Evolution of diagnostic approaches in betalactam hypersensitivity

ABSTRACT

Introduction: Betalactams are the most widely used drugs against infections and the primary cause of antibiotic hypersensitivity reactions. Reaction patterns for different betalactams have been changing in accordance with consumption trends, and vary among countries. As a consequence, in vivo and in vitro tests have had to change with to keep up with new tendencies.

Areas covered: This review is focused on advances in betalactam hypersensitivity diagnosis. Changes in in vivo methods have been limited to the inclusion of new haptens. In contrast, major progress has been achieved for in vitro tests since the 1960s, from the first description of immunoassays, the basophil activation test and the lymphocyte transformation test, to the more sophisticated assays developed in last years.

Expert commentary: Issues with diagnosis are related to test sensitivity. In vivo tests show higher sensitivity, however they can be risky, especially in severe and life-threatening reactions. Therefore, we believe that in vitro tests should be the preferred method. Current efforts are under way to enhance their sensitivity. Only multidisciplinary approaches involving immunology, proteomics, nanotechnology and chemistry can help us to fully understand conjugate structures and mechanisms involved in hypersensitivity reactions to betalactams, and consequently lead to advances in in vitro methods.

KEYWORDS:

• Basophil activation test
• betalactam
• drug allergy
• drug provocation test
• histamine release test
• immunoassay
• lymphocyte transformation test
• skin test

Acknowledgment

We thank Dr James R. Perkins for his help with the final English language version of this manuscript.

Declaration of interest

TD Fernandez holds a ‘Ramon y Cajal’ research contract by Ministry of Economy and Competitiveness (RYC-2013-13138). C Mayorga holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. I Doña holds a ‘Joan Rodes’ research contract (JR15/00036) and MI Montañez holds a ‘Miguel Servet I’ research contract (CP15/00103), both of them supported by Institute of Health ‘Carlos III’ of the Ministry of Economy and Competitiveness (grants cofunded by European Social Fund (ESF)). A Ariza thanks ‘pFIS fellowship’ (FI08/00385) from ISCIII and Andalucia ‘Talent Hub Fellowship’ (TAHUB/II-004) cofunded by the Junta de Andalucia and the European Union, VII Framework Programme of the European Commission (grant agreement No. 291780). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The present study has been supported by Institute of Health ‘Carlos III’ of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): PI12/02529, PI15/01206, CP15/00103, RETICs RIRAAF (RD12/0013/0001) and ARADyAL (RD16/0006/0001; RD16/0006/0033; RD16/0006/0019), and by Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by European Regional Development Fund (ERDF): CTS-06603); Andalusian Regional Ministry Health (grants: PI-0699-2011, PI-0352-2012, PI-0179-2014 and PI-0241-2016), “Premio UNICAJA a la innovación en biomedicina y salud” and Merck-Serono Research Grant from Fundacion Salud 2000.