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