Antimicrobial
Stewardship: Focus on
IV to PO Antibiotics
Michaelia Dunn, Pharm.D., BCPS
Clinical Pharmacist, IUAH
February 22nd, 2012
mdunn4@iuhealth.org
Disclosure
 Nothing to disclose
Objectives
 Summarize key points from the 2007
SHEA/IDSA guidelines for antimicrobial
stewardship
 Discuss a general approach for deescalation and streamlining antibiotics
Objectives
 Differentiate between the inclusion and
exclusion criteria for IV to PO
conversions
 Describe the potential impact on costs
and clinical outcomes
“Antibiotics are the only
medications that affect
other people”
-a really smart ID physician
2007 SHEA/IDSA Guidelines
 Appropriate selection, dosing, ROUTE, and
duration of antimicrobial therapy
 Supported from:
 American Academy of Pediatrics, American Society
of Health-Systems Pharmacists, Infectious Diseases
Society for Obstetrics and Gynecology, Pediatric
Infectious Disease Society, Society for Hospital
Medicine, Society of Infectious Disease Pharmacists
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. Clin Infect Dis. 2007; 44:159-177.
Primary Goal
 Optimize clinical outcomes while
minimizing unintended consequences,
including toxicity, selection of pathogenic
organisms (Clostridium difficile), and
emergence of resistance
 Supported by ASP here at IUAH
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. Clin Infect Dis. 2007; 44:159-177.
Secondary Goals
 Reduce healthcare costs while not
adversely impacting quality of care
 Supported by ASP here at IUAH
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. Clin Infect Dis. 2007; 44:159-177.
Antimicrobial Stewardship
Program (ASP)- IUAH
 Multidisplinary team
 Purpose:
 Improve time to effective therapy, appropriate
empiric treatment, duration of therapy, de-escalate
therapy when appropriate, and ultimately improve
patient care
 Activities:
 Development of protocols, pathways, criteria,
guidelines
 Data review and analysis over time
 Direct educational efforts
Core Strategies for
Antimicrobial Stewardship
 1. Prospective audit with intervention
and feedback
 Results in reduction of inappropriate use of
antimicrobials
 Consultations - ID colleagues
 Clinical pharmacists monitoring culture
results and sensitivities
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 2. Formulary restriction and
preauthorization
 Current ID restrictions include:
 Fidaxomicin (Dificid®)
 Linezolid (Zyvox®)
 Daptomycin (Cubicin®)
 Micafungin (Mycamine®)
 Voriconazole (Vfend®)
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 3. Education - Essential element
 Provides a foundation of knowledge, influences
prescribing behaviors, and increases acceptance of
stewardship strategies
 Education alone without active intervention is only
marginally effective
 Hospitalist presentations
 Stress ulcer prophylaxis, asymptomatic bacteruria
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 4. Guidelines and clinical pathways
 Evidence-based practice guidelines
incorporating microbiology and resistance
patterns
 Clinical pathways have been explored, but
not currently available at IUAH
 Resident project- Criteria for use of specific
antimicrobials as supported by ID and ASP
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 5. Antimicrobial Cycling
 Insufficient data to support this as a means
of preventing or reducing antimicrobial
resistance over a prolonged time
 Not utilized or supported by ASP here at
IUAH
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 6. Antimicrobial order forms
 Effective component and helps facilitate
practice guidelines
 Focused Management Order Sets
 Pneumonia- Completed and currently available
on PowerChart
 Urinary Tract Infections- Currently underway and
expected to be completed in the next couple
months
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 7. Combination Therapy
 Insufficient data to support this as a means
of preventing or reducing antimicrobial
resistance over a prolonged time
 Does have a role in certain clinical context
 Empiric therapy for critically ill patients at risk
with multidrug-resistant organisms
 ASP does not have a recommendation
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 8. Streamling or de-escalation of therapy
 Can more effectively target the causative
pathogen
 Results in decreased antimicrobial exposure
and substantial cost savings
 ASP strongly recommends
 Clinical pharmacists are encouraged to
recommend based on cultures and
sensitivities
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 9. Dose optimization
 Dose based on individual patient characteristics,
causative organism, site of infection,
pharmacokinetic and pharmacodynamic properties,
renal function, sensitivities
 Clinical pharmacists assisting in antimicrobial
dosing
 Extended infusion of beta-lactams (Pip/Tazo,
Meropenem, Cefepime, Ceftazidime, Amp/Sulb)
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. Clin Infect Dis. 2007; 44:159-177.
Core Strategies for
Antimicrobial Stewardship
 10. Parenteral to Oral Conversion
 Can decrease length of hospital stay and
health care costs
 ASP supports IV to PO conversion when
appropriate
 Clinical pharmacists are expected to
collaborate with physicians to make
recommendations
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. Clin Infect Dis. 2007; 44:159-177.
De-escalation and
Streamlining Antimicrobials
 Continuing broad spectrum antibiotics
lead to selection of resistant pathogens
 More targeted therapy, decreases broad
spectrum antimicrobial exposure, and
helps to contain cost
 Discontinuation of empiric antimicrobial
therapy based on negative cultures
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. Clin Infect Dis. 2007; 44:159-177.
General Approach for
De-escalation and Streamlining
 Recognize and avoid redundant
antimicrobial combinations
 Example- Pipercillin/Tazobactam PLUS
metronidazole for Bacteroides fragilis
(anaerobe) coverage
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. Clin Infect Dis. 2007; 44:159-177.
General Approach for
De-escalation and Streamlining
 Recognize and avoid redundant
antimicrobial combinations
 Choose an antimicrobial that has specific
or more narrow organism coverage
 Helpful with cultures and sensitivities
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. Clin Infect Dis. 2007; 44:159-177.
General Approach for
De-escalation and Streamlining
 Recognize and avoid redundant
antimicrobial combinations
 Choose an antimicrobial that has specific
or more narrow organism coverage
 Good-excellent bioavailability
 Moxifloxacin, Doxycycline, Ciprofloxacin,
Linezolid, Amoxicillin, Cephalexin,
Voriconazole, Fluconazole, Clindamycin,
Metronidazole, SMX/TMP
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. Clin Infect Dis. 2007; 44:159-177.
General Approach for
De-escalation and Streamlining
 Recognize and avoid redundant
antimicrobial combinations
 Choose an antimicrobial that has specific
or more narrow organism coverage
 Good-excellent bioavailability
 Penetration to the site of action
 Example- Moxifloxacin into respiratory tissue
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. Clin Infect Dis. 2007; 44:159-177.
Benefits of IV to PO
 Take 3-5 minutes for group discussion
Benefits of IV to PO
 Decrease risk or avoidance of adverse
effects or potential complications




Infection
Thrombophlebitis
Thromboembolism
Excess fluid administration
Benefits of IV to PO
 Decrease risk or avoidance of adverse
effects or potential complications
 Decrease risk or avoidance of medication
errors
 More complex preparation and delivery by
pharmacy
 More complex administration procedures
Benefits of IV to PO
 Decrease risk or avoidance of adverse
effects or potential complications
 Decrease risk or avoidance of medication
errors
 Increase in patient comfort and mobility
Benefits of IV to PO
 Decrease risk or avoidance of adverse effects
or potential complications
 Decrease risk or avoidance of medication
errors
 Increase in patient comfort and mobility
 Decrease healthcare costs
 Medication costs
 Savings by elimination of Alaris pumps and IV sets
Benefits of IV to PO
 Decrease risk or avoidance of adverse effects
or potential complications
 Decrease risk or avoidance of medication
errors
 Increase in patient comfort and mobility
 Decrease healthcare costs
 Significant decrease in hospital length of stay
with no adverse effect on clinical outcomes
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. Clin Infect Dis. 2007; 44:159-177.
Inclusion Criteria
 Take 3-5 minutes for group discussion
Inclusion Criteria
 Functioning GI tract
 Tolerating a PO diet, a clear liquid diet, tube
feeds without high residuals, other PO meds
Inclusion Criteria
 Functioning GI tract
 Afebrile for 24 hours
Inclusion Criteria
 Functioning GI tract
 Afebrile for 24 hours
 Improving trend in WBC
Inclusion Criteria




Functioning GI tract
Afebrile for 24 hours
Improving trend in WBC
Other clinical signs of improvement
Inclusion Criteria





Functioning GI tract
Afebrile for 24 hours
Improving trend in WBC
Other clinical signs of improvement
Received at least 24 hours of IV therapy
when appropriate
Halm EA, et al. What factors influence physicians' decisions to switch from intravenous to oral antibiotics for community-acquired
pneumonia?. J Gen Intern Med. 2001;16(9):599-605.
Exclusion Criteria
 Take 3-5 minutes for group discussion
Exclusion Criteria
 NPO or scheduled for surgery
Exclusion Criteria
 NPO or scheduled for surgery
 Recent therapeutic failure on PO therapy
Exclusion Criteria
 NPO or scheduled for surgery
 Recent therapeutic failure on PO therapy
 Malabsorption disorders
 Short gut syndrome, severe N/V/D,
inflammatory bowel disease, bowel
obstruction, ileus, continuous NG suctioning,
active GI bleed
Exclusion Criteria




NPO or scheduled for surgery
Recent therapeutic failure on PO therapy
Malabsorption disorders
Patient is hypotensive (SBP<100 or
DBP<60)
Exclusion Criteria




NPO or scheduled for surgery
Recent therapeutic failure on PO therapy
Malabsorption disorders
Patient is hypotensive (SBP<100 or
DBP<60)
 Neutropenia that is not resolving
Exclusion Criteria






NPO or scheduled for surgery
Recent therapeutic failure on PO therapy
Malabsorption disorders
Patient is hypotensive (SBP<100 or DBP<60)
Neutropenia that is not resolving
Infections where adequate antibiotic
concentrations are not easily achieved or PO
antimicrobials are inappropriate
 Meningitis, bacteremia, endocarditis, deep joint
infections, bone infections, etc.
Halm EA, et al. What factors influence physicians' decisions to switch from intravenous to oral antibiotics for community-acquired
pneumonia?. J Gen Intern Med. 2001;16(9):599-605.
Impact on Costs and
Clinical Outcomes
Trial
Patients
Outcomes
Conclusion
Randomized,
double-blind,
multicenter trial,
ITT and valid
populations
671 patients with
complicated intraabdominal
infections, IV CIP/
MTZ or IV IMI vs.
IV/PO CIP/MTZ
(when PO
feeding)
•Success rates (ITT):
CIP/MTZ IV vs. CIP/MTZ
IV/PO vs. IMI IV (82% vs.
84% vs. 82%)
•Success rates (valid):
CIP/MTZ IV vs. CIP/MTZ
IV/PO vs. IMI IV (84% vs.
86% vs. 81%)
Conversion to oral
therapy with
CIP/MTZ appears as
effective as
continued IV therapy
in patients able to
tolerate oral feedings
Solomkin JS, et al. Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus
metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group. Ann Surg.
1996;223(3):303-315.
Impact on Costs and
Clinical Outcomes
Trial
Patients
Outcomes
Conclusion
Intervention of
pharmacist-initiated
IV to PO program,
prospective, over 12
months
240 patients (200
converted)
determined to
have “mild to
moderate”
infections
•Decreased hospital
LOS by 1.53 days
(p<0.003)
•Drug acquisition cost
savings: $15,149
•Reduced LOS costs:
$161,072
Intervention program
was found to be costeffective without
compromising patient
care
Przybylski KG, et al. A pharmacist-initiated program of intravenous to oral antibiotic conversion. Pharmacotherapy 1997;
17:271–276.
Impact on Costs and
Clinical Outcomes
Trial
Pharmacist
intervention (PI),
3 study periods
of 3 months
each,
prospective
Patients
Outcomes
Conclusion
250 CAP patients, 3
groups: IV beta-lactam
+ macrolide (no PI), IV
beta-lactam + IV/PO
macrolide (PI switch),
IV to PO moxifloxacin
(Automatic PI
sequential)
•Clinical success on day 3
of therapy was improved
in the PI sequential group
•Similar in all 3 groups on
day 7 of therapy and at
the end of therapy.
•Hospital LOS was similar
(mean, 4.39 days).
•Antibiotic costs were
significantly reduced
($110/ patient) in the PI
sequential group.
•IV to PO was
accomplished more
quickly for the same
agent
•Reduced cost
without
compromising
efficacy
Davis SL. Pharmacoeconomic Considerations Associated with the Use of Intravenous-to-Oral Moxifloxacin for CommunityAcquired Pneumonia. CID 2005;41(Suppl 2): S136-S143.
Impact on Costs and
Clinical Outcomes
Trial
Patients
Randomized, ITT
230 complicated skin
and soft tissue
infection patients, IV
Vancomycin vs. PO
Linezolid
Outcomes
•Median LOS was five
days shorter for the
linezolid group than the
vanco group (9 vs. 14
days, p = 0.052)
Conclusion
Linezolid can reduce
LOS for patients
with complicated
SSTI from
suspected or
confirmed MRSA
Li JZ, et al. Effect of linezolid versus vancomycin on length of hospital stay in patients with complicated skin and soft tissue
infections caused by known or suspected methicillin-resistant staphylococci: results from a randomized clinical trial. Surg
Infect (Larchmt) 2003; 4:57–70.
Impact on Costs and
Clinical Outcomes
Trial
Prospective,
multicenter,
randomized,
open-label,
parallel-group
study
Patients
636 CAP patients,
Cefuroxime IV BID or
TID for 48 to 72 h
followed by oral
cefuroxime for 7 days,
Outcomes
•Clinical response rates
were equivalent for TID
and BID groups (cure/
improvement, 79% and
84%, respectively) and at
follow-up (maintained
cure, 87% and 82%,
respectively)
Conclusion
Effective and welltolerated as rapid
switch therapy and
has the potential to
reduce overall
health care costs
and improve patient
satisfaction
Van den Brande P, Vondra V, Vogel F, et al. Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired
pneumonia. Chest. Aug 1997;112(2):406-415
Impact on Costs and
Clinical Outcomes
 Other studies demonstrating decrease costs
and hospital LOS while not affecting patient
outcomes





Ramirez JA, et al. Early switch from intravenous to oral antibiotics and early hospital
discharge: a prospective observational study of 200 consecutive patients with communityacquired pneumonia. Arch Intern Med. 1999;159(20):2449-2454.
Ramirez JA. Managing antiinfective therapy of community-acquired pneumonia in the
hospital setting: focus on switch therapy. Pharmacotherapy. 2001;21(7 Pt 2):79S-82S.
Gollin G, et al. Oral antibiotics in the management of perforated appendicitis in children.
Am Surg. 2002;68(12):1072-1074.
Starakis I, et al. Results of a prospective, randomized, double blind comparison of the
efficacy and the safety of sequential ciprofloxacin (intravenous/oral) + metronidazole
(intravenous/ oral) with ceftriaxone (intravenous)+metronidazole (intravenous/oral) for the
treatment of intra-abdominal infections. Int J Antimicrob Agents. 2003;21(1):49-57.
Tomera KM, et al. Ertapenem versus ceftriaxone followed by appropriate oral therapy for
treatment of complicated urinary tract infections in adults: results of a prospective,
randomized, double-blind multicenter study. Antimicrob Agents Chemother.
2002;46(9):2895-900.
Impact on Costs and
Clinical Outcomes





Hamilton-Miller J. Cefixime for switch therapy. Chemotherapy. 1998;44
(Suppl 1):24-27.
Fernandez P, et al. Community acquired pneumonia: from intravenous to
oral cephalosporin sequential therapy]. Rev Med Chil. 2000;128(3):267272.
Parola D, et al. Efficacy and safety of clarithromycin in the treatment of
community-acquired pneumonia. Recenti Prog Med. 2000;91(1):12-15.
Martinez MJ, et al. Clinical and economic impact of a pharmacistintervention to promote sequential intravenous to oral clindamycin
conversion. Pharm World Sci. 2000;22(2):53-58.
Finch R, et al. Randomized controlled trial of sequential IV and oral
moxifloxacin compared with sequential IV and oral co-amoxiclav with or
without clarithromycin in patients with community-acquired pneumonia
requiring initial parenteral treatment. Antimicrob Agents Chemother.
2002;46(6):1746-54.
Summary
 Vast amount of studies that evaluate
costs and clinical outcomes of IV to PO
 Many of studies evaluated hospital LOS
and clinical success rates
 Potential impact for pharmacist
interventions
Conclusions
 2007 IDSA guidelines recommend several core
strategies for antimicrobial stewardship,
including IV to PO conversions
 Patients should be carefully assessed for
appropriate inclusion and exclusion criteria to
be converted to oral regimens
 IV to PO conversions have several benefits
beyond costs
Conclusions
 Several studies show IV to PO
conversions decrease drug and
hospitalization costs, decrease hospital
LOS, and do not adversely affect clinical
outcomes
Questions?
Antimicrobial
Stewardship: Focus on
IV to PO Antibiotics
Michaelia Dunn, Pharm.D., BCPS
Clinical Pharmacist, IUAH
February 22nd, 2012
mdunn4@iuhealth.org