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Title: Investigation into non-immediate hypersensitivity reactions to intravenous antibiotics in patients with cystic fibrosis
Author: Whitaker , Paul
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Antibiotic hypersensitivity represents a major clinical challenge in patients with cystic fibrosis (CF). Many patients have significant restrictions in antibiotic choice as a result of multiple previous hypersensitivity reactions; this often leads to suboptimal treatment. The majority of reactions are non-immediate and in similar cohorts of non-CF patients it has been demonstrated that they are T cell mediated. In this study we aimed to investigate the mechanism of hypersensitivity in a cohort of patients with CF and established hypersensitivity. As demonstrated in recent studies skin testing had low sensitivity in our cohort of patients. Only 13% of patients developed positive intradermal tests to piperacillin; no positives were seen with other beta-Iactams. In contrast, in-vitro Iymphocyte proliferation was seen in 68% of patients with piperacillin hypersensitivity. This is the first time drug specific Iymphocytes have been identified in patients with CF and supports the clinical viewpoint that the non-immediate reactions seen are T-cell mediated. Positive proliferation was also seen in patients with colistin hypersensitivity, including patients with neurological symptoms such as headache. Interestingly, the group of patients with neurological symptoms secondary to colistin also had positive drug specific IgG antibodies further supporting an immune mechanism. Whilst desensitisation is performed with some success at present it is not known whether any immune modulation takes place. The piperacillin model provides us with a useful tool to characterise the mechanisms of drug hypersensitivity and desensitisation. Prospective studies are needed to assess how drug sensitivity develops and whether clinical practice could be modified to reduce the risk.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available