In this article two pharmacists identify five important considerations when switching from IV to PO antibiotics.
Authored By: Katherine Lee, Pharm.D. and Nick Mercuro, Pharm.D.
[Last updated 18 September 2019]
Implementation of intravenous (IV) to oral (PO) conversion protocols/ pathways is strongly recommended by the Infectious Diseases Society of America (IDSA) and Centers for Disease Control and Prevention’s (CDC) guidance for antimicrobial stewardship programs [1,2]. Pharmacists have championed IV to PO interventions for decades and evidence for improving patient outcomes is well documented [3,4].
Secondary benefits of IV to PO conversion may include additional cost savings from reductions in length of hospital stay, avoidance of central-venous catheter (CVC) placement, reduction in labor intensive IV monitoring/ administration, and less complicated drug acquisition for oral products . Note too that…
- Up to 10% of peripherally inserted central catheters (PICCs) are associated with vascular access complications during outpatient antimicrobial therapy (OPAT) 
- Approximately 1 in 40 PICC lines become infected 
- Patients maintained on IV antibiotics spend 1-2 days longer in the hospital compared to those who are converted to oral therapy 
Given that IV to PO is such an important topic within healthcare today, we composed this article to discuss five important things to consider when switching from IV to PO antibiotics. Note that many of these points should also be considered for IV to PO of non-antibiotic drugs.
1. Appropriate drug absorption
Oral antibiotics must be sufficiently absorbed to achieve effective antimicrobial activity. Concern for malabsorption is an important reason to maintain intravenous treatment, particularly in patients who are suffering from ileus, severe diarrhea, or other gastrointestinal motility disorders.
Best practices involve an assessment of ongoing sepsis versus clinical stability by monitoring fever, hypotension, and leukocytosis; shock can reduce gut perfusion, causing delayed gastric emptying and less extensive drug absorption . Other medications and supplements such as iron, magnesium, calcium, and sucralfate can also reduce absorption of certain antimicrobials (e.g., tetracyclines, fluoroquinolones). Adjustments in administration timing can be made to preserve efficacy for some drug-drug and drug-food interactions of this kind.
2. Indication and source control
While there is no large randomized trial to date that has proven superiority of IV over PO therapy, careful consideration should be given for each patient and indication. After receiving adequate empiric/IV therapy, a switch to PO agents is often a non-inferior approach, rather than continuing IV.
Oral therapy for uncomplicated urinary, respiratory, intra-abdominal, and soft tissue infections is strongly supported. More recently, large randomized trials  also indicate efficacy of a switch to oral for more severe infections . However, study populations from randomized trials can significantly differ from those encountered in daily care.
Patients with complex diseases such as bloodstream infections, osteomyelitis, endovascular infections, or infections caused by multi-drug resistant organisms can benefit from consultation with an infectious diseases specialist before transitioning to definitive therapy, where an oral agent may or may not be appropriate. Additionally, patients who undergo removal of the focal source of infection (abscesses, fluid collections, catheters, stents, etc.) will have better outcomes and this intervention should always be pursued as adjunctive treatment to definitive antimicrobials.
3. Pharmacokinetics, pharmacodynamics (PK/PD), and bioavailability
Many antimicrobials have relatively high bioavailability such as quinolones, tetracyclines, and SMX/TMP, thus similar PK and PD attainment can often be presumed given normal absorption . More hydrophilic agents such as beta-lactams and fosfomycin are not fully absorbed systemically. However, concentrations at the site of infection and pharmacodynamic target attainment are more significant predictors of success than bioavailability alone. For example, oral fosfomycin would be a poor choice for a bloodstream infection given its poor serum levels, but in the urine it can be found at more than 200 times serum concentration.
The relationship between drug presence at infection site, organism, and resistance should always be evaluated.
Risk and benefit are at constant balance when managing patients with infections. Aside from risks related to the presence of a CVC, fluid volume and electrolyte disturbances are other hazards associated with IV antimicrobials.
One example is that SMX/TMP every 6 hours at high intravenous doses carries a daily D5W fluid load of two liters . Another example is that metronidazole 500 mg IV given every 8 hours contains about 2400 mg/day of sodium. These IV administrations can often be avoided as both drugs are highly bioavailable.
Agents such as quinolones have excellent efficacy in the appropriate setting, but at the expense of increasing drug resistance, C. difficile, and other rare but serious adverse events. Comorbid conditions and drug interactions can exacerbate these risks. On the other hand, oral beta-lactams are well tolerated but have lower serum levels, more frequent administration, and possibly increased risk of microbiologic failure (for urinary tract infections in particular).
Targeted, thoughtful selection and dose of antimicrobials should be given to every case.
5. Access and administration
Pharmacists can assist with smooth transition from inpatient IV to inpatient/outpatient PO therapy. Barriers to regimen adherence may include cost, convenience, and appropriate administration timing around food/supplements.
Although prices can vary substantially, some oral antimicrobials that can be notably expensive include 2nd/3rd generation cephalosporins, linezolid, fosfomycin, moxifloxacin, XR formulations in general, isavuconazole, posaconazole, and letermovir. Insurance claims can be processed prior to discharge to mitigate these issues. Institutions utilizing medication-to-bedside services can involve both the outpatient and inpatient pharmacy in overseeing the delivery of correct medication, dose, and duration to the patient at time of discharge.
Most patients receive about half of their total therapy during hospitalization . Additional and unnecessary antimicrobial exposures can be costly and harmful and total days of therapy should include the sum of inpatient and outpatient duration .
Ideally, all patients should have follow-up with their provider following a hospital admission or an infection.
So… what can we do?
In brief, some of the most important considerations when converting to orals include assessments of clinical stability, pharmacokinetics, pharmacodynamics, safety, medication access, and supporting evidence for the switch. What else can be done within your antimicrobial stewardship program to improve outcomes for patients on intravenous antimicrobials?
- Protocols for IV to PO conversions
- Electronic health records (EHR) support for stewarding highly bioavailable IV antimicrobials
- EHR support for identifying drug/supplement interactions
- Engage bedside nurses and infection preventionists to assess need for parenteral access and/or ability to take enteral medications
- Employ stewardship at transitions of care with review of discharge regimens
- Emphasize hard stop dates in the EHR
- Facilitate infectious diseases/ antimicrobial stewardship consultation for complicated oral antimicrobial therapy (a.k.a. ‘Co-PAT’)
REFERENCES & READINGS
1. Barlam TM, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines from the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America. Clinical Infectious Diseases. 2016; 62(10):e51-e77.
2. Core Elements of Hospital Antibiotic Stewardship Programs. Hospital Stewardship. https://cd.gov/antibiotic-use/core-elements/hospital.html.
4. Kuti JL, Le TN, Nightingale CH, Nicolau DP, Quintiliani R. Pharmacoeconomics of a pharmacist-managed program for automatically converting levofloxacin route from IV to oral. Am J Health-Syst Pharm. Nov 2002; 59: 2209-15.
5. Sallach-Ruma R, Nieman J, Sankaranarayanan J, et al. Correlates and economic and clinical outcomes of an adult IV to PO antimicrobial conversion program at an academic medical center in Midwest United States. Journal of Pharmacy Practice. 2015; 28(3): 238-48.
6. Shrestha NK, Shrestha J, Everett A, et al. Vascular access complications during outpatient parenteral antimicrobial therapy at home: a retrospective cohort study. Journal of Antimicrobial Chemotherapy. 2016;71:506-12.
7. Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critical ill patient- concepts appraised by the example of antimicrobial agents. Advanced Drug Delivery Reviews. 2014; 77: 3-11.
9. Al Hasan MN, Rac H. Transition from intravenous to oral antimicrobial therapy in patients with uncomplicated and complicated bloodstream infections. Clinical Microbiology and Infection. 2019. In press.
ABOUT THE AUTHORS
Katherine Lee, Pharm.D.
Katherine Lee is originally from Athens, Georgia where she earned her Bachelor of Science in Microbiology from the University of Georgia in 2014. Her desire to escape the southern humidity led her to Hartford, Connecticut where she earned her Doctor of Pharmacy degree from the University of Saint Joseph in 2018.
Katherine is currently completing a PGY-1 at Beth Israel Deaconess Medical Center in Boston, MA with interests in infectious diseases and antimicrobial stewardship.
Nick Mercuro, Pharm.D.
Nick Mercuro is an infectious diseases pharmacotherapy specialist practicing at Beth Israel Deaconess Medical Center in Boston, MA. He completed his Doctor of Pharmacy degree at the University of Rhode Island, a PGY1 pharmacy practice residency at Henry Ford Hospital in Detroit, MI, and an Infectious Diseases PGY2 in Portland, ME. At Wayne State University Nick studied public health and graduated from a research outcomes fellowship focused in antimicrobial stewardship. His practice interests are in antimicrobial resistance, quality improvement, and transitions of care. You can find him on Twitter @N_Mercuro.
RECOMMENDED TO YOU