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Introduction to Antimicrobial Resistance
and Antibiotic Stewardship
Mandelin Cooper, PharmDClinical Pharmacist in Infectious Diseases
Wesley Medical CenterJuly 12, 2012
1
Objectives
• Explain the importance of antibiotic resistance
• Review strategies to prevent and reduce bacterial resistance
• Describe antibiotic stewardship programs and strategies
• Describe the stewardship programs in Wichita
2
Resistance is Increasing
3www.CDC.gov
Resistance is Increasing
4http://www.cddep.org/ResistanceMap/use
Impact of Resistance
• Infections with resistant organisms:– More likely to be hospitalized– Longer length of stay– Higher rates of death
• Estimated cost of treating infections with resistance in the USA is several billion dollars
6
AAC 2008;Mar;52(3):813-21.
Resistance & Prescribing Practices
7
Emergence of Resistance
• Two Primary Components– Endogenous expression of resistance that
occurs because of selective pressure (i.e. antibiotic use)
– Person-to-person spread• Good Infection Control Practices are Essential!
8
Basic Types of Resistance
• Intrinsic resistance– Lack of drug binding site– Drug unable to penetrate
• Acquired resistance– Mutations– Plasmids– Exchange of DNA
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Selection Pressure
• Squeezing the Balloon– Extensive use of single drug classes leads to
an increased amount of resistance– Heterogeneity through individualization of
drug selection may stabilize the selection of resistance
10JAMA 1998; 208 (14): 1270-1.
Selection for antimicrobial-resistant Strains
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Resistant StrainsRare
xx
Resistant Strains Dominant
Antimicrobial Exposure
xx
xx
xx
xx
xx
www.cdc.gov Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Accessed 6/17/2010
Collateral Damage
Use of broadspectrum antibiotics can cause unintended resistance to develop in pathogens that are not being targeted for treatment
12JAMA 1998; 208 (14): 1270-1.
Collateral Damage• C. difficile
– Use of almost every antibiotic has been reported to cause C. difficile
– Broader spectrum and prolonged use of antibiotics increases the risk of development
– However, it has been known to occur with only ONE dose
– Decreasing usage of fluoroquinolones & cephalosporins have been associated with decreased incidence of C. difficile
13Infect Control Hosp Epidemiol 2010; 31(5)JAC Advanced Access June 2011 doi:10.1093/jac/dkr253.CID 2011; 53(1): 42-8.
Collateral Damage
• Vancomycin Resistant Enterococcus (VRE)– Fluoroquinolones and Cephalosporins
• Methicillin Resistant Staph Aureus (MRSA)– Patients exposed to antibiotics are 2 times as
likely to acquire MRSA as patients who are not exposed
– Patients exposed to quinolones are 3 times as likely to acquire MRSA
14AAC 2002;46(6):1619-28.Ann Intern Med 2001;135:175-83.J Antimicro Chemo 2008; 61:26-38
Collateral Damage
• Carbapenem-Resistant Enterobacteriaceae (CRE or KPC)– Carbapenems, cephalosporins,
fluoroquinolones, and vancomycin– Antimicrobial stewardship would be most
effective if efforts are directed toward an overall decrease in antimicrobial use rather than targeting a specific antimicrobial class
15CID 2011; 53(1): 60-7.
Other Examples
• Fluoroquinolones select for resistance to carbapenems in Pseudomonas aeruginosa
• Fluoroquinolones may have caused the Hyper-producing toxin strains of C. difficile
• Clindamycin usage is a known cause of C. difficile• Ceftazidime increases the amount of
ESBLs
16
CID 2007; 45:S112-21.CID 2005; 41:1254-60.CID 2008; 46:S19-31
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Kansas And Antibiotic Usage
18http://www.cddep.org/ResistanceMap/use
Number of Rx per 1000 population
= Higher than the National Average
Did You Know?
According to the literature:
Up to 50% of antimicrobial use is inappropriate
19CID 2007;44:159-77.
Inappropriate and unnecessary antimicrobial
use leads to increased resistance
20CID 2007;44: 159-77
Antibiotics and Emergence of Resistance
• Changes in antimicrobial use are paralleled by changes in resistance
• Patients with resistant organisms are more likely to have received prior antimicrobials
• Areas with the highest amount of resistance have the highest amount of antibiotic use
• Increased duration of antibiotics increases the risk of colonization with resistant organisms
21CID 2007;44: 159-77
Use Antibiotics Appropriately
Goal: Use antibiotics to effectively treat a patient and minimize the development of resistance
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Use Antibiotics Appropriately
• Minimize the risk of infection– Hand hygiene– Remove unnecessary lines and catheters etc.
• Only treat a patient if they have an infection– Do NOT treat contamination– Do NOT treat colonization– Do NOT treat asymptomatic bacteriuria
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Use Antibiotics Appropriately
• Initial therapy MUST be appropriate– Use antibiogram data – Know the difference between community and
nosocomial infections– Use Evidence Based Guidelines
• Meningitis, Pneumonia, Endocarditis, Vancomycin, C difficile, MRSA etc.
– Use Appropriate Doses of Antibiotics• Ex. Vancomycin troughs <10 → increased
resistance
24CID 2011; 52: 1-38.
Antibiogram
• A cumulative summary of bacteria species susceptibility to antibiotics in a specific hospital within a defined period of time
• Each hospital will have their own antibiogram– Intranet at each respective institution– Pocket cards are available
• Updated annually
Antibiogram
• Divided into Sections*• Most common and clinically relevant isolates are included• Percentage is the # of isolates susceptible to the antibiotic • Percentage includes every isolate tested• Gray areas are not tested or not susceptible
Limitations of Antibiograms
• Not reflective of each individual unit but describes the hospital overall– Some patient areas will have less resistance
and some will have more– Antibiogram specific for the ICUs
• Not reflective of specific types of infection but all cases where the bacteria was isolated
Use Antibiotics Appropriately
• Obtain appropriate specimens to aid in diagnosis and treatment of infections
• De-escalate antibiotics as early as possible
• Maximize the efficacy and minimize the toxicity of the agent used
• Minimize the duration of antibiotics– Ex. do not use prolonged antibiotics post-
operatively (<24 hours for most surgeries)
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Duration of Therapy
CID 2011; 52(10): 1232-40
Duration of Therapy
• Post-op Prophylaxis: < 24 hours needed for most surgeries
• CAP: 5 days– 5 RCTs show that 5 days is as effective as
longer courses
• VAP: 7 days per guidelines– 8 vs 15 days showed similar outcomes
• Intra-abdominal: – 4-7 days after source control
30
CID 2011; 52(10): 1232-40.CID 2007; 44: S27-72.Am J Respir Crit Care Med 2005; 171:388-416.JAMA 2003; 290: 2588-98.
Duration of Therapy
• Pyelonephritis– Guidelines 14 days– Meta-analysis of short course (7-14 days) vs
long course (14-21 days) showed no significant differences
31
CID 2011; 52(10): 1232-40.CID 2011; 52: e103-20.CID 2010; 50: 133-64.
What is Antibiotic Stewardship?
The optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of an infection, with minimal toxicity to the patient and minimal impact on subsequent development of resistance
32Diag Microbial Infect Dis 2007; 57 (suppl 3) S77-83.
Stewardship
• Stewardship NOT ONLY limits inappropriate antibiotic usage– Optimizes antibiotic selection– Dosing– Route – Duration of Therapy
33CID 2007;44:159-77
The Stewardship Team
• Infectious Diseases Physician
• Clinical Pharmacist with Infectious Disease training
• Microbiology
• Infection Control
• Hospital Epidemiologist
• Information System Specialist
34CID 2007; 44 (159-77)
Stewardship Methods
• Education
• Guidelines and Clinical Pathways
• Antimicrobial Order Forms (i.e. Pre-printed order sets)
• Dose optimization
• Parenteral to Oral Conversion
• Streamlining or de-escalation of therapy
35CID 2007;44:159-77.
Wichita Antibiotic Stewardship Programs
• Both Programs– Dr. Creswell is the medical director– Full time pharmacist who follows patients
concurrently and makes written/oral recommendations
– IV to PO
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Wichita Antibiotic Stewardship Programs
• Both Programs– Formulary restriction (multiple therapeutic
interchanges)– Work closely with Microbiology and Infection
Control– Develop and maintain order sets and
clinical pathways
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Wichita Stewardship Programs
• Wesley: Mandelin Cooper, PharmD– Clinical Pharmacists in every unit– Adult Renal Dosing Program– Kinetic service
• Via Christi: Jennifer Schmitz, PharmD– Clinical Pharmacists throughout the hospital– Adult renal dosing in place for multiple
medications– Kinetic service coming soon
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Goals of Our Stewardship Programs
• Improve patient outcomes
• Optimize antibiotic therapy for patients
• Minimize the development of resistance on a patient, hospital and citywide basis
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Goals of Our Stewardship Programs
• Reserve agents that treat MDR organisms for cases of resistance
• Educate on appropriate use of antibiotics
• Reduce antibiotic expenditures
• Meet CMS Core Measures
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Daily Stewardship Functions
• List of patients on antibiotics
• Review by clinical pharmacist
• Potential changes identified
• Chart reviewed
• Consultation with ID physician
• Additional micro information obtained
• Prescribing physician contacted
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Does Stewardship Work?
• Improves Patient Outcomes– Optimizing empiric antibiotic selection– Optimizing dosing of antibiotics
• Decreases Resistance– Improve or maintain antibiotic susceptibilities
• Decreases cost for patients and hospitals
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Wesley Results - 2011• Because of - Appropriate Gentamicin usage
we have reduced P. aeruginosa resistance• Because of - Appropriate Ceftazidime usage
we have reduced P. aeruginosa resistance• Because of - Appropriate Fluoroquinolone
usage we have retained P. aeruginosa susceptibilities
• Many institutions have lost the ability to use the older, less toxic drugs due to less than optimal use
Wesley Results 2010 & 2011
Patient Stewardship Case
• AB is a 69 yr old F from a nursing home admitted to MICU for possible HCAP and is started on Cefepime/Tobramycin/Vancomycin empirically
• PMH: DM, HTN, COPD, Pseudomonas pneumonia 2 years ago
• Scr 1.0, CrCl = 65 ml/min
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Patient Stewardship Case
• Day #1: RPh would review the patient for drug selection and dosing
• Patient has a history of Pseudomonas so duplicate coverage empirically is recommended
• Past Pseudomonal culture results are compared to the antibiotics prescribed
• Cefepime: Dosing would be automatically adjusted at order entry
• Vancomycin/Tobramycin: Prescriber would be contacted if changes were necessary or if RPh consulted to dose they would be dosed for pneumonia
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Patient Stewardship Case
• Day #2: – Sputum gram stain shows GNR and has early
growth of gram negative rods– RPh would review culture and recc to d/c the
vancomycin
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Patient Stewardship Case
• Day #3: – Sputum Culture grows pan sensitive
Pseudomonas and is finalized– RPh would recc to d/c the vancomycin (if not
already done) and the tobramycin• Once sensitivities are known duplicate coverage
for pseudomonas is unnecessary • One agent improves patient outcomes by
decreasing the risk of toxicity
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AAC 1997; 41 (5): 1127-33.AAC 2003; 47 (9): 2756-64.Pharmacotherapy 2011; 31 (6): 598-608.
Patient Stewardship Case
• Day #8: – AB is on Cefepime D#8 for pseudomonas
pneumonia • CXR improved• Patient is clinically stable
– RPh would discuss with MD length of therapy and recc to d/c or place stop dates
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Take Home Message
• Antibiotic resistance is a problem and we have limited antibiotics in the pipeline
• Stewardship is a group effort between multiple disciplines
• Only give patients antibiotics if they have an infection
• De-escalate antibiotics as early as possible
• Treat for the appropriate length of time
50
Introduction to Antimicrobial Resistance
and Antibiotic Stewardship
Mandelin Cooper, PharmDClinical Pharmacist in Infectious Diseases
Wesley Medical CenterJuly 12, 2012
51
