ECFS 2020 - Optimizing pharmaceutical care in cystic fibrosis

172    www.ecfs.eu OPTIMIZING PHARMACEUTICAL CARE IN CYSTIC FIBROSIS EVALUATION AND MANAGEMENT OF BETA-LACTAM ANTIBIOTIC DRUG REACTIONS CHAPTER 10 unavailable. In this situation, the only means of determining whether someone is truly hypersensitive is by performing a drug provocation test. J Provocation tests are contraindicated in patients who have had severe hypersensitivity reactions. This includes severe cutaneous reactions and reactions with systemic involve- ment including hematologic reactions J Provocation tests may not be needed if an alternative and effective drug is available J Provocation tests must be performed under the strictest safety conditions. Resuscitation facilities and appropri- ately trained staff must be available Different protocols for provocation tests are available and should be tailored to the indi- vidual patient’s risk [25]. Risk assessment should include information relating to the historical reaction as well as the patient’s current health status. Higher-risk patients include those with advanced lung disease or other risk factors such as pregnancy. In cases of patients who are very low risk (e.g. those who had an unknown reaction over 10 years earlier with no evidence to suggest an IgE-mediated reaction), it may be possible to directly perform a single full- dose provocation test without the need for skin testing. In patients with a moderate risk history, such as those with a docu- mented skin reaction without features of anaphylaxis, a graded antibiotic challenge can be performed if the skin test result is negative. An example of a graded chal- lenge would be one-hundredth of the full dose, followed by one-tenth of the full dose, before finally administering the full Patch tests and intradermal tests are gener- ally considered comparable, although there is some evidence to suggest that intra- dermal testing is more sensitive [19]. It is now accepted that the sensitivity of skin testing in patients with non-imme- diate reactions to beta-lactam antibiotics is low. Padia et al. [20] found that only 9% of patients developed positive delayed intra- dermal readings, while Lammintausta et al. [21] reported patch test positivity in only 4% of patients with non-immediate reac- tions to cephalosporins. Blanca-Lopez et al. observed positive patch or intradermal test results in only 5% of children with non-im- mediate beta-lactam reactions and a posi- tive provocation test [22]. In patients with CF only 14% had positive intradermal test results for piperacillin despite testing posi- tive in in vitro tests [3]. In vitro tests The most established assay for identifying drug-specific T cells is the lymphocyte transformation test (LTT). In the LTT the proliferation of activated T cells is meas- ured by the incorporation of radioactive thymidine. This is useful test, with sensi- tivity ranging from 50–80% for beta-lactam antibiotics [23]. In a cohort of patients with CF and non-immediate reactions to pipera- cillin the sensitivity was 68% [24]. Unfortu- nately, the LTT is not widely available and its use is largely limited to research given the complexity of the assay. 2.2. Drug provocation tests For the majority of patients with CF and suspected hypersensitivity, skin-test results will be negative and in vitro studies