antimicrobial stewardship: focus on iv to po antibiotics michaelia dunn, pharm.d., bcps clinical...

Antimicrobial Antimicrobial Stewardship: Focus Stewardship: Focus on IV to PO on IV to PO AntibioticsAntibioticsMichaelia Dunn, Pharm.D., BCPSMichaelia Dunn, Pharm.D., BCPS

Clinical Pharmacist, IUAHClinical Pharmacist, IUAH

February 22February 22ndnd, 2012, 2012

[email protected]@iuhealth.org

DisclosureDisclosure

Nothing to discloseNothing to disclose

ObjectivesObjectives

Summarize key points from the 2007 Summarize key points from the 2007 SHEA/IDSA guidelines for antimicrobial SHEA/IDSA guidelines for antimicrobial stewardship stewardship

Discuss a general approach for de-Discuss a general approach for de-escalation and streamlining antibioticsescalation and streamlining antibiotics

ObjectivesObjectives

Differentiate between the inclusion and Differentiate between the inclusion and exclusion criteria for IV to PO exclusion criteria for IV to PO conversionsconversions

Describe the potential impact on costs Describe the potential impact on costs and clinical outcomesand clinical outcomes

“Antibiotics are the only medications that affect other people”-a really smart ID physician

2007 SHEA/IDSA Guidelines2007 SHEA/IDSA Guidelines

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.

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

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


Secondary Goals

Reduce healthcare costs while not adversely impacting quality of care

Supported by ASP here at IUAH


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



2. Formulary restriction and preauthorization Current ID restrictions include:

Fidaxomicin (Dificid®) Linezolid (Zyvox®) Daptomycin (Cubicin®) Micafungin (Mycamine®) Voriconazole (Vfend®)



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



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



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



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



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



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



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)



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


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


General Approach for General Approach for De-escalation and De-escalation and StreamliningStreamlining

Recognize and avoid redundant antimicrobial combinations Example- Pipercillin/Tazobactam PLUS

metronidazole for Bacteroides fragilis (anaerobe) coverage


Recognize and avoid redundant antimicrobial combinations

Choose an antimicrobial that has specific or more narrow organism coverage Helpful with cultures and sensitivities




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




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



Benefits of IV to PO Benefits of IV to PO

Take 3-5 minutes for group discussionTake 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


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



Decrease risk or avoidance of medication errors

Increase in patient comfort and mobility




Increase in patient comfort and mobility Decrease healthcare costs

Medication costs Savings by elimination of Alaris pumps and IV sets




Increase in patient comfort and mobility Decrease healthcare costs Significant decrease in hospital length of stay

with no adverse effect on clinical outcomes


Inclusion CriteriaInclusion Criteria


Inclusion CriteriaInclusion 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


Exclusion CriteriaExclusion 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 Impact on Costs and Clinical OutcomesClinical Outcomes

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.

Trial Patients Outcomes Conclusion

Randomized, double-blind,

multicenter trial, ITT and valid populations

671 patients with complicated intra-

abdominal 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

Impact on Costs and Clinical Outcomes

Przybylski KG, et al. A pharmacist-initiated program of intravenous to oral antibiotic conversion. Pharmacotherapy 1997;

17:271–276.


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 cost-

effective without compromising patient

care



Pharmacist intervention (PI), 3 study periods

of 3 months each,

prospective

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 Community-

Acquired Pneumonia. CID 2005;41(Suppl 2): S136-S143.


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.


Randomized, ITT

230 complicated skin and soft tissue

infection patients, IV Vancomycin vs. PO

Linezolid

•Median LOS was five days shorter for the linezolid group than the vanco group (9 vs. 14 days, p = 0.052)

Linezolid can reduce LOS for patients with complicated

SSTI from suspected or

confirmed MRSA



Prospective, multicenter, randomized, open-label,

parallel-group study

636 CAP patients, Cefuroxime IV BID or

TID for 48 to 72 h followed by oral

cefuroxime for 7 days,

•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)

Effective and well-tolerated 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


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 community-acquired 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.


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):267-272.

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 pharmacist-intervention 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 Antimicrobial Stewardship: Focus Stewardship: Focus on IV to PO on IV to PO AntibioticsAntibioticsMichaelia Dunn, Pharm.D., BCPSMichaelia Dunn, Pharm.D., BCPS

Clinical Pharmacist, IUAHClinical Pharmacist, IUAH

February 22February 22ndnd, 2012, 2012

[email protected]@iuhealth.org

antimicrobial stewardship: focus on iv to po antibiotics michaelia dunn, pharm.d., bcps clinical...

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