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Joseph Brayson, Scott Barrett, Wasim Baqir, David Campbell, Tamsin Oswald, Simon Ellis, Nikhil Premchand, CATALYST: challenging antibiotic allergy status, Journal of Antimicrobial Chemotherapy, Volume 78, Issue 5, May 2023, Pages 1241–1244, https://doi.org/10.1093/jac/dkad081
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Abstract
To develop a transferable process, CATALYST (challenging antibiotic allergystatus), to assess and challenge penicillin allergy status of inpatients within an NHS Foundation Hospital.
A multidisciplinary team (MDT) steering group reviewed existing literature and protocols enabling penicillin allergy assessment, challenge and de-labelling. Using this, they identified five key steps forming the basis of CATALYST: clinical assessment of the nature of allergy; inclusion/exclusion criteria; consent; direct oral penicillin challenge; and removal of allergy label. A pharmacist-led pilot was conducted to assess the process, during which a continuous PDSA (plan-do-study-act) cycle was observed. This included formally auditing endpoint data such as accuracy of allergy status in medical records post-intervention.
CATALYST was successfully developed with key resources produced to support clinicians. It was piloted in 304 patients, with 172 patients excluded and 132 successful allergy challenges. There was one incident of an adverse event (acute kidney injury) in the 132 successful patients, which occurred as a delayed reaction following 22 days of penicillin therapy. Only 64% of permanent records (held by GP) were appropriately updated when audited at the end of the pilot.
CATALYST is a transferable process to facilitate safe assessment, challenge and removal of spurious penicillin allergy labels. Handover between care sectors forms a key element of allergy removal to ensure all records are updated and work is needed to ensure this process is done effectively.
Background
The current reported penicillin allergy rate within UK hospitals is between 10% and 20%; however, around 90% of these patients do not have a true penicillin allergy.1
A penicillin allergy label can result in inappropriate antimicrobial therapy,2 increase the risk of healthcare-associated infections,3 contribute to the acceleration of antimicrobial resistance4 and is associated with worse clinical outcomes.5 As such, assessing and removing incorrect penicillin-allergy labels has been shown to be a clinically beneficial, cost-effective intervention for patient care.6,7
Penicillin-allergy challenging refers to exposing potentially penicillin-allergic patients to penicillin to test the veracity of their allergy label. This has traditionally been conducted in immunology clinics with skin-prick tests followed by systemic challenges, but there is mounting evidence8,9 that low-risk patients can be safely and effectively4 challenged through other methodology, e.g. direct oral penicillin challenge (DOPC).
There exists a precedent for DOPC processes globally, including significant progress in Australia.10–12 There has also been some progress within the UK including tools and resources developed by the Scottish Antimicrobial Prescribing Group (SAPG).13 This work has been led by varied members of the multidisciplinary team (MDT; including medical doctors, pharmacists and nurses) with good success rates;10,14 however, there has been limited adoption across the NHS thus far.
More recently, the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) released guidance setting out parameters for secondary care organizations to develop internal processes, such as CATALYST (challenging antibiotic allergystatus), to safely undertake DOPC.15
There is a sparsity of evidence addressing why dubious penicillin allergies remain a largely unanswered problem within the UK and robust education and detailed protocols and processes are needed to help assuage clinician hesitancy.
Methodology
Our primary aim was to develop a transferable process (CATALYST) to assess and challenge penicillin allergy status of inpatients within an NHS Foundation Hospital.
A steering group including antimicrobial pharmacists and infectious disease and microbiology consultants screened literature databases (PubMed®, Embase®, MEDLINE®) using keywords and Boolean logic, reviewed existing practice and provided expert opinion with a view to formulate clinical guidance and supporting documents. No national guidance/consensus was in existence at the time.
A needs assessment was undertaken internally to identify any organization-specific barriers and establish what from existing literature was translatable to local practice and what novel material needed to be developed.
Five key areas were identified with protocols/documents developed for each area: (i) clinical assessment of nature of allergy; (ii) inclusion/exclusion criteria; (iii) consent; (iv) DOPC; and (v) removal of allergy label. Firstly, a clinical allergy assessment was developed to allow a clinician to establish the nature of the allergy, which could then be risk-stratified using existing tools, primarily PEN-FAST.14
Next, inclusion/exclusion criteria were agreed, (Table 1) including specific clinical signs that would exclude a patient on the grounds of potential high-risk reaction. These criteria were decided according to existing protocols, e.g. SAPG,15 as well as expert opinion of the steering group. A patient information leaflet (PIL) was produced to support informed, written consent.
Inclusion and exclusion criteria decided by the steering group to determine patient eligibility for CATALYST
| Inclusion . | Exclusion . |
|---|---|
| Age ≥ 18 years Labelled as penicillin allergic Currently on or requiring antibiotic therapy Capacity/ability to consent (e.g. no cognitive impairment) Inpatient | Regular antihistamine Regular immunosuppressant medication, including but not limited to: systemic anticancer treatments (SACT); disease-modifying anti-rheumatoid drugs (DMARDS); biologics Taking corticosteroids at any dose (excluding topical and low-dose inhaled, e.g. beclomethasone 1000 μg/day or fluticasone 500 μg/day or equivalent). Note: must be 24 h clear of stat doses of corticosteroids, e.g. intra-operatively Receiving inotropic support Planning pregnancy or currently pregnant or breastfeeding History of poorly controlled asthma Clinical signs of severe allergy:
|
| Inclusion . | Exclusion . |
|---|---|
| Age ≥ 18 years Labelled as penicillin allergic Currently on or requiring antibiotic therapy Capacity/ability to consent (e.g. no cognitive impairment) Inpatient | Regular antihistamine Regular immunosuppressant medication, including but not limited to: systemic anticancer treatments (SACT); disease-modifying anti-rheumatoid drugs (DMARDS); biologics Taking corticosteroids at any dose (excluding topical and low-dose inhaled, e.g. beclomethasone 1000 μg/day or fluticasone 500 μg/day or equivalent). Note: must be 24 h clear of stat doses of corticosteroids, e.g. intra-operatively Receiving inotropic support Planning pregnancy or currently pregnant or breastfeeding History of poorly controlled asthma Clinical signs of severe allergy:
|
Inclusion and exclusion criteria decided by the steering group to determine patient eligibility for CATALYST
| Inclusion . | Exclusion . |
|---|---|
| Age ≥ 18 years Labelled as penicillin allergic Currently on or requiring antibiotic therapy Capacity/ability to consent (e.g. no cognitive impairment) Inpatient | Regular antihistamine Regular immunosuppressant medication, including but not limited to: systemic anticancer treatments (SACT); disease-modifying anti-rheumatoid drugs (DMARDS); biologics Taking corticosteroids at any dose (excluding topical and low-dose inhaled, e.g. beclomethasone 1000 μg/day or fluticasone 500 μg/day or equivalent). Note: must be 24 h clear of stat doses of corticosteroids, e.g. intra-operatively Receiving inotropic support Planning pregnancy or currently pregnant or breastfeeding History of poorly controlled asthma Clinical signs of severe allergy:
|
| Inclusion . | Exclusion . |
|---|---|
| Age ≥ 18 years Labelled as penicillin allergic Currently on or requiring antibiotic therapy Capacity/ability to consent (e.g. no cognitive impairment) Inpatient | Regular antihistamine Regular immunosuppressant medication, including but not limited to: systemic anticancer treatments (SACT); disease-modifying anti-rheumatoid drugs (DMARDS); biologics Taking corticosteroids at any dose (excluding topical and low-dose inhaled, e.g. beclomethasone 1000 μg/day or fluticasone 500 μg/day or equivalent). Note: must be 24 h clear of stat doses of corticosteroids, e.g. intra-operatively Receiving inotropic support Planning pregnancy or currently pregnant or breastfeeding History of poorly controlled asthma Clinical signs of severe allergy:
|
The DOPC protocol was agreed as follows; staff trained in advance life support (ALS), resuscitation equipment and intensive care facilities were available at all stages: (1) assess patient and get consent; (2) complete baseline observations (blood pressure, heart rate, oxygen saturations); (3) administer a single, oral dose of amoxicillin 500 mg; (4) observe for 30 min; and (5) after 30 min, repeat the observations in Step 2.
‘Rules’ were built within the electronic prescribing system (MedChart®) to co-prescribe supportive medication for the management of an allergic reaction. All ward staff were informed of a proposed DOPC and were involved in the process. Patients were advised to self-monitor for adverse reactions occurring beyond the 30 min observation period and report any delayed-onset side-effects immediately. The outcome of each CATALYST assessment was recorded in hospital medical records and information would be sent to the patient’s GP.
Once established, the process was piloted by a team of 12 senior clinical pharmacist at a single acute care hospital across two surgical and six medical wards between 1 May 2021 and 28 February 2022. Patients were identified for the pilot using daily, digital reporting on all patients admitted in the previous 24 h with a penicillin allergy; all patients identified in the search were included for screening. All pharmacists involved were ‘independent prescribers’ (registered pharmacists in the UK with additional endorsements allowing them to prescribe medication without supervision from another healthcare professional).
All-cause adverse events associated with penicillin therapy were recorded during the pilot, independently assessed by the patient’s clinical team and a member of the pilot steering group and graded 1–5 (1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; and 5 = death). Medical records were audited 1–3 months post-CATALYST intervention to ensure allergy labels were being appropriately updated.
Results
A penicillin-allergy assessment and challenge process (CATALYST) was successfully developed, with three key documents forming the ‘backbone’.
Firstly, a risk stratification tool (Data S1, available as Supplementary data at JAC Online) to allow clinical assessment of a reported penicillin allergy. ‘Level-1’ incorporates symptoms in keeping with an intolerance or side effect of penicillin that has been misreported as an allergy. This is the lowest-risk group and with appropriate education and consent the clinician could often remove or modify the penicillin-allergy label appropriately without the need for a DOPC. ‘Level-2’ represents an historic and/or ambiguous reported reaction that is not clearly classifiable as an intolerance but conveys a low pre-test probability of a true, severe allergy. ‘Level-3’ indicates clinical signs of a true, severe allergy to penicillin and would exclude a patient from the process, as per the exclusion criteria. Secondly a PIL (Data S2) was developed to condense available literature and expert opinion into accessible language. Lastly, a combined questionnaire and consent process (Data S3) was developed for clinician and patient to complete together, ensuring a standardized approach and robust consent process.
CATALYST was piloted in 304 patients. Fifty-seven percent of patients (n = 172) were excluded based on the criteria in Table 1. The remaining 43% (n = 132) successfully had their penicillin allergy label removed (‘de-labelled’).
Of the successful patients, 55% (n = 73) fell into ‘Level-2’ of the risk assessment and received a penicillin challenge, whilst the other 45% (n = 59) fell into ‘Level-1’ and had their allergy removed from their record without a need for a penicillin challenge (‘direct de-label’).
The all-cause adverse event rate was 0.76% (n = 1); this was an acute kidney injury (possible interstitial nephritis) (grade 3) occurring after 22 days of penicillin therapy. The patient did not have a history of renal impairment. No other allergic symptoms (e.g. rash/eosinophilia) were observed.
The auditing of medical records following CATALYST intervention revealed only 52% of permanent medical records (held by the GP) were correct 1–3 months following intervention by the pilot team. This increased to 64% by the end of the pilot following co-development of handover with the GP practice via electronic discharge summary (EDS).
Discussion
We have demonstrated CATALYST is a safe method of challenging spurious penicillin allergies in an inpatient setting and, with the toolkits developed, could be transferred to similar healthcare organizations. We acknowledge the limitations of the development of CATALYST, particularly the small sample size used in the pilot and the single-centre nature. It would have also been preferable to include an allergist in the initial MDT steering group, which was not possible at the time. Future developments will include a collaborative approach, including allergists, across other organizations to further test and refine CATALYST.
The high proportion of patients being risk-stratified to ‘Level-1’ indicates the potential success of a multisector approach incorporating primary and secondary care. Work is ongoing to explore this as an extension of CATALYST.
The high exclusion rate (57%) is an expected outcome due to largely unprecedented nature of this type of work within the NHS. The steering group intentionally made the inclusion/exclusion criteria restrictive to ensure maximal safety and minimal impact on antimicrobial stewardship. CATALYST could be expanded to include patients likely to need antibiotics in the near future (e.g. surgical prophylaxis, high-risk groups, e.g. bronchiectasis).
There are variations between CATALYST and the now-published BSACI guidance, including optional use of a graded DOPC and fewer exclusion criteria in BSACI, particularly relating to concurrent medications, e.g. immunosuppressants, prednisolone. These were included in CATALYST as potential modulators of an allergy response; these will be reviewed in line with the new guidance and will also confer a decreased exclusion rate.
All pharmacists utilizing CATALYST were non-allergists/infection specialists and fed back that the process was intuitive and self-explanatory. CATALYST could be transferred to other organizations with suitably qualified healthcare professionals. All staff involved fed back positively on the process.
Following the midpoint, post-intervention audit, compliance was improved by engaging with primary care stakeholders who fed back that EDSs were often received by non-medical administrators and explicit ‘requests/actions’ would be more likely to be followed than stating clinical information under ‘allergies’, which was often missed. Further work is needed to avoid erroneous ‘relabelling’ of previously removed allergies.
Patient testimonials indicate CATALYST to be a positive care intervention. Formal collation of patient experience data on CATALYST is ongoing and will form a crucial element of future service development.
Acknowledgements
Special thanks to the medical director and senior clinicians at Northumbria Healthcare NHS Foundation Trust for their support of this project and to the pharmacy, medical and nursing teams for engaging in the scoping exercises and to the pharmacy team for their subsequent hard work in piloting the process.
We also acknowledge the work of other centres that supported the set-up of our own work, including the work by the Scottish Antimicrobial Prescribing Group (SAPG) and the work in Australia led by J. Trubiano.
Funding
All work has been undertaken as part of routine work within the organization.
Transparency declarations
None to declare.
Supplementary data
Data S1–S3 are available as Supplementary data at JAC Online.
