Diminishing Returns: The "MIC Creep" Dilemma with Vancomycin

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The story of vancomycin all started when a missionary from Boreno sent a sample of dirt to a friend at Eli Lilly. The compound isolated had activity against most gram positive organisms. In fact, it got its name from the word 'vanquish.' Vancomycin was FDA-approved in 1958. [1]

Vancomycin is still a powerful tool against gram positive organisms, but there are some important learning points for using it properly in the critically ill ED patient.

First, a little history...
The original minimum inhibitory concentration (MIC) cutoff for S. aureus susceptibility was ≤ 4 mcg/mL. This was decreased to ≤ 2 mcg/mL in 2007 despite the emergence of vancomycin intermediate S. aureus (VISA). [2] Remember, MIC is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation (thanks Wikipedia). MICs can vary based on testing method utilized (by 1-2 fold).

What is MIC Creep?
Over time it seems the MIC needed for vancomycin to eradicate MRSA is increasing, as evidenced by increasing vancomycin MIC distribution in S. aureus isolates. [3] 

What's the problem?
Patients are dying from bacteremias even with MICs ≤ 2 mcg/mL that appear as 'susceptible' on institutional reporting tools. This is scary!

• Vancomycin MIC of 2 mcg/mL was an independent predictor of mortality. [4]
• MIC break point ≥ 1.5 mcg/mL was associated with an increased probability of vancomycin treatment failure. [5]

These two findings were verified by a systematic review/meta-analysis. [6] The authors also found that vancomycin treatment failures and mortality for MRSA infections occurred regardless of source of infection or MIC testing methodology!

What it all means

Although in the ED we often don't have access to the patient's susceptibility data, make sure to look at previous records from your institution or the transferring institution. Just because the culture report says 'S' (for susceptible), the MIC may be between 1.5 and 2 mcg/mL.

• For bacteremias/endocarditis: if the S. aureus MIC ≥ 1.5 mcg/mL, don't use vancomycin!
• For all other MRSA infections: if the S. aureus MIC ≥ 2 mcg/mL, don't use vancomycin!

Proper Vancomycin Dosing in the ED [7]

• Stop using a default dose of 1 gm for all patients. Vancomycin is dosed based on total body weight.
• An initial dose of 15-20 mg/kg should be started in the ED. For critically ill patients, loading doses (25-30 mg/kg) can be considered.
• The initial dose should not be adjusted down based on renal function (we can adjust the dosing interval later).

Thanks to Emily Heil, PharmD, BCPS for providing much of the information for this post.

Original: January 16, 2013
Last updated: January 17, 2013


References

1. Levine DP. Vancomycin: A History. Clin Infect Dis 2006;42(Supplement 1):S5-S12. 
2. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. CLSI Document M100-S22. Wayne, PA: Clinical and Laboratory Standards Institute; 2012. 
3. Steinkraus G, et al. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001-05. J Antimicrob Chemother 2007;60(4):788-94. [PMID 17623693] 
4. Soriano A, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008;46(2):193-200. [PMID 18171250] 
5. Lodise TP, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother 2008;52(9):3315-20. [PMID 18591266] 
6. van Hal SJ, et al. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis 2012;54(6):755-71. [PMID 22302374] 
7. Rybak MJ, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009;66(1):82-98. [PMID 19106348] 

If you are interested, you can view the results of the Peer Review Demographics data.

Is the 6-12-12 adenosine approach always correct?

The ACLS-recommended dosing strategy of 6 mg, 12 mg, and 12 mg for adenosine may not be appropriate in every situation. There are a few instances when lower or higher dosing should be considered.

Caveat: All recommendations are data-based, but many factors affect successful conversion of paroxysmal supraventricular tachycardia (PSVT) including proper line placement and administration technique.


Option 1: Starting at higher dose

Caffeine is an adenosine blocker and can interfere with the successful reversion of PSVT. In fact, ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduced its effectiveness in the treatment of PSVT. An increased initial adenosine dose may be indicated for these patients.

Remember that theophylline may require higher dosing as well, because it is similar to caffeine (another methylxanthine), but is not prescribed much in the U.S. anymore.

Recommended dosing strategy [1]:

• 1st dose: 12 mg (instead of 6)
• 2nd/3rd doses: 18 mg (instead of 12)

Option 2: Starting at lower dose
Every so often a patient arrives in PSVT with their only IV access being through a hemodialysis port. The initial adenosine dose should be reduced if administered through a central line. Remember a central line delivers the adenosine right where you need it. This recommendation is supported by the 2010 ACLS guidelines. Cases of prolonged bradycardia and severe side effects have been reported after full-dose adenosine through a central line.

Also consider lower doses in patients concomitantly taking carbamazepine or dipyridamole or in those with a transplanted heart.

Recommended dosing strategy [2, 3, 4]:

• 1st dose: 3 mg (instead of 6)
• 2nd/3rd doses: 6 mg (instead of 12)

References

1. Cabalag MS, et al. Recent caffeine ingestion reduces adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia. Acad Emerg Med 2009;17(1):44-9. [PMID 20003123]
2. Chang M, et al. Adenosine dose should be less when administered through a central line. J Emerg Med 2002;22(2):195-8. [PMID 11858927]
3. Neumar RW, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S729-S767. [PMID 20956256]
4. McIntosh-Yellin NL, et al. Safety and efficacy of central intravenous bolus administration for termination of supraventricular tachycardia. J Am Coll Cardiol 1993;22:741-5. [PMID 8354807]

Losing faith in "evidence-based medicine": Etomidate and sepsis

In an era where evidence-based medicine is the goal, it is vitally important for practitioners to understand how to prioritize and interpret the onslaught of data coming at us. 

This fact was driven home for me with a recent publication. Several weeks ago an article was published in Critical Care Medicine entitled "Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis."

The point of this post is not to debate if etomidate should be used to intubate septic patients. Etomidate very well may kill people with sepsis. I just don't know from the data currently available. Using this meta-analysis as an example, the goal is to point out two important areas where we could stand to sharpen our literature evaluation skills.

Point #1: Choose (and interpret) your titles wisely.

It is an overwhelming task to skim through several journals' Table of Contents each month. In a specialty such as Emergency Medicine, many relevant articles appear in non-EM journals making it even more challenging. It's tempting to think we know what an article concluded, based solely on its title.

This point particularly applies to those who publish. But readers also should use extreme caution if only reading titles and abstracts. Given that the last several articles on this topic found that etomidate did not increase mortality when given as an induction agent to septic patients, I was quite surprised to see this bold title declaring etomidate is associated with mortality. We're all so busy that it would be very easy to simply see this title and assume it to be true, without ever reading the article. That is very dangerous medicine, in my opinion. And, this principle extends far beyond this one meta-analysis. 

I've already seen etomidate avoided in a hypotensive, septic patient based on this article. I've also heard colleagues giving a quick summary of the article to students and residents saying this article "confirms what we already knew." What?!? When did we definitively "know" this? I still can't believe a highly regarded journal such as Critical Care Medicine would allow this article to be published with this title.

Point #2: The meta-analysis is not the end-all-be-all of publications.

We've all sat through some sort of literature evaluation class back in school. When the meta-analysis was described to me as a student, I remember thinking how awesome it was. Let me get this straight... people way smarter than me are going to take all of the articles published on a given topic, perform some fancy (way over my head) statistics, and give us an evidence-based conclusion? Sign me up. Coming out of pharmacy school, I pretty much thought meta-analyses were the cream of the crop when it came to the published literature. How wrong I was.

I shouldn't have to go back and analyze each of the articles the authors used, but that is exactly what I did in this case. Here is what I found:

With regard to mortality, 5 trials were included. The 4 smaller ones mostly demonstrated that etomidate did not increase mortality compared to other agents. However, the one larger trial encompassing 499 of the 865 total patients (58%) did show an increase in mortality. It was published by Cuthbertson, et al in Intensive Care Medicine in 2009.

Let's take a closer look at this ICM study. 

It was such a large contributor to the meta-analysis outcome, it seems important to understand what that trial was all about. Despite the authors calling it an a-priori sub study of the CORTICUS trial, it was actually a post-hoc analysis looking at etomidate's association with mortality. You can read the two published commentaries to the Cuthbertson study by Pallin and Andrade, which each highlight several major issues with the data in this trial. 

The bottom line is that the trial by Cuthbertson was highly flawed and really doesn't give us any insight as to etomidate's contribution to mortality. In fact, one of the biggest critiques was that physicians in the CORTICUS trial were instructed to avoid etomidate due to its propensity to suppress cortisol production. So, when physicians did use it, there was likely a reason for it (ie, the patient was hemodynamically unstable and they didn't have many other good induction agent options). Therefore, etomidate was probably given to the sicker patients already more likely to die from the start. 

If you dig even deeper, you'll find that the Cuthbertson group used two logistical regression models. One showed a nonsignificant increase in mortality while the other showed a significant increase. Of course the statistically significant one was reported in the abstract. The bottom line is that if you use bad data to construct a meta-analysis, you'll end up with a bad meta-analysis.

So where does this leave us?

In part, it means we have to remain as skeptical as ever when reading published articles. We already know titles and abstracts don't give the full picture. Taking into account reporting biases, funding sources, and even authors' personal/professional agendas, it seems we can't always rely on the peer-review process to uphold the highest standards of integrity. The best journals out there aren't immune. One reason I love Free Open Access Meducation (FOAMed) is that the peer-review process is instant and no holds barred. If you post something that is inaccurate or controversial on Twitter or a medical education blog, you will get called out on it. The best part is that the ensuing conversations inevitably lead to knowledge sharing and learning. Isn't that what research is supposed to be about after all?

Dr. Joe Lex said it best on Twitter:

I couldn't agree more.



References:

1. Chan CM, et al. Etomidate is associated with mortality and adrenal insufficiency: A meta-analysis. Crit Care Med 2012;40(11):2945-53. [PMID 22971586]
2. Cuthbertson BH, et al. The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Med 2009;35(11):1868-76. [PMID 19652948]
3. Pallin DJ, Walls RM. The safety of single-dose etomidate. Intensive Care Med 2010;36(7):1268-70. [PMIS 20405278]
4. Andrade FM. Is etomidate really that bad in septic patients? Intensive Care Med 2010;36(7):1266-70. [PMID 20405279]

Trick of the Trade: Searching for Comments to a Published Article

One day back in 2005 during my PGY-1 pharmacy practice residency, I remember a conversation with my residency director. He was a Surgical/Trauma ICU pharmacist. There had been a recent article published (I think it may have been one linking 'tight' glucose control to decreased mortality in ICU patients). Funny how times change...

Anyway, he mentioned all of the 'discussion' surrounding the article in terms of comments submitted to the journal. It was my first introduction to the idea that published literature could be challenged through an avenue provided by the journal.

Just this past week during EM residency journal club, we were discussing the recent Etomidate/Sepsis Meta-Analysis published in Critical Care Medicine (more to come on that soon in another post). I mentioned to my group how one could search for submitted comments. Most seem surprised to learn this trick of the trade.

Medical Education Trick of the Trade: Look for comments at bottom of Pubmed citation

• Locate the article of interest on PubMed.
• At the bottom will be any comments submitted to and published by the journal.
• Click on the link and it will bring you to the comment.

Test out these "Comment In" links from the above example:

• Comment: frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. [Ann Pharmacother. 2009]
• Comment: Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. [Ann Pharmacother. 2008]

Some comments are written to suggest solutions to a problem identified by the article (see above). Others are more contentious when controversial topics are published and/or subpar methods, statistics, results, or conclusions are reported (see below).

Links for the "Comment In" section:

• Safety of etomidate bolus administration in patients with septic shock. [CJEM. 2011]
• The safety of single-dose etomidate. [Intensive Care Med. 2010]
• Is etomidate really that bad in septic patients? [Intensive Care Med. 2010]

I highly recommend reading them. The tone is generally more pointed then the original article. Typically, the author(s) are given a chance to reply and those are also listed. It's a great learning exercise to read how other experts in the field critique a study and how the author responds.

Mythbuster: Urgent dialysis following IV contrast?

Have you ever had to promise the radiologist that you would arrange emergent dialysis for your end-stage renal disease (ESRD) patient after receiving IV contrast?

This myth is even perpetuated in the field of nursing. In fact, what prompted this post was overhearing this very topic discussed between a nurse and a new nurse trainee.

Although there is no supportive data, two theoretical risks have been suggested:

1. An oliguric dialysis patient could progress to an anuric state after IV iodinated contrast administration.
2. The osmotic load from IV contrast could result in pulmonary edema and anasarca in a dialysis patient unable to clear the excess volume.

Mythbuster:
Despite the theoretical concerns, there is no need for urgent dialysis after IV contrast administration in an ESRD patient on chronic dialysis.

The patient should be able to wait until their next scheduled dialysis session. In fact, the 2012 American College of Radiology's Manual on Contrast Media states, "Unless an unusually large volume of contrast medium is administered or there is substantial underlying cardiac dysfunction, there is no need for urgent dialysis after intravascular iodinated contrast medium administration."

As an FYI, the average amount of contrast volume infused for a typical CT scan is around 100 mL.

There you have it, although I'm sure you already knew (or at least suspected).

For a nephrologist's perspective, the Renal Fellow Network blog has a great post on this topic as well: http://renalfellow.blogspot.com/2009/08/prophylactic-hemodialysis-for-iv.html

References

• Younathan CM, et al. Dialysis is not indicated immediately after administration of nonionic contrast agents in patients with end-stage renal disease treated by maintenance dialysis. AJR Am J Roentgenol 1994;163(4):969-71. PMID 8092045
• Morcos SK, et al., and members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR). Dialysis and Contrast Media. Eur Radiol 2002;12(12):3026-30. PMID 12439587

Trick of the Trade: IV ceftriaxone for gonorrhea

How many times have you given your patient IM ceftriaxone for that presumed gonococcal infection? ... still counting?

Many of us learned (or at least thought we learned) that ceftriaxone has to be administered IM to get the ‘depot’ effect.

Myth busted: There is no depot effect. IV and IM ceftriaxone have very similar pharmacokinetic profiles. Let me prove it to you, straight from the FDA-approved ceftriaxone package insert.

Time after dose administration (hrs) and Average plasma concentration (mcg/mL)

Dose/route	0.5 hr	1 hr	2 hr	4 hr	6 hr	8 hr	12 hr	16 hr	24 hr
0.5 g IV	82	59	48	37	29	23	15	10	5
0.5 g IM	22	33	38	35	30	26	16	unknown	5

• The plasma concentrations are almost identical after IM and IV administration through 24 hours.
• The volume of distribution is the same for both parenteral routes, too. This means that its penetration into the “affected area” is similar.
• For further proof, the CDC Guidelines recommend IV or IM ceftriaxone interchangeably for most gonococcal infections in infants and children.

Trick of the Trade: 
If the patient already has an IV line, give IV ceftriaxone instead of IM .

While most of the time patients with STD (or STI, if you prefer) complaints don’t have an IV line established, occasionally they do. My hospital stocks 1 gm and 2 gm premixed IV bags of ceftriaxone, so we just give 1 gm IV in these rare cases. But 250mg IV should be just fine.

Of course, the other way to avoid the painful injection is to mix the ceftriaxone with lidocaine... or avoid contracting gonorrhea altogether.


References:

Product Information: ROCEPHIN(R) IV, IM injection, ceftriaxone sodium IV, IM injection. Genentech USA, Inc. (per Manufacturer), South San Francisco, CA, 2010.

Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010;59(RR-12):1-110. [

PMID: 

21160459]. Free MMWR PDF download.

Tricks of the Trade: Calcium gel for hydrofluoric acid burns

From AccessMedicine.com

A 41 y/o m presents to your ED after an occupational exposure to 30% hydrofluoric acid (HF). The thumb and index finger of his right hand were affected. Upon visual examination, the site of exposure looks relatively benign but the patient is complaining of extreme pain. Beyond giving opioids, what can you do?

Topical calcium gluconate is the treatment for minor to moderate cutaneous burns from HF.

It would be really nice if there were a commercially available calcium gluconate gel available. Wait, there is! But it's pretty expensive and most hospitals won't stock it. Generic versions of 2.5% calcium gluconate gel are also hard to come by.

Trick of the Trade:
Make your own calcium gluconate gel.

What you'll need:

1. Calcium carbonate tablets (Tums^®), calcium gluconate powder, or solution
2. A water-soluble jelly (K-Y Jelly^® works great)

How to prepare: Mix any of the following with 5 ounces of K-Y Jelly^®:

• 10 g of calcium carbonate tablets, or
• 3.5 g calcium gluconate powder, or 
• 25 mL of calcium gluconate 10% solution

How to administer:

1. Thoroughly irrigate the area with water. 
2. Apply your concoction directly to the affected area. 
3. The best trick is to add the gel into a surgical glove and have the patient wear it for at least 30 minutes.

Don't expect your gel to look like one you could sell for profit. I'm a pharmacist with training in compounding and it still comes out pretty ugly (especially with Tums^®).

Other routes of calcium administration for topical burns include intradermal, intravenous, and intraarterial. An IV Bier block technique using 25 mL of 2.5% calcium gluconate has also showed some success.

Disposition

All patients with digital exposures should be observed over 4-6 hours. The pain usually recurs and you may need to reapply the gel (or maybe even try an alternative therapy). Make sure your patient has good discharge instructions and has access to specialized followup and wound care.



References

Anderson WJ, Anderson JR. Hydrofluoric acid burns of the hand: mechanism of injury and treatment. J Hand Surg. 1988;13:52-7. [PMID: 3351229]

Chick LR, Borah G. Calcium carbonate gel therapy for hydrofluoric acid burns of the hand. Plastic Reconstr Surg. 1990;86:935-9. [PMID: 2236319]

Bracken WM, Cuppage F, McLaury RL, et al. Comparative effectiveness of topical treatments for hydrofluoric acid burns. J Occup Med. 1985;27:733-9. [PMID: 4067676]

Upfal M, Doyle C. Medical management of hydrofluoric acid exposure. J Occup Med. 1990;32:726-31. [PMID: 2401930]

Burkhart KK, Brent J, Kirk MA, et al. Comparison of topical magnesium and calcium treatment for dermal hydrofluoric acid burns. Ann Emerg Med. 1994;24:9-13. [PMID: 8010555]

Kirkpatrick JJ, Burd DAR. An algorithmic approach to the treatment of hydrofluoric acid burns. Burns. 1995;21:495-9. [PMID: 8540974]

Su M. Chapter 105. Hydrofluoric Acid and Fluorides. In: Su M, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011.

Peeing into the wind? Urine drug screens, part 2 (opiates)

Apart from benzodiazepines, the opiate urine drug screen (UDS) is probably the most frequently utilized and misunderstood.

BACKGROUND
For a brief history of the UDS and a review of the test for benzodiazepines, check out part 1 of our two-part series.

OBJECTIVE
To properly interpret the UDS for opiates.

First, a couple of prerequisites... 

1) Opiate vs. Opioid

• These two terms are often used interchangeably and really shouldn't be.
• Think of it like this: 'Opioid' is the broad category name while 'opiate' simply refers to the naturally occurring opioids. The term 'opioid' encompasses opiates, semi-synthetic, and synthetic agents. The chart below gives a few examples of each.

2) Forgive me in advance for the structures, but I think it's important to understand why a drug may or may not show up on the UDS. I can't get rid of the chemist in me... 

• The point here isn't to analyze structures, but simply to see the similarities between morphine, heroin, and oxycodone. 
• Oxycodone, a semi-synthetic, is similar to morphine.
• Methadone, a synthetic, has a completely unrelated structure.

LEARNING POINTS

1. Notice the name of the UDS next time you order one. It is opiates (not opioids).
2. The test was designed to look for heroin (technically a semi-synthetic) via its metabolite, 6-monacetyl morphine. It also picks up morphine and codeine.
3. The test does not specifically look for oxycodone, hydromorphone, hydrocodone, etc. They can trigger a positive result due to their structural similarities, but not in every case. Therefore, a negative result doesn't rule out use of these common drugs of abuse.
4. Synthetics will never cross-react with the opiate UDS. They are too structurally dissimilar. That's why we have a separate test for methadone.

BOTTOM LINE
A negative result doesn't rule out opioid ingestion and a positive result only guarantees that heroin, morphine, or codeine is present. Like the benzo screen... not very helpful, in my humble opinion.

Peeing into the wind? Urine drug screens, part 1 (benzodiazepines)

Let’s be honest.

When was the last time results from the urine drug screen (UDS) changed your management plan?

Many times it takes hours for the patient to give the urine sample anyway. And, with all of the false positives out there, how do we know what the heck the result is actually telling us?

OBJECTIVE 
Today’s post will help you properly interpret the UDS, particularly focusing benzodiazepines.

Introduction:
The original UDS was termed the NIDA-5 (amphetamines, cannabinoids, cocaine, opiates, and phencyclidine) because they are the five drugs that were recommended by the National Institute on Drug Abuse (NIDA) for drug screening of federal employees back in the late 1980s. Drug-screening immunoassays are also frequently done for barbiturates and benzodiazepines and less frequently for methadone.

That has to raise some caution flags right off the bat! This test was not designed for Emergency Departments or hospitals for that matter. It was developed to screen federal employees. The fact that we have made it part of our standard practice affords various limitations.

In general, the qualitative UDS for each drug is looking for a particular structure. If the immunoassay identifies that structure (or one similar), it will trigger the test positive. Let's take a closer look at the test for benzos.

Benzodiazepines:
Benzodiazepines are pretty popular. In the U.S., alprazolam, clonazepam, lorazepam, and diazepam are among the most commonly prescribed medications in the outpatient setting. Here are the important points regarding this test:

1. Most benzo screens look for oxazepam. If you're wondering how this could possibly be helpful since few patients are on oxazepam, you're not alone. However, diazepam and chlordiazepoxide both are metabolized to oxazepam. So, by looking for oxazepam, you actually pick up three benzos in one.
2. The test does not specifically look for alprazolam, clonazepam, lorazepam (or many others). Therefore, a negative result does not necessarily rule out use of these agents.
3. The tricky part is that benzos vary in reactivity and potency and can trigger a positive result due to cross-reactivity.

BOTTOM LINE
A negative result doesn't rule out benzodiazepine ingestion and a positive result only guarantees that oxazepam, diazepam, or chlordiazepoxide is present. Not very helpful, in my humble opinion.

Next time we'll fully explore the opiate screen. Stay tuned...

Busting the myth: The 10% cephalosporin-penicillin cross-reactivity risk

To give or not to give a cephalosporin in penicillin-allergic patients?

I remember back to my days in pharmacy school when I learned that there was approximately a 10% risk of cross-reactivity, if a cephalosporin was given to a penicillin-allergic patient. They probably said something about the risk being less with 3rd and 4th generations cephalosporins, but lets be honest... who remembers anything but that magic 10%? When I started working more with physicians, I found that they also learned the same 10% rule in medical school. Well, I guess that means it’s fact, right? Not so fast!

It turns out that prior to 1980, penicillins and cephaloporins were often produced using the same fungus and the chance for contamination during the manufacturing process was high. The belief was that the beta-lactam ring similarities must be the cause. How wrong we were.

More recent studies have determined that the actual risk of cross-reactivity relates more to a side chain similarity and probably not the beta-lactam ring at all. Therefore it makes sense that if a penicillin and a cephalosporin share that particular (R-1) side-chain similarity, the risk of cross-reactivity is increased. Such is the case with amoxicillin or ampicillin with:

• 1st generation cephalosporins: cefadroxil, cefatrizine, cephalexin, cephradine
• 2nd generation cephalosporins: cefaclor, cefprozil

A new review article of 27 articles on this very topic just came out reporting:

• Overall cross-reactivity rate between cephalosporins and penicillins in patients reporting a penicillin allergy = 1%. 
• Overall cross-reactivity rate in patients with a confirmed penicillin allergy = 2.5%. 

Other key findings to note:

1. The true incidence of an allergy to penicillin in patients believed to have such allergy is <10% (it’s like we have a built in 10-fold safety factor).
2. Cross-reactivity between penicillins and MOST 1st and 2nd generation cephalosporins is negligible.
3. Cross-reactivity between penicillins and ALL 3rd and 4th generation cephalosporins is negligible.
4. If a patient has an allergy to amoxicillin or ampicillin, avoid cefadroxil, cefaclor, cefatrizine, cefprozil, cephalexin, and cephradine.

Bottom Line:

You can feel comfortable clicking past the flashing allergy alert as you enter that ceftriaxone order in your patient with a documented penicillin allergy. If the patient has an allergic reaction, it's more likely a unique allergy to that cephalosporin than any cross-reactivity with a penicillin.

References:
Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: A literature review. J Emerg Med. 2012;42(5):612-20. Pubmed . 

Welcome to the blog team: Bryan Hayes, PharmD

Bryan Hayes, PharmD, DABAT

Have you been read Bryan Hayes' mind-blowing pearls in the world of ED pharmacology and toxicology on Twitter (@PharmERToxGuy)? If not, you are missing out. I usually end up hitting "favorite" for all of his tweets to review again later. So for purely selfish reasons, I asked Bryan to see if he'd be willing to expand his 140 character gems on this blog. Much to my delight, he said yes!

On a quick web search, I think Bryan may be the first ED clinical pharmacist ever to have a meducation blog!

Here is a little blurb bio about Bryan:

• Clinical Assistant Professor, University of Maryland (UM) Schools of Pharmacy and Medicine
• Clinical Pharmacy Specialist, EM & Toxicology, UM Medical Center

After finishing my Pharm.D. degree (2005) and PGY-1 pharmacy practice residency (2006) in Worcester  MA, I moved down to Baltimore MD to complete a two-year Clinical Toxicology Fellowship (2008) at University of Maryland. I then joined the University of Maryland Medical Center's team as its first emergency medicine clinical pharmacist. I hold dual Clinical Assistant Professor appointments with the University of Maryland Schools of Medicine and Pharmacy and is board-certified in Clinical Toxicology. I hope to add a unique pharmacy/toxicology perspective on EM-related matters to this outstanding blog team.