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. Author manuscript; available in PMC: 2020 Jul 1.
Published in final edited form as: Ann Allergy Asthma Immunol. 2019 Apr 19;123(1):16–34. doi: 10.1016/j.anai.2019.04.009

Table 3.

Penicillin skin testing-based beta-lactam allergy pathways in acute care settings

Study Location Setting Patient Selection Study Design Intervention Description Outcome(s) measured
Harris (1999)41 Boston, MA, US Academic medical center Penicillin allergy patients identified from pharmacy searching

  • Allergy history excluding anaphylaxis, serum sickness, erythema multiforme, or toxic epidermal necrolysis

  • ABX regimen might change if PST were negative

  • Patient not on antihistamines >72 hours

  • Current ABX course considered >24 hours

 Prospective PST study

  1. PST on eligible patients

  2. Creation of ABX treatment guidelines to standardize treatment created.

  3. A note containing suggested ABX regimen with a BL ABX was left for patients with PST negative and also recommendations called to responding clinician

 PST outcome 100 reviewed: 56 excluded
44 skin tested: 38 (86%) negative; 3 (7%) positive; 3(7%) indeterminate
BL use BL used in 36% of screened and 82% of enrolled patients Cephalosporins (15), penicillin (7), penicillin and cephalosporin (1)
Alternative ABX use 46 days of vancomycin use avoided; Vancomycin (n=11), fluoroquinolone (n=12), clindamycin (n=10) were stopped
Cost Cost savings of ABX regimens was $103 per patient
Arroliga(2000)42 Cleveland, OH, US Academic medical center Intensive care unit adult patients with penicillin allergy Prospective PST study PST performed by AI consultation PST outcome 24 enrolled: 3 not tested because of IgE histories
21 skin tested: 20(95%) negative; 1 (5%) indeterminate
BL use 10 of 21 (48%) were treated with a penicillin ABX
Alternative ABX use Prior ABXs: Ciprofloxacin (n=5), clindamycin (n=2), imipenem (n=2), and erythromycin (n=1)
Safety No BL ADRs
Forrest (2001)43 Vancouver, Canada Academic medical center Infection with positive culture susceptible to penicillin, or cellulitis, in patients with penicillin allergy history Pre/Post (64 pre patients/95 post patients) Skin testing guideline PST by AI consultation Guideline disseminated as posters and pocket cards to housestaff Number of allergy evaluations Increase in skin testing from 17% pre to 64% post in eligible patients (p<0.001)
PST outcome 61 skin tested in post-period: 58 (95%) negative; 3 (5%) positive
BL use 54 of 58 (93%) skin test negative patients switched to treatment with penicillin
Cost No significant difference between actual costs and projected cost of alternative ABX
Arroliga (2003)44 Cleveland, OH, US Academic medical center Intensive care unit adult patients with penicillin allergy Prospective PST study PST performed by AI consultation PST outcome 100 enrolled: 4 not tested (serum sickness (n=2), patient refusal (n=2))
96 skin tested: 85 (89%) negative; 1 (1%) positive; 10 (10%) indeterminate
BL use 31 of 38 (82%) received a BL (38 of the 96 patients were initially receiving therapeutic ABXs)
Alternative ABX use Prior ABXs: 73 patients (73%) received vancomycin, 27 patients (27%) received quinolones, 11 patients (11%) received a third-generation cephalosporin, and 6 patients (6%) received ABXs such as clindamycin or metronidazole
Safety No adverse events related to either PST or BL administration
Macy (2004)36 San Diego, CA, US Community hospital General medical and surgical patients hospitalized with a penicillin allergy history Nested case-cohort (compares convenience sample of PST inpatients to age and sex-matched controls) PST performed by allergy registered nurse PST outcome 8.7% of penicillin-allergic inpatients tested
141 skin tested: 133 (94%) negative; 8 (6%) positive
BL use PST patients more frequently had more penicillins (17% vs 7%) and cephalosporins (59% vs 48%)
Alternative ABX use Vancomycin use low overall and nonsignificantly lower in cases than controls (19 cases/24 courses vs 29 controls/39 courses)
Safety No adverse reactions associated with skin testing
ADRs: 0.7% tested vs 1.4% controls
Tested patient ADR was to macrolide (not BL)
Wall (2004)37 West Des Moines, IA, US Academic medical center

  • Adult inpatients with penicillin allergy history

  • Not pregnant and not severely immunosuppressed

  • Allergy to penicillin not a type I reaction to penicillin during the preceding five years or confirmed history of a type II-IV reaction to penicillin

  • Ordering physician feels the information provided from PST would be beneficial

  • Skin adequate for testing

 Prospective PST evaluation ID physician ordered PST, which was performed by allergist-trained pharmacists. Challenge performed for indeterminate tests

BL use at discretion of physician with full dose.		 PST outcome 26 enrolled: 3 patients did not receive PST due to mild initial ADR but were switched to a penicillin or BL

23 skin tested: 22 (96%) negative; 1 (4%) indeterminate

23 of 23 not allergic after challenge
BL use All 26 patients enrolled in the skin testing service received a penicillin or BL
Alternative ABX use An average of 48 doses of vancomycin and 12 doses of levofloxacin per patient were avoided
Safety No reactions occurred
Rimawi (2013)39 Greenville, NC, US Community teaching hospital

  • Medical, surgical, labor and delivery wards, intensive care units, and emergency department identified from ASP database

  • Patients with allergy histories that were unknown, non IgE, or recent anaphylaxis excluded

  • Patients on medication interfering with testing excluded

  • Patient skin conditions interfering with testing excluded

 Prospective PST evaluation PST by ID trainee PST outcome 482 considered and 146 skin tested
145 (99%) negative; 1(1%) positive
BL use 145 of 146 (99%) switched to BL treatment without an adverse reaction
Alternative ABX use Prior to intervention: 31 patients received aztreonam, 26 received ciprofloxacin, 14 received vancomycin, 14 received clindamycin, 12 received a combination of ciprofloxacin and clindamycin, 12 received linezolid, 12 received moxifloxacin, 6 received tobramycin, 4 received doxycycline, 3 received daptomycin, 3 received trimethoprim/sulfamethoxazole, 1 received gentamycin, and 1 received a combination of ciprofloxacin and tobramycin
Safety No adverse reactions to BLs
Cost Cost savings of $225/patient. Projected annual savings of $82,000
Ward (2015)45 London, United Kingdom Academic medical center Patients with infective endocarditis and penicillin allergy history PST outcome 16 patients skin tested: 16 (100%) negative
BL use 14 of 16 patients (88%) had first-line BL use: flucloxacillin (7), amoxicillin (3), benzyl penicillin (3) and ceftriaxone (1)
Alternative ABX use Prior to intervention: vancomycin (13), gentamycin (5), meropenem (2), fusidic acid (1), rifampicin (1)
Safety 1 patient (7%) developed BL rash
King (2016)46 Summit, NJ, US Community teaching hospital

  • Hospitalized medical and surgical patients with BL allergy

  • Patients on a high-cost, broad-spectrum agents (aztreonam, tigecycline, daptomycin, linezolid)

  • Pharmacist screening

  • Discussion with attending +/− ID or AI consultation

 Retrospective analysis of PST patients PST by hospital-affiliated allergist by AI consultation. If negative, multi-step graded amoxicillin challenge. PST outcome 50 PST: 50 (100%) negative
49 (98%) patients tolerated amoxicillin challenge
BL use 37 patients (76%) switched to a BL
Alternative ABX use Reduction in the number of patients on a non-BL due to historical BL allergy
Safety 1 patient has anaphylactic reaction
Cost Patients switched to a BL after PST led to savings of $11,005 or $297 per patient
Heil (2016)38 Baltimore, MD, US Academic medical center Patients selected from:

  • ASP ABX/chart reviews, ID consult service, primary team consult.

  • Exclusion criteria: anaphylaxis 5 or fewer years ago, tolerated desired abx in past, non type I HSR, taking antihistamines

 Prospective observational study PST by ID trainee Number of allergy evaluations Year prior PST service, 21 patients received PST compared to 76 PST in 11 months after established PST service
PST outcome 90 assessed, 76 skin tested
64 (84% ) negative; 3(4%) positive; 9 (12%) indeterminate
BL use 54 of 64 (84%) negative patients had ABX changes
55% changed to penicillin, 40% to cephalosporin, and 5% to carbapenem
ABX appropriateness 63% narrower spectrum ABXs; 80% more effective therapy
Safety No serious adverse effects; 3 patients had a benign delayed rash to BLs after tolerating challenge
Cost 61% less costly therapy. Cost savings of $26,000 per year
Chen (2017)40 Dallas, TX, US Academic medical center Adult inpatients with penicillin allergy screened by pharmacist with a prioritization schema. Patients excluded if on antihistamines and then prioritized by: no discharge order, on ABX, on carbapenem or monobactam, comorbidities of HIV/malignancy/diabetes mellitus Prospective identification through Epic Hyperspace daily report of patients with active penicillin allergy In person evaluation by pharmacist who did history-appropriate PST PST outcome 252 evaluated, 247 skin tested performed, 228 completed testing: 223 negative
BL use 77 of the 223 patients with negative tests (34%) switched to a penicillin or cephalosporin, 8 patients (3.6%) were discharged with BL treatment
Alternative ABX use After testing, decrease in active orders for vancomycin, clindamycin, fluoroquinolones, carbapenems, and aztreonam
Allergy documentation 228 of 252 (91%) had their allergy removed.
Blumenthal and Wickner(2017)34 Boston, MA, US Academic medical center In period with PST, PST offered to all adult medicine inpatients on therapeutic ABX with a penicillin allergy history Pre/post analysis adjusted for period differences PST by moonlighting allergy trainees PST outcome Of 278, 179 eligible and 43 tested
Testing not completed for reasons including: coordination (58), patient refusal (28), team refusal (21), other (29)43 of 43 (100%) negative
BL use Unadjusted BL use increased from 50% to 60% in skin tested patients (0.30) Adjusted inpatient BL use in skin tested patients increased 570% (adjusted OR 5.7 [95% CI 2.6 to 12.5) Adjusted discharge BL use in skin tested patients increased 250% (adjusted OR 2.5 (95% CI 1.04 to 6.2])
Safety There were no adverse events
Leis (2017)20 Toronto, Canada 3 community hospitals In period with PST, PST offered when BL allergy history interfered with prescribing of the preferred BL.
PST exclusions also included:
Severe non-IgE reaction, IgE reaction in last 3 months, discharge anticipated within 24 hours, or patient declined.		 Pre/post analysis PST offered M-F by ASP pharmacist at the instruction of an ID physician

Negative tests included BL challenge with 4-hour observation. Intervention included EHR update and letter to patients.		 PST outcome 386 patients in intervention periods: 232 (60%) received preferred BL therapy and 154 were PST eligible.
Of 154 PST eligible, 64 (42%) were excluded and 90 (58%) had PST
90 PST: 85 (94%) negative; 1 (1%) positive; 4 (4%) nondiagnostic
BL use 92% with negative PST were switched to BL
The number of days of penicillin use tripled (11% to 32%, p<0.0002).
Alternative ABX use Carbapenem and fluoroquinolone use decreased more than half (28% vs 13%, p<0.0002)
ABX appropriateness Overall BL 50% pre-period vs 81% PST post-period
Safety Frequency of ADRs: 4% pre-period and 3% post-period (p=0.40)
Jones (2017)47 Savannah, GA, US Community health system Stewardship pharmacist evaluates patients for PST considering allergy history and medication exclusions Pharmacy screened patients with self-reported PCN allergy. PST initiative promoted by pharmacists with allergist oversight. PST performed by nurses and ASP pharmacist PST outcome 36 skin tested: 36 (100%) negative
BL use 27 of 36 patients (75%) changed to a penicillin or cephalosporin, the most common change was a switch from carbapenem (with or without vancomycin) to a penicillin or cephalosporin (n=12).
Alternative ABX use Carbapenem to BL change occurred in 12 patients
Safety No reactions to BL
Cost Average cost savings per patient was approximately $314, summing to $7554.
Chen (2018)48 Dallas, TX, US Academic medical center Inpatients with penicillin allergy on aztreonam received clinical decision support tool

Patients with histories of severe cutaneous adverse reactions, recent anaphylaxis within 4 weeks, and severe cardiac or pulmonary comorbidities excluded		 Pre/Post (250 pre-period and 91 pos-period) A clinical decision support tool that encourages providers to order PST

Orders reviewed by allergy-trained pharmacist who performed history-appropriate PST and oral challenge

Pre-period was active surveillance		 Number of allergy evaluations Penicillin allergy patients receiving aztreonam who received PST increased (24% to 85%, p<0.001)

Patients not tested for reasons including: antihistamine use (19), discharge before evaluation (14), altered mental status (11), cardiopulmonary instability (4), provider cancellation (5), and patient refusal (3)
PST outcome Of 77 consults placed, 58 were seen and 21 PST performed
21 skin tested: 21 (100%) negative
BL use Penicillins increased from 0.32 to 0.71 (p=0.046) administrations per patient-day 58% increased penicillin exposure (p=.046)
Alternative ABX use Aztreonam use declined 2.54 to 1.47 administrations per 1000 patient-days (p=0.016)
Cost 53% savings post-period compared to pre-period ($1266 pre and $592 post)
Allergy documentation 21 of 21 negative tests had allergy removed

Abbreviations: ABX, antibiotics; PST, penicillin skin test; BL, beta-lactam; AI, allergy/immunology; ADR, adverse drug reaction; ID, infectious diseases; HSR, hypersensitivity reaction; ASP, antibiotic stewardship program