Oral vs. IV antimicrobials

What’s the difference between oral (PO) and IV medications? When do you use PO vs. IV antimicrobials? When are they interchangeable? These are the questions we’ll address in this post.

info intravenously picture
by Dalya Ferguson, MD

Bioavailability is an important concept to understand when considering IV to PO interchange.

Bioavailability = the measure of the amount of an orally administered medication that reaches the bloodstream.

Antimicrobials with >90% bioavailability are the antimicrobials we can target for
IV to PO interchange.

Antimicrobials where bioavailability >90%:
(therefore, can be switched to PO)

  • Metronidazole
  • Fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin)
  • Trimethoprim-Sulfamethoxazole
  • Tetracyclines (doxycycline, minocycline)
  • Linezolid
  • Rifampin
  • Fluconazole/Voriconazole
  • Clindamycin
  • Azithromycin (only ~40% bioavailable, but the concentration achieved by
    oral ingestion is just as effective as IV for treatment)


IV medication = medication given intravenously
– medication takes effect immediately after the infusion
– administers a bolus of the medication quickly (within 5 minutes)
– requires an IV line
– bypass first pass metabolism in the liver

PO medication = medication administered per oral route
– medication takes effect in ~30 minutes to 6 hours
– requires ability to swallow, absorb the medication, and also undergoes
first pass metabolism prior to reaching the circulatory system

Why is PO preferable to IV?

  • Cheaper3
  • Does not require IV access
  • Easier and faster to administer
  • No IV complications (i.e. phlebitis, thrombosis, bloodstream infection)
  • Avoidance of a long-term catheter such as a PICC line
  • Less unnecessary fluid administration


When to consider IV antimicrobials?

  • when patient is unable to take PO or unable to absorb the medication
  • when you want immediate effect of the medication
  • when the spectrum of activity desired is only available with IV antibiotics
  • when no PO option is available to treat the pathogen
  • when PO medications will not achieve high enough concentrations or penetrations to the location of the infection
    • Critically ill patients; sepsis/bacteremia
    • Endocarditis
    • CNS/ocular infection
    • Osteomyelitis/Septic arthritis (*a study is currently under way, looking at whether certain oral antibiotics are non-inferior to IV antibiotics in
      bone infections7)
      *You may occasionally see these syndromes treated with oral antibiotics, because each case is different. But in general, consider these syndromes as ones where IV antibiotics are preferred, especially as initial therapy.



  • IV antimicrobials are NOT “stronger” or “better” than oral antimicrobials
    – it depends on each individual medication
  • PO antibiotics should be used unless there is a reason to use IV antibiotics (and not the other way around)
  • When PO and IV versions of an antimicrobial are similar, make every concerted effort to make sure your patients are not on IV medications unnecessarily


Questions? Comments? Suggestions for future posts? Leave a comment below.




  1. Kwong, L.H et al. (2015). An unsupported preference for intravenous antibiotics. PLoS medicine, 12(5): e1001825. DOI: 10.1371/journal.pmed.1001825
  2. MacGregor, R.R. et al. (1997). Oral administration of antibiotics: a rational alternative to the parenteral route. 24: 457-467. PMID: 9114201
  3. Chan, R. et al. (1995). Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open, randomized, controlled trial. BMJ. 310: 1360-1362. PMID: 7787537
  4. Baddour et al. (2016). Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications. Circulation. 132: 1435-1486.
    DOI: 10.1161/CIR.0000000000000296.
  5. Tunkel, A.R. et al. (2004). Practice Guidelines for the Management of Bacterial Meningitis. CID. 39: 1267-1284. DOI: 10.1086/425368
  6. World Health Organization, Occupational Health. (date published unknown). Comparison of pharmacokinetics and efficacy of oral and injectable medicine [Powerpoint slides]. Retrieved from http://www.who.int/occupational_health/activities/5injvsora.pdf
  7. Li, H.K et al. (2015). Oral versus intravenous antibiotic treatment for bone and joint infections (OVIVA): study protocol for a randomized controlled trial. BMC Trials. 16:583. DOI: https://doi.org/10.1186/s13063-015-1098-y
  8. Wisplinghoff, H. et al. (2004). Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 39(3): 309-317. DOI: 0.1086/421946


Peer-reviewed by Jeff Pearson, 2nd year PharmD resident

Antimicrobials: spectrum of activity

One of the most difficult concepts to understand is the spectrum of activity of different antimicrobials. We are all taught each antimicrobial in silos of the other ones and I always found it difficult to create conceptual charts in my head. Thankfully, I’ve found some amazing charts on the internet (from reputable sources, of course) that shows antimicrobials in relation to one another that may be helpful to you.

Here, I will present the best ones I’ve found so far for antibiotics, antivirals, and antifungals for you to use as a reference guide. At the bottom, I will list a few caveats to take into account when using these charts, because as always, ID is never as simple as the charts imply.


Antibiotic spectrum of activityIntensive Care Drug Manual: Wellington ICU. Appendix 5.

Re-writing the fine print of the chart in case it’s not easily readable:
*For simplicity, atypical organisms are not included above. Partial columns indicate incomplete coverage. ESBL-producing organisms are not susceptible to most antibiotics containing a beta-lactam ring; carbapenems are the usual agent of choice.
1: C. difficile should only be treated with metronidazole or vancomycin
2: ESCHAPPM are β-lactamase producing organisms. These are Enterobacter, Serratia, Citrobacter freundii, Hafnia, Acinetobacter/Aeromonas, Proteus (not mirabilis), Providencia & Morganella morganii. See my 1st post on SPICE organisms for more info.
3: Not effective against Clostridium

4: Metronidazole is not effective against Peptostreptococcus
5: Teicoplanin is not effective against Enterococcus faecium
6: Gentamicin is not appropriate mono therapy for Staphylococcus aureus & should only be used in conjunction with a β-lactam
7: Due to increasing MIC, Cefuxorime is not recommended therapy for Moraxella
8: Although it has other actions, Ceftazidime should only be used for Pseudomonas

*This chart is intended as a guide, pending specific identification & sensitivities – it does not replace expert ID advice. Local antibiotic sensitivities & preferences will vary.

My notes:
ClindamycinCommunity-acquired MRSA strains have been found to be resistant to clindamycin and thus, this is often not a safe option for empiric therapy against MRSA.
usually used as an adjunct with another antibiotic against most infection. Would not recommend its use in isolation against infections.
would not use against enterococcus or empirically against MRSA in the hospital/ICU
Moxifloxacin — has some anaerobic coverage while levofloxacin and ciprofloxacin do not.
Metronidazole – no longer the 1st choice for C.diff infection. Instead, use PO vancomycin or PO fidaxomicin. (Thanks to a commenter for pointing that out to me!)



This chart was made by me but inspired by Aliyah Baluch, MD, Msc from USF who did an amazing review of antimicrobials used in stem cell transplant recipients. I thought it was a great way to demonstrate the spectrum of activity of antivirals and I hadn’t seen anything similar prior to that. Check out IDpodcasts.net for other lectures on ID topics.


antiviral spectrum of activity

*This chart only covers the herpes virus family, and does not include other virus families
*Just because foscarnet and cidofovir are considered the most broad-spectrum of the bunch does not mean they are always the best options. These drugs are quite toxic and should only be used in special circumstances, often with the involvement of an ID specialist.


This is a great chart taken from a wonderful review on antifungals from Mayo Clinic Proceedings.

Screenshot-2018-3-18 Current Concepts in Antifungal Pharmacology - pdfLewis, R.E. Mayo Clin Proc 2011


1.Lewis, R.E. (2011). Current Concepts in Antifungal Pharmacology. Mayo Clinic Proceedings. 86(8):805-817. DOI: 10.4065/mcp.2011.0247
2.IDpodcasts.org: Bugs, Drugs, and Stem Cells podcast. July 2017. http://idpodcasts.net/podcasts/bugs-drugs-and-stem-cells/
3.Intensive Care Drug Manual: Wellington ICU. Appendix 5. Updated 2017. http://drug.wellingtonicu.com/
4.Santos, C.A.Q. (2016). Cytomegalovirus and other beta-herpesviruses. Seminars in Nephrology. 36(5): 351-361.
DOI: 10.1016/j.semnephrol.2016.05.012
5.Razonable, R.R. (2011).
Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus. Mayo Clinic Proceedings. 86(10): 1009–1026. DOI:  10.4065/mcp.2011.0309

Peer-reviewed by Jeffrey Pearson, 2nd year pharmacy resident



CNS penetration of antimicrobials

Have you ever noticed how the indicated dosages for antimicrobials increase for CNS infections? This is because antimicrobials have a difficult time penetrating the blood brain barrier and the blood-CSF barrier, leading to difficulty of some antimicrobials to achieve therapeutic concentration levels in the CSF to properly treat a CNS infection.


(Bhaskar et al. 2010.)

Disclaimer: the penetration of antimicrobials into the CSF is much more complicated than three columns and a list of antibiotics. It’s been shown that levels of drugs differ between ventricular, cisternal, and lumbar CSF. Additionally, the treatment of CNS infections depends on more than just the CNS penetration of a certain antimicrobial, thus if any questions arise, please discuss with your ID consultants and ID pharmacists.

For the sake of this review, we will keep it simple.

Antimicrobials can be broken down into 3 rough

Excellent/Good penetration of the CSF Good penetration only in inflamed meninges Poor penetration of the CSF
Fluoroquinolones Glycopeptides (vancomycin) Beta-lactams3
TMP/SMX Macrolides (azithromycin) Aminoglycosides
Metronidazole Rifampin Tetracyclines (doxy, tigecycline)
Chloramphenicol Ethambutol Clindamycin4
Fosfomycin1 Daptomycin
Isoniazid Colistin
Pyrazinamide Fusion inhibitors (enfurvitide)
Zidovudine Tenofovir
5-flucytosine Amphotericin B5
Voriconazole/fluconazole Echinocandins
Pyrimethamine Itraconazole/posaconazole
Albendazole >>> Praziquantel

1 only FDA-approved for UTI treatment
2 no studies have been published looking at CNS penetration; however has been used successfully in clinical CNS infections
3 overcome by increase in dosages – higher dosages of beta-lactams obtain adequate levels in the CSF and tend to be 1st line agents in bacterial meningitis due to their efficacy and bactericidal properties
4 however has been shown to effectively treat susceptible CNS infections
5 however clinical trials have shown good outcomes when used in treatment of CNS infections

*If the class of drug was not mentioned in this list, it is likely because no studies have been done to assess CNS penetration of that drug.

Why are beta-lactams recommended for empiric
bacterial meningitis treatment?  

Despite the poor CSF penetration, beta-lactams have the most research documenting successful treatment of community-acquired meningitis compared to other antibiotic classes.

  • When the beta-lactam dose is increased, CNS penetration increases.
  • Beta-lactams are well-tolerated even at high dosages
  • Ceftriaxone treats S. pneumoniae, N. meningitidis, H.influenzae, and many aerobic gram-negatives such as E.coli and K. pneumoniae.

*Vancomycin is added to empiric regimens to treat the ceftriaxone-resistant S. pneumoniae strains that have been seen in community-acquired meningitis.

empiric meningitis tx IDSA guidelines                                                            (IDSA practice guidelines for Bacterial Meningitis, 2004.)


  • Not all antimicrobials penetrate the BBB. Take into account an antimicrobial’s CNS penetration properties when treating CNS infections
  • Beta-lactams are still 1st line therapy for empiric meningitis treatment due to their efficacy against the most common pathogens and ability to achieve high levels with increased doses of the medication
  • When treating CNS infections, deviation from the guidelines warrants involvement of the ID pharmacist and the ID consult team to ensure the best treatment regimen for the patient

1. Bhaskar, S., Tian, F. et al. (2010). Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: Perspectives on tracking and neuroimaging. Particle and fibre toxicology. 7(1)3. DOI: 10.1186/1743-8977-7-3.
2. Nau, R., Sorgel, F, and Eiffert, H. (2010). Penetration of Drugs through the Blood-Cerebrospinal fluid/Blood-Brain Barrier for the treatment of central nervous system infections. Clinical Microbiology Reviews. 23(4): 858-883. DOI: 10.1128/CMR.00007-10
3. Letendre, S. (2011). Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Topics in antiviral medicine. 19(4): 137-142.
4. Marra, C. (2014). Central nervous system penetration of ARVs: Does it matter? [powerpoint]. Presented at Northwest Aids Education and Training Center on May 15th, 2014.
5. Cherubin, C.E., Eng, R.H, et al. (1989). Penetration of newer cephalosporins into cerebrospinal fluid. Review of Infectious Diseases.11(4):526-548.
6. Tunkel, A.R., Hartman, B.J, et al. (2004). Practice Guidelines for the management of bacterial meningitis. CID. 39:1267-1284.

Peer-reviewed by Jeffrey Pearson, 2nd year ID pharmacy resident