Antibiotics: A Quick and Dirty Guide
My face when hearing about the ZoVan admission
It is a truth universally acknowledged, that a doctor in possession of a cellulitis patient, must be in want of an antibiotic recommendation from pharmacy....
Once, a medical resident called me to ask about a patient on the floor I was covering.
The patient was 23, and in good health. He showed up to the ED overnight because of a worsening red/swollen wound he received doing construction work a few days prior. He was afebrile.
The overnight team admitted him to the hospital and started on Vanc and Zosyn (I like to call it "ZoVan").
For those reading that are in their first year or two of pharmacy school, the gravity of this story may not have sunk in. Basically, using Vancomycin and Zosyn in this patient is like bringing an atom bomb to a knife fight.
It's like burning down your house because you saw a spider in it.
It's overkill.
For this patient, after a quick check up by the attending, we discharged him on PO Bactrim.
The point of this story? Infectious disease is a high impact area for pharmacists. The more you know about antibiotics the more beneficial you will be to your patients...
And the better you'll perform on the NAPLEX.
But if you're like everyone else (except this guy, or this guy), there's just too much to memorize. So many bugs, so many drugs. PK:PD. Empiric therapies. It's enough to make your head spin.
tl;dr pharmacy has a cure for what ails you. What follows is a bare bones, "under the hood" look at the most important concepts in antimicrobial therapy. There are three areas of focus:
Bugs and Drugs
Renal Adjustments
PK:PD
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Bugs and Drugs
The best starting point is knowing what drugs cover what bugs. This is admittedly daunting. So I recommend prioritizing.
Let me be clear by saying that the more you know the better off you'll be. That said, we both know you're here because you have a test tomorrow and time is a factor. So I think you'll get the most bang for your buck by focusing on the resistant pathogens. These are the things that are
Difficult to treat
Cause excessive morbidity
And are just generally all-around assholes
If these pathogens were people, they'd always eat the last slice of pizza. They'd show up to a party with chips but no dip. They'd "forget" to bring their wallet everywhere so you always end up covering for them.
I'm talking MRSA, VRE, SPACE, CRE, KPC, C. diff, and any other cool sounding acronym. These are the things you're most likely to be tested on.
Not coincidentally, they're also the things you'll be asked most about in real life.
At a minimum, you should know how to treat the Big Three:
MRSA
Pseudomonas
VRE
We created some charts to help you do this. To my knowledge, they are complete in terms of drugs available in the US at the time of this writing (Article last updated January 2020).
Just remember the "real world" limits. You need to know all of these treatment options for a test, but if you start recommending chloramphenicol for MRSA patients the ID team is going to have a serious chat with you.
We're also not including fosfomycin and methenamine in the charts below. They technically have activity against MRSA and Pseudomonas (and a whole bunch of other things), but their use is limited to UTIs.
HA-MRSA |
|---|
| vancomycin |
| daptomycin |
| linezolid |
| tedizolid |
| ceftaroline |
| delafloxacin |
| telavancin |
| dalbavancin |
| oritavancin |
| tigecycline |
| teicoplanin |
| quinupristin/dalfopristin [Synercid] |
| chloramphenicol |
| eravacycline |
| rifampin[*](used as adjunctive therapy for certain infections. Not for monotherapy) |
CA-MRSA |
|---|
| sulfamethoxazole/trimethoprim [Bactrim] |
| doxycycline |
| minocycline |
| clindamycin |
| linezolid |
| tedizolid |
| delafloxacin |
| eravacycline |
| moxifloxacin[*]...technically has activity, but probably shouldn't be used |
Pseudomonas |
|---|
| ticarcillin/clavulanate [Timentin] |
| piperacillin/tazobactam [Zosyn] |
| ceftazidime |
| ceftazidime/avibactam [Avycaz] |
| ceftolozane/tazobactam [Zerbaxa] |
| cefepime |
| aztreonam |
| ciprofloxacin |
| levofloxacin |
| delafloxacin |
| imipenem/cilastatin [Primaxin] |
| meropenem |
| meropenem/vaborbactam [Vabomere] |
| doripenem |
| aminoglycosides[*]gentamicin, tobramycin, and amikacin |
| colistin |
| cefiderocol |
| imipenem/cilastin/relebactam [Recarbrio] |
VRE |
|---|
| linezolid |
| tedizolid |
| daptomycin |
| oritavancin |
| tigecycline |
| eravacycline |
| quinupristin/dalfopristin [Synercid][*]Enterococcus faecium only...NOT effective against E. faecalis |
| teicoplanin |
| telavancin |
So find a way to commit these to memory. Make mental shortcuts for yourself.
For example, all of the carbapenems treat pseudomonas EXCEPT ertapenem. Delafloxacin is the ONLY quinolone that can be used for both MRSA and Pseudomonas.
That sort of thing. Your GPA will thank you for it.
For additional information, you can check out IDSA for current treatment guidelines. There's also excellent stuff (created by a pharmacist!) over at IDStewardship.com.
Antibiotic Renal Adjustments
Many of us struggle to remember which antibiotics need to be dose-adjusted in renal disease.
Luckily there is a work around. It turns out that there are only a handful of antibiotics that don't need a renal adjustment. Make your life easier by memorizing those and knowing that everything else needs to be adjusted.
You'll be able to knock out a few multiple choice options on the NAPLEX. And in real life, you'll know that the dose needs to be adjusted and you can look it up.
There's more. Let's say it's a test, so you can't look up the renal dose. How do you decide the appropriate dose adjustment?
It all depends on whether the antibiotic exhibits time or concentration-dependent killing.
In general, for time-dependent antibiotics, you want to decrease the dose, but keep the dosing interval the same.
It's the opposite for concentration-dependent drugs. With those, you'll keep the dose the same, but increase the dosing interval.
We'll explain more about time vs. concentration-dependent in the next section. For now, here's a short list of the most commonly used antibiotics that do not require a renal adjustment:
Nafcillin
Oxacillin
Ceftriaxone
Clindamycin
Azithromycin
Erythromycin
Moxifloxacin
Doxycycline
Tigecycline
Rifampin
So you can remember 10 antibiotics that do not need an adjustment. Or dozens of antibiotics that do. Which is easier?
Use mental shortcuts here too. For example, note that moxifloxacin is the only fluoroquinolone that doesn't need renal adjustment. Or that clarithromycin is the only macrolide that does require adjustment.
This helps because now in your head you can say "Cephalosporins need a dose adjustment...except ceftrixaone." The list of what you have to memorize just went from 30 items to 1 item. #Winning.
PK:PD, MIC, AUIC
Finally, we want to dose antibiotics in such a way that takes advantage of their pharmacokinetics and pharmacodynamics (PK:PD). There's a lot that can go into doing this, so let's simplify and make it as painless as possible.
How an antibiotic kills bacteria may fall into one of two (very broad) categories:
Time-dependent killing
Concentration-dependent killing
There's an important number we look at when referencing time or concentration-dependent killing. The Minimum Inhibitory Concentration (MIC).
The MIC is that number you see reported when you look at the sensitivities of a sputum culture of the patient you're following on your APPE rotation. It's the minimum concentration an antibiotic has to reach, at the site of the infection, to inhibit bacterial growth.
In other words, it's the main "thing" that determines if an antibiotic is going to work or not.
That "at the site of the infection" part above is important. If the drug doesn't get to where it needs to be in the body, it doesn't matter how effective it is against the organism.
As an example, moxifloxacin is generally not used for UTIs. Not because it's not active against the organisms. But because it doesn't concentrate in the urine. This makes sense, because as we learned above, it doesn't require a renal adjustment.
You'll see this same principle in pneumonia, meningitis, cellulitis, and every other bacterial infection. Make sure the antibiotic you've selected will actually be able to reach the site of the infection.
Going back to time vs. concentration dependent killing...
This curve represents the amount of antibiotic in your blood stream after administering a single dose. Concentration is on the vertical axis, and time is on the horizontal.
That lovely (and very straight) line going across horizontally represents the MIC. You can see how the antibiotic concentration spends some amount of time above the MIC. Then as your body metabolizes and excretes it, the concentration drops below the MIC.
As you administer subsequent doses (ie. 1 gm q12 hrs), the total picture will look like this:
So here's the crux of time-dependent vs. concentration dependent....
With time-dependent antibiotics, your goal is to keep the drug concentration above the MIC for as long as possible. In fact, in a perfect time-dependent world, you'd administer it as a continuous infusion. We actually do this sometimes for certain patients. The graph would look like this:
More often, we dose the antibiotic intermittently (ie. every 6 - 8 hours). It's just easier to coordinate their antibiotic with any other medications the patient is getting that way.
But even with intermittent dosing, we try to dose the antibiotic frequently enough to keep the concentration above the MIC, as in the graph above. The most important 'thing' for a time-dependent antibiotic is the amount of time spent above the MIC. That's how they kill bacteria.
Your time dependent antibiotics are beta lactams (all of them) and vancomycin. That might not sound like a ton, but think about it. That's a crap-ton of antibiotics. All of the penicillins. All of the cephalosporins. All of the carbapenems. Aztreonam. There are a few dozen antibiotics there.
On the other hand, there's concentration-dependent antibiotics. With them, the big thing is getting that peak as high as possible.
What you're maximizing here is the area under the curve that's above the MIC. We call this the AUIC.
Your concentration-dependent antibiotics are fluoroquinolones and aminoglycosides.
Post Antibiotic Effect
Now would be a good time to bring up the Post Antibiotic Effect (PAE). This is something you see primarily with concentration-dependent antibiotics.
Basically, the PAE is a period where the antibiotic is still killing the bacteria (or suppressing the growth)....even after the concentration has dropped below the MIC. This PAE typically lasts for a few hours.
What causes the PAE? The current thinking is that it's due to impaired DNA function in the bacteria.
This provides a helpful way to memorize which antibiotics cause PAE. It's the ones that work on DNA or ribosomes (not so much the cell wall inhibitors).
So again, the fluoroquinolones and aminoglycosides fit here. But you can also see some (less pronounced) PAE with tetracyclines and clindamycin.
Tying all of this together, you can see why we renally adjust time and concentration-dependent antibiotics the way we do.
For example. When you adjust levofloxacin, you don't change the dose from 500 mg q24h to 250 mg q24h. You'd lose that magnificent peak and decrease the AUIC. Which is how levofloxacin works. So you adjust it to 500 mg q48h. You adjust the dosing interval, not the dose.
But when you adjust a beta lactam, you start by decreasing the dose and keeping the dosing interval the same. So with meropenem, you'd adjust from 1 gm q8h to 500 mg q8h. Again, this makes sense because you want to keep the antibiotic concentration above the MIC.
Just to be clear, these are the initial renal adjustments. As kidney function continues to decline, you don't have a choice but to increase the dosing interval in meropenem (and other beta lactams). You have to "make the cut" from somewhere.
So eventually, the meropenem dose will be 500 mg q12h, and then even q24h. However, at this stage, the kidney is working poorly enough that the concentration is likely not dipping below MIC.
Either way, you can use this theory on the NAPLEX. Knowing how the antibiotics should be adjusted, you can weed out multiple choice answers even if you don't know the specific dose.
Bacteriocidal vs. Bacteriostatic
Another way to sort antibiotics is to group them by their activity on bacteria. Some antibiotics kill bacteria (bacteriocidal) while others just inhibit bacteria growth (bacteriostatic).
This isn't a 'black or white' scenario as bacteriostatic antibiotics will kill some bacteria and cidal agents won't kill everything. But it works for a broad grouping.
I've tried for years to come up with an easy way to sort whether an antibiotic would be static or cidal. There is no perfect system that I've found. There are too many exceptions to the rule. However, you can get pretty close with the following:
Bacteriocidal agents tend to work on the bacterial cell wall or membrane
Bacteriostatic agents tend to work on bacterial ribosomes and protein synthesis
Again, there are exceptions. Fluoroquinolones inhibit DNA, and they're cidal. Aminoglycosides work on ribosomes, but they are cidal. However, this system does work in the majority of cases.
Does it ever matter whether you use cidal or static? Yes. Typically, you'd want to use cidal antibiotics in those "Oh shit" clinical scenarios. Things like meningitis, endocarditis, osteomyeltitis, and febrile neutropenia.
On the flip side, some static antibiotics (like clindamycin) have shown an ability to decrease toxin production in staph and strep. This is significant enough to reduce the risk of toxic shock syndrome and to prevent amputations in CA-MRSA infections. So you'll often see clindamycin added to the regimen for this purpose.
Do you want all of this information as a handy cheat sheet?
We've covered a crap-ton of information here. Would you like us to simplify it for you?
Done.
We've created a super-handy antibiotic cheat sheet. It is the most comprehensive, yet easy to use reference that exists for antimicrobials. It includes antibiotics to treat the resistant organisms. It includes antibiotics that don't need a renal adjustment. It includes body distributions and PK:PD dosing theories. It's very handsome. You can hang it on your wall, or take it along in your notebook.
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