Intravenous-to-Oral Antibiotic Switch Therapy

Presented By:

Ohoud Awad Al-Juhani

Outlines

I. Introduction

II. Misconception of (IV vs. PO) switch

III. Antibiotic cost factors

IV. Four Scenarios of IV:PO Conversions of antibiotic

V. Cost of selected intravenous and oral antibiotic

I. Introduction The term "anti-infective conversion“ describes the practice of converting IV anti-infection therapy to an alternative oral formulation As conversion therapy was based on empirical observations rather than on clinical studies or outcomes, there was concern that oral therapy was less effective In addition, no clinical trials were available to support the conversion from the IV route to oral administration

Factors of the Scientific Basis of IV:PO Conversion

These include:1) Newer concepts of antimicrobial PD action

2) The advent of newer, more potent, broad-spectrum oral agents that achieve higher and more consistent serum & tissue concentrations

3) The availability of randomized clinical trials comparing various IV and oral therapeutic strategies

Advantages

Oral therapy can be as effective as parenteraly administered anti-infectives in the treatment of infections ranging from mild to moderate to severe

Decreasing adverse effects associated with IV therapy Oral anti-infectives are easier to administer than IV

preparations, require less time to prepare, and often improve patient comfort, mobility, and independence

Oral anti-infectives are often less expensive than parenteral agents

II. Misconceptions The main obstacle limiting IV:PO conversion is the

notion that IV anti-infectives are better than oral One erroneous concept is that all patients with an

infectious disease needs IV treatment Anti-infective therapy should be evaluated regardless of

route of administration

Another misconception is the same agent must be used both IV and orally

It has been thought that conversion therapy should be

used only at discharge

Common Misconception in that the Antibiotics Chosen for a Switch Regimen Must be of the Same Type or Class

This is not the case at all. The only requirement is that the agents cover essentially the same spectrum and have the same characteristics of tissue penetration

For example, if IV Ampicillin is being used, oral Ampicillin would not be appropriate in a switch program because it does not give anything close to the blood and tissue levels achieved by IV administration.

Cont… Another example, IV Ceftriaxone has no oral

equivalent, but oral TMP-SMX provides exactly the same spectrum of activity and tissue penetration; even though the two drugs are from dissimilar classes and work by different mechanisms, they are therapeutically equivalent

It is not necessary that both oral and IV forms of a given agent be available to use in switch therapy. As noted, the task is to be sure that the spectrum of activity and the PK of IV and oral drugs are similar

Inclusion Criteria for Conversion Therapy

Completion of 48-72 hours of IV therapy

Functioning gastrointestinal tract

A febrile < 99.6°F for 8-24 hours

WBC count < 15,000/mm3 &/or decreasing

Improvement of signs and symptoms of infection

Exclusion Criteria for Conversion Therapy

× Patients who cannot use oral route (risk of aspiration, need for complete bowel rest)

× Patients with an unreliable response to oral medication (severe N/V, continuous nasogastric suction, malabsorption syndrome)

× Patients whose disease state or infection does not permit conversion (e.g. high-risk neutropenia, meningitis, endocarditis)

Antimicrobial Switch Therapy Recommendations in KFAFH

Suggested Oral Conversion Parenteral Agent

Ciprofloxacin or Ofloxacin Ceftazidime, Cefepime

Cefixime Ceftriaxone, Cefotaxime

Clindamycin Clindamycin

Ciprofloxacin or Ofloxacin+Metronidazole

Imipenem/cilastatin, Meropenam

Metronidazole Metronidazole

III. Antibiotic Cost Factors

The costs of administering IV antibiotics to hospitalized patients are tremendous, and great

efforts are being made to reduce these costs

To accomplish a reduction, factors that are important in determining the institutional cost

of antimicrobial therapy must be understood

Antibiotic Cost Factors in Hospitalized Patients, with Strategies for Cost Containment

Cost- Saving Strategies

Obvious Cost

Purchase bulk through groups or consortia

Price of acquisition (cost per dose or per day)

Cost- Saving Strategies Hidden CostsUse antibiotics with long half-lives that may be given q12h or q24hUse IV-to-PO switch programs

Cost of IV administration (US average: $10 per dose)

Avoid nephrotoxic drugs that require monitoring

Cost of monitoring (e.g. determination of BUN, SrCr )

Minimize or avoid use of antibiotics associated with emergence of resistant organisms

Cost of increased antibiotic resistance and outbreaks due to resistant organisms

Cont…

Cont…

Cost- Saving Strategies Hidden CostsAvoid poorly tolerated antibiotics such as erythromycin, clarithromycin and especially those associated with seizures, phlebitis, and diarrhea

Cost of adverse reactions

Avoid antibiotics likely to fail because of improper spectrum (e.g. ciprofloxacin for skin or soft-tissue infection( Avoid antibiotics with poor tissue penetration (e.g. penicillin for group A streptococcal pharyngitis)

Cost of therapeutic failure

IV. Four Scenarios of IV:PO Conversions of Anti-Infective Drugs

Comments Absorption of the

Medication

Examples of Conversions

IV PO

Drug Characteristic

> 95% Conversion to same drug withvirtually equivalent concentrations

70-85% Ciprofloxacin Ciprofloxacin

1. Same Drug/Same AUC

> 95% Metronidazole Metronidazole

75-90% Clindamycin Clindamycin

Cont…

Comments Absorption of the

Medication

Examples of Conversions

IV PO

Drug Characteristic

Conversion and efficacy are depend on MIC

40-50% Cefuroxime Cefuroxime

2. Same Drug/Lower AUC 50-80% Erythromycin

Erythromycin

40% Azithromycin Azithromycin

Cont…

Comments Examples of Conversions IV PO

Drug Characteristic

Conversion may be easily done fromanother class of anti-infectives; the only requirement is that the agent must cover the same spectrum and have the same characteristics of penetration

Ceftazidime Ciprofloxacin

3. Different Drug/Good Bioavailability

Imipenem/cilastatin Ciprofloxacin + metronidazole

Ampicillin/sulbactam or amoxicillin/clavulanate (60%) Levofloxacin + metronidazole or amoxicillin/clavulanate

Cont…

Comments Absorption of

the Medication

Examples of Conversions

IV PO

Drug Characteristic

Depends on infection site and MIC of organism

< 50% Ceftriaxone Cefixime

4. Different Drug/Bioavailability < 50%

V. Cost of selected IV and oral antibiotic Cost of

Administration /day ($)

Cost/day($) Dosage IV drugs

10 25.05 1g Ceftriaxone

20 52.42 500 mg q12h Ciprofloxacin

10 0.69 240 mg q24h Gentamicin

10 2.82 1 g q24h Metronidazole

20.00 51 2 g q12h Cefepime

30 81 1 g q8h Meropenem

Cost of Administration/day

($)

Cost/day ($) Dosage Oral drugs

--- 0.6 1 g q8h Amoxicillin

--- 5.46 500 mg q12h Ciprofloxacin

--- 10.68 500 mg q12h Cefuroxime axetil

--- 0.04 500 mg q12h Metronidazole

--- 0.6 500 mg q6h Erythromycin

Cont…

Antibiotics with Excellent Bioavailability Both Orally & IV

Amoxicillin Doxycycline Trimethoprim-sulfamethoxazole (TMP-SMX) Azithromycin Metronidazole Chloramphenicol Levofloxacin Ciprofloxacin Clindamycin

Take Home Messages

Every attempt should be made to switch hospitalized patients from IV to oral antibiotic therapy as soon as clinical improvement makes it possible

In addition to tremendous cost savings, the advantages

of oral therapy are impressive and include a decrease in the number of nosocomial infections, shorter length of hospital stay, and lower incidence of IV-line infections

The Main Barrier to the Acceptance of Switch Therapy is a Lack of Understanding of its:

Efficacy

Safety

Cost Advantages

Special Thanks to..

My Colleague: Sherihan Abbas

References:

Rodvold KA. Pharmacokinetic and pharmacodynamic considerations for antimicrobial use. Infect Med 2000;12:16-25A

Ballow CH. Cost considerations in oral antibiotic therapy. Adv Ther 2003;12(4):199-206

J Hosp Infect. 2005 Aug;60(4):340-7 http://www.medscape.com/pharmacists/journals http://www.emedicine.com/med/topic3549.htm