An ongoing dialogue on HIV/AIDS, infectious diseases,
May 16th, 2013
ID Learning Unit — Antibiotics with Excellent Oral Absorption
Guaranteed: Every day at a hospital near you, a patient is receiving antibiotic therapy for an infection, and the orders include the following:
- A slew of various oral medications, both continued from outpatient care and started anew on admission.
- An intravenous antibiotic.
Even worse, someone may be discharged from the hospital on intravenous antibiotics — risking all the problems of parenteral access (clots, infection, pain, and myriad catheter malfunctions which only happen in the middle of the night/weekends) — when there are multiple oral options that will do the job just as well.
As a result, all ID doctors have encoded deep in their genome a list of antibiotics that can be given orally in place of their IV counterparts, or even more importantly, substituted for something IV on discharge.
Here’s the list, with a miscellaneous comment or two:
- Fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin): Yes, we both love them and hate them.
- Trimethoprim-sulfamethoxazole: 1) A double-strength tablet is gigantic, but it also comes in liquid form for the pill-averse; 2) I always ask our ID fellows to tell me precisely (individual drugs and dose) what’s in a double-strength tablet of “Bactrim”, and about half of them know. Do you?
- Metronidazole: 1) I am amazed that after decades of use of this drug, there is still no significant resistance among Bacteroides spp. 2) A ID colleague of mine, who is married to a gastroenterologist, named her bird “Flagyl.” How perfect is that??!!!
- Clindamycin: What a wonderful drug this would be — effective for a whole range of things — if it weren’t for that nasty C diff problem.
- Doxycycline: We’re heading into the “doxycycline deficiency” season here in New England. Start those tick checks!
- Rifampin: You can pretty much guarantee that if a patient needs intravenous rifampin, he/she also needs an ID consult.
- Linezolid: 1) This is the only oxazolidinone antibiotic; 2) I don’t know what “oxazolidinone” means, nor how to pronounce it; 3) I do know that this is by far the most expensive oral antibiotic out there. Wow!
- Fluconazole: We take it for granted today, but the leap from ketoconazole to fluconazole when it first came out was truly gigantic. Sometimes newer really is better.
What’s missing? Most importantly, the entire class of beta-lactam and beta-lactam-like antibiotics — there isn’t a penicillin or cephalosporin that achieves high blood levels with oral administration (amoxicillin and cefadroxil the closest thing), and if there’s an oral carbapenem out there, someone has been hiding it from me.
Finally, as I went through this list on rounds, the residents and medical students were trying to come up with some sort of mnemonic, but were stymied since all the drugs start with consonants. Any suggestions? And did I miss anything?
(Part of a series inspired by attending on the medical service.)
Hi Paul,
What about azithromycin? Even though its oral bioavailability isn’t great (~40%), oral dosing achieves very good and prolonged tissue/cellular levels and therefore it should perform very well for intracellular pathogens such as Legionella pneumophila.
Krispin, good point. In practice oral azithromycin is just as good as IV, but blood levels are substantially lower (which is why I didn’t include it).
Paul
Here is the closest I have been exposed to: DR CALM Q’S
Doxycycline
Rifampin
Clindamycin
Azoles/ Azithromycin
Linezolid
Metronidazole
Quinolones
Sulfamethoxazole/ Trimethoprim
This was told to me by my ID attending Dr Cutona, hope it is somewhat useful.
Dr. Sax,
Other drug information resources such as Micromedex/Drugdex, package inserts, statements by the American Society of Health-Systems Pharmacists, and the Sanford Guide to Antimicrobial Therapy list certain beta-lactams as having high oral bioavailability.
For example, the Sanford guide lists the following beta-lactams with oral bioavailability >80%
– Amoxicillin
– 1st generation cephalosporins (cefadroxil, cephalexin)
– 2nd generation cephalosporins (cefaclor, cefprozil)
– 3rd generation cephalosporins (ceftibuten)
What is your experience with these oral beta-lactams in particular?
Other reference: http://www.ashp.org/DocLibrary/MemberCenter/ClinicalSpecialistsandScientists/IVtoPO.pdf
Thanks!
I think there are two issues with beta lactams and oral administration that makes them not comparable to the antibiotics listed above, even if they are well absorbed: 1) the doses still don’t approach what you can give intravenously (e.g., we commonly give 6 grams of cefazolin daily to treat serious staph infections), so achievable blood levels will still be much lower; 2) at a certain point, increasing the oral dose no longer increases the blood concentrations.
Would welcome thoughts of others on this issue!
Paul
Don’t forget fidaxomicin in price issues, for what it’s worth (or not):
http://www.goodrx.com/dificid/price
Julian, good one — forgot about fidaxomicin, a completely UNABSORBED antibiotic!
10 day course fidaxomicin (200 mg bid @ $157/pill): $3100
10 day course linezolid (600 mg BID @ $115/pill): $2300
We have a new champion!
Paul
Dear Paul,
How about a drug where oral bioavailability exceeds that of iv – namely, Chloramphenicol. Of course in the U.S. it is no longer used but where I practice in Tanzania it is still widely used, as in many other resource-poor settings around the world.
How about “Mother Trims Cynthia’s Locks For First Real Dance?”
As pricey as linezolid p.o. is, IV vancomycin for a similar 10 day course of 1GM BID is ~$6400-7,300 from the goodrx.com site
PO meds still come out ahead….
The push-back I often encounter as a pharmacist trying to convert to, or initiate with, oral antibiotics is that patients will no longer meet criteria for inpatient care. Case managers will often state that oral antimicrobials will not generate a high enough intensity of service. It seems like a futile battle for something as simple as an IV-to-PO conversion. Of course, if the patient is well enough, they are likely able to be discharged anyway, but of course, it is not a black-and-white picture.
Paul
Do not forget oral fosfomicin a good alternative for resistent e coli and some pseudomonas , most in tract urinaru infections
Mnemonic: Clindamycin For Diarrhea, FMT, Likely Relief
Love that bird’s name!
Yep. There’s always the matter of meeting criteria for inpatient care. Nevermind the tele monitor or I/O monitoring, but the exact moment you convert from IV to PO antibiotics, the case manager and/or PMD come a calling.
Here’s a mneumoic; had to change fluconozole to A for antifungal
Frequently Fluoroquinolones
Taken Trimethoprim
Meds Metronidazole
Can Clinda
Definitely Doxy
Reduce Rifampin
Lengthy Linezoid
Admissions Antifungal = fluconazole
Now we just need to convince Medicare that oral antibiotics should be equivalent to IV in determining coverage criteria for inpatient stay, as Medicare is tightening all of its criteria often leaving IV meds as one of very few ways of justifying hospitalization of truly sick patients.
oRal Drugs May Treat Certain Little Fevers First
Hi Paul,
While I agree that Oral Antibiotics are equally effective, economic and safe when compared to IV medications, there are situations like poor oral absorption due to gastroenteritis and other gastrointestinal problems. Moreover, patients with CD 4 count less than 100 and having opportunistic diseases ( quite common in our place) are having problems in their GI tract (clinically obvious or not), they are responding better only with Intravenous antibiotics rather than oral antibiotics. Oral antibiotic medications may be suitable for patients with CD4 count more than 200 and without any gastroenteritis.
For So Many Can Deliver Like Fried Rice
Hi Paul,
Yes they have been hiding it from you! It is a terrifying thought for some, but an oral carbapenem is available in Japan. See the following article for some background http://www.ncbi.nlm.nih.gov/pubmed/23041363.
I’m not sure about the price that Rob quoted for the vancomycin IV. The cost of Vancomycin 1 gm IV q12h at our hospital is $6.26/day putting the cost of 10 days of vancomycin lower than a single oral dose of linezolid.