View as “PDF version”
Patient Safety Tip
of the Week
July 21, 2020
Is This Patient Allergic to
Penicillin?
We haven’t given much attention to the issue of
penicillin allergy in our patient safety columns. Penicillin, of course, is one
of our oldest antibiotics and has been widely used since the 1950’s. Its
analogs and second and third generation cousins have been used to treat
millions of infections as well as serving as prophylactic agents to prevent
infection in surgery and other procedures. In patients who cannot receive penicillins we often have to resort to other antibiotics,
leading to antibiotic resistance to those other antibiotics. In addition, use
of many of those other antibiotics may lead to unwanted consequences such as C.
diff infection. So, good antibiotic stewardship needs to focus not just on
antibiotic use, per se, but also on how the issue of penicillin allergy might
be impacting antibiotic use.
We have discussed problems with the electronic health record (EHR) that may
either lead to inappropriate administration of a penicillin in a patient who is
allergic to it, or in the opposite direction, avoiding penicillins
in a patient who is not really allergic to them. Our January 2013 What's New in
the Patient Safety World column “More IT Unintended Consequences” gave an example of a patient who was
allergic to penicillin developing anaphylaxis after being given ampicillin. The
information about the allergy had been entered into part of the EHR that was
not linked to the allergy portion of the pharmacy computer system that would
have triggered an alert if the allergy had been recognized. On the other hand,
our July 2020 What's New in the Patient Safety World column “Patient Requests for EHR Corrections” noted a scenario where your own electronic
health record (EHR) says you are allergic to penicillin buy you are not, in
fact, allergic to penicillin. Yet, you might at some time in the future be
denied appropriate use of penicillins or other
antibiotics cross-reacting with penicillin.
So, why is it so important to know whether
your patient has a true penicillin allergy? Probably the best example is the
patient about to undergo surgery. A study published in Clinical Infectious Disease
looked at surgical site infections (SSI’s) in over 9000 surgical procedures and
found that patients giving a history of penicillin allergy had 50% increased
odds of SSI (Blumenthal
2018). Reason: they received second-line perioperative
antibiotics. They were administered less cefazolin (12% vs 92%) and more clindamycin
(49% vs 3%), vancomycin (35% vs 3%), and gentamicin (24% vs 3%) compared with
those without a reported penicillin allergy. The authors conclude that clarification
of penicillin allergies as part of routine preoperative care may decrease SSI
risk.
Some hospitals now
include penicillin allergy tesitng as
part of their preoperative patient optimization. In our April 7, 2020 Patient
Safety Tip of the Week “From Preoperative Assessment to Preoperative
Optimization” Aronson
and colleagues (Aronson
2020)
detailed how they established a comprehensive preoperative assessment and
management program to optimize patients for surgery at Duke University Hospital
and School of Medicine. Their multidisciplinary group implemented a
Preoperative Anesthesia and Surgical Screening (PASS) Clinic to screen patients
and to more proactively and efficiently manage modifiable
risks at the time a patient’s surgical candidacy is first considered.
One of their specific optimization programs was a preoperative penicillin
allergy testing clinic,
Interestingly, Kimberly
Blumenthal, M.D., author of the study noted previously, says “But just because
you were told you had a penicillin allergy, or had one in the past, does not
mean you have one now. People with a penicillin allergy history have their
allergy disproved with allergy testing more than 90% of the time.” (Blumenthal 2019). So, confirming or ruling out a penicillin
allergy through allergy testing could justify the risk, or potentially avert it
by allowing use of beta-lactams. The first step is skin testing for penicillin allergy.
Anyone with a positive skin test to penicillin — usually itching, redness, and
swelling at the site of the skin prick — is allergic and should avoid
penicillin. People who have no reaction to the skin test can then safely
undergo the amoxicillin challenge. In that test, the allergist gives the person
amoxicillin and observes signs and symptoms for at least one hour. This is done
under medical supervision.
In a recent AORN
Journal interview, it was noted that beta lactams, the group of antibiotics related
to penicillin, are the most widely used antibiotics to prevent surgical site
infections (Sunshine 2020). The author interviews Valeria Fabre, MD,
associate medical director of the Antimicrobial Stewardship Program and at The
Johns Hopkins Hospital. Dr. Fabre begins by noting the statistic from the
Blumenthal study mentioned above. She goes on to note that most people who have
a penicillin allergy label are actually not allergic
and that, with an appropriate protocol in place, these patients can safely receive
that beta-lactam antibiotic at the time of surgery. Sometimes, intolerance of
an antibiotic may be erroneously labelled and allergy. For example, isolated
diarrhea or headache after an antibiotic more likely represents intolerance and
not a true allergy.
- What
was the reaction?
- How
did it look (if a rash)?
- When
did it happen (i.e. at what age)?
- How
soon after the antibiotic was given?
- What
other antibiotics has the patient had since the reaction?”
She notes what we are
most concerned about is the risk of anaphylaxis in a patient with a true
penicillin allergy. This needs to be differentiated from a previous reaction
that is actually
at low risk for
anaphylaxis. She gives a great example regarding a rash occurring after
administration of a penicillin. She notes that the most common reaction to
penicillin or penicillin-related antibiotics is a skin rash that appears
usually after two or three days of taking the antibiotic. It’s
a diffuse rash that may appear over several areas of the body, feels rough to
touch, and is usually red. It’s called a delayed rash
and, though it can be very impressive, it is a benign rash. If the patient takes
the same antibiotic, it may not happen again. That’s not
a rash that will transform into anaphylaxis. It’s very
important to distinguish that type of delayed rash from an immediate reaction,
which usually occurs within a couple of hours after antibiotic administration.
This type of rash is hives and can be associated with anaphylaxis. She again
emphasizes that after 10 years, 8 out of 10 patients who had a true penicillin
allergy will overcome that allergy. Most people think or fear that if they had
an allergy it’s a lifelong situation—and that’s not
the case.
Fabre states that, if the patient is having
an elective surgery, there’s time to assess the patient and determine if the
patient can have the recommended beta-lactam for surgical prophylaxis.
She further notes that understanding responses
to previous antibiotics may also be helpful. For example, if a patient is
allergic to penicillin, there is a 95% chance of being allergic to amoxicillin
too. Why? Because those two antibiotics are very similar.
But a patient allergic to penicillin is highly unlikely to have a reaction to a
third-or a fourth-generation cephalosporin. Knowing that a patient tolerated a cephalosporin
in the past can be very helpful.
Fabre notes that Johns Hopkins has an antimicrobial
stewardship toolkit that includes a section on
penicillin allergy:
There are, of course,
costs and delays associated with the need for penicillin allergy testing prior
to surgery. Recently, Australian researchers developed a clinical decision
rule to identify low-risk penicillin allergies that potentially do not
require penicillin skin testing by a specialist (Trubiano 2020). They looked at 622 patients who had been
allergy-tested to derive the clinical decision rule. Patients who reported a
penicillin allergy underwent penicillin allergy testing using skin prick,
intradermal, or patch testing and/or oral challenge (direct or after skin
testing). The 4 features associated with a positive penicillin allergy test
result on multivariable analysis were summarized in the mnemonic “PEN-FAST”:
penicillin allergy five or fewer years ago, anaphylaxis or angioedema, severe
cutaneous adverse reaction (SCAR), and treatment required for allergy episode.
They assigned points for major and minor criteria: allergy event occurring 5 or
fewer years ago (2 points), anaphylaxis/angioedema or SCAR (2 points), and treatment
required for an allergy episode (1 point). For internal validation, a cutoff of
less than 3 points for PEN-FAST was chosen to classify a low risk of penicillin
allergy, for which only 17 of 460 patients (3.7%) had positive results of
allergy testing, with a negative predictive value of 96.3%. External validation
resulted in similar findings.
The authors conclude that PEN-FAST is a
simple rule that accurately identified low-risk penicillin allergies that do
not require formal allergy testing. The results suggest that a PEN-FAST score
of less than 3, associated with a high negative predictive value, could be used
by clinicians and antimicrobial stewardship programs to identify low-risk penicillin
allergies at the point of care.
Think
about the numbers here. For patients who have a “history” of penicillin
allergy, which accounts for about 10% of patients undergoing surgery, there is
a potential to reduce their risk of incurring a surgical site infection by up to
50% by doing penicillin allergy testing or assessment. There are very few
interventions we do that can reduce SSI risk by 50%! We’re
surprised more healthcare systems have not begun to incorporate formal
penicillin allergy programs into their preoperative assessment programs.
Of
course, it’s not just in the surgery patient for whom assessment
of the risk for penicillin allergy exists. There are many other infections where
treatment with penicillin or other beta-lactam antibiotic would be preferable to
other antibiotics.
This also
raises the question about how we use our EHR’s to document allergies. In some,
someone simply enters the name of a drug into an allergy field. Better EHR’s
would prompt for a description of what sort of reaction occurred to that drug.
And it reminds us that we need to ensure that such information gets updated in
any other IT systems that may not be fully interoperable. Each healthcare
organization or practice should also have protocols for who and how EHR data
for allergies can be amended so that an inappropriate designation of an allergy
does not get perpetuated.
Recent comprehensive reviews of penicillin
allergy have appeared in the New England Journal of Medicine (Castells
2020) and JAMA (Shenoy
2019).
The
Castells review concludes that, in contemporary clinical practice, more than 90%
of patients labeled as allergic to penicillin can safely receive the drug. They
note that, on average, 8 to 15% of unselected international patients are
labeled as allergic to penicillin, meaning that many patients labeled as
allergic to penicillin could safely receive it.
The Shenoy review notes that the goals of
antimicrobial stewardship are undermined when reported allergy to penicillin
leads to the use of broad-spectrum antibiotics that increase the risk for
antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus
aureus and vancomycin-resistant Enterococcus, or the risk of developing Clostridium
difficile infection. The authors suggest that direct amoxicillin challenge is
appropriate for patients with low-risk allergy histories and moderate-risk
patients can be evaluated with penicillin skin testing, which carries a
negative predictive value that exceeds 95% and approaches 100% when combined
with amoxicillin challenge.
References:
Blumenthal KG, Ryan EE, Li Y, et al. The
impact of a reported penicillin allergy on surgical site infection risk. Clin
Infect Dis 2018; 66(3): 329-336
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850334/
Aronson S, Murray S, Martin G, et al. Roadmap
for transforming preoperative assessment to preoperative optimization. Anesth Analg 2020; 130: 811-819
Blumenthal K. Do you really have a penicillin
allergy? Harvard Health Blog 2019; February 26, 2019
https://www.health.harvard.edu/blog/do-you-really-have-a-penicillin-allergy-2019022616017
Sunshine WL. Perioperative Antibiotics and
Infection Prevention: Demystifying Penicillin Allergies. AORN Journal 2020; 111(5):
491-493 First published: 28 April 2020
https://aornjournal.onlinelibrary.wiley.com/doi/10.10-2/aorn.13016
Trubiano JA, Vogrin S, Chua KYL, et al. Development and Validation of a
Penicillin Allergy Clinical Decision Rule. JAMA Intern Med 2020; Published
online March 16, 2020
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2762878
Johns Hopkins Medicine. Toolkit to Enhance
Nursing and Antibiotic Stewardship Partnership.
https://www.hopkinsmedicine.org/antimicrobial-stewardship/nursing-toolkit/index.html
Castells M, Khan DA, Phillips EJ, et al. Penicillin
Allergy. N Engl J Med 2019; 381: 2338-2351
https://www.nejm.org/doi/full/10.1056/NEJMra1807761
Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation
and management of penicillin allergy: a review. JAMA 2019; 321(2): 188-199
https://jamanetwork.com/journals/jama/article-abstract/2720732
Print “PDF version”
|
|
http://www.patientsafetysolutions.com/