Abstract
Beta-lactam (BL) antibiotic “allergy” labels are common, but often overdiagnosed. Although much research has been focused on the BL allergy and the delabelling process in the West, studies from other parts of the world remain sparse. This review outlines the contrasting global epidemiology, shifting clinical practices and disparities of BL allergy in the Asia-Pacific region compared with the West. Innovative strategies to overcome barriers in BL allergy workup are discussed and potential directions for future research and service development are also proposed.
Introduction
Antibiotics can result in a plethora of adverse drug reactions presenting as both immune-mediated (i.e., allergies) and non-immune mediated manifestations (i.e., intolerance) (1). Although most adverse reactions are non-immune mediated, they are frequently mislabelled as “allergies” and these labels often remain lifelong without further evaluation. Owing to their widespread use as first-line therapy for most infections, beta-lactam antibiotics (BL) remain as one of the leading culprits of drug “allergy” (2–4). However, most BL allergy labels are incorrect with only 5%–15% confirmed to be genuine after allergological evaluation (5, 6). Even among genuine BL allergic patients, sensitivities diminish over time and only around 10% of individuals remain sensitized after 10 years following avoidance (7, 8).
Among those labelled with BL allergy, the obligatory use of less effective and more harmful second-line antibiotics is associated with poorer clinical outcomes such as higher admission rates, in-hospital mortality, and risk of infection from multidrug resistant organisms (including Clostridioides difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus) (9–11). These adverse outcomes are especially accentuated among vulnerable and immunocompromised individuals, such as patients with underlying immunological diseases and the elderly (9, 11, 12). In the era of COVID-19, patients with BL allergy labels were shown to have higher rates of ICU admission, acute respiratory failure, need for mechanical ventilation and overall mortality (13, 14).
From a public health perspective, suboptimal therapy because of mislabelled BL allergy can be a waste of efficiency and healthcare resources. BL allergy labels are also associated with higher mean antibiotic costs, as well as higher cost during hospital admission and discharge, wherein lengthier hospital stays increase healthcare expenditure up to ten-fold (15). BL allergy delabelling has been shown to effectively reduce prescriptions of second-line antibiotics and promote re-uptake of first-line penicillins in delabelled patients (16–18). From Australian experience, antibiotic stewardship was enhanced with increased narrow-spectrum penicillin usage (19), with a low risk of anaphylaxis recurrence (20). Economically, delabelling has been shown to generate potential savings of $2000USD per patient-year and switching from other broad-spectrum antibiotics to BL has also been found to lower inpatient and outpatient prescription costs by up to $609USD and $193USD per patient respectively (15, 21). Studies on the Australian Penicillin Allergy Delabelling Program have also demonstrated cost-savings of $20.51 per effectively delabelled patients, even significantly reducing costs as compared to outpatient testing strategies (22).
Identifying genuine BL allergy, i.e., delabelling the mislabelled, is thus vital for healthcare optimization at both individual and institutional levels. However, existing practices on BL allergy and delabelling are widely substantiated based on inputs and experience from “the West”, which includes Europe, North America, Australia and New Zealand in this article, warranting attention to this predicament from an Asia-Pacific perspective.
Epidemiology: East vs. West
The prevalence of BL allergy varies across regions. Global estimates derived primarily from United States and European studies report an approximate 10% (8%–15%) prevalence within the general population (23, 24). The reported rate of BL allergy labels in hospitalized patients is even higher, ranging from 13%–25% (3, 4, 25–28). Within the BL group, penicillins accounts for most allergic reactions and the prevalence of penicillin allergy labels is often quoted as 8%–10% (3). For cephalosporins, an United States study reported a baseline prevalence of suspected cephalosporin allergy history of 0.9%, and a rate of new reports of cephalosporin allergy as 0.5% per treatment course (29). In comparison, allergies to carbapenem or monobactam are much rarer, with respective prevalences of only 0.007% and 0.001% (30).
Across Asia-Pacific countries (excluding Oceania unless otherwise specified, same hereafter), the regional prevalence of BL allergy labels in both the general population and hospitalized patients are generally lower although the disease burden is still considerable. Regional figures in hospitalized patients from mainland China, Hong Kong and Japan range from 4% to 5.6% (31–33). In Hong Kong, although the point prevalence of BL allergies was only 2% among the general population, population-wide data demonstrated a cumulative incidence of over 100 per 100,000 population (5).
Furthermore, there is a higher rate of documented allergic reactions to second-line broad-spectrum BL in Asia-Pacific. A study comparing patients referred for suspected BL allergies in Hong Kong and the United Kingdom found significantly more referrals in the Hong Kong cohort for suspected hypersensitivity to broad-spectrum antibiotics, including amoxicillin-clavulanate, piperacillin-tazobactam and meropenem (33). Recent studies also show a marked increase in reported allergies to piperacillin-tazobactam in Hong Kong, likely attributable to a more-than 150% increase in local prescription rates between 2015 and 2019 (34). Nonetheless, the pervasiveness of broad-spectrum antibiotic prescription and allergy labels are not unique to Hong Kong but also other Asia-Pacific territories. Piperacillin-tazobactam and cefoperazone-sulbactam rank among the commonest causative agents for BL hypersensitivity in India (35); and broad-spectrum antibiotics such as third generation cephalosporins and piperacillin are top culprits for BL anaphylaxis in Korea (36).
Reasons for these observed regional variations are likely multifactorial, whether it be more robust electronic health record documentation (37), or genuine biological ethnic-specific differences. Historically, certain high-risk HLA alleles were identified to be associated with carbamazepine and allopurinol-induced drug allergy among Asian patients, but not BL or anti-microbials (38, 39). Interestingly, a recent Thai study found HLA-B*48:01 to be associated with immediate-type reactions to BL, whereas HLA-C*04:06, HLA-C*08:01 and HLA-DRB1*04:06 were associated with delayed reactions (40). In contrast, studies from the West have reported HLA-B62 as a possible risk factor for drug reaction with eosinophilia and systemic symptoms to piperacillin/tazobactam (41). From a perspective of antimicrobial stewardship, these may also be related to the regional differences in antibiotic prescription patterns, such as higher rates of over-the-counter availability of antibiotics (42), local microbial sensitivity and resistance patterns prompting need for broad-spectrum antibiotics and adherence to regional antimicrobial stewardship programs (43, 44).
Differences in skin testing and sensitization
Sensitization patterns to penicillin allergic determinants also vary through time and space. For example in Australia, the sensitization rate to only penicillin determinants (benzylpenicilloyl polylysine (PPL) ± minor determinant mixture (MDM) ± benzylpenicillin (BP)) was 9.5% while in the UK, only 8% of patients were monosensitized to PPL or MDM (45). In a 13-year United States study, the rate of positive penicillin skin tests dropped from more than 10% to below 5% (46). Another recent Spanish study also showed a progressive decrease in sensitization rate to penicillin determinants from 57.6% to 22.1% over the last 25 years, echoing past European findings that the diagnostic sensitivity of PPL, MDM and BP has dropped to only 20% and omission of these determinants in skin test was justified (47–49). Differences in sensitization patterns between Asia-Pacific and European countries have been directly compared. A cross-sectional population study in Hong Kong found that 20.4% and 10.2% of patients were only monosensitized to PPL and MDM respectively (5). Therefore, although omission for penicillin determinants have been popularized in selected Western populations, we advocate that PPL and MDM should remain components of the routine panel testing in selected populations – especially in light of high rates of PPL/MDM monosensitization at least among predominant Chinese populations (5).
Variability in the use and availability of skin test reagents will also determine differences in sensitization patterns. For example, in the United States, there is no commercially available MDM so many centers did not comprise that as a component in penicillin skin test but only use PPL and BP (50). Even for PPL, its commercial form used to be withdrawn from the United States market since 2004, until it regained full approval from the United States Food and Drug Administration in 2009, significantly impacting clinical practice as well as resultant statistics and studies during the period (46, 51). Alternatively, in Europe and Hong Kong, PPL, MDM, BP, amoxicillin are commercially available and routinely included in skin testing for penicillin allergy (5, 52, 53). This is, however, not the common case in other Asia-Pacific regions. In a study surveying 13 countries in the Asia-Pacific (with Australia included in the study) regarding their diagnostic practices in drug allergy, although 100% of them performed skin test, only 60% of them had access to commercial penicillin kit of PPL and MDM (54).
Furthermore, testing patterns may reflect regional policy differences. For instance, regulations of mainland China mandate routine intradermal test prior to penicillin prescription even in patients with no clinical history of penicillin-induced hypersensitivity reaction (32, 55). Concernedly, screening by skin tests irrespective of clinical history can produce false positive results, creating unnecessary healthcare burden despite good intentions.
Identifying roadblocks and innovating the practice
Severely limited allergy services and overburdened medical infrastructure seems ubiquitous amongst many Asia-Pacific countries. While the Asia-Pacific represents the majority of the world population and likely the biggest burden of mislabelled “allergy”, there remains a limited supply of Allergists to meet the overwhelming demand (56). Severely low Allergist-to-population ratios are observed even in high-income locales, such as Hong Kong, with each Allergist serving up to 1.17 million population (56). Additional roadblocks in optimizing the efficacy of antibiotic allergy delabelling in resource-limited settings include impeded access to laboratory facilities and reagents, as well as paucities in territory-specific drug allergy guidelines or recommendations (39, 54). It is not possible nor efficient to rely on Allergists alone to tackle the huge burden of BL allergies, therefore innovative and novel strategies have been introduced to facilitate penicillin allergy workup and delabelling in recent years especially in the Asia-Pacific region.
Risk stratification
A popular and important tactic adopted in many clinical settings is to stratify and triage patients into different groups according to their risk of a genuine allergy. Various clinical predictors have been validated to identify low, medium and high-risk features of genuine BL allergy (18, 33, 45, 53, 57). Studies have shown that risk triage by a comprehensive history alone purports an excellent negative predictive value for low-risk cases which is comparable to skin testing (45, 58, 59). Increasingly so, there is a trend towards using direct drug challenge (usually with oral amoxicillin) in low-risk cases without the need for skin tests (60, 61). Additionally, prioritizing special populations that have imminent need for BL have also been advocated. For example, prioritizing patients with suspected BL allergy pre-operatively in elective orthopedic and obstetric operations have been shown to reduce economic burden, alter antibiotic choices and reduce hospitalization (62–66). At the moment, the risk stratification programs in many Asian locales are still in their infancy and bear striking similarities to Western protocols since both of which are largely based on the research findings in the West (67).
Multidisciplinary collaborations
With proper risk stratification, further drug allergy workup strategies may be adopted to incorporate a multidisciplinary team with collaboration between Allergists, non-allergists and allied health professionals. Various clinical models that have gained popularity in the past decade include multidisciplinary collaborations with pharmacists, nurses, and non-allergist physicians to implement BL allergy workup among low-risk patients (16–18, 68). With appropriate guidance and training, non-allergists have shown to independently evaluate low-risk cases and conduct delabelling. For example, the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) has published consensus statements to guide penicillin allergy testing by non-allergists and delabelling is now performed by non-allergists in various “Spoke” Clinics across Hong Kong supported by an Allergist in the “Hub” under a “Hub-and-Spoke” model (53). In fact, experience from HK-DADI has demonstrated that a nurse-led, protocol-driven evaluation was not only safe and effective in penicillin allergy delabelling, but led to an even higher rate of future penicillin use following delabelling and mitigated the need for unnecessary skin testing (18).
Telemedicine
There is great potential for telemedicine growth in the implementation of delabelling, especially in Asia-Pacific regions where accessibility to Allergist services and facilities may be limited (69). Telemedicine has been used to facilitate Allergist verification of skin tests performed by trained assistants, as well as review and identify patients appropriate for in-consult allergy evaluations (70). These telemedicine-based delabelling program for adult and paediatric patients demonstrated successful antibiotic de-escalation, savings in cost, and reduced active physician time while offsite (70, 71). These programs also report high satisfaction rates, with the majority of patients rating the experience as comparable to in-person encounters (69, 72). However, still suboptimal internet and mobile phone penetration rates as compared to developed countries, drastic urban-rural disparities and integration into existing healthcare systems remain challenges for telemedicine implementation in certain Asia-Pacific nations (73, 74).
Future steps in connecting the Asia-Pacific and West
The epidemic of BL allergy overdiagnosis is a global problem. More robust epidemiological data to determine and understand the burden and differences of BL allergy, especially in Asia-Pacific, are urgently needed. The outcome and enduring impact of delabelling should not just be limited to the delabelling process and it is important to recognize the clinical, psychosocial, and economic impacts beyond the initial delabelling process. Important data long-term clinical outcomes, which are especially scarce among Asian populations, include patterns of microbial resistance, patient quality of life and overall cost-effectiveness in the years following delabelling. Multi-centre, multi-cultural, international prospective studies are needed for better representation in the Asia-Pacific region.
As mentioned, HLA genetic variations might partially explain the discrepancies between BL allergies between Asia-Pacific and the West and may carry powerful diagnostic potential. However, regional differences in HLA-gene frequency, accessibility of screening facilities, and local availabilities of drug alternatives for high-risk individuals would likely affect the cost-effectiveness and feasibility of prescreening for BL allergy by HLA-genotype in different countries (67). Large inter-ethnic studies would be required to confirm these associations and investigate the potential role of HLA-based strategies for BL allergy workup in the future.
Nonetheless, various large-scale studies within the Asia-Pacific region have demonstrated clinical and economic benefits of BL allergy delabelling. The gains from successful BL allergy delabelling programs demonstrated in these Australian studies provide forays into the potential benefits that could be generated across the Asia-Pacific with widespread implementation of BL delabelling programs in the region.
In conclusion, overdiagnosed BL allergy is a significant public health challenge to be tackled globally. In view of the substantial geographical differences, it is in urgent need for Asia-Pacific to establish more evidence and customize its own delabelling practice to best fulfil its huge and unique demand. Collaborations among disciplines and countries are direly called for. After all, it is the effort and responsibility of every one of us to tackle the global burden of misdiagnosed BL allergies.
Statements
Author contributions
PL contributed to conception and design. HM and MY wrote the first draft of the manuscript. JW and VC wrote sections of the manuscript. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1.
Demoly P Adkinson NF Brockow K Castells M Chiriac AM Greenberger PA et al International consensus on drug allergy. Allergy. (2014) 69(4):420–37. 10.1111/all.12350
2.
Versporten A Coenen S Adriaenssens N Muller A Minalu G Faes C et al European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe (1997–2009). J Antimicrob Chemother. (2011) 66(suppl_6):vi13–vi23. 10.1093/jac/dkr454
3.
Macy E . Penicillin and beta-lactam allergy: epidemiology and diagnosis. Curr Allergy Asthma Rep. (2014) 14(11):476. 10.1007/s11882-014-0476-y
4.
Trubiano JA Chen C Cheng AC Grayson ML Slavin MA Thursky KA et al Antimicrobial allergy ‘labels’ drive inappropriate antimicrobial prescribing: lessons for stewardship. J Antimicrob Chemother. (2016) 71(6):1715–22. 10.1093/jac/dkw008
5.
Li PH Yeung HHF Lau C-S Au EYL . Prevalence, incidence, and sensitization profile of β-lactam antibiotic allergy in Hong Kong. Jama Network Open. (2020) 3(5):e204199. 10.1001/jamanetworkopen.2020.4199
6.
Sacco KA Bates A Brigham TJ Imam JS Burton MC . Clinical outcomes following inpatient penicillin allergy testing: a systematic review and meta-analysis. Allergy. (2017) 72(9):1288–96. 10.1111/all.13168
7.
Trubiano JA Adkinson NF Phillips EJ . Penicillin allergy is not necessarily forever. JAMA. (2017) 318(1):82. 10.1001/jama.2017.6510
8.
Blanca M Torres MJ García JJ Romano A Mayorga C De Ramon E et al Natural evolution of skin test sensitivity in patients allergic to β-lactam antibiotics. J Allergy Clin Immunol. (1999) 103(5):918–24. 10.1016/s0091-6749(99)70439-2
9.
Wong JCY Cheong N Lau CS Li PH . Prevalence and impact of misdiagnosed drug allergy labels among patients with hereditary angioedema. Front Allergy. (2022) 3:953117. 10.3389/falgy.2022.953117
10.
Li PH Chung H Lau C . Epidemiology and outcomes of geriatric and non-geriatric patients with drug allergy labels in Hong Kong. Hong Kong Med J. (2021) 27(3):192–7. 10.12809/hkmj208716
11.
Chan SCW Yeung WWY Wong JCY Chui ESH Lee MSH Chung HY et al Prevalence and impact of reported drug allergies among rheumatology patients. Diagnostics. (2020) 10(11):918. 10.3390/diagnostics10110918
12.
Wong JCY Li PH . Drug allergy management in the elderly. Curr Opin Allergy Clin Immunol. (2021) 21(4):340–5. 10.1097/ACI.0000000000000761
13.
Kaminsky LW Dalessio S Al-Shaikhly T Al-Sadi R . Penicillin allergy label increases risk of worse clinical outcomes in COVID-19. J Allergy Clin Immunol Pract. (2021) 9(10):3629–37.e2. 10.1016/j.jaip.2021.06.054
14.
Stollings JL Koo G Lindsell CJ Dear ML McCoy A Rice TW et al Risk-stratified management to remove low-risk penicillin allergy labels in the patients with COVID-19 in the intensive care unit. J Allergy Clin Immunol Pract. (2022). 10.1016/j.jaip.2022.08.043
15.
Mattingly TJ Fulton A Lumish RA Williams AMC Yoon S Yuen M et al The cost of self-reported penicillin allergy: a systematic review. J Allergy Clin Immunol Pract. (2018) 6(5):1649–54.e4. 10.1016/j.jaip.2017.12.033
16.
Devchand M Kirkpatrick CMJ Stevenson W Garrett K Perera D Khumra S et al Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention. J Antimicrob Chemother. (2019) 74(6):1725–30. 10.1093/jac/dkz082
17.
du Plessis T Walls G Jordan A Holland DJ . Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital. J Antimicrob Chemother. (2019) 74(5):1438–46. 10.1093/jac/dky575
18.
Kan AKC Hui HKS Li TS Chiang V Wong JCY Chan TS et al Comparative effectiveness, safety and real-world outcomes of a nurse-led, protocol-driven penicillin allergy evaluation from the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). J Allergy Clin Immunol Pract. (2022) 10.1016/j.jaip.2022.08.052
19.
Chua KYL Vogrin S Bury S Douglas A Holmes NE Tan N et al The penicillin allergy delabeling program: a multicenter whole-of-hospital health services intervention and comparative effectiveness study. Clin Infect Dis. (2021) 73(3):487–96. 10.1093/cid/ciaa653
20.
Trubiano JA Vogrin S Copaescu A Nasra M Douglas A Holmes NE et al Direct oral penicillin challenge for penicillin allergy delabeling as a health services intervention: a multicenter cohort study. Allergy. (2022) 77(3):1038–42. 10.1111/all.15169
21.
Macy E Shu YH . The effect of penicillin allergy testing on future health care utilization: a matched cohort study. J Allergy Clin Immunol Pract. (2017) 5(3):705–10. 10.1016/j.jaip.2017.02.012
22.
Brusco NK Bury S Chua KYL Vogrin S Holmes NE Trubiano JA . Penicillin Allergy Delabeling Program: an exploratory economic evaluation in the Australian context. Intern Med J. (2021). 10.1111/imj.15532. [Online ahead of print]
23.
Albin S Agarwal S . Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population. Allergy Asthma Proc. (2014) 35(6):489–94. 10.2500/aap.2014.35.3791
24.
Castells M Khan DA Phillips EJ . Penicillin allergy. N Engl J Med. (2019) 381(24):2338–51. 10.1056/nejmra1807761
25.
Knezevic B Sprigg D Seet J Trevenen M Trubiano J Smith W et al The revolving door: antibiotic allergy labelling in a tertiary care centre. Intern Med J. (2016) 46(11):1276–83. 10.1111/imj.13223
26.
Van Dijk SM Gardarsdottir H Wassenberg MWM Oosterheert JJ De Groot MCH Rockmann H . The high impact of penicillin allergy registration in hospitalized patients. J Allergy Clin Immunol Pract. (2016) 4(5):926–31. 10.1016/j.jaip.2016.03.009
27.
Picard M Bégin P Bouchard H Cloutier J Lacombe-Barrios J Paradis J et al Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol Pract. (2013) 1(3):252–7. 10.1016/j.jaip.2013.01.006
28.
Zhou L Dhopeshwarkar N Blumenthal KG Goss F Topaz M Slight SP et al Drug allergies documented in electronic health records of a large healthcare system. Allergy. (2016) 71(9):1305–13. 10.1111/all.12881
29.
Macy E Contreras R . Adverse reactions associated with oral and parenteral use of cephalosporins: a retrospective population-based analysis. J Allergy Clin Immunol. (2015) 135(3):745–52.e5. 10.1016/j.jaci.2014.07.062
30.
Liang EH Chen LH Macy E . Adverse reactions associated with penicillins, carbapenems, monobactams, and clindamycin: a retrospective population-based study. J Allergy Clin Immunol Pract. (2020) 8(4):1302–13.e2. 10.1016/j.jaip.2019.11.035
31.
Tsutsui A Yahara K Shibayama K . Trends and patterns of national antimicrobial consumption in Japan from 2004 to 2016. J Infect Chemother. (2018) 24(6):414–21. 10.1016/j.jiac.2018.01.003
32.
Jiang Z Zhang H Xiao H Xiao X Meng J . Negative impact of penicillin allergy labels on antibiotic use in hospitalized patients in Chinese Mainland. World Allergy Organization J. (2022) 15(8):100677. 10.1016/j.waojou.2022.100677
33.
Li PH Siew LQC Thomas I Watts TJ Ue KL Rutkowski K et al Beta-lactam allergy in Chinese patients and factors predicting genuine allergy. World Allergy Organ J. (2019) 12(8):100048. 10.1016/j.waojou.2019.100048
34.
Wong JC Au EY Yeung HH Lau C-S Li PH . Piperacillin-tazobactam allergies: an exception to usual penicillin allergy. Allergy Asthma Immunol Res. (2021) 13(2):284. 10.4168/aair.2021.13.2.284
35.
Bhagwat B Anuradha HV . Evaluation of immediate reactions to β lactam antibiotics using a comprehensive diagnostic protocol. Int J Basic Clin Pharmacol. (2017) 6(10):2366. 10.18203/2319-2003.ijbcp20174360
36.
Park CS Yang M-S Kang D-Y Park HJ Park S-Y Nam Y-H et al Risk factors of beta-lactam anaphylaxis in Korea: a 6-year multicenter retrospective adult case-control study. World Allergy Organ J. (2021) 14(9):100580. 10.1016/j.waojou.2021.100580
37.
Moskow JM Cook N Champion-Lippmann C Amofah SA Garcia AS . Identifying opportunities in EHR to improve the quality of antibiotic allergy data. J Am Med Inform Assoc. (2016) 23(e1):e108–e112. 10.1093/jamia/ocv139
38.
Thong BYH Vultaggio A Rerkpattanapipat T Schrijvers R . Prevention of drug hypersensitivity reactions: prescreening and premedication. J Allergy Clin Immunol Pract. (2021) 9(8):2958–66. 10.1016/j.jaip.2021.04.006
39.
Jantararoungtong T Tempark T Koomdee N Medhasi S Sukasem C . Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art. Expert Opin Drug Metab Toxicol. (2021) 17(9):1049–64. 10.1080/17425255.2021.1946514
40.
Association of HLA genotypes with beta-lactam antibiotic hypersensitivity in children. Asian Pac J Allergy Immunol. (2021). 39(3):197–205. 10.12932/ap-271118-0449
41.
Rutkowski K Taylor C Wagner A . HLA B62 as a possible risk factor for drug reaction with eosinophilia and systemic symptoms to piperacillin/tazobactam. J Allergy Clin Immunol Pract. (2017) 5(3):829–30. 10.1016/j.jaip.2016.10.008
42.
Chang J Xu S Zhu S Li Z Yu J Zhang Y et al Assessment of non-prescription antibiotic dispensing at community pharmacies in China with simulated clients: a mixed cross-sectional and longitudinal study. Lancet Infect Dis. (2019) 19(12):1345–54. 10.1016/s1473-3099(19)30324-x
43.
Lee TH Lye DC Chung DR Thamlikitkul V Lu M Wong AT et al Antimicrobial stewardship capacity and manpower needs in the Asia Pacific. J Glob Antimicrob Resist. (2021) 24:387–94. 10.1016/j.jgar.2021.01.013
44.
Raghunath D . Emerging antibiotic resistance in bacteria with special reference to India. J Biosci. (2008) 33(4):593–603. 10.1007/s12038-008-0077-9
45.
Siew LQC Li PH Watts TJ Thomas I Ue KL Caballero MR et al Identifying low-risk beta-lactam allergy patients in a UK tertiary centre. J Allergy Clin Immunol Pract. (2019) 7(7):2173–81.e1. 10.1016/j.jaip.2019.03.015
46.
Macy E Schatz M Lin C Poon K-Y . The falling rate of positive penicillin skin tests from 1995 to 2007. Perm J. (2009) 13(2):12–8. 10.7812/TPP/08-073
47.
Campanón Toro MDV Moreno Rodilla E Gallardo Higueras A Laffond Yges E Muñoz Bellido FJ Gracia Bara MT et al Changes in sensitization patterns in the last 25 years in 619 patients with confirmed diagnoses of immediate hypersensitivity reactions to beta-lactams. Biomedicines. (2022) 10(7):1535. 10.3390/biomedicines10071535
48.
Torres J Romano A Mayorga C Carmen M Guzman AE Reche M et al Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing. Allergy. (2001) 56(9):850–6. 10.1034/j.1398-9995.2001.00089.x
49.
Blanca M Romano A Torres MJ Férnandez J Mayorga C Rodriguez J et al Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. (2009) 64(2):183–93. 10.1111/j.1398-9995.2008.01916.x
50.
Bourke J Pavlos R James I Phillips E . Improving the effectiveness of penicillin allergy de-labeling. J Allergy Clin Immunol Pract. (2015) 3(3):365–74.e1. 10.1016/j.jaip.2014.11.002
51.
Raja AS Lindsell CJ Bernstein JA Codispoti CD Moellman JJ . The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency department setting. Ann Emerg Med. (2009) 54(1):72–7. 10.1016/j.annemergmed.2008.12.034
52.
Elaine AYL Veronica CL Eric CYT Roland L . HKIA guidelines on management of beta-lactam antibiotic allergy (2022). Available from: http://www.allergy.org.hk/HKIA%20-%20Guildelines%20on%20Management%20of%20Beta-Lactam%20Antibiotic%20Allergy%20(Final).pdf.
53.
Li P Wong J Chan J Chik T Chu M Ho G et al Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus statements for penicillin allergy testing by nonallergists. Front Allergy. (2022) 3:974138. 10.3389/falgy.2022.974138
54.
Tang M-M Fok JS Thong BY-H Yun J Li PH Kang H-R et al Diagnostic procedures & practices in drug allergy/hypersensitivity: a survey of 13 Asian countries. Asia Pac Allergy. (2020) 10(4):e36. 10.5415/apallergy.2020.10.e36
55.
Torres MJ Adkinson NF Caubet J-C Khan DA Kidon MI Mendelson L et al Controversies in drug allergy: beta-lactam hypersensitivity testing. J Allergy Clin Immunol Pract. (2019) 7(1):40–5. 10.1016/j.jaip.2018.07.051
56.
Lee T-H Leung T-F Wong G Ho M Duque JR Li PH et al The unmet provision of allergy services in Hong Kong impairs capability for allergy prevention-implications for the Asia Pacific region. Asian Pac J Allergy Immunol. (2019) 37(1):1–8. 10.12932/ap-250817-0150
57.
Trubiano JA Vogrin S Chua KYL Bourke J Yun J Douglas A et al Development and validation of a penicillin allergy clinical decision rule. Jama Intern Med. (2020) 180(5):745. 10.1001/jamainternmed.2020.0403
58.
Koo G Yu R Phillips EJ Stone CA Jr . Retrospective stratification of cephalosporin allergy label risk using validated penicillin allergy frameworks. J Allergy Clin Immunol Pract. (2022) 10(9):2472–5.e1. 10.1016/j.jaip.2022.05.032
59.
Mohamed OE Beck S Huissoon A Melchior C Heslegrave J Baretto R et al A retrospective critical analysis and risk stratification of penicillin allergy delabeling in a UK specialist regional allergy service. J Allergy Clin Immunol Pract. (2019) 7(1):251. 10.1016/j.jaip.2018.05.025
60.
Fransson S Boel JB Mosbech HF Poulsen LK Ruff S Garvey LH . Safe de-labeling of patients at low risk of penicillin allergy in Denmark. Int Arch Allergy Appl Immunol. (2022) 183(6):640–50. 10.1159/000521708
61.
Stevenson B Trevenen M Klinken E Smith W Yuson C Katelaris C et al Multicenter Australian study to determine criteria for low- and high-risk penicillin testing in outpatients. J Allergy Clin Immunol Pract. (2020) 8(2):681–9.e3. 10.1016/j.jaip.2019.09.025
62.
Cook E Ramirez M Turrentine M . Time has come for routine penicillin allergy testing in obstetrics. Am J Perinatol. (2020) 10(01):e15–9. 10.1055/s-0039-3401801
63.
Wolfson AR Mancini CM Banerji A Fu X Bryant AS Phadke NA et al Penicillin allergy assessment in pregnancy: safety and impact on antibiotic use. J Allergy Clin Immunol Pract. (2021) 9(3):1338–46. 10.1016/j.jaip.2020.10.063
64.
Raso J Kamalapathy PN Puvanesarajah V Labaran L Hassanzadeh H . Penicillin allergy in spine surgery: increased rates of sepsis, emergency room visits, and readmission. World Neurosurg. (2022) 162:e91–8. 10.1016/j.wneu.2022.02.079
65.
Lee OC Cheng DC Paul JL Ross BJ Hawkins BJ Sherman WF . Economic burden of patient-reported penicillin allergy on total hip and total knee arthroplasty. J Arthroplasty. (2021) 36(9):3067–72. 10.1016/j.arth.2021.04.032
66.
Pagani NR Moverman MA Puzzitiello RN Menendez ME Barnes CL Kavolus JJ . Preoperative allergy testing for patients reporting penicillin and cephalosporin allergies is cost-effective in preventing infection after total knee and hip arthroplasty. J Arthroplasty. (2021) 36(2):700–4. 10.1016/j.arth.2020.08.045
67.
Thong BY-H Lucas M Kang H-R Chang Y-S Li PH Tang MM et al Drug hypersensitivity reactions in Asia: regional issues and challenges. Asia Pac Allergy. (2020) 10(1):e8. 10.5415/apallergy.2020.10.e8
68.
Louden NJ Hansen LA Rimal A Norton LE . Implementation of a pharmacist-driven penicillin and cephalosporin allergy assessment tool: a pilot evaluation. J Pediatr Pharmacol Ther. (2021) 26(7):696–701. 10.5863/1551-6776-26.7.696
69.
Ramsey A Mustafa SS Portnoy JM . Patient and clinician attitudes toward telemedicine for allergy and immunology. J Allergy Clin Immunol Pract. (2022) 10(10):2493–9. 10.1016/j.jaip.2022.05.008
70.
Staicu ML Holly AM Conn KM Ramsey A . The use of telemedicine for penicillin allergy skin testing. J Allergy Clin Immunol Pract. (2018) 6(6):2033–40. 10.1016/j.jaip.2018.04.038
71.
Pulvirenti F Cinetto F Milito C Bonanni L Pesce AM Leodori G et al Health-related quality of life in common variable immunodeficiency Italian patients switched to remote assistance during the COVID-19 pandemic. J Allergy Clin Immunol Pract. (2020) 8(6):1894–9.e2. 10.1016/j.jaip.2020.04.003
72.
Mustafa SS Yang L Mortezavi M Vadamalai K Ramsey A . Patient satisfaction with telemedicine encounters in an allergy and immunology practice during the coronavirus disease 2019 pandemic. Ann Allergy Asthma Immunol. (2020) 125(4):478–9. 10.1016/j.anai.2020.06.027
73.
Jha AK Sawka E Tiwari B Dong H Oh CC Ghaemi S et al Telemedicine and community health projects in Asia. Dermatol Clin. (2021) 39(1):23–32. 10.1016/j.det.2020.08.003
74.
Suzuki T Hotta J Kuwabara T Yamashina H Ishikawa T Tani Y et al Possibility of introducing telemedicine services in Asian and African countries. Health Policy Technol. (2020) 9(1):13–22. 10.1016/j.hlpt.2020.01.006
Summary
Keywords
penicillin, allergy, Asia-Pacific, West, beta-lactam
Citation
Mak HWF, Yeung MHY, Wong JCY, Chiang V and Li PH (2022) Differences in beta-lactam and penicillin allergy: Beyond the West and focusing on Asia-Pacific. Front. Allergy 3:1059321. doi: 10.3389/falgy.2022.1059321
Received
01 October 2022
Accepted
07 November 2022
Published
22 November 2022
Volume
3 - 2022
Edited by
Mariana C. Castells, Harvard Medical School, United States
Reviewed by
Natasha E. Holmes, University of Melbourne, Australia
Updates
Copyright
© 2022 Mak, Yeung, Wong, Chiang and Li.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Philip H. Li liphilip@hku.hk
These authors have contributed equally to this work
Specialty Section: This article was submitted to Drug, Venom & Anaphylaxis, a section of the journal Frontiers in Allergy
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.