Hospital Pharmacy - February 2020 - 59

Harmon et al
aureus (MRSA), and vancomycin-resistant Enterococcus
(VRE) in patients with recorded penicillin allergies, as shown
by a retrospective cohort study comparing patients with or
without penicillin allergies on file.6 Differences among
groups were potentially due to the propensity for penicillin
allergic patients to receive fluoroquinolones, vancomycin,
and clindamycin.
The use of more expensive, broad-spectrum agents in
patients with reported penicillin allergies is a cost burden to
patients and institutions. An 861-bed tertiary care hospital
estimated an annual savings of US $82,000 through incorporation of PST to guide antibiotic choices for 146 patients
tested.7
This study was performed to assess the feasibility and
potential benefits to be obtained by incorporating PST into
antimicrobial stewardship practices in a 120-bed community
hospital. The primary objective was to determine the amount
of penicillin allergies clarified using PST. Secondary objectives included the number of patients whose therapy was deescalated after a negative skin test and quantifying patient
charges related to antimicrobial therapy before and after
PST. Some current PST protocols exclude patients who have
recent exposure to medications with antihistamine properties; however, our study did not exclude these patients to
observe the effect antihistamines would have on PST, and
our protocol included a positive control to assess histamine
response.

Methods
The study was performed in a 120-bed community hospital.
In May 2017, a protocol allowing pharmacists and pharmacy residents to provide PST was approved by the
Pharmacy and Therapeutics committee. In August 2017,
administrative processes were completed. These processes
included the approval of a consent form for the procedure,
acquisition of the supplies, and the development of an order
set and procedure chart note within the electronic medical
record. Pharmacists were trained by an allergist, and testing
began in September 2017. The study was approved by the
hospital ethics committee.
Patients were prospectively identified between September
2017 and May 2018 to receive PST based on identification
via a clinical decision support software alert. This alert would
flag any patients admitted as an inpatient who had a reported
penicillin allergy regardless of severity who were receiving a
nonoptimal antibiotic regimen. Patients who provided written informed consent and who met all qualifications received
the skin test, results were documented in the electronic medical record (EMR), and allergy profiles were updated as necessary. Patients were eligible for inclusion if they were
admitted to inpatient status and had a recorded penicillin
allergy on profile, including rash, hives, anaphylaxis, or
unknown. Patients were excluded if they had a history of
extreme non-IgE hypersensitivity to penicillins, such as

59
Stevens-Johnson syndrome, toxic epidermal necrolysis, or
mucocutaneous eruption with epidermal detachment.
Pregnant patients and pediatric patients less than 18 years of
age were excluded. Patient selection is summarized in Figure
1. One notable difference in this study compared with other
PST protocols is the lack of exclusion for the use of antihistamines. One aim of this study was to observe the effects of
antihistamines on the ability of the patients to produce a histamine response, which is required to proceed with testing.
Baseline patient data collected included recorded allergy,
reaction type, and age at which the reaction was experienced.
Current antimicrobial therapy and indication for use were
noted. Other data included the preferred antibiotic for the
indicated infection and whether recommendations to change
therapy after PST were accepted. Optimal therapy was determined by adherence to empiric treatment pathways approved
by the hospital's antimicrobial stewardship team. The treatment pathways were developed based on the Infectious
Diseases Society of America guidelines, local susceptibility
data, and taking into account patient-specific factors including, but not limited to, organ function and drug interactions.
We prioritized screening for PST on patients who were
receiving nonoptimal antibiotics which included meropenem, ertapenem, daptomycin, linezolid, or any other deviation from standard of care. Use of medications with
antihistamine properties was recorded to assess how this
affected the histamine response in these patients. Medications
with antihistamine properties considered in this study
included diphenhydramine, trazodone, amitriptyline, famotidine, loratadine, and ranitidine.
Skin testing was performed using a 3-step protocol. Step 1
involved a skin prick test using benzylpenicilloyl polylysine
and a compounded penicillin G dilution 10 000 U/mL as the
test solutions, saline as the negative control, and histamine as
the positive control. A negative result was indicated by an
induration of ≥5 mm at the histamine (ALK-Abello Pharm
Inc., Horsholm, Demark) site, with an induration of <3 mm at
the saline, benzylpenicilloyl polylysine (AllerQuest,
Plaineville, Connecticut, USA), and penicillin G (Pfizer, New
York, USA) sites. If negative, the patient proceeded to step 2.
A positive result on step 1 was indicated by an induration of
≥3 mm at the site of testing for benzylpenicilloyl polylysine
or penicillin G, and the patient would not move on. An indeterminate test was indicated by an induration of ≥3 mm at the
saline site or an induration of <3 mm at the histamine site.
Patients with an indeterminate test did not proceed. Step 2
involved intradermal testing using benzylpenicilloyl polylysine and penicillin G dilution, as well as saline for a negative
control. A negative result was indicated by a <3 mm difference between the saline and the antigens. If negative, the
patient proceeded to step 3. A positive result was indicated by
an induration ≥3 mm difference between the saline and either
antigen, and the patient would not move on. Step 3 was a challenge dose of oral amoxicillin 250 mg or intravenous ampicillin if the patient could not tolerate oral administration. A set of

Hospital Pharmacy - February 2020

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