Table 4.

Comprehensive beta-lactam allergy pathways in acute care

Study	Location	Setting	Patient Selection	Study Design	Type of Intervention	Outcome(s) measured
Blumenthal (2015)30	Boston, MA, US	Academic medical center	All patients with penicillin or cephalosporin allergy histories needing ABX were eligible	Pre/Post (49 pre patients/183 post patients)	Comprehensive guideline (Figure 1): History, skin testing, test doses. Guideline uses challenge doses (“test doses”) some with prior PST and guides AI and ID consultations. PST by AI consultation Guideline distributed as pocket cards/posters/and accessed with hospital guidelines	Number of allergy evaluations	Increase in number of BL test doses in postperiod (183 post-period vs 49 pre-period)
						Alternative ABX use	Guideline-driven test doses significantly decreased vancomycin (68% vs 37%), aztreonam (12% vs <1%) aminoglycosides (6% vs 1%) and fluoroquinolones (15% vs 3%) in test dose patients
						Safety	ADRs frequency/severity in post-period were no different from pre-period (where allergy consulted on all patients getting test doses) Pre-period 6% vs post-period 4%, p=0.44
Blumenthal (2016)6	Boston, MA, US	Academic medical center	All patients with methicillin-sensitive Staphylococcus aureus bacteremia	Pre/Post (464 patients)	Comprehensive guideline Blumenthal 201528	ABX appropriateness	Methicillin-sensitive Staphylococcus aureus bacteremia patients reporting PCN allergy increased first-line ABX from 41% preperiod to 88% post-period (p = 0.02)
Blumenthal and Wickner(2017)34	Boston, MA, US	Academic medical center	Internal medicine patients with penicillin allergy histories ordered for therapeutic ABX	Pre/Post adjusting for period differences (148 patients in pre-period and 199 patients in post-period)	Comprehensive guideline from Blumenthal 201528 supported electronically with mobile-friendly website (“app”)	BL use	Increased adjusted odds of penicillin or cephalosporin use overall in eligible patients overall 1.8 [95 % CI 1.1 to 2.9]
						Safety	No serious ADRs; one patient developed erythema and pruritus
Blumenthal (2017)33	Boston area, MA, US	Large healthcare system comprised of 2 academic and 3 community sites	All patients with penicillin or cephalosporin allergy histories on ABX were eligible	Implementation methods study	Comprehensive guideline from Blumenthal 201528 supported electronically with mobile-friendly website (“app”) and computerized support including best practice alert and order set	Cost	Total projected annual cost savings with complete implementation across 5 hospitals: $8.9 million-13.7 million
Lambl (2018, abstract only)35	Salem, MA, US	Community teaching hospital	Medical or surgical patients with penicillin or cephalosporin allergy histories Excluded anaphylaxis and type II-HSR	Retrospective cohort (336 patients who received BL test doses)	Comprehensive guideline from Blumenthal 201528 supported electronically with mobile-friendly website (“app”) and computerized support including best practice alert and order set	Alternative ABX use	Decreased aztreonam use by85% and vancomycin use by 77%
						BL use	Penicillins increased 42% and cephalosporins increased by 79%
						ABX appropriateness	308/321 (96%) had narrowing of ABX
						Safety	No major ADRs/HSRs, but 7 reactions: rash (4), throat irritation (1), urticaria (1), wheezing (1)
						Cost	Pharmacy cost savings of $38,281 ($630 per patient)
Ramsey (2018)49	Rochester , NY, US	Community hospital	Adult inpatients on parenteral vancomycin, daptomycin, aztreonam, moxifloxacin, linezolid generated a pharmacy report Review by ID pharmacist looking for those with penicillin allergy with priority for those where BL would be first-line based on culture data or planned empiric course for 7 or more days	Prospective PST evaluation	Penicillin Allergy History Algorithm (PAHA, Figure 2) on selected patients for history taking, then AI consultation and PST based on this result	PST outcomes	64 approached: 50 skin tested Not tested included 9 for possible SCAR and 5 declined 50 skin tested: 47 (94%) negative; 2 (4%) positive; 1 (2%) not interpretable
						BL use	28 (56%) of skin test negative patients transitioned to PCN ABXs, 13 (26%) to first- or second-generation cephalosporins, 12 (24%) to a third- or fourth-generation, 2 (4%) to carbapenem, and 7 (14%) received a combination of these ABXs
						Alternative ABX use	Prior to PST, ABXs were: vancomycin 41 (82%), aztreonam 11 (22%), moxifloxacin 3 (6%), daptomycin 2 (4%), linezolid 1 (2%) 863 days of vancomycin were avoided
						ABX appropriateness	982 days of second-line ABX exposure averted
						Safety	No immediate ADRs or HSRs; 1 patient delayed rash; 1 patient neutropenia
						Cost	$70 per patient saved considering cost of ABXs
Sacco (2019)50	Jacksonville, FL, US	Community teaching hospital	General internal medicine patients with reported penicillin allergy	Pre/Post (42 pre-period patients and 57 post-period patients, with 8 patients receiving BL test doses in the post period)	Educational initiative and algorithm modified from Blumenthal 201528	Alternative ABX use	Vancomycin use decreased 14%
						BL use	Penicillin use increased 250% and cephalosporin use increased 120%
						Safety	One patient transient rash to ceftriaxone
						Hospital length of stay	Unchanged
						Allergy documentation	EHR penicillin allergy documentation improved from 5% to 65%
Blumenthal (2019)32	Boston area, MA, US	Large healthcare system comprised of 2 academic and 3 community sites	All patients with penicillin or cephalosporin allergy histories on ABX were eligible	Retrospective cohort (1,046 patients who received BL test doses)	Comprehensive guideline from Blumenthal 201528 supported electronically with mobile-friendly website (“app”) and computerized support including best practice alert and order set	BL use	1,046 BL test doses were performed: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems
						Safety	78 patients (7.5%; 95%CI 5.9% to 9.2%) had signs or symptoms of an ADR, with 40 (3.8%; 95% CI 2.8% to 5.2%) confirmed HSRs HSRs were rash (n=19), itching (n=6), hives (n=2), tingling (n=1), bronchospasm/wheezing (n=5), angioedema/swelling (n=4), hypotension/dizziness (n=3), anaphylaxis (n=1), severe cutaneous adverse reactions (n=1) and acute interstitial nephritis (n=1) 3 HSR patients (8%) were treated with intramuscular epinephrine for anaphylaxis
Staicu (2018)51	Rochester, NY, US	Community medical center	Penicillin-allergic adult inpatients on antibiotics; patients on high risk ABX (fluoroquinolones, clindamycin, vancomycin) and those on second-line therapy were prioritized.	Prospective observational study of 338 ST eligible inpatients	Pharmacist used Penicillin Allergy History Algorithm (PAHA, Figure 2). If PST was indicated, allergy/immunology physician assistant performed testing followed by synchronous allergy/immunology telemedicine consultation	Number of allergy evaluations	Of 338 screened, 50 were tested (15%)
						Alternative ABX use	Reduction in use of vancomycin, metronidazole, aztreonam, aminoglycosides, and clindamycin
						BL use	Of 46 PST negative patients, 33 (72%) were transitioned to a BL
						Safety	No adverse reactions immediately or reported through follow up phone calls
						Cost	About $350 per patient saved considering ABX cost PST performance by physician assistant rather than allergist saved about $7,600

Abbreviations: ABX, ABXs; PST = Penicillin Skin Test; AI., allergy/immunology; BL, BL ABXs; ABX=ABX(s); DOT=days of therapy; ADR=adverse drug reaction, AAL=ABX allergy label, HSR= hypersensitivity reaction