Antimicrobial Foundations and Stewardship

Evan Slagle, PharmD, BCPS

Antimicrobial Stewardship Pharmacist

Penn State Health St. Joseph

Reading, Pennsylvania

Morning Report: Family Practice Medicine Residency Group

Objectives

• Define common antibiotic-related terminology

• Review bacterial physiology related to antibiotics

• Review broad classes of antimicrobials and features

• Identify mechanisms of antibiotic resistance

• Review some infectious disease pearls

Objectives

• Describe the need for antimicrobial stewardship (ASP)

• Define antimicrobial stewardship

• Explain the benefits of an ASP

• Identify key stakeholders and new regulations and requirements

• Explain the components of our ASP

• Describe future strategies and program goals

Definitions

• Bactericidal: actively kills organisms • Bacteriostatic: arrests further growth of organisms • Minimal inhibitory concentration (MIC): lowest

concentration of a drug that can still inhibit microbial growth

• Concentration-dependent activity: efficacy of drug dependent on high concentrations (high dose given over a short time)

• Time-dependent activity: efficacy of drug dependent on amount of time that the concentration is above the MIC (lower doses given more frequently)

Definitions

• Empiric therapy: typically broad spectrum agents that cover pathogens likely to be the cause of infection-started prior to having definitive information such as culture results

• Prophylactic therapy: prevent onset of infection • Synergy: co-administration of two antimicrobials that results in

greater effectiveness than one would predict from simply treating with two antimicrobials

• Antibiogram: a tool that displays compiled antimicrobial sensitivity data from an institution’s patients over a defined timeframe

• Enterobacteriaceae: Citrobacter, Enterobacter, E. coli, Klebsiella, Morganella, Proteus, Providencia, Salmonella, Serratia, Shigella

Bacterial Physiology

• Gram positive (+)

– Thick outer layer of peptidoglycan (cell wall),

– Thin inner cell membrane (contains efflux pumps)

– Internal structure contains DNA/RNA, plasmids and ribosomes

• Gram negative (-)

– Thin peptidoglycan layer (cell membrane)

– Thin outer membrane (contains porins and efflux pumps)

– Internal structure contains DNA/RNA, plasmids and ribosomes.

Antibiotic Mechanisms of Action

https://www.orthobullets.com/basic-science/9059/antibiotic-classification-and-mechanism

β-Lactams

• Includes penicillins, cephalosporins, carbapenems

• Inhibit PBP & prevent cross-linking of peptidoglycan in the final steps of formation of the cell wall

• Generally are BACTERICIDAL

– Especially against rapidly growing bacteria

• β-lactam structure is consistent across all antibiotics, but the ring attached to it varies

• Backbone of most antimicrobial therapy

β-Lactams

• Addition of ‘chains’ enhances activity against certain organisms, but can decrease activity against others

• Lacks atypical coverage

• Lacks coverage of MRSA

– Ceftaroline is exception (5th generation cephalosporin)

• Side effects include hypersensitivity reactions, seizures (carbapenems)

– Range from rash to life-threatening anaphylaxis

• Renally dosed…consult your friendly pharmacist

Natural Penicillins

• Spectrum:

– Good: MSSA, most Streptococci

– Poor gram – coverage (some N. gonorrhoeae, mouth anaerobes)

• Relatively poor CNS penetration with uninflamed meninges

• TIME DEPENDENT killing (time above MIC)

– Must be given q4 or q6

– Can be given as continuous infusion (home)

Natural Penicillins Penicillin VK: • Absorption: oral 60-73%

– Take on empty stomach • Tastes nasty! (even the

tablets)

Penicillin G: • Absorption: oral <30%

(destroyed by acidic environment of stomach)

• Use IV • Elimination: urine (mainly by

tubular secretion)

Penicillin G procaine (Bicillin C-R):

• Absorption: IM (slow) • Penetration across the

BBB is poor – Clinical Pearls: Do

NOT give IV

Penicillin G benzathine (Bicillin L-A):

• Absorption: IM (slow)

Antistaphylococcal Penicillins

• Nafcillin, Oxacillin

– Gram + coverage only (NOT MRSA)

– TIME DEPENDENT killing

– Short half-life (Give q6, q4 or continuous infusion)

– Significant phlebitis

– CNS penetration is generally well accepted as decent

– Good for endocarditis, osteo, SSTI

– Faster killing than vancomycin (better mortality data)

Aminopenicillins

• Spectrum of Activity: Strep pneumoniae and limited gram negative (H. influenzae, M catarrhalis, E. coli)

• Good gram + coverage

• Limited gram – coverage

• Active against some anaerobes

• β-lactamase inhibitor adds activity against anaerobes

• Good penetration into CSF with inflamed meninges (low when not inflamed) – IV forms only

Aminopenicillins • Amoxicillin

– Absorption: oral 74-92%

• Amoxicillin + clavulanate:

– Absorption: both well absorbed – Distribution: both widely distributed into lung, pleural fluid,

peritoneal fluid, synovial fluid, bone, middle ear, placenta, breast milk

– Clavulanate inactivates β-lactamase, adds some gram negative stability

– Augmentin ES- have higher amoxicillin to clavulanate concentration (contraindicated in severe renal impairment)

– In general: higher clavulanate causes GI discomfort (diarrhea)

Aminopenicillins • Ampicillin:

– Distribution: bile, CSF with inflamed meninges only

– DOC for GBS, susceptible Enterococcus, Listeria (add aminoglycoside for synergy)

• Ampicillin + sulbactam (Unasyn): – Distribution: bile, tissue fluids, poor CSF with uninflamed

meninges

– Metabolism: Half-life: fairly short, should be dosed q6

– May increase coverage of MSSA and Gram – organisms

– Increased anaerobic coverage

– Sulbactam inactivates β-lactamase

Antipseudomonal Penicillins

• Spectrum of Activity: Primarily gram negative, including Pseudomonas and some gram positive (Enterococcus)

• AE: rash, elevated LFTs, thrombocytopenia, leukopenia

• β-lactamase inhibitor adds activity against anaerobes

• No oral absorption

• Widely distributed into tissues and body fluids

• CSF poor if meninges uninflammed

Antipseudomonal Penicillins

• Piperacillin/tazobactam (Zosyn):

– Niche: Pseudomonas and anaerobes

– Monitor renal function & CBC while on therapy

– Neutropenia after >2 weeks of therapy

– Very broad spectrum (lower respiratory tract, intra-abdominal, urinary tract, gynnecological infections); so commonly used as empiric agent

Cephalosporins

• Structurally related to pencillins: cross sensitivity can occur (~10%)- [likely much less (<1%)]

• Four generations with new fifth generation

• Time-dependent killing

• Renal dose adjustment required

• As the class moves from 1st to higher generations, add in more gram negative coverage

Cephalosporins: 1st Gen • Clinical use: primarily surgical prophylaxis (pre-op & post-

op) and simple SSTIs or GU infections

• Cefazolin: IV (Ancef) – Good gram + coverage

– Limited gram – coverage

– Good choice for MSSA (q8 vs. q6h dosing)

• Cephalexin: PO (Keflex) – Good gram + coverage

– Limited gram – coverage (E.coli)

Cephalosporins: 2nd Gen

• Spectrum of Activity: greater Gram - spectrum than 1st generation (respiratory pathogens), some Gram + cocci and anaerobic activity

• AE: rash, bleeding, elevated hepatic enzymes, GI disturbances

• Not much utility as a class, not much benefit with more toxicity

• Primary Use: PID, GU and GI surgical ppx, sinusitis

Cephalosporins: 2nd Gen

• Cefotetan:

– Mixed Gram + and Gram – coverage

• Cefoxitin:

– Low activity against aerobic gram positive bacteria

– Mixed Gram + and Gram – coverage

– Less active against staph and strep than 1st generation

• Cefaclor /Cefprozil /Cefuroxime – all oral options

Cephalosporins: 3rd Gen

• Spectrum of Activity: adds broad spectrum activity against enteric Gram - rods

• Widely distributed throughout the body including the CSF

• No cephalosporins active against Enterococcus

Cephalosporins: 3rd Gen • Cefdinir:

– Oral option

– Can be dosed either once daily or BID

– Still maintains fairly good activity against staph & strep

– Not recommended <60 days of age

– Q12: osteo Q24: everything else

• Cefixime: – Preferred oral agent for uncomplicated cysitis (simple Gram

negatives)

– Can be given to patients < 30 days of age

Cephalosporins: 3rd Gen

• Ceftriaxone: – Use caution in neonates

– Long half-life allows for once daily dosing

– Good CSF penetration

– Q12: meningitis Q24: everything else

– Good activity against most gram negative except Pseudomonas, steno, Listeria, and anaerobes

– Increasing resistance

– Gall bladder issues +/- bili issues

– Calcium interacts (precipitates in kidneys, lungs in neonates

Cephalosporins: 3rd Gen

• Cefotaxime: – Similar spectrum to ceftriaxone

– Can be dosed every 4-6 hours for meningitis (time-dependent killing)

– Q6: meningitis Q8: everything else

– Used more inpatient

• Ceftazidime: – Broad Gram negative coverage including Pseudomonas

– Increasing resistance with Pseudomonas, Klebsiella, Enterobacter

Cephalosporins: 4th Gen • Spectrum of Activity: greater Gram - coverage than other

cephalosporins (decreased resistance and good coverage against Pseudomonas. Offers some coverage of gram + bacteria (Strep, no staph or enterococcus coverage)

• No anaerobic coverage

• Cefepime: – Less ESBL production than 3rd generation cephalosporins – Recommended as empiric therapy in febrile neutropenia – Good activity against gram + and gram – infections – Pseudomonas coverage – Does NOT work against MRSA, enterococcus, Listeria

Carbapenems

• Spectrum of Activity: gram positive including MSSA and gram negative organisms including Pseudomonas aeruginosa, nosocomial bugs, and anaerobic infections

• AE: seizures, diarrhea, thrombocytopenia

• Time dependent killing

• Possible cross-sensitivity in patients with PCN or cephalosporin allergies (more structurally similar to cephs)

Carbapenems

• Meropenem:

– Less seizures and CSF side effects than imipenem/cilastatin

– Restricted use to ID

• Ertapenem:

– Once daily dosing

– No Pseudomonas activity

Glycopeptides

• Interfere with cell wall formation in steps that create glycan chains (prior to cross linking) – blocks PBP from linking chains

• Large, complex structures

• Only active against gram + (too large to affect gram negative membranes)

Vancomycin

• MRSA, resistant Strep pneumo, PCN-resistant Enterococcus

• IV

• PO for C.diff only (not orally absorbed)

• Empirically: Q8 or Q6 (rare, with good renal function)

• Monitor levels

• Resistance occurs either by altered PBP (vanc can’t bind - VRE) or increased production of peptidoglycan (VISA)

Vancomycin

• Goal: AUC/MIC ratio >400

• Generally means troughs around 10 in children

• Have to push it higher with bone and CSF : 15-20

• Skin and soft tissue infections

• Simple bacteremia

OK closer to 10

Daptomycin

• Cyclic glycopeptide

• MOA: Induces rapid depolarization of membrane potential, leads to disruption of DNA, RNA, protein synthesis

• Gram + ONLY (staph, enterococcus, strep)

• IV only

• Q24 (q12h in preemies)

• Inactivated by surfactant – cannot use for lung infections

• Monitor for rhabdomyolysis (and hold statins)

Aminoglycosides • MOA: Inhibits bacterial protein synthesis by binding to

30s and 50s ribosomal subunits resulting in a defective bacterial cell membrane

• Spectrum of Activity: mainly gram negative organisms, Pseudomonas, Klebseilla, Enterobacter

• Poor penetration into CNS, requires higher peaks to penetrate even at low concentration

• Frequently paired with β-lactam to create synergistic antibacterial activity

• Recommended empirically for superbugs: Pseudomonas, Klebsiella, Enterobacter – until susceptibilities are reported

Aminoglycosides

• Gentamicin, tobramycin, amikacin

– Concentration dependent killing

– AE: ototoxicity, nephrotoxicity, vertigo, muscle cramps, tremor, weakness

– Monitor peak (efficacy) and trough (toxicity)

– Toxicity is dose-dependent and cumulative

– Peaks are more closely correlated with dose, and trough with interval…

Macrolides

• MOA: Inhibits bacterial RNA dependent protein synthesis by binding to the 50s subunit of the bacterial ribosome; bacteriostatic

• Spectrum of Activity: gram positive, gram negative, atypical (Legionella, Chlamydia, Mycoplasma)

• AE: arrhythmias,

• Time-dependent killing

• Good alternative for patients with PCN allergy

• Better tissue penetration than serum

Macrolides

• Azithromycin

– Half-life: extremely long (50+ hours), long post-antibiotic effect due to extended half-life

– Preferred in pregnancy (new evidence in C-section)

– Minimal drug interactions compared to others in the class

– Newest CAP guidelines say 3 days of therapy (vs. 5 days)

Macrolides

• Clarithromycin

– DOC for MAC (preferred over Azithro unless multiple DIs or CI)

– CYP substrate & inhibitor, so always consider drug interactions

• Erythromycin

– Preferred in pregnancy

– Can be used for diabetic gastroparesis

– Can cause hypertropic pyloric stenosis in neonates

– Primary use now is for GI prophylaxis – as prokinetic agent

– Many dosage forms now unavailable….confirm with a pharmacy prior to ordering (especially for outpatients)

Fluoroquinolones • MOA: target DNA synthesis: DNA gyrase and

topoisomerase IV (responsible for breaking and unwinding overcoiled DNA so it can replicate

• Resistance can develop in many different ways and resistance from multiple different mechanisms can be additive – primarily due to mutation on binding site on DNA gyrase

• “Preclinical juvenile animal toxicity data” in 1970s suggested toxicity (beagle puppies)

• No quinolone-associated arthropathy has been documented clearly in children

Fluoroquinolones • Ciprofloxacin (Cipro)

– Good gram – coverage, lacks good gram + coverage

– Pseudomonas coverage (only oral option)

– Not active against anaerobes

• Levofloxacin (Levaquin) – Good against strep and MSSA (enhanced gram + coverage)

– Good coverage of gram – (similar to cipro, although less for Pseudomonas)

– Some activity against anaerobes

– PO, IV

– Once daily dosing

Tetracyclines

• MOA: bind reversibly to ribosome which prevents elongation of growing peptide

• Effective against many gram-positive and gram-negative bacteria as well as single cell parasites

• Bind to teeth and bones in growing children; causing permanent staining of teeth directly proportional to # of tetracycline courses prescribed

• *single course not associated with clinically detectible change*

Doxycycline

• Some activity against gram + (strep viridans, GAS, enterococcus)

• Active against CA-MRSA

• Active against gram –

• Good coverage of atypicals and anaerobes

• First line therapy for: Rickettsia, Ehrlichia, Anaplasma (RMSF), tularemia, brucellosis, cholera, Lyme disease, STARI, Bacillus anthracis

Linezolid

• MOA: binds to ribosome and inhibits protein synthesis

• Good gram + activity (including VRE and VRSA/VISA)

• Some anaerobe coverage; mycobacterial coverage

• Generally used for SSTI, respiratory tract infections

• Neutropenia (> 2 weeks)

• Potentially irreversible neuropathy (> 4-6 weeks)

• **MAOI side effects** (should not use with SSRI)

Clindamycin

• Binds to 50S ribosomal subunit, inhibits protein formation

• Gram + and anaerobes (generally enterococcus is resistant); no other gram negative activity except anaerobic bugs (bacteroides, fusobacterium)

• Great tissue penetration (not so much serum)

• NO Endovascular Coverage!

• Does not cross into CSF at any dose

• Toxin-mediated infections (ie necrotizing fasciitis)

Sulfamethoxazole / Trimethoprim • MOA: Sulfamethoxazole interferes with bacterial folic

acid synthesis; trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate (necessary for DNA purine production) resulting in sequential inhibition of enzymes of the folic acid pathway

• Spectrum of Activity: Gram positive (MSSA, MRSA) and gram negative organisms

• AE: rash, Stevens-Johnson syndrome, hypersensitivity, photosensitivity, myelosuppression with long-term exposure

• Concentration-dependent killing

Sulfamethoxazole / Trimethoprim

• IV infusion is a large volume

• IV is only compatible with D5W (including line flushing)

• Rare indications for IV (PCP, and invasive Stenotrophomonas infections)

• Drug Interactions:

– Increase effects of warfarin, antidiabetic agents, methotrexate

Metronidazole

• MOA: poorly defined; thought to be related to a reduction reaction (deprives organism of necessary entities to proceed with reduction phase)

• Anaerobic infections and certain protozoa (Trichomonas, Giardia)

• Great CSF penetration (even as an oral agent) (not much benefit for IV if able to tolerate PO)

• GI side effects

Rifampin • MOA: Inhibits RNA polymerase (transcription of DNA into

RNA); no protein translation

• Spectrum: Staph and strep only, mycobacterium

• TONS of drug interaction (pretty much everything): – Azole antifungals

– Anti-epileptics

– HIV medications

– Macrolides

– Immunosuppressants

• Never use as monotherapy, always use as additive agent with another antimicrobial

Review: Antibiotic Features • Covers hospital-MRSA

– Vancomycin – Linezolid (Zyvox)* – Daptomycin (Cubicin)* *VRE coverage

• Covers community acquired MRSA strains (usually) • Clindamycin (Cleocin) • SMX/TMP (Bactrim) • Doxycycline • Tigecycline (Tygacil)

Review: Antibiotic Features

• Covers Atypicals

– Azithromycin (Zithromax)

– Clarithromycin

– Levofloxacin (Levaquin)

– Doxycycline

– Tigecycline (Tygacil)

• Covers anaerobes – Piperacillin/tazobactam (Zosyn) – Amoxicillin/clavulanate

(Augmentin) – Ampicillin/sulbactam (Unasyn) – Cefotetan (Cefotan) – Cefoxitin (Mefoxin) – Meropenem (Merrem) – Ertapenem (Invanz) – Metronidazole (Flagyl) – Clindamycin (Clinda)

Review: Antibiotic Features

• Covers Pseudomonas: – Piperacillin/Tazobactam (Zosyn) – Meropenem (Merrem) – Aztreonam (Azactam) – Cefepime (Maxipime) – Ciprofloxacin (Cipro) – Levofloxacin (Levquin) – Gentamicin/Tobramycin – Amikacin

Antibiotic Pearls

• Antibiotics (even one dose) wipe out normal flora allowing more resistant and virulent bacteria to infect host

• Carefully consider differential and most common organisms, special circumstances – Will the antibiotic penetrate the site? (CNS, bone, lung)

– Age, allergies, previous exposure/cultures, prosthetics, etc

• Consider Na content in certain populations (CHF) – Zosyn 3.375 Gm q6h = 768 mg Na/day

– Cefepime = 0 grams

Antibiotic Pearls

• MICs are unique and standard for each antibiotic

• DO NOT compare the MICs for different antibiotics

• If double covering for pseudomonas, make sure antibiotics have different mechanisms of action (i.e. avoid pip/tazo + cefepime or meropenem)

• Daptomycin (Cubicin) is inactivated by lung surfactant, therefore it is not effective in treating pneumonia

• In general, presumed anaerobic infections do not require double coverage (ie with metronidazole)

Antibiotic Pearls

• Hospital antibiogram

– An effective tool to measure the success of an Antibiotic Stewardship Program (ASP) • Reports the hospital’s MRSA, VRE, & ESBL rates

• Useful for benchmarking with other hospitals

– Reports sensitivity of Pseudomonas & other Gram negative bacteria against first-line antimicrobials

– Updated yearly based on compiled data from our own lab

– Can vary greatly between institutions even a few miles apart

Useful Resources • Infectious Diseases Society of America

– www.idsociety.org – Updated practice guidelines for infectious disease states per body system

• Centers for Disease and Control

– www.cdc.gov – Epidemiological data, threat reports

• Sanford Guide – Preferred regimens per body system, agent-specific antimicrobial spectra – Dosing in special populations

• John Hopkins Guide to Antimicrobial Therapy

Antibiotic Resistance

Main Mechanisms of Resistance

1. Production of an enzyme that destroys the antibiotic

2. Alteration of the antibiotic target site

3. Prevention of antibiotic access to the target site

Mechanisms of Resistance

• Alterations in Penicillin-Binding Protein (PBP) Affected antibiotics: Penicillins, cephalosporins, carbapenems,

monobactams Example organsims: MRSA, Strep pneumo, E. coli, Neisseria, H. flu • Enzymatic inactivation of β-lactam antibiotics Affected antibiotics: penicillins ESBL: penicillins, cephalosporins Carbapenemase: penicillins, cephalosporins, carbapenems, monobactams Example organsisms: Enterobacteriaceae, Pseudomonas, Acinetobacter •Alteration of DNA gyrase (FQ target) Affected Antibiotics: fluoroquinolones Example organisms: S. aureus, S. epidermidis, Enterobacteriaceae

The Need for Stewardship

• Antimicrobial use is the single most important factor leading to resistance around the world – Methicillin-Resistant Staphylococcus aureus (MRSA)

– Vancomycin-Resistant Enterococcus (VRE)

– Extended-Spectrum Beta-Lactamase producing Gram negative bacteria (ESBLs)

– Multi-Drug Resistant Organisms (MDROs)

• Antimicrobial pipeline is dwindling – Only 13 new agents have been FDA-approved in the last 15

years

The Need for Stewardship

• Antimicrobial agents typically account for a large proportion of inpatient pharmacy expenditures

– PSHSJ spent over $785,000 on anti-infectives in the last 12 months alone

– Goal is to have less than 15% of total drug budget

• It has been estimated that 30 to 50% of antimicrobial use in hospitals is inappropriate

Resistance in the US

• At least 2 million people acquire serious infections with resistant organisms yearly

– At least 23,000 people die as a direct result

• At least 250,000 patients are treated for C. difficile infections yearly

– At least 14,000 patients die as a direct result

• $20 billion in excess direct healthcare costs yearly (2008 dollars)

The Need for Stewardship

• The toll of resistance includes:

– Increased mortality • Associated with a 6.5% mortality rate

– Increased costs both during hospitalization and after discharge • Average $18,588 - $29,069 per inpatient

– Extended length of hospital stay • Prolongs stay by 6.4 – 12.7 days

– Increased rate of treatment failure

– Increased need for isolation precautions

Antimicrobial Stewardship

• Antimicrobial stewardship is defined as the optimal selection, dosage, and duration of antimicrobials that results in:

– Best clinical outcomes for treatment and prevention of infections

– Minimum toxicity to patients

– Minimum impact on subsequent bacterial resistance

Key Stakeholders

• The Joint Commission

• CMS (Centers for Medicare and Medicaid Services)

• CDC (Centers for Disease Control and Prevention)

• The White House

• FDA (US Food and Drug Administration)

Current Pharmacy-Driven Strategies

• Prior Authorization (Restrictions) – Used for expensive, high-risk, broad-spectrum agents

– Requires ID consult

– May send the 1st dose pursuant to ID consult

– Examples: daptomycin, meropenem, amphotericin B

• Vancomycin, aminoglycoside consult service – “Pharmacy to dose”

– Pharmacokinetic dosing and monitoring by pharmacy

– Pharmacist writes for necessary labs and dosing changes

– Pharmacy follows up on each shift

Current Pharmacy-Driven Strategies

• Renal Monitoring Report – Optimize dose, frequency based on indication and current

renal function

– Pharmacy to adjust at any time

– Daily report run in pharmacy

• IV to PO conversion – P&T protocol with set criteria

– Avoids unnecessary IV doses (decreases cost and risk of infection)

– Daily report run in pharmacy

Current Pharmacy-Driven Strategies

• Automatic Stop Date

– Currently set at 7 days

– New order required for treatment beyond 7 days

– Shown to prevent antimicrobials from passive (and often unnecessary) continuation

• Drug Interaction Monitoring

– Active surveillance of potential drug interactions

– Ex) QTc prolongation for macrolides and FQs

Current Pharmacy-Driven Strategies

• Orders sets/bundles

– Pre-defined regimens based on current guidelines

– Ex) Sepsis, pneumonia

• Antibiogram

– Updated yearly in collaboration with microbiology

– Tracks rate of resistance based on culture data

– Contains formulary-specific information

Current Pharmacy-Driven Strategies

• Shortage reports, strategies – Keep providers up-to-date on shortages

– Provide safe and effective therapeutic alternatives

• Formulary management – Formal approval process for new agents

– Prevents redundancy of agents/classes

– Defines appropriate use and restrictions

• Committee Involvement – Infection Control, P&T, etc.

Upcoming Strategies

• Increased surveillance via Theradoc/Cerner – Standardized metrics for tracking usage

– Real-time culture data

– Bug-drug mismatches

– Provider feedback (report cards)

• Education – Initial education for new staff

– Ongoing education and in-services

– Patient education

Upcoming Strategies

• Antibiotic “Time Out” – 48-hour “soft stop”

– Pharmacy-generated report run daily

– Look to de-escalate or discontinue based on early culture results

• Resident Research Projects – Current two-phase project underway looking at the impact of

the 48-hour “time out”

• Medication Use Evaluations (MUE) – Often focusing on broad-spectrum, restricted, expensive agents

Resident Research Project

• Impact of implementing an antibiotic time out on the time to de-escalation of broad spectrum antibiotics in a community teaching hospital

– Two-phase study, 50 patients in each phase

– 48-hour “soft stop” run by pharmacy

– Pharmacist actively looked to de-escalate therapy

– Time to de-escalation went from 5.73 days to 3.27 days

– Hospital length of stay decreased from 10 days to 8.04 days

Medication Use Evaluation: Daptomycin

• 6-month period

– April 30th, 2016 to October 27th, 2016

• 30 patients received at least one dose

• $127,000 = total spent on daptomycin

• 43% of cases could have been optimized

– Included treatment of MSSA, AKI on vancomycin

• $18,570 = potential cost savings by using alternative agents (namely vancomycin)

Medication Use Evaluation: Levofloxacin

• 3-week period – November 11, 2016 to December 2, 2016

• 50 patients received at least one dose

• 96% of patients were prescribed appropriately based on current criteria – Pneumonia (CAP,HAP,VAP), Bronchitis, Intra-abdominal

Infections, Osteomyelitis, Urinary Tract Infection (complicated, uncomplicated, and pyelonephritis), Sepsis

• Duration of therapy was inappropriate in 62% of cases

• Look to remove indication of bronchitis and uncomplicated UTI based on new studies

Future Areas of Focus

• Active surveillance with Theradoc

• Vancomycin use

• Fluoroquinolone use

• Asymptomatic UTIs

• C. difficile treatment and rates

• Education

Summary

• By making Antimicrobial Stewardship part of our daily practices: – We can improve patient safety and care

– Reduce the unnecessary use of valuable resources

– Reduce bacterial resistance

• Support is needed across the health system

• Special thanks to: – Debra Powell, MD Infectious Disease Specialist

References • Gallagher J, MacDougall C. Antibiotics simplified. 2nd ed. Jones and Bartlett

Learning: 2012. • Dellit TH, et al. Infectious diseases society of America and the society for

healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clinical Infectious Diseases (2007) 44: 159–77.

• Roberts RR, Hota B, Ahmad I, et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis.2009 Oct 15;49(8):1175-84.

• CDC. US Department of Health and Human Services. Antibiotic resistance threats in the united states, 2013. Atlanta GA. 23 Apr 2013. Available at: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed January 10, 2017.

• Theuretzbacher U. CDDEP. Recent FDA antibiotic approvals: Good news and bad news. 12 Mar 2015. Available at: http://cddep.org/blog/posts/recent_fda_antibiotic_approvals_good_news_and_bad_news/

References • McNeil V, Cruickshank M, Duguid M. Safer use of antimicrobials in

hospitals: the value of antimicrobial usage data. Med J Aust 2010; 193(8 Suppl): S114 – 7.

• Owens RC, Shorr AF, Deschambeault AL. Antimicrobial stewardship: sheparding precious resources. Am J Health Syst Pharm 2009; 66(12 Suppl 4): S15 – 22.

• Martin C, Ofotokun I, Rapp R, et al. Results of an antimicrobial control program at a university hospital. American Journal Health-System Pharmacy. 2005; 62:732-8.

• Davey P, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Systematic Review. 2005; 19(4):CD003543.

• Drew RH. Antimicrobial stewardship programs: How to start and steer a successful program. J Manag Care Pharm 2009; 15 (2 Suppl): S18 – 23.

Quotes!!! “Within one linear centimeter of your lower

colon there lives and works more bacteria (about 100 billion) than all humans who have ever been born. Yet many people continue to assert that it is we who are in charge of the world.”

-Neil DeGrasse Tyson

“It is a terrifying thought that life is at the mercy of the multiplication of these minute bodies [microbes], it is a consoling hope that Science will not always remain powerless before such enemies…” – Louis Pasteur