Inaccurate penicillin allergy labels are like a plague upon modern medicine, often forcing providers to unnecessarily select second or third line agents. Luckily, penicillin skin testing exists as a means for differentiating true versus false penicillin allergy labels. Here an infectious diseases pharmacist and academician discusses penicillin skin testing as an antimicrobial stewardship tool.
Authored By: Christopher Bland, Pharm.D., BCPS, FIDSA & Bruce M. Jones, Pharm.D., BCPS
We all know the frustration: Wanting to utilize a beta-lactam when a patient has a self-reported allergy.
Approximately 10% of the population in the United States carries a listed allergy to penicillin, which makes this problem a daily event for many practitioners, both outpatient and inpatient [1]. This results in limited treatment options, increased healthcare costs, and increased resistance with the use of other broad-spectrum agents. Up to 90% of patients reporting hypersensitivity do not truly have a penicillin allergy, making a thorough allergy history from the patient a priority. Unfortunately these type I, or IgE-mediated, reactions cannot be diagnosed by history alone due to the fact that the allergy can “wane” or lose its sensitivity over time. If the patient reports an IgE-mediated reaction or the patient does not recall the reaction, then penicillin skin testing (PST) might be an option.
Pharmacists are in a unique position to help facilitate penicillin skin testing at many institutions – both as outpatients and inpatients; however, many want to begin skin testing as an antimicrobial stewardship initiative but are unsure how to carry it out practically.
The purpose of this article is to highlight clinical pearls for evaluating a patient for a penicillin allergy as well as give some practical tips for implementing a skin testing protocol [2]. We give these pearls based on our experience of testing over 200 patients in the inpatient and outpatient setting at St. Joseph’s/Candler Health System, a community health system in Savannah, GA.
Question #1 – Why is penicillin skin testing worth it?
There are many clinical indications where beta-lactam therapy is clinically superior or preferred. Some examples include surgical prophylaxis, infections due to methicillin-susceptible Staphylococcus aureus (MSSA), severe infectious due to Pseudomonas aeruginosa, and several sexually transmitted infections, most notably syphilis.
The longitudinal financial implications of “carrying” a penicillin allergy have been well demonstrated with increased hospital length of stay and increased usage of broader spectrum antimicrobials such as fluoroquinolones and carbapenems. Removing the allergy via penicillin skin testing can not only benefit the patient for that acute episode, but also for the rest of their lives with subsequent episodes where antimicrobials may be prescribed.
Question #2 – What approach is best for structuring the testing process?
This is probably the most common question we receive from pharmacists attempting to begin penicillin skin testing at their facilities. There are a number of successful models for penicillin skin testing that have been published [3,4]. Pharmacists, physicians, infectious diseases fellows, nursing, or a mix of any of the above have demonstrated successful programs. While allergists are a great resource for providing skin testing, their availability is very limited at most facilities.
Each facility should perform an “inventory” of resources available for the penicillin skin testing process and decide which model works best for them. This is generally the greatest rate limiting step in the entire process.
Question #3 – Who should be tested?
Most patients are appropriate for testing. The key point is that a detailed screening evaluation of any patient with a listed allergy to penicillin is a great stewardship initiative, regardless of availability of penicillin skin testing.
A detailed patient interview to ascertain their history of allergy should be undertaken, asking:
- Is this really an “allergy”?
Several problems exist when identifying a drug allergy. First, defining the difference between an adverse drug reaction and a true allergy can be confusing, especially for a patient. Another issue in identifying drug allergies is assigning blame. Many times patients receive multiple drugs, especially if they are inpatients at a hospital. If a patient were to develop hives after initiating therapy, antimicrobials are often an easy option to point blame. Many times patients are not re-challenged on suspected medications and they then carry the suspected allergy with them for the rest of their lives.
Along the same lines of identifying the culprit in a drug allergy is the lack of reliable diagnostic procedures and in vitro assays to detect true allergy. In vitro assays carry a high specificity, but a low sensitivity specific to penicillin. This means a negative in vitro test will not adequately exclude a penicillin allergy. Using an immediate hypersensitivity skin test to detect IgE-mediated penicillin allergies is the preferred method [1].
- Have they received penicillins in the past?
While it is simple to perform a detailed medication history, we frequently encounter penicillin “allergic” patients who have received penicillins after documentation of their “allergy.” This would eliminate the need for skin testing for that particular patient. This was demonstrated recently with aztreonam when investigators showed that often their penicillin allergy was erroneous thus leading to discontinuation of aztreonam therapy [5].
- Who is not a candidate?
Any patient with a history or serious cutaneous reaction such as Drug reaction with eosinophilia and systemic symptoms (DRESS), Toxic epidermal necrolysis (TEN), and Stevens-Johnson Syndrome (SJS). Also, any patient that reports a reaction of hepatitis, interstitial nephritis, or hemolytic anemia would not be a candidate. From our experience we have excluded the following patients as well:
- History of anaphylaxis to beta-lactam agents within the last 10 year (note: some centers exclude anaphylaxis only up to 5 years)
- Anaphylaxis due to any cause within the 4 weeks prior to inpatient status
- History of severe skin reaction associated with the use of beta-lactam agents
- Skin condition that could interfere with accurate reading of test results
- Patients unable to be treated effectively for anaphylaxis
- Patients who are severely immunocompromised (HIV/AIDS with absolute CD4 count less than or equal to 200 cells/mm3, cystic fibrosis, etc.)
If a decision is made to skin test, are they receiving anything that would affect results (i.e. antihistamines)? Current receipt of antihistamines may decrease the potential effectiveness of skin testing. We recommend holding antihistamines for 48-72 hours prior to testing.
Question #4 – What are some potential roadblocks with testing?
Most of the issues with testing patients for penicillin allergies can be avoided with a strong plan up front to address the following issues:
A. Ownership
B. Training
C. Time Commitment
A. Ownership
From our experience, having a central person take ownership of the process is crucial in the program succeeding. Adding the penicillin skin testing medication to formulary and developing system protocols to guide the process is much easier to accomplish with a single person tasked with the duty. As questions come up with testing and new information becomes available, there will then be an expert at the institution.
B. Training
Physicians, pharmacists, nursing personnel, and any other interested parties should be trained on the process of the test. If the decision is made to adopt penicillin skin testing, the company is available to come on site for a comprehensive training. Once a person is trained and credentialed to perform the test, they are then able to train others in the health system.
Deciding who will perform the test is also important to identify at this stage. If an allergist is on staff at your particular institution and is willing to participate, they would be an ideal candidate. Other facilities have used physicians in residency training or an infectious diseases fellow. Pharmacists can be an option depending on individual state law. Our institution is a community-based health system without allergists, medical residents, or fellows, so our decision was made to have a nursing driven process with clinical pharmacist involvement. At our facility, the antimicrobial stewardship pharmacist (ASP) evaluates all patients prescribed PST for exclusions for use and any medications that would interfere with conducting the test. The test is then performed by a registered nurse per a developed protocol for administration under the oversight of the ASP pharmacist. The protocol includes specific documentation of the results and interpretation of the test. By having the ASP pharmacist present, there is a 2nd evaluation of the patient and a consistent member to the process. The ASP pharmacist is then responsible for updating patient allergies in the electronic medical record and contacting prescribing physician for changes in antimicrobial therapy.
C. Time Commitment
Testing an individual usually consists of ~40 minutes, with only 10 minutes of that timeframe being true hands-on time. What has to also be taken into account is time to evaluate the patient through interview, profile the order set and prepare the product, and then follow-up after the procedure.
If a patient has a positive reaction they are counseled and the allergy is updated in the electronic medical record to reflect testing. If the skin test is negative, the patient is counseled that they need to inform other providers that they are no longer allergic, the allergy is removed from their medical record, and the ordering physician is contacted for a change in therapy, if needed.
Another issue is controlling volume of tests ordered. At our facility, we decided to restrict prescribing to infectious disease physicians and antimicrobial stewardship pharmacist recommendation.
Question #5 – What are potential pitfalls after a negative penicillin skin test?
Patients are often relieved after their penicillin skin test comes back negative. However, in order for them not to be labeled penicillin allergic, certain tasks should be performed so that they are not “relabeled” as penicillin allergic.
First, the medical record at the testing institution should immediately document the lack of penicillin allergy. Instead of deleting the allergy, we have found that entering a “place holder” allergy with details of the negative penicillin skin test has been more successful in preventing relabeling of the patient with the allergy.
Second, the patient and family members should be educated that all providers that may prescribe antibiotics to the patient should be informed of their skin testing which demonstrated a lack of penicillin allergy. This includes their primary care provider, any specialist, dentist, etc.
Third, patients often will present to different healthcare facilities where allergy records may differ. Again the patient will have to educate their providers of the negative penicillin skin tests. We are attempting in our city to develop a citywide databank for all negative penicillin skin test patients to be shared with the stewardship pharmacists/physicians to prevent this occurrence but this is definitely a work in progress.
Final thoughts
I hope by the end of the article you are excited to begin penicillin skin testing!
While there are a number of factors to work through before beginning the process, the benefits are incredible from a stewardship perspective. Think about this…how many stewardship initiatives can you perform that will not only benefit that patient at that moment, but for the rest of their lives? This is what makes penicillin skin testing such a powerful intervention. By providing PST to patients with self-reported penicillin allergy after appropriate screening, there is great potential to reduce the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within the health system both in the inpatient as well as outpatient setting in the vast majority of patients with a self-reported penicillin allergy.
References
- Solensky R, Khan DA, et al. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010; 105:259-73.
- National Action Plan for Combating Antibiotic-Resistant Bacteria. March 2015. Available: https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed 21st March 2017.
- Heil EL, Bork JT, Schmalzle SA, et al. Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service. Open Forum Infect Dis. 2016;23:ofw155.
- Jones BM, Bland CM, Penicillin skin testing as an antimicrobial stewardship initiative. Am J Health Syst Pharm. 2017;74:232-37.
- Estep PM, Ferreira JA, Dupree LH et al. Impact of an antimicrobial stewardship initiative to evaluate beta-lactam allergy in patients ordered aztreonam. Am J Health Syst Pharm. 2016;73(5 Suppl 1):S8-S13.
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