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Antimicrobial Stewardship in
Oncology Care
Aliyah Baluch, MD, MSc, FACP
Assistant Member, Division of Infectious Diseases
Moffitt Cancer Center
Rod Quilitz, PharmD, BCOP
Clinical Pharmacy Coordinator – Infectious Diseases &
Antimicrobial Stewardship
Moffitt Cancer Center
Nov. 5, 2016
10:15 am to 11:00 am
Disclosures
We have no disclosures to make
http://www.parentguide.ca/stages/toddler-and-preschooler/do-bugs-need-drugs/
Learning Objectives (1 of 2)
• Review risk factors for infections in the
oncology patient population
• Discuss the impact on infections by multi-drug
resistant (MDR) organisms on oncology
patient outcomes
Learning Objectives (2 of 2)
• Review the concept of antimicrobial
stewardship (AS) and the most recent IDSA
guideline and the upcoming Joint Commission
standard pertaining to AS
• Describe the implementation of an AS
Program at a NCI-designated Comprehensive
Cancer Center
Which of the following bacterial infections
is most problematic in your institution?
• A. Enterococcus faecium
– VRE
• B. Staphylococcus aureus
– MRSA, VISA, hVISA
• C. Enterobacteriaceae such as E. coli,
Klebsiella, Enterobacter
– ESBL, AmpC, or Carbapenemase producing
• D. Acinetobacter
• E. Pseudomonas aeruginosa
What is the status of Antimicrobial
Stewardship at your institution?
• A. No formal ASP exists and no active plans to
start one exist
• B. ASP is currently in the planning stages
• C. ASP exists but has minimal involvement in
the oncology patient population at this time
• D. Formal ASP exists and is actively engaged
in the care of oncology patients receiving
antimicrobial therapy
Pre-Test
What is the primary purpose of
Antimicrobial Stewardship?
• A. Institutional adherence to regulatory
standards, such as the Joint Commission
• B. Reduce drug costs
• C. Improve patient outcomes
• D. Managing critical antibiotic shortages
Which of the following are key
components to an ASP program?
• A. Pre-authorization of restricted antibiotics
• B. Prospective audit and feedback
• C. Antibiotic cycling
• D. All of the above
• E. A and B
Which of the following are mandated
in the proposed Joint Commission
Standard?
• A. Multi-disciplinary team
• B. Antibiotic data reporting and quality
improvement activities
• C. Institutional leadership support
• D. Staff and practitioner education
• E. Patient and caregiver education
• F. All of the above
• G. A and B
Learning Objectives (1 of 2)
• Review risk factors for infections in the
oncology patient population
• Discuss the impact on infections by multi-drug
resistant organisms on oncology patient
outcomes
General Risk Factors
• Invasive IV access
– PICC
– Port
– Tunneled vs. non tunneled catheter
• Mucositis / enteritis
• Low IgG due to disease status
• Anatomic issues related to tumors
– Obstruction
– Erosion and rupture
Immunocompromised Hosts
Neutropenia 7d+
• Malignant Hematology
• Hematopoietic Cell
Transplant (HCT)
– Autologous HCT
– Allogeneic HCT
• CAR-T
Neutropenia <7d or low
IgG
• Oncology
• Common variable
immunodeficiency
disease
Allogeneic HSCT
‘Transplant’ Required
Family Member is
a potential match
Matched Related
Donor
Mismatched Related
Donor
Haploidentical
No Match in the family
National Registry or
International
Registries
Matched Unrelated
Donor
Mismatched
Unrelated
Donor
Cord Registry
Double
Cord
Net State of Immunosuppression
• Immunosuppression
in order to maintain
graft
•Steroids
•Calcineurin
Inhibitors
•mTOR inhibitors
•Nucleotide
synthesis
inhibitors
•Monoclonal
antibodies
• Infection risk
•Bacterial infection
•Fungal infection
•CMV
•EBV/PTLD
•HSV
•VZV
•mTB reactivation
•Cancer risk
Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell
Transplantation Recipients: A Global Perspective, Biol BMT, 2009
Neutrophil Recovery
• G-CSF mobilized PBSC
– 2 wks
• Marrow grafts
– 3 wks
• Umbilical cord blood
grafts
– 4 wks
– With Thiotepa  may be
even longer
• First recovered
– Monocyte, Neutrophil, and
NK-cells
• 2nd
– B and T-cells
• 3rd
– RBCs and platelets
Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell
Transplantation Recipients: A Global Perspective, Biol BMT, 2009
Dictates Prophylaxis in alloHSCT:
cipro/ fluc vs micaf vs vori/ ACV
Phases of Infection in alloHCT
Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell
Transplantation Recipients: A Global Perspective, Biol BMT, 2009
Phases of Infection in alloHCT
Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell
Transplantation Recipients: A Global Perspective, Biol BMT, 2009
Phases of Infection in alloHCT
Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell
Transplantation Recipients: A Global Perspective, Biol BMT, 2009
Colonization / Previous Infections
• Colonization with
– MRSA
– VRE
– Fluoroquinolone resistant Strep viridans (GVS)
– Fluoroquinolone resistant gram negative rods
– Fluoroquinolone screening for prostate patients
Colonization / Previous Infections
• Colonization with
– MRSA (PCR of nares)
– VRE (PCR of perianal area)
– Fluoroquinolone resistant Strep viridans (GVS)
• Historical positive blood cultures
– Fluoroquinolone resistant gram negative rods
• Historical positive blood cultures
– Fluoroquinolone screening for prostate patients
• Rectal swab pre prostate biopsy
Baker et al, The growing threat of MDR GNR in patients with heme malignancies, Leukemia and
Lymphoma, 2016
ESKAPE Organisms
• (E)nterococcus faecium
– Daptomycin/linezolid resistance
• (S)taphylococcus aureus
– Daptomycin/linezolid resistance
• (K)lebsiella pneumoniae
– ESBL producing , Carbapenem-resistant Enterobacteriacae
(CRE)
• (A)cinetobacter baumannii
• (P)seudomonas aeruginosa
• (E)nterobacter species
– AmpC de-repression, CRE
BSI with ESBL producing
organism was an independent
predictor of mortality, prolonged
length of stay, delay of
appropriate antimicrobials and
total hospital stay cost.
Boucher et al, Bad Bugs, No Drugs: No ESKAPE, CID, 2009
Baker et al, The growing threat of MDR GNR in patients with heme malignancies, Leukemia and
Lymphoma, 2016
• Carbapenemase-producing gram-negative bacilli
– Polymyxins are polypeptide antibiotics that work by
affecting outer membranes of bacteria leading to
death
• MCR-1 gene
– Described initially in 2015, plasmid-mediated colistin
resistance
– Now has been found in human, animal and
environmental sources
– SENTRY project reviewed 21,006 samples of E. coli and
K. pneumoniae from 2014-2015 and there was only a
prevalence of 0.1%
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– Coverage needed for Pseudomonas
• Choice: (A-I)
– Anti-pseudomonal cephalosporin (i.e. cefepime)
– Piperacillin-tazobactam
– Anti-pseudomonal carbapenem (i.e. meropenem)
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– Coverage needed for Pseudomonas
• Choice: (A-I)
– Anti-pseudomonal cephalosporin (i.e. cefepime)
– Piperacillin-tazobactam
– Anti-pseudomonal carbapenem (i.e. meropenem)
• If with hypotension, pneumonia or hx of multidrug
resistance
– Aminoglycoside, fluoroquinolone, IV vancomycin
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– ***NOTE***
• IV vancomycin (or other gram positive coverage) is NO
LONGER recommended as part of standard initial
coverage for NP fever (A-I)
• Unless there is a cause for it
– For example: cellulitis or catheter-related infection
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– Special caveats
• MRSA colonized/ hx of MRSA infection
– Consider early use of IV vancomycin, linezolid, daptomycin (B-
III)
• VRE colonized/ hx of VRE infection
– Consider early use of linezolid or daptomycin (B-III)
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– Special caveats
• ESBL hx of infection
– Consider early use of a carbapenem (B-III)
• KPC hx of infection
– Consider early use of polymixin-colistin or tigecycline (C-III)
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• High risk patient that is admitted
– Allergy to Penicillin
• Assess severity
– Age of symptoms
– Anaphylaxis vs. rash
• Most tolerate cephalosporins as long as without hx of
immediate-type hypersensitive reaction
• If true allergy utilize mono-bactam ring antibiotic
– Consider IV vancomycin and aztreonam
– Consider IV vancomycin and ceftazidime
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Neutropenic (NP) Fever:
Initial Therapy
• Inpatient treatment
– If the pt is on IV vancomycin, linezolid or
daptomycin
• Work-up is negative
– In 48 hrs  d/c gram positive coverage (A-II)
– If the pt is hemodynamically unstable after initial
antibiotics
• Consider adding coverage for resistant organisms,
anaerobes and/or fungi (A-III)
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Special note:
Antifungal Prophylaxis
• Prophylaxis vs. Candida spp.
– Needed in pts at risk for invasive candidal
infections
• Salvage induction chemotherapy for acute leukemia
• Allogeneic hematopoietic stem cell transplants (HSCT)
– Options
• Fluconazole, triazoles, echinochandins
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
Antifungal Prophylaxis
• Prophylaxis vs. Aspergillus infection
– Patients that are neutropenic with prior history of
invasive aspergillosis (A-III)
– Patients with anticipated prolonged neutropenia
i.e. more than 2 wks (C-III)
– Patients with prolonged neutropenia immediately
prior to HSCT (C-III)
Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic
Patients … IDSA, CID, 2010
ASP vs. NP Fever
• Prospective trial
– N of 307 febrile neutropenia cases in 169 subjects
– Rate of adherence to ASP was only 53%
– ASP adherence still showed that it was
independently associated with lower mortality
• Hazard Ratio -0.36 (95% CI 0.14-0.92)
Rosa et al, Assoc between adherence to an ASP and mortality among hospitalized cancer
patients with febrile neutropenia, BMC Infectious Diseases, 2014
Learning Objectives (1 of 2)
• Review risk factors for infections in the
oncology patient population
• Discuss the impact on infections by multi-drug
resistant organisms on oncology patient
outcomes
First a Few Words About
Laboratory Testing
Gold Standard: Culture
• Blood Culture
• Fungal Blood Culture
• Acid Fast Bacilli (AFB) Blood Culture
• Tissue Culture
– Bone Marrow Culture
– CSF Culture
Rapid Diagnostics: PCR Panels
• Blood Culture Identification (BCID) Panel
– 27 Targets
• Respiratory Panel
– 20 Targets
• Gastrointestinal Panel
– 21 Targets
• Increasing number of panels available
commercially
FilmArray Blood Culture Identification
(BCID) Panel
FilmArray Blood Culture Identification
(BCID) Panel
Evaluation of FilmArray BCID
• 206 blood culture bottles analyzed
– 153/167 (91.6%) identified monomicrobial growth
• 13/167 (7.8%) microorganisms not covered in panel
– 6/167 (3.6%) FilmArray detected an additional
microorganism compared to blood culture
– 3/206 (1.5%) FilmArray was invalid
• Results were reproducible
Altun et al, Clinical Evaluation of the FilmArray BCID in Identification of Bacteria and Yeasts
from Positive Blood Culture Bottles, JCM, 2013
Shortcomings of PCR Panels
• Lack of culture
– There is a lack of sensitivity data
• Thus an inability to assess for resistance
– Only gives information ‘Yes, I am here’
Rapid Diagnostics: Mass Spectrometry
• Matrix-assisted laser desorption/ ionization time of
flight mass spectrometry (MALDI-TOF-MS)
– Identification is based on protein fingerprints
• There is no culture so there is no added information available
about sensitivity to drugs
• Additional prep steps for yeasts compared to bacteria that are
time consuming
Alam et al, Comparative evaluation of 1,3 β-d-glucan, mannan and anti-mannan antibodies and
Candida species-specific snPCR in pts with candidemia, BMC ID, 2007
Rapid Diagnostics: Urine Antigens
• Legionella urine antigen
– Only measures serotype 1 of Legionella pneumophila
• Approximately 80% of Legionella cases
– Can be negated with 1 dose of appropriate therapy
• Streptococcus pneumoniae urine antigen
– S. pneumoniae is the etiology of ~40% of community acquired
pneumonia
• Histoplasmosis urine antigen
– Can follow quantitative urine antigen while on treatment
Johansson et al, Etiology of community-acquired pneumonia, CID, 2010
Tools for Work-up of Infection
Basnayake et al, Rapid diagnostic tests for defining the cause of community-acquired
pneumonia, Current Opinion, 2015
Impact on Oncology Patients
• Neutropenic fever rates after cytotoxic
chemotherapy
– Prostate cancer 0.9 – 1.1%
– Breast cancer 4 – 5%
– Colorectal 5 – 6%
– NHL 22 – 29%
– Acute leukemia 85 – 95%
• Invasive BSI in 20 – 25% of these patients
• If early effective and empiric antibacterial therapy
for neutropenic fever  mortality is decreased
from 21% to 2 – 10%
Bow, There should be no ESKAPE for febrile neutropenic cancer patients …, J Antimicrob
Chemother, 2013
Impact on Oncology Patients
• Heme malignancy
– ESBL GNR bacteremia increases overall mortality by
25%
• Neutropenic patients
– CRE bacterial colonization / infection is on the rise
• Hot spots: NY, NJ, Spain, Israel and India
– Greater than 100 million residents of the Indian subcontinent are
already colonized with carbapenem resistant gram-negative
bacilli
– CRE bacteremia related mortality is approximately
69% (95% CI 42 – 87%)
Bow, There should be no ESKAPE for febrile neutropenic cancer patients …, J Antimicrob
Chemother, 2013
If Carbapenem Use Decreases … What
is the Effect on Steno?
Utilizing MedMind Program at MCC
Learning Objectives (2 of 2)
• Review the concept of antimicrobial
stewardship (AS) and the most recent IDSA
guideline and the upcoming Joint Commission
standard pertaining to AS
• Describe the implementation of an AS
Program at a NCI-designated Comprehensive
Cancer Center
2007
CID 2007; 44:159-77
2007 IDSA Guidelines:
Antimicrobial Stewardship (AS)
• An Antimicrobial Stewardship Program is a
rational, systematic approach to the use of
antimicrobial agents in order to:
– Optimize clinical outcomes
– Minimize unintended consequences
• Toxicity
• Collateral damage, such as Clostridium difficile
• Emergence of resistance
• Intended to provide evidence-based guidelines to
develop hospital-based ASPs
CID 2007; 44:159-77
Core Elements for ASP
• Education
– Can icrease acceptance of ASP
– Only marginally effective w/o active intervention
• Guidelines and clinical pathways
– Multidisciplinary development
– Consider local microbiology and resistance
• Antimicrobial order forms
• Streamlining or de-escalation of therapy
• Dose optimization
• IV to PO conversion
• Antimicrobial cycling
• Combination therapy
CID 2007; 44:159-77
How Do We Do It?
• Tools for ASP
– Formulary restriction and preauthorization
– Prospective audit with intervention and feedback
– Education
– Guidelines / clinical pathway development
– Monitor and provide feedback regarding resistance
(eg, antibiogram)
– Document the impact on relevant outcomes
• Computer surveillance & decision-support
systems can facilitate good AS
CID 2007; 44:159-77
Recommended ASP Team Members
• Infectious Disease Physician
• Clinical Pharmacist with ID training
• Infection Control Professionals
• Hospital Epidemiologist
• Clinical Microbiologist
• Information System Specialist
• ASP Personnel should be actively involved
with Infection Control and P&T Committees
CID 2007; 44:159-77
2016
CID 2016;62:e51-e77
2016 ASP Recommendations
• Reauthorization and/or prospective audit and
feedback
• Do not rely solely on passive didactic education
• Facility-specific clinical practice guidelines with
dissemination & implementation plan
• Reduce use of antibiotics with high risk of CDI
• Antibiotic time-outs or stop orders
• Computerized clinical decision support at time of
prescribing
CID 2016;62:e51-e77
2016 ASP Recommendations
• Antimicrobial cycling is not recommended
• Pharmacokinetic programs for
aminogyclosides & vancomycin
• Alternative dosing strategies for broad-
spectrum ß-lactams to decrease costs
• Appropriate oral antibiotics for initial therapy
and facilitate IV to PO transition
• Allergy assessments and penicillin skin testing
CID 2016;62:e51-e77
2016 ASP Recommendations
• Reduce therapy to shortest effective duration
• Develop stratified antibiograms
• Selective and cascade reporting of antibiotic
susceptibility test results
• Rapid viral testing for respiratory pathogens
• Rapid diagnostic testing on blood cultures
• Serial procalcitonin testing in ICU patients
with suspected infection
CID 2016;62:e51-e77
2016 ASP Recommendations
• Antifungal stewardship
– Heme/Onc patients: Nonculture-based fungal
markers (galactomanan, BDG, PCR)
• Days of therapy (DOT) > Defined daily dose (DDD)
• Measuring antibiotic cost based on use
• Facility-specific Neutropenic Fever guidelines
• Provide support to providers in decisions relating to
antibiotic treatment for terminally ill patients
2016
Issued on June 22, 216
Applies to Hospitals and Critical Access Hospitals
Effective January 1, 2017
Joint Commission AS Standard
• Standard MM.09.01
– The hospital has an antimicrobial stewardship
program based on current scientific literature.
• Elements of Performance
– Leaders establish AS as an organizational priority
– Educate staff & practitioners about antimicrobial
resistance & AS practices
• Upon hire or granting initial privileges
• Periodically thereafter
– Educate patients and caregivers about appropriate use
of antimicrobials, including antibiotics
JC Elements of Performance for ASP
(continued)
• Multidisciplinary ASP Team
– ID Physician
– Infection Preventionist(s)
– Pharmacist(s)
– Practitioner
• Core elements
– Leadership commitment
– Accountability – single physician leader
– Drug expertise – single pharmacist leader
– Action – implementation of recommended actions
– Tracking – monitoring antibiotic use & resistance
– Reporting – to doctors, nurses, relevant staff (i.e. P&T)
– Education
JC Elements of Performance for ASP
(continued)
• ASP uses organization approved protocols
– Policies and procedures
– Guidelines such as CAP, SSTI, UTIs, CDI, IV to PO
– Preauthorization requirements for restricted
antimicrobials
• Hospital collects, analyzes, and reports data
on its ASP
• Hospital takes action on improvement
opportunities identified by ASP
Learning Objectives (2 of 2)
• Review the concept of antimicrobial
stewardship (AS) and the most recent IDSA
guideline and the upcoming Joint Commission
standard pertaining to AS
• Describe the implementation of an AS
Program at a NCI-designated Comprehensive
Cancer Center
www.mapsoftheworld.com, www.worldatlas.com www.moffitt.org
SMART Pocket Guide
Restricted Antimicrobials
• Level 1
– Require approval from Infectious Diseases or
Antimicrobial Stewardship Program
– Non formulary antimicrobials
• Level 2
– ID/ASP approval not required to start therapy for
specified clinical indications
– ID/ASP approval required for other indications
Level 1 Restriction
2012
• Amikacin
• Colistimethate
• Doripenem
• Flucytosine
• Fosfomycin
• Imipenem-cilasatin
• Minocycline IV
• Posaconazole*
• Tigecycline
• TMP-SMX IV
2016
• All of the stuff on the left +
• AmphoB Lipid Complex
• Ceftaroline
• Cefepime**
• Ceftazidime/avibactam
• Ceftolozane/tazobactam
• Cidofovir
• Ertapenem
• Foscarnet
• Ganciclovir
• Isavuconazonium IV
• Meropenem
• Piperacillin/tazobactam***
• Pyrimethamine
• Ribavarin for inhalation
• Trifluridine
• Valganciclovir
*except in prophylaxis for acute leukemics and HCT
**except for febrile neutropenia in BMT or penicillin allergy non-severe
***except for febrile neutropenia
Level 2 Restriction
2012
• Amphotericin B
deoxycholate or liposomal
• Aztreonam
• Ertapenem
• Meropenem
• Daptomycin
• Linezolid
• Micafungin*
• Voriconazole*
2016
• Amphotericin B
deoxycholate or liposomal
• Aztreonam
• Ceftazidime
• Daptomycin
• Isavuconazonium PO
• Linezolid
• Micafungin*
• Voriconazole*
*except in prophylaxis for acute leukemics and HCT
Goal 1: Reduce Carbapenem Utilization
Antimicrobial Stewardship Program implementation lead to ~50% reduction in
carbapenem DOT
Be aware of potential ASP induced fatigue
– Quarter 2 of 2016, SMART reported daily lists of patients on carbapenems
to ID & ASP team to focus attention on the increased usage
Goal 2: Reduce Broad Spectrum Gram-
Positive Antibiotic Use
Goal 3: Promote Cost Effective
Antimicrobial Therapy
• ASP initiated 11/1/12 in middle of FY2013
– FY2012 = first FY prior to program
– FY2014 = first FY after program initiation
• $1,713,930 cost avoidance FY’14 vs FY’12
• $397,214 cost avoidance FY’15 vs FY’14
– 14.5% reduction
• Annual Antimicrobial Purchases
$0
$1,000,000
$2,000,000
$3,000,000
$4,000,000
$5,000,000
$6,000,000
$7,000,000
FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014
Challenge: Antimicrobial Shortages
• December ‘14 Piperacillin-Tazobactam
– Changed to Level 1 Restricted Antibiotic
– Ended quarterly Neutropenic Fever cycling
• July ‘15 Cefepime
– Alternative dosing schema auto-sustitution approved
• 2g IV Q12H to 1g IV Q8H
• 2g IV Q8H to 1g IV Q6H except for neutropenic fever
• Provider education re: Risk Factors for Pseudomonas
• March ‘16 Cefuroxime IV
– Replaced peri-operative antibiotic orders with Cefazolin
– Level 1 Restricted Antibiotic
• September ‘16 Cefepime
– Cefepime to Level 1 Restricted Antibiotic except for NF & BMT or PCN allergy
– Piperacillin-tazobactam remains Level 1 except for NF
– De-escalation of therapy in culture negative NF at discretion of ID Attending
Antimicrobial Shortages & Utilization
September 2016 Update
Piperacillin-Tazobactam supply improving as Cefepime supply worsening
Cefepime and Piperacillin-Tazobactam utilization is therefore being reversed
Challenge: Antimicrobial Drug
Cost Escalations in 2015
• Ribavirin for Inhalation for RSV/HMPV
– Cost increased to ~$25,000 per day of therapy
– In 2012, ASP replaced this agent with oral ribavirin (<$10 per day)
– 100% nebulized ribavirin would have cost ~$2.5 million in 2015
• Pyrimethamine for Toxoplasmosis
– Cost increased from $1,763 to $75,000 for #100 tablets ($750/tab)
– ~$300,000 for initial 6 months of therapy
– Resulted in update in IDSA Toxoplasmosis guidelines
• Flucytosine for Cryptococcus meningitis
– Cost increased to $4,353 or $10,721 per 100 capsules
– Cost for 2 weeks in US: ~$14,000 to $28,000 vs UK: ~$308
• All these agents are now Level 1 Restricted Antimicrobials
Antimicrobial Stewardship Initiatives:
Antimicrobial Guide
• Antimicrobial Dosing Guide Approved by P&T and
Medical Executive Committees
– Allows pharmacists to correct antimicrobial dosing per policy
• Vancomcyin/Aminoglycoside Dosing and Monitoring
• Expanded Intravenous to Oral Medication Policy
• Automatic Formulary Substitution Policies
• Suggested Antibiotic Therapy by Infection Site for
Patients at Low Risk for Pseudomonas
Antimicrobial Stewardship Initiatives:
Antimicrobial Guide
• Antimicrobial Therapy: UTI, Pyelonephritis
• Clostridium difficile colitis treatment algorithm
• Peri-operative Antibiotic Dosing & Redosing Criteria
• Interventional Radiology Antibiotic Prophylaxis
• Culture targeted prophylaxis for transrectal ultrasound guided
prostate biopsy
Antimicrobial Adverse Drug Reactions
Following SMART Implementation
Conclusion
• ASP programs are now required by Joint
Commission as of Jan 1, 2017
– Many components intertwined in ASP including
education
• Improves utilization of antimicrobials without
an increase in mortality
– An extra tool to help navigate the waters with
ongoing antimicrobial shortages
Gratis of Ramon Sandin, MD
Post-Test
What is the primary purpose of
Antimicrobial Stewardship?
• A. Institutional adherence to regulatory
standards, such as the Joint Commission
• B. Reduce drug costs
• C. Improve patient outcomes
• D. Managing critical antibiotic shortages
Which of the following are key
components to an ASP program?
• A. Pre-authorization of restricted antibiotics
• B. Prospective audit and feedback
• C. Antibiotic cycling
• D. All of the above
• E. A and B
Which of the following are mandated
in the proposed Joint Commission
Standard?
• A. Multi-disciplinary team
• B. Antibiotic data reporting and quality
improvement activities
• C. Institutional leadership support
• D. Staff and practitioner education
• E. Patient and caregiver education
• F. All of the above
• G. A and B
Acknowledgement: Thanks to SMART at
Moffitt Cancer Center
Circa 10/4/2016
SMART Team Members
• Infectious Diseases Attending Physicians
– John Greene, MD
– Ana Velez, MD
– Aliyah Baluch, MD, MSc
• Infectious Diseases Clinical Pharmacists
– Rod Quilitz, PharmD, BCOP
– Yanina Pasikhova, PharmD, BCPS-AQ ID, AAHIVP
– Wonhee So, PharmD, BCPS
• Microbiology
– Ramon Sandin, MD, MS, FCAP, ABP-MM
– Dawn Ruge, BS, MT (ASCP)
• Infection Prevention
– Stacy Martin, RN, BSN, CIC
– Kay Sams, RN, BSN, CIC
– Stephanie Carraway, Infection Prevention Specialist
– Patricia Tomasini, Infection Prevention Specialist
– Julie Gnage, Infection Prevention Specialist
Addendum 1:
Moffitt Cancer Center Antibiogram
52 52 54 50 49 50 44
52 52 53
50
47
0
10
20
30
40
50
60
70
80
90
100
2009 2010 2011 2012 2013 2014 2015
%Susceptible
Year
E.coli
Ampicillin
Cefazolin
Ceftriaxone
Ceftazidime
Cefepime
Ciprofloxacin
Levofloxacin
Trimeth/Sulfa
Pip/Tazo
Meropenem
Imipenem
Ciprofloxacin
0
10
20
30
40
50
60
70
80
90
100
2009 2010 2011 2012 2013 2014 2015
%Susceptible
Year
K. pneumoniae
Amp/Sulbactam
Cefazolin
Ceftriaxone
Ceftazidime
Cefepime
Ciprofloxacin
Levofloxacin
Trimeth/Sulfa
Pip/Tazo
Meropenem
Imipenem
92 91
97 97 95
86
95
82
89
77
82
86
0
10
20
30
40
50
60
70
80
90
100
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
%Susceptible
Year
S. maltophilia
Levofloxacin
Trimeth/Sulfa
Minocycline
Trimeth/Sulfa
90 90
84
89
93
86
91
95 93
90
87
94 94 95
88
80
87
91 92 94 96
0
10
20
30
40
50
60
70
80
90
100
2009 2010 2011 2012 2013 2014 2015
%Susceptible
Year
P. aeruginosa
Ceftazidime
Cefepime
Ciprofloxacin
Levofloxacin
Pip/Tazo
Meropenem
Imipenem
Tobramycin
81
72
79 80
70 69 71
100
97
90
95
90
98 98
0
10
20
30
40
50
60
70
80
90
100
2009 2010 2011 2012 2013 2014 2015
%Susceptible
Year
E. cloacae Ceftriaxone
Ceftazidime
Cefepime
Ciprofloxacin
Levofloxacin
Trimeth/Sulfa
Pip/Tazo
Meropenem
Imipenem
Tobramycin
Pip/Tazo
Meropenem
Synthesis graphics gratis of Yanina Pasikhova, PharmD
Questions
• Rod Quilitz, PharmD, BCOP
– Clinical Pharmacy Coordinator – Infectious
Diseases & Antimicrobial Stewardship
– Rod.Quilitz@moffitt.org
• Aliyah Baluch, MD, MSc, FACP
– Assistant Member, Division of Infectious Diseases
– Aliyah.Baluch@moffitt.org

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Antimicrobial Stewardship in Oncology Care

  • 1. Antimicrobial Stewardship in Oncology Care Aliyah Baluch, MD, MSc, FACP Assistant Member, Division of Infectious Diseases Moffitt Cancer Center Rod Quilitz, PharmD, BCOP Clinical Pharmacy Coordinator – Infectious Diseases & Antimicrobial Stewardship Moffitt Cancer Center Nov. 5, 2016 10:15 am to 11:00 am
  • 2. Disclosures We have no disclosures to make http://www.parentguide.ca/stages/toddler-and-preschooler/do-bugs-need-drugs/
  • 3. Learning Objectives (1 of 2) • Review risk factors for infections in the oncology patient population • Discuss the impact on infections by multi-drug resistant (MDR) organisms on oncology patient outcomes
  • 4. Learning Objectives (2 of 2) • Review the concept of antimicrobial stewardship (AS) and the most recent IDSA guideline and the upcoming Joint Commission standard pertaining to AS • Describe the implementation of an AS Program at a NCI-designated Comprehensive Cancer Center
  • 5. Which of the following bacterial infections is most problematic in your institution? • A. Enterococcus faecium – VRE • B. Staphylococcus aureus – MRSA, VISA, hVISA • C. Enterobacteriaceae such as E. coli, Klebsiella, Enterobacter – ESBL, AmpC, or Carbapenemase producing • D. Acinetobacter • E. Pseudomonas aeruginosa
  • 6. What is the status of Antimicrobial Stewardship at your institution? • A. No formal ASP exists and no active plans to start one exist • B. ASP is currently in the planning stages • C. ASP exists but has minimal involvement in the oncology patient population at this time • D. Formal ASP exists and is actively engaged in the care of oncology patients receiving antimicrobial therapy
  • 8. What is the primary purpose of Antimicrobial Stewardship? • A. Institutional adherence to regulatory standards, such as the Joint Commission • B. Reduce drug costs • C. Improve patient outcomes • D. Managing critical antibiotic shortages
  • 9. Which of the following are key components to an ASP program? • A. Pre-authorization of restricted antibiotics • B. Prospective audit and feedback • C. Antibiotic cycling • D. All of the above • E. A and B
  • 10. Which of the following are mandated in the proposed Joint Commission Standard? • A. Multi-disciplinary team • B. Antibiotic data reporting and quality improvement activities • C. Institutional leadership support • D. Staff and practitioner education • E. Patient and caregiver education • F. All of the above • G. A and B
  • 11. Learning Objectives (1 of 2) • Review risk factors for infections in the oncology patient population • Discuss the impact on infections by multi-drug resistant organisms on oncology patient outcomes
  • 12. General Risk Factors • Invasive IV access – PICC – Port – Tunneled vs. non tunneled catheter • Mucositis / enteritis • Low IgG due to disease status • Anatomic issues related to tumors – Obstruction – Erosion and rupture
  • 13. Immunocompromised Hosts Neutropenia 7d+ • Malignant Hematology • Hematopoietic Cell Transplant (HCT) – Autologous HCT – Allogeneic HCT • CAR-T Neutropenia <7d or low IgG • Oncology • Common variable immunodeficiency disease
  • 14. Allogeneic HSCT ‘Transplant’ Required Family Member is a potential match Matched Related Donor Mismatched Related Donor Haploidentical No Match in the family National Registry or International Registries Matched Unrelated Donor Mismatched Unrelated Donor Cord Registry Double Cord
  • 15. Net State of Immunosuppression • Immunosuppression in order to maintain graft •Steroids •Calcineurin Inhibitors •mTOR inhibitors •Nucleotide synthesis inhibitors •Monoclonal antibodies • Infection risk •Bacterial infection •Fungal infection •CMV •EBV/PTLD •HSV •VZV •mTB reactivation •Cancer risk
  • 16. Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective, Biol BMT, 2009
  • 17. Neutrophil Recovery • G-CSF mobilized PBSC – 2 wks • Marrow grafts – 3 wks • Umbilical cord blood grafts – 4 wks – With Thiotepa  may be even longer • First recovered – Monocyte, Neutrophil, and NK-cells • 2nd – B and T-cells • 3rd – RBCs and platelets Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective, Biol BMT, 2009
  • 18. Dictates Prophylaxis in alloHSCT: cipro/ fluc vs micaf vs vori/ ACV Phases of Infection in alloHCT Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective, Biol BMT, 2009
  • 19. Phases of Infection in alloHCT Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective, Biol BMT, 2009
  • 20. Phases of Infection in alloHCT Tomblyn et al, Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective, Biol BMT, 2009
  • 21. Colonization / Previous Infections • Colonization with – MRSA – VRE – Fluoroquinolone resistant Strep viridans (GVS) – Fluoroquinolone resistant gram negative rods – Fluoroquinolone screening for prostate patients
  • 22. Colonization / Previous Infections • Colonization with – MRSA (PCR of nares) – VRE (PCR of perianal area) – Fluoroquinolone resistant Strep viridans (GVS) • Historical positive blood cultures – Fluoroquinolone resistant gram negative rods • Historical positive blood cultures – Fluoroquinolone screening for prostate patients • Rectal swab pre prostate biopsy
  • 23. Baker et al, The growing threat of MDR GNR in patients with heme malignancies, Leukemia and Lymphoma, 2016
  • 24. ESKAPE Organisms • (E)nterococcus faecium – Daptomycin/linezolid resistance • (S)taphylococcus aureus – Daptomycin/linezolid resistance • (K)lebsiella pneumoniae – ESBL producing , Carbapenem-resistant Enterobacteriacae (CRE) • (A)cinetobacter baumannii • (P)seudomonas aeruginosa • (E)nterobacter species – AmpC de-repression, CRE BSI with ESBL producing organism was an independent predictor of mortality, prolonged length of stay, delay of appropriate antimicrobials and total hospital stay cost. Boucher et al, Bad Bugs, No Drugs: No ESKAPE, CID, 2009
  • 25. Baker et al, The growing threat of MDR GNR in patients with heme malignancies, Leukemia and Lymphoma, 2016
  • 26. • Carbapenemase-producing gram-negative bacilli – Polymyxins are polypeptide antibiotics that work by affecting outer membranes of bacteria leading to death • MCR-1 gene – Described initially in 2015, plasmid-mediated colistin resistance – Now has been found in human, animal and environmental sources – SENTRY project reviewed 21,006 samples of E. coli and K. pneumoniae from 2014-2015 and there was only a prevalence of 0.1%
  • 27. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – Coverage needed for Pseudomonas • Choice: (A-I) – Anti-pseudomonal cephalosporin (i.e. cefepime) – Piperacillin-tazobactam – Anti-pseudomonal carbapenem (i.e. meropenem) Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 28. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – Coverage needed for Pseudomonas • Choice: (A-I) – Anti-pseudomonal cephalosporin (i.e. cefepime) – Piperacillin-tazobactam – Anti-pseudomonal carbapenem (i.e. meropenem) • If with hypotension, pneumonia or hx of multidrug resistance – Aminoglycoside, fluoroquinolone, IV vancomycin Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 29. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – ***NOTE*** • IV vancomycin (or other gram positive coverage) is NO LONGER recommended as part of standard initial coverage for NP fever (A-I) • Unless there is a cause for it – For example: cellulitis or catheter-related infection Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 30. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – Special caveats • MRSA colonized/ hx of MRSA infection – Consider early use of IV vancomycin, linezolid, daptomycin (B- III) • VRE colonized/ hx of VRE infection – Consider early use of linezolid or daptomycin (B-III) Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 31. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – Special caveats • ESBL hx of infection – Consider early use of a carbapenem (B-III) • KPC hx of infection – Consider early use of polymixin-colistin or tigecycline (C-III) Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 32. Neutropenic (NP) Fever: Initial Therapy • High risk patient that is admitted – Allergy to Penicillin • Assess severity – Age of symptoms – Anaphylaxis vs. rash • Most tolerate cephalosporins as long as without hx of immediate-type hypersensitive reaction • If true allergy utilize mono-bactam ring antibiotic – Consider IV vancomycin and aztreonam – Consider IV vancomycin and ceftazidime Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 33. Neutropenic (NP) Fever: Initial Therapy • Inpatient treatment – If the pt is on IV vancomycin, linezolid or daptomycin • Work-up is negative – In 48 hrs  d/c gram positive coverage (A-II) – If the pt is hemodynamically unstable after initial antibiotics • Consider adding coverage for resistant organisms, anaerobes and/or fungi (A-III) Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 34. Special note: Antifungal Prophylaxis • Prophylaxis vs. Candida spp. – Needed in pts at risk for invasive candidal infections • Salvage induction chemotherapy for acute leukemia • Allogeneic hematopoietic stem cell transplants (HSCT) – Options • Fluconazole, triazoles, echinochandins Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 35. Antifungal Prophylaxis • Prophylaxis vs. Aspergillus infection – Patients that are neutropenic with prior history of invasive aspergillosis (A-III) – Patients with anticipated prolonged neutropenia i.e. more than 2 wks (C-III) – Patients with prolonged neutropenia immediately prior to HSCT (C-III) Freideld et al, Clinical Practice Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients … IDSA, CID, 2010
  • 36. ASP vs. NP Fever • Prospective trial – N of 307 febrile neutropenia cases in 169 subjects – Rate of adherence to ASP was only 53% – ASP adherence still showed that it was independently associated with lower mortality • Hazard Ratio -0.36 (95% CI 0.14-0.92) Rosa et al, Assoc between adherence to an ASP and mortality among hospitalized cancer patients with febrile neutropenia, BMC Infectious Diseases, 2014
  • 37. Learning Objectives (1 of 2) • Review risk factors for infections in the oncology patient population • Discuss the impact on infections by multi-drug resistant organisms on oncology patient outcomes
  • 38. First a Few Words About Laboratory Testing
  • 39. Gold Standard: Culture • Blood Culture • Fungal Blood Culture • Acid Fast Bacilli (AFB) Blood Culture • Tissue Culture – Bone Marrow Culture – CSF Culture
  • 40.
  • 41.
  • 42. Rapid Diagnostics: PCR Panels • Blood Culture Identification (BCID) Panel – 27 Targets • Respiratory Panel – 20 Targets • Gastrointestinal Panel – 21 Targets • Increasing number of panels available commercially
  • 43. FilmArray Blood Culture Identification (BCID) Panel
  • 44. FilmArray Blood Culture Identification (BCID) Panel
  • 45. Evaluation of FilmArray BCID • 206 blood culture bottles analyzed – 153/167 (91.6%) identified monomicrobial growth • 13/167 (7.8%) microorganisms not covered in panel – 6/167 (3.6%) FilmArray detected an additional microorganism compared to blood culture – 3/206 (1.5%) FilmArray was invalid • Results were reproducible Altun et al, Clinical Evaluation of the FilmArray BCID in Identification of Bacteria and Yeasts from Positive Blood Culture Bottles, JCM, 2013
  • 46.
  • 47. Shortcomings of PCR Panels • Lack of culture – There is a lack of sensitivity data • Thus an inability to assess for resistance – Only gives information ‘Yes, I am here’
  • 48. Rapid Diagnostics: Mass Spectrometry • Matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF-MS) – Identification is based on protein fingerprints • There is no culture so there is no added information available about sensitivity to drugs • Additional prep steps for yeasts compared to bacteria that are time consuming Alam et al, Comparative evaluation of 1,3 β-d-glucan, mannan and anti-mannan antibodies and Candida species-specific snPCR in pts with candidemia, BMC ID, 2007
  • 49. Rapid Diagnostics: Urine Antigens • Legionella urine antigen – Only measures serotype 1 of Legionella pneumophila • Approximately 80% of Legionella cases – Can be negated with 1 dose of appropriate therapy • Streptococcus pneumoniae urine antigen – S. pneumoniae is the etiology of ~40% of community acquired pneumonia • Histoplasmosis urine antigen – Can follow quantitative urine antigen while on treatment Johansson et al, Etiology of community-acquired pneumonia, CID, 2010
  • 50. Tools for Work-up of Infection Basnayake et al, Rapid diagnostic tests for defining the cause of community-acquired pneumonia, Current Opinion, 2015
  • 51. Impact on Oncology Patients • Neutropenic fever rates after cytotoxic chemotherapy – Prostate cancer 0.9 – 1.1% – Breast cancer 4 – 5% – Colorectal 5 – 6% – NHL 22 – 29% – Acute leukemia 85 – 95% • Invasive BSI in 20 – 25% of these patients • If early effective and empiric antibacterial therapy for neutropenic fever  mortality is decreased from 21% to 2 – 10% Bow, There should be no ESKAPE for febrile neutropenic cancer patients …, J Antimicrob Chemother, 2013
  • 52. Impact on Oncology Patients • Heme malignancy – ESBL GNR bacteremia increases overall mortality by 25% • Neutropenic patients – CRE bacterial colonization / infection is on the rise • Hot spots: NY, NJ, Spain, Israel and India – Greater than 100 million residents of the Indian subcontinent are already colonized with carbapenem resistant gram-negative bacilli – CRE bacteremia related mortality is approximately 69% (95% CI 42 – 87%) Bow, There should be no ESKAPE for febrile neutropenic cancer patients …, J Antimicrob Chemother, 2013
  • 53. If Carbapenem Use Decreases … What is the Effect on Steno? Utilizing MedMind Program at MCC
  • 54. Learning Objectives (2 of 2) • Review the concept of antimicrobial stewardship (AS) and the most recent IDSA guideline and the upcoming Joint Commission standard pertaining to AS • Describe the implementation of an AS Program at a NCI-designated Comprehensive Cancer Center
  • 56. 2007 IDSA Guidelines: Antimicrobial Stewardship (AS) • An Antimicrobial Stewardship Program is a rational, systematic approach to the use of antimicrobial agents in order to: – Optimize clinical outcomes – Minimize unintended consequences • Toxicity • Collateral damage, such as Clostridium difficile • Emergence of resistance • Intended to provide evidence-based guidelines to develop hospital-based ASPs CID 2007; 44:159-77
  • 57. Core Elements for ASP • Education – Can icrease acceptance of ASP – Only marginally effective w/o active intervention • Guidelines and clinical pathways – Multidisciplinary development – Consider local microbiology and resistance • Antimicrobial order forms • Streamlining or de-escalation of therapy • Dose optimization • IV to PO conversion • Antimicrobial cycling • Combination therapy CID 2007; 44:159-77
  • 58. How Do We Do It? • Tools for ASP – Formulary restriction and preauthorization – Prospective audit with intervention and feedback – Education – Guidelines / clinical pathway development – Monitor and provide feedback regarding resistance (eg, antibiogram) – Document the impact on relevant outcomes • Computer surveillance & decision-support systems can facilitate good AS CID 2007; 44:159-77
  • 59. Recommended ASP Team Members • Infectious Disease Physician • Clinical Pharmacist with ID training • Infection Control Professionals • Hospital Epidemiologist • Clinical Microbiologist • Information System Specialist • ASP Personnel should be actively involved with Infection Control and P&T Committees CID 2007; 44:159-77
  • 61. 2016 ASP Recommendations • Reauthorization and/or prospective audit and feedback • Do not rely solely on passive didactic education • Facility-specific clinical practice guidelines with dissemination & implementation plan • Reduce use of antibiotics with high risk of CDI • Antibiotic time-outs or stop orders • Computerized clinical decision support at time of prescribing CID 2016;62:e51-e77
  • 62. 2016 ASP Recommendations • Antimicrobial cycling is not recommended • Pharmacokinetic programs for aminogyclosides & vancomycin • Alternative dosing strategies for broad- spectrum ß-lactams to decrease costs • Appropriate oral antibiotics for initial therapy and facilitate IV to PO transition • Allergy assessments and penicillin skin testing CID 2016;62:e51-e77
  • 63. 2016 ASP Recommendations • Reduce therapy to shortest effective duration • Develop stratified antibiograms • Selective and cascade reporting of antibiotic susceptibility test results • Rapid viral testing for respiratory pathogens • Rapid diagnostic testing on blood cultures • Serial procalcitonin testing in ICU patients with suspected infection CID 2016;62:e51-e77
  • 64. 2016 ASP Recommendations • Antifungal stewardship – Heme/Onc patients: Nonculture-based fungal markers (galactomanan, BDG, PCR) • Days of therapy (DOT) > Defined daily dose (DDD) • Measuring antibiotic cost based on use • Facility-specific Neutropenic Fever guidelines • Provide support to providers in decisions relating to antibiotic treatment for terminally ill patients
  • 65. 2016 Issued on June 22, 216 Applies to Hospitals and Critical Access Hospitals Effective January 1, 2017
  • 66. Joint Commission AS Standard • Standard MM.09.01 – The hospital has an antimicrobial stewardship program based on current scientific literature. • Elements of Performance – Leaders establish AS as an organizational priority – Educate staff & practitioners about antimicrobial resistance & AS practices • Upon hire or granting initial privileges • Periodically thereafter – Educate patients and caregivers about appropriate use of antimicrobials, including antibiotics
  • 67. JC Elements of Performance for ASP (continued) • Multidisciplinary ASP Team – ID Physician – Infection Preventionist(s) – Pharmacist(s) – Practitioner • Core elements – Leadership commitment – Accountability – single physician leader – Drug expertise – single pharmacist leader – Action – implementation of recommended actions – Tracking – monitoring antibiotic use & resistance – Reporting – to doctors, nurses, relevant staff (i.e. P&T) – Education
  • 68. JC Elements of Performance for ASP (continued) • ASP uses organization approved protocols – Policies and procedures – Guidelines such as CAP, SSTI, UTIs, CDI, IV to PO – Preauthorization requirements for restricted antimicrobials • Hospital collects, analyzes, and reports data on its ASP • Hospital takes action on improvement opportunities identified by ASP
  • 69. Learning Objectives (2 of 2) • Review the concept of antimicrobial stewardship (AS) and the most recent IDSA guideline and the upcoming Joint Commission standard pertaining to AS • Describe the implementation of an AS Program at a NCI-designated Comprehensive Cancer Center
  • 71.
  • 73. Restricted Antimicrobials • Level 1 – Require approval from Infectious Diseases or Antimicrobial Stewardship Program – Non formulary antimicrobials • Level 2 – ID/ASP approval not required to start therapy for specified clinical indications – ID/ASP approval required for other indications
  • 74. Level 1 Restriction 2012 • Amikacin • Colistimethate • Doripenem • Flucytosine • Fosfomycin • Imipenem-cilasatin • Minocycline IV • Posaconazole* • Tigecycline • TMP-SMX IV 2016 • All of the stuff on the left + • AmphoB Lipid Complex • Ceftaroline • Cefepime** • Ceftazidime/avibactam • Ceftolozane/tazobactam • Cidofovir • Ertapenem • Foscarnet • Ganciclovir • Isavuconazonium IV • Meropenem • Piperacillin/tazobactam*** • Pyrimethamine • Ribavarin for inhalation • Trifluridine • Valganciclovir *except in prophylaxis for acute leukemics and HCT **except for febrile neutropenia in BMT or penicillin allergy non-severe ***except for febrile neutropenia
  • 75. Level 2 Restriction 2012 • Amphotericin B deoxycholate or liposomal • Aztreonam • Ertapenem • Meropenem • Daptomycin • Linezolid • Micafungin* • Voriconazole* 2016 • Amphotericin B deoxycholate or liposomal • Aztreonam • Ceftazidime • Daptomycin • Isavuconazonium PO • Linezolid • Micafungin* • Voriconazole* *except in prophylaxis for acute leukemics and HCT
  • 76. Goal 1: Reduce Carbapenem Utilization Antimicrobial Stewardship Program implementation lead to ~50% reduction in carbapenem DOT Be aware of potential ASP induced fatigue – Quarter 2 of 2016, SMART reported daily lists of patients on carbapenems to ID & ASP team to focus attention on the increased usage
  • 77. Goal 2: Reduce Broad Spectrum Gram- Positive Antibiotic Use
  • 78. Goal 3: Promote Cost Effective Antimicrobial Therapy • ASP initiated 11/1/12 in middle of FY2013 – FY2012 = first FY prior to program – FY2014 = first FY after program initiation • $1,713,930 cost avoidance FY’14 vs FY’12 • $397,214 cost avoidance FY’15 vs FY’14 – 14.5% reduction • Annual Antimicrobial Purchases $0 $1,000,000 $2,000,000 $3,000,000 $4,000,000 $5,000,000 $6,000,000 $7,000,000 FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014
  • 79. Challenge: Antimicrobial Shortages • December ‘14 Piperacillin-Tazobactam – Changed to Level 1 Restricted Antibiotic – Ended quarterly Neutropenic Fever cycling • July ‘15 Cefepime – Alternative dosing schema auto-sustitution approved • 2g IV Q12H to 1g IV Q8H • 2g IV Q8H to 1g IV Q6H except for neutropenic fever • Provider education re: Risk Factors for Pseudomonas • March ‘16 Cefuroxime IV – Replaced peri-operative antibiotic orders with Cefazolin – Level 1 Restricted Antibiotic • September ‘16 Cefepime – Cefepime to Level 1 Restricted Antibiotic except for NF & BMT or PCN allergy – Piperacillin-tazobactam remains Level 1 except for NF – De-escalation of therapy in culture negative NF at discretion of ID Attending
  • 80. Antimicrobial Shortages & Utilization September 2016 Update Piperacillin-Tazobactam supply improving as Cefepime supply worsening Cefepime and Piperacillin-Tazobactam utilization is therefore being reversed
  • 81. Challenge: Antimicrobial Drug Cost Escalations in 2015 • Ribavirin for Inhalation for RSV/HMPV – Cost increased to ~$25,000 per day of therapy – In 2012, ASP replaced this agent with oral ribavirin (<$10 per day) – 100% nebulized ribavirin would have cost ~$2.5 million in 2015 • Pyrimethamine for Toxoplasmosis – Cost increased from $1,763 to $75,000 for #100 tablets ($750/tab) – ~$300,000 for initial 6 months of therapy – Resulted in update in IDSA Toxoplasmosis guidelines • Flucytosine for Cryptococcus meningitis – Cost increased to $4,353 or $10,721 per 100 capsules – Cost for 2 weeks in US: ~$14,000 to $28,000 vs UK: ~$308 • All these agents are now Level 1 Restricted Antimicrobials
  • 82. Antimicrobial Stewardship Initiatives: Antimicrobial Guide • Antimicrobial Dosing Guide Approved by P&T and Medical Executive Committees – Allows pharmacists to correct antimicrobial dosing per policy • Vancomcyin/Aminoglycoside Dosing and Monitoring • Expanded Intravenous to Oral Medication Policy • Automatic Formulary Substitution Policies • Suggested Antibiotic Therapy by Infection Site for Patients at Low Risk for Pseudomonas
  • 83. Antimicrobial Stewardship Initiatives: Antimicrobial Guide • Antimicrobial Therapy: UTI, Pyelonephritis • Clostridium difficile colitis treatment algorithm • Peri-operative Antibiotic Dosing & Redosing Criteria • Interventional Radiology Antibiotic Prophylaxis • Culture targeted prophylaxis for transrectal ultrasound guided prostate biopsy
  • 84. Antimicrobial Adverse Drug Reactions Following SMART Implementation
  • 86. • ASP programs are now required by Joint Commission as of Jan 1, 2017 – Many components intertwined in ASP including education • Improves utilization of antimicrobials without an increase in mortality – An extra tool to help navigate the waters with ongoing antimicrobial shortages Gratis of Ramon Sandin, MD
  • 88. What is the primary purpose of Antimicrobial Stewardship? • A. Institutional adherence to regulatory standards, such as the Joint Commission • B. Reduce drug costs • C. Improve patient outcomes • D. Managing critical antibiotic shortages
  • 89. Which of the following are key components to an ASP program? • A. Pre-authorization of restricted antibiotics • B. Prospective audit and feedback • C. Antibiotic cycling • D. All of the above • E. A and B
  • 90. Which of the following are mandated in the proposed Joint Commission Standard? • A. Multi-disciplinary team • B. Antibiotic data reporting and quality improvement activities • C. Institutional leadership support • D. Staff and practitioner education • E. Patient and caregiver education • F. All of the above • G. A and B
  • 91. Acknowledgement: Thanks to SMART at Moffitt Cancer Center Circa 10/4/2016
  • 92. SMART Team Members • Infectious Diseases Attending Physicians – John Greene, MD – Ana Velez, MD – Aliyah Baluch, MD, MSc • Infectious Diseases Clinical Pharmacists – Rod Quilitz, PharmD, BCOP – Yanina Pasikhova, PharmD, BCPS-AQ ID, AAHIVP – Wonhee So, PharmD, BCPS • Microbiology – Ramon Sandin, MD, MS, FCAP, ABP-MM – Dawn Ruge, BS, MT (ASCP) • Infection Prevention – Stacy Martin, RN, BSN, CIC – Kay Sams, RN, BSN, CIC – Stephanie Carraway, Infection Prevention Specialist – Patricia Tomasini, Infection Prevention Specialist – Julie Gnage, Infection Prevention Specialist
  • 93. Addendum 1: Moffitt Cancer Center Antibiogram
  • 94.
  • 95. 52 52 54 50 49 50 44 52 52 53 50 47 0 10 20 30 40 50 60 70 80 90 100 2009 2010 2011 2012 2013 2014 2015 %Susceptible Year E.coli Ampicillin Cefazolin Ceftriaxone Ceftazidime Cefepime Ciprofloxacin Levofloxacin Trimeth/Sulfa Pip/Tazo Meropenem Imipenem Ciprofloxacin 0 10 20 30 40 50 60 70 80 90 100 2009 2010 2011 2012 2013 2014 2015 %Susceptible Year K. pneumoniae Amp/Sulbactam Cefazolin Ceftriaxone Ceftazidime Cefepime Ciprofloxacin Levofloxacin Trimeth/Sulfa Pip/Tazo Meropenem Imipenem
  • 96. 92 91 97 97 95 86 95 82 89 77 82 86 0 10 20 30 40 50 60 70 80 90 100 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 %Susceptible Year S. maltophilia Levofloxacin Trimeth/Sulfa Minocycline Trimeth/Sulfa 90 90 84 89 93 86 91 95 93 90 87 94 94 95 88 80 87 91 92 94 96 0 10 20 30 40 50 60 70 80 90 100 2009 2010 2011 2012 2013 2014 2015 %Susceptible Year P. aeruginosa Ceftazidime Cefepime Ciprofloxacin Levofloxacin Pip/Tazo Meropenem Imipenem Tobramycin
  • 97. 81 72 79 80 70 69 71 100 97 90 95 90 98 98 0 10 20 30 40 50 60 70 80 90 100 2009 2010 2011 2012 2013 2014 2015 %Susceptible Year E. cloacae Ceftriaxone Ceftazidime Cefepime Ciprofloxacin Levofloxacin Trimeth/Sulfa Pip/Tazo Meropenem Imipenem Tobramycin Pip/Tazo Meropenem Synthesis graphics gratis of Yanina Pasikhova, PharmD
  • 98. Questions • Rod Quilitz, PharmD, BCOP – Clinical Pharmacy Coordinator – Infectious Diseases & Antimicrobial Stewardship – Rod.Quilitz@moffitt.org • Aliyah Baluch, MD, MSc, FACP – Assistant Member, Division of Infectious Diseases – Aliyah.Baluch@moffitt.org

Editor's Notes

  1. If on FQ prophy, using ceftaz then must use vanc
  2. Why?
  3. (Cost avoidance based on difference in units purchased X cost per unit)