variability in how long antibitics were prescribed but late career (>24 years) and mid career (11-24 years) more likely to prescribe longer durations (>8 days) showing that these prescribers haven’t adapted to the new concept of “shorter is better” -Variety of new studies come out – outlined in this table comparing short usually <7 day durations to long durtaions – including CAP, UTI, SSTI, etc. No harm -CAP specifically 3-5 days course equal compard with a 7,8 or 10 day course – way to reduce unnecessary antibiotic use
4. What duration of antibiotic therapy is needed?
• Uncomplicated, late-onset group B Streptococcal (GBS) bacteremia
• ≤ 8 vs. > 8 days IV antibiotics• No difference in GBS reoccurrence
• Gram-negative bacteremia• 7 vs. 14 days - noninferior
• Surgical prophylaxis• No post-operative antibiotics for clean and clean-contaminated
procedures• Limit to < 24 hours Berrios-Torres SI, Umscheid CA, Bratzler DW. JAMA Surgery; 2017;152(8):784-791.
Coon ER, Srivastava R, Stoddard G, et al. Pediatrics. 2018;14(5):e201803345.Yahav D, et al. Clin Infed Dis. 2019;69(7):1091-98.
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In addition – variety of literature has been published recently looking at shorter durations beyond -GBS bacteremia in infants – no difference in long vs short IV treatment; reduce hospitalization, days with IV lin -Gramnegative bacteremia – 7 vs 14 days traditional – noninferior -Surigical prophylaxis – hardest to adopt 2017 CDC guideline for clean and clean contaminated procedures beyond the pre-op dose no antibiotics required; overall limit use to < 24 hours – huge area for stewardship efforts
Summary
• Consequences of inappropriate antibiotic use include resistance, adverse effects, and cost.
• APPs have a role in antimicrobial stewardship as they are frequent prescribers of antibiotics.
• Opportunities for optimization of antibiotic prescribing exist within each step of antibiotic decision-making.
