ANTIBIOTIC STEWARDSHIP

Brian Mayhue, Pharm D, CGP Director of Pharmacy

Palm Beach Gardens Medical Center

Antibiotic Resistance “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body…there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” -Alexander Fleming, Nobel prize lecture, 1945

Antibiotic Resistance

Bad Bugs, No Drugs • IDSA expressed their concerns with the drying

pipeline of new antibiotics – Resistant bacteria cause infection in the young and old,

the healthy and frail – 2 million people acquire healthcare associated

infections (HAI); 90,000 die annually – Higher healthcare costs - ≈$5 billion annually – Big Pharma can’t turn a profit with antibiotics – 10 – 20 years and $800 million – $1.7 billion to bring a

drug to market – National and global security problem – Dwindling drug discovery and increasing antibiotic

resistance are increasing threats to the US public health

Antibiotic Development

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'83-'87 '88-'92 '93-'97 '98-'02 '03-'07 '08-'12

Tot

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ibac

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Year Introduced Class of Drug 1935 Sulfonamides

1941 Penicillins

1944 Aminoglycosides

1945 Cephalosporins

1949 Chloramphenicol

1950 Tetracyclines

1952 Macrolides/lincosamides/streptogramins

1956 Glycopeptides

1957 Rifamycins

1959 Nitroimidazoles

1962 Quinolones

1968 Trimethoprin

2000 Oxazolidinones

2003 Lipopeptides

IDSA’s multi-pronged approach to antibiotic resistance

• fix the broken antibiotic drug pipeline • support the development and utilization of new rapid

diagnostic tests • enact the Strategies to Address Antimicrobial Resistance

(STAAR) Act (H.R. 2400) • implement effective infection prevention and control

programs • support the development of new vaccines and appropriate

immunization policies • stop non-judicious uses of antibiotics on U.S. farms

(animal and plant agriculture) • view antibiotic resistance as a global health issue • promote the judicious use of antibiotics in human

medicine (antimicrobial stewardship)

Magnitude of Antimicrobial Use • Antibiotics are the second most commonly used class of

drugs in the United States • More than 8.5 billion dollars are spent on anti -infectives

annually 200-300 million antimicrobials prescribed annually 53% for outpatient use

• 30-50% of all hospitalized patients receive antibiotics • Studies estimate up to 50% of antibiotic use is either

unnecessary or inappropriate across all type of health care settings

Unnecessary Use of Antimicrobials in Hospitalized Patients

• Prospective observational study in ICU • 576 (30%) of 1941 antimicrobial days of therapy deemed

unnecessary

Hecker MT et al. Arch Intern Med. 2003;163:972-978.

Most Common Reasons for Unnecessary Days of Therapy

192 187

94

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Duration of TherapyLonger than Necessary

Noninfectious orNonbacterial Syndrome

Treatment ofColonization orContamination

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Antibiotic Misuse • Given when they are not needed • Continued when they are no longer necessary-

duration • Given at the wrong dose-renal and weight-based

dosing • Broad spectrum agents are used to treat very

susceptible bacteria • The wrong antibiotic is given to treat an infection

Summary • Multi-drug resistant pathogens are becoming more

common everywhere • New antibiotics with novel mechanisms of action are not

being produced by Big Pharma • Antibiotic stewardship is meant to optimize the use of

antibiotics, not to police them • California SB 739, CASPI can help kick-start national

legislation of ASP as a requirement for participation in CMS reimbursement

• We all need to do our part in the responsible prescribing of antibiotics; it effects all of us

Guidelines to develop an institutional Antimicrobial Stewardship Program (ASP)

• Antimicrobial Stewardship committee • Computer surveillance and decision support

software • Proactive microbiology lab • Monitoring of process and outcomes

measures • Elements of an ASP

– Active Strategies – Supportive Strategies

Goals of Antimicrobial Stewardship Programs

Optimize Patient Safety

Decrease or Control Costs

Reduce Resistance

Antimicrobial Stewardship Goals

• Improve patient outcomes • Optimize selection, dose and duration of Rx • Reduce adverse drug events including secondary infection

(e.g. C. difficile infection) • Reduce morbidity and mortality • Limit emergence of antimicrobial resistance • Reduce length of stay • Reduce health care expenditures

MacDougall CM and Polk RE. Clin Micro Rev 2005;18(4):638-56.

Ohl CA. J. Hosp Med. In press. Dellit TH, et. al. Clin Infect Dis. 2007;4

• Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile infection (CDI). – Up to 85% of patients with CDI have antibiotic

exposure in the 28 days before infection1

• 20% of patients admitted to the ICU with CDI were receiving antibiotics without evidence of infection with an accompanying 28% in-hospital mortality2

1 Infect Control Hosp Epidemiol 2007; 28:926–931.

2 BMC Infect Dis 2007; 7:42

Antibiotic misuse adversely impacts patients- C. difficile

PBGMC C. Diff Rate

• Rate based on cases per 10000 admissions

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2012 2013

Challenges • Literature often not clear in Infectious Diseases • Everyone thinks they know how to use antibiotics • Providers perceive autonomy is lost • Difficulty proving impact (no national measures) • Financial pressures dictating decisions

– Pharmaceutical manufacturers – Hospitals – Insurance companies – Patients

Getting Started Multidisciplinary team

– Physician champion – Clinical pharmacist (with ID training)

Decentralized (on the units) – Additional

– clinical microbiology – Information systems specialist – Infection prevention professional/ hospital

epidemiologist

Multidisciplinary Team Approach

* Hospital Epidemiologist

Infection Prevention

Medical Information Systems

Microbiology Laboratory

Infectious Diseases Director,

Quality

Chairman, P&T Committee

Partners in Optimizing Antimicrobial Use such as ED, hospitalists, intensivists and surgeons

Hospital and Nurse Administration

AMP Directors • Cl. Pharmacist • Physician Champion

Clinical Pharmacy Specialists

Decentralized Pharmacy Specialist

Modified: Dellit et al. ClD 2007;44:159-177. *based on local resources

Physician Champion • Basic knowledge of antibiotics*(does not have to

be an infectious disease MD but helps) • Must show interest in taking a leadership role in

the hospital • Respected by his or her peers • Good interpersonal skills • Good team player • Basic understanding of human factors and culture

transformation

Key Elements for Successful ASP

• Establish compelling need and goals for ASP • Senior leadership support • Effective physician champion • Adequate resources (pharmacy, infection prevention [IP],

microbiology, information technology [IT]) • Primary objectives: optimize clinical outcomes and reduce

adverse events, not necessarily reduce costs • Good teamwork and follow up

PBGMC Antibiotic Stewardship Program

• Prospective audit with intervention and feedback

• Streamlining or de-escalation of therapy • Dose optimization • Formulary restriction and pre-authorization • Parenteral to oral conversion

Prospective Audit and Feedback Back-end Approach

Physician writes order

Antibiotic Dispensed

At a later date, time antibiotics reviewed

Prescribing physician contacted and recommendations made

Prospective Audit and Feedback

• Advantages – Prescriber autonomy maintained – Educational opportunity provided – Patient information can be reviewed before

interaction – Inappropriate antibiotic use decreased – De-escalation

Prospective Audit and Feedback

• Disadvantages – Voluntary compliance – Identification of patients require computer

support (IT pharmacist helpful) – Prescribers reluctant to change if patient is

doing well – Some inappropriate antibiotic use permitted

Dose Optimization • New evidence for duration of therapy

– Uncomplicated urinary tract infection: 3-5 days1 – Community-acquired pneumonia: 3-7 days2 – Ventilator-associated pneumonia: 8 days3 – CR-BSI Coagulase-negative staphylococci: 5-7 days4 – Acute Hem Osteomyelitis in children-21 days5 – Meningococcal meningitis-7 days6 – Uncomplicated secondary peritonitis with source control: 4-7 days7

• Avoid 10-14 day course of antibiotic therapy

Dose Optimization

• Other steps taken at PBGMC – Implementation of extended infusion of

Pip/Tazo (started in Feb 2013) • Dosing based on renal function (either Pip/Tazo

3.375g IV q12hrs or q8hrs over 4 hr period)

– Renal Dosing Policy • Allows pharmacist to change dose/ frequency based

on renal function

Pip/Tazo purchases

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Pip/Tazo

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Formulary Restriction

• Restrict high cost antibiotics to infectious disease physicians – Examples: daptomycin, linezolid, tigecycline

IV to PO Conversion

• Develop a policy specifically targeting antibiotics which have same bioavailability to change to oral if certain criteria are met. – Azithromycin – Fluconazole – Fluoroquinolones (ciprofloxacin, levofloxacin) – Metronidazole – Linezolid – Clindamycin – Doxycycline

IV to PO Conversion

• Inclusion Criteria (must meet one) – Tolerating a regular or modified diet for at least

24 hours – Tolerating enteral nutrition for at least 24 hours – Receiving other scheduled medications by the

oral route – Signs and symptoms of infection have resolved

or are improving

IV to PO Conversion

• Exclusion criteria (must have none) – Unable to swallow, NPO, high risk for aspiration – Active N/V/D, GI obstruction, IBS, malabsorption, or ileus – Signs and symptoms of infection have not improved – Experienced severe trauma within last 72 hrs – Active GI bleed – Neutropenia (ANC<5000 – Documented CNS infection or endocarditis – Pneumonia with AIDS or severely immunocompromised – Pseudomonas infection and on antibiotics <24 hrs – Candidemia treated <7 days – Other infections where IV therapy is the preferred standard of care

(osteomyelitis)

Other Interventions

• Post antibiogram on line through our physician portal

• Work with Pharmacy Informatics to get computer generated reports to help clinical pharmacists identify opportunities

• Future opportunities (procalcitonin) to identify sepsis

PBGMC Antibiotic Spending

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2012 2013

Lessons Learned

• Physician push back was a huge problem – Education does not always work- because they

“know” better – A peer (trusted colleague/ physician champion)

is the key to success – Showing physicians financial data vs their peers

does work

Lessons Learned

• One ID physician changing prescribing habits can make all the difference

• Getting simple policy and procedures thru P&T is not always simple

• Whatever is the driving force for starting an ASP it can be successful and can help substantially cut medication costs

Conclusion

• Effective empiric antimicrobial selection based on your particular hospital (antibiogram)

• Optimize dose and route of administration • Administer for the shortest duration

possible • De-escalate once susceptibility known • Stop if no infection identified