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Effects of Interventions for Delabeling Penicillin Allergy in Hospitalized Patients: A Systematic Review
Filip Z Jovčić1, Miloš N Milosavljević2, Milena Cmiljanić3
1Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Background And Objective:
Penicillin allergy labels are common among hospitalized patients, yet most represent inaccurate or nonimmune-mediated reactions and may contribute to suboptimal antibiotic prescribing. This systematic review aimed to evaluate the effectiveness and safety of hospital-based penicillin allergy delabeling interventions and their impact on antibiotic prescribing.
Methods:
PubMed/MEDLINE, CENTRAL, Scopus, and Web of Science were systematically searched up to January 2026. Additional records were identified through ClinicalTrials.gov and citation tracking. Eligible studies included hospitalized patients with documented penicillin or β-lactam allergy labels who underwent structured delabeling interventions with a comparator group. Given substantial heterogeneity in study design, interventions, and outcomes, findings were synthesized narratively.
Results:
Nine studies were included (three randomized controlled trials and six nonrandomized studies). Delabeling success rates ranged from approximately 4% to over 95%, depending on intervention approach, risk of bias, and local workflows. The greatest success was observed in interventions using direct oral challenge for patients at low risk of true penicillin allergy. Pharmacist-led and antimicrobial stewardship-based interventions also effectively identified inaccurate allergy labels and supported safe delabeling. Adverse events were uncommon and predominantly mild. Delabeling was associated with improved prescribing practices, including greater use of narrow-spectrum β-lactams.
Conclusions:
Hospital-based penicillin allergy delabeling interventions appear safe and locally effective when implemented within structured clinical pathways. However, the current evidence base is structurally fragmented, and extreme clinical and methodological heterogeneity limits the formulation of universal hospital protocols. Standardized, multi-center randomized controlled trials are urgently needed to establish uniform risk stratification algorithms and outcome metrics.
Prospero Registration Number:
CRD420251246346.
