β-lactam antibiotics are the most widely used drugs in the treatment of infectious diseases due to their efficacy, spectrum of activity, and safety. Their prescription can be limited by bacterial resistance and the appearance of adverse reactions, among which hypersensitivity is of special relevance. Penicillin allergy is the most commonly reported type of drug allergy.1

About 10% of patients report a history of allergy; however, it is estimated that less than 1% of the population is actually allergic. According to the American Academy of Allergy, Asthma, and Immunology, 80% of patients with IgE antibody-mediated penicillin allergy lose sensitivity after 10 years.2

Of note, the rate of cross-reactivity between penicillins and cephalosporins is less than 1%.3

Nevertheless, β-lactam therapy is often completely avoided in patients with no real allergies or with mild reactions.

Of greater relevance are IgE-mediated allergic reactions (type I allergic reactions), which usually occur within the first hour of drug administration. Symptoms include urticaria, angioedema, shortness of breath, wheezing, and anaphylaxis. Other severe reactions, which are not IgE-mediated (late allergic reactions, type II, III, and IV), include Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hemolytic anemia, acute serum sickness, or drug sensitivity syndrome with eosinophilia and systemic symptoms (DRESS).

The unwarranted avoidance of β-lactam antibiotics is of concern in several respects: it may lead to the use of potentially less effective antibiotics (e.g. vancomycin is less effective than cloxacillin against methicillin-sensitive Staphylococcus aureus), and it may promote the use of agents with a broader spectrum of activity and a higher likelihood of resistance development, potentially leading to an increased risk of toxicity (e.g. the selection of Clostridioides difficile, [CD] and methicillin-resistant S. aureus). Furthermore, poorly characterized allergies are associated with delays in the first administration of antibiotic therapy, higher rates of rehospitalization and prolonged hospitalizations, an increased risk of surgical site infection, increased adverse reactions, mortality, and higher associated costs.4

Antibiotic resistance is a worldwide public health problem. It has been estimated that in the United States, 2.8 million infections are caused by resistant bacteria every year resulting in over 35 000 deaths.5 It has also been estimated that in the European Union, 670 000 infections are caused by resistant bacteria each year resulting in 33 000 deaths.6

The inappropriate use of antibiotics has been found to be the most relevant modifiable risk factor for resistance development. Therefore, the promotion of the appropriate use of antibiotics in all clinical settings is essential, and the pharmacists' role is integral to achieving this goal. Antimicrobial Stewardship Programs (AMSP) comprise a set of strategies that promote the appropriate use of antibiotics. These strategies attempt to optimize the effectiveness of antibiotics, minimize adverse events and toxicities associated with their use, limit the development of resistant bacteria, and reduce unnecessary costs associated with the excessive and inappropriate use of antibiotics.7–10

Pharmaceutical organizations such as the American Society of Health-System Pharmacists (ASHP) and the Society of Infectious Diseases Pharmacists (SIDP) have published guidelines on the role of pharmacists in AMSPs in hospital and outpatient settings, respectively.11–13

Currently, establishing protocols for managing suspected β-lactam allergies is a high priority for hospital infection control groups; however, despite their multidisciplinary profile, the role of pharmacists remains underdeveloped in these groups.

The main objective of this review was to analyze the role played by clinical pharmacists and its impact on AMSPs in the setting of suspected allergy to β-lactam antibiotics.

In total, 35 studies were identified that met the search criteria. After applying the inclusion and exclusion criteria, 12 studies were finally selected. Fig. 1 shows the study selection process.

Fig. 1.

Selection of studies.

(0,38MB).

A number of studies were excluded on the following grounds: 8, because they did not include pharmacist participation; 4, because they only analyzed differences in the pattern of antibiotic prescription; 3, because they only analyzed costs; 1, because it was not written in Spanish, Portuguese, or English; and 7, because the complete texts could not be located.

Of the included studies, 11 were quasi-experimental studies and 1 was an observational study.

Table 1 shows the results of the studies.

Establishing protocols for managing suspected β-lactam allergies is one of the main priorities for hospital infection control groups. Several recent publications have analyzed the efficacy, safety, and cost-effectiveness of such measures.24–26

Clinical pharmacists are members of these groups and, together with the rest of the team, are fully involved in this activity; however, there are few published reports of such activity being led by these professionals.

In our review, the main pharmaceutical interventions were structured interviews (telephone or face-to-face) with patients with suspected allergy, skin tests, and oral challenge tests under surveillance, direct de-labeling of patients considered non-allergic after confirmation of the clinical history, and referral to immuno-allergology specialists for further specific tests.

After analyzing the results of studies reviewed, we found that they offer a certain degree of guidance or recommendations on the best course of action to take in patients with suspected allergies. However, they are not decisive or of sufficient scientific robustness to decide whether pharmacists are appropriate healthcare staff to provide leadership in this role.

Despite the lack of conclusive results, pharmacists have increasing presence and visibility in infection control groups, which is a situation endorsed by both international and national regulations. For example, in Portugal, the regulation Direçao geral de Saude (DGS) of September 202228 requires the implementation of such groups in both public and private hospitals with the aim of promoting activity related to AMSPs and reducing the risk of antimicrobial resistance. It is mandatory that such groups include at least 1 pharmacy specialist.

In light of the results, simple measures such as computer tools or patient questionnaires to clarify histories of allergic reactions29 can be used to de-label “low-risk” patients and refer them to immuno-allergologists, thus improving the use of penicillins and reducing the need for second-line antibiotics. This approach is likely to reduce the risk of iatrogenic and multidrug-resistant infections, and reduce healthcare costs.

However, there is no consensus on clinical decision rules for de-labeling and classifying “false” allergies as intolerances. Furthermore, many of these decision rules, such as Pen-Fast,29 are not specifically validated for use by healthcare staff other than physicians.

Although previous studies have reported pharmacists conducting oral penicillin challenge and desensitization skin tests, these are very specific cases in that the pharmacists received specialized training by immuno-allergologists. However, no details on such training are provided regarding the objectives, duration, or competencies to be acquired.15–18,21,23,30,31 Furthermore, the highly heterogeneous nature of the health and policy frameworks in which these studies were conducted makes it difficult to extrapolate such training into the daily practice of hospital pharmacists.

In the case of Spain and Portugal, this activity is conducted by immuno-allergologists.

In addition, of the 12 studies reviewed, only 7 refer to safety variables and the outcomes are not defined. However, the number of adverse effects reported was low and those reported were considered to be mild.

This review offers detailed and current information from published studies, specifically focussing on the role of well-trained clinical pharmacists. It assesses how this role impacts patients with suspected or reported β-lactam allergies, particularly in terms of directly de-labeling or referring patients to immuno-allergology specialists.

The latest scientific evidence suggests that involving pharmacists in the evaluation of patients suspected of having β-lactam allergies is effective, safe, and applicable in clinical practice. Standardized protocols to clarify allergy histories and evaluation tools, such as structured questionnaires, would provide a straightforward screening method for de-labeling or referral to an immunology/allergy service in specific situations. Thus, patients with false allergies could be de-labeled and first-line antibiotics could be used safely. In addition, there would be a decrease in the consumption of alternative antibiotics, which carry a higher risk of the resistance development.

However, these potential benefits are based on highly heterogeneous studies employing low-quality methodology. Randomized clinical trials with sound methodology are needed to provide higher quality results based on the available evidence.

Specific training in this area would enable pharmacists to provide added value and broaden the range of competencies within our specialization, both in Portugal and Spain. This aspect represents a future challenge for the pharmaceutical profession.

None declared.

Jesus Cotrina Luque, Maria José Rei, and Miriam Capoulas contributed to the conceptualization, design, definition of the intellectual content, preparation, review, and editing of the manuscript, and assume responsibility of the work.

Jesus Cotrina Luque and Maria José Rei contributed to the literature search and data collection and analysis.