ECFS 2020 - Optimizing pharmaceutical care in cystic fibrosis

European Cystic Fibrosis Society   173  OPTIMIZING PHARMACEUTICAL CARE IN CYSTIC FIBROSIS EVALUATION AND MANAGEMENT OF BETA-LACTAM ANTIBIOTIC DRUG REACTIONS CHAPTER 10 logical and antibacterial properties of each drug, and are important sites of immune recognition and cross-reactivity between antibiotics. Cross-reactivity to the common beta-lactam ring is infrequent. Aztreonam is a monobactam that contains a beta-lactam nucleus with no adjoining ring. Fortunately, reactions in CF appear to be highly drug specific, with little cross-reac- tivity. In cases of non-immediate reactions the T cells are stimulated in vitro with the chemical entity to which the patient was exposed at the time of the reaction, but not with closely related drugs or other drugs commonly used in people with CF [3]. It is not until the patient has developed several separate drug reactions that their antibi- otic options are truly restricted. However, caution is required with ceftazidime and aztreonam, which share an identical side chain, making cross-reactivity possible. Moss et al. studied the tolerability of aztre- onam in 20 patients with previous beta- lactam hypersensitivity [26], and found that 19 patients tolerated aztreonam; the patient who failed had had a previous reaction to ceftazidime. In individuals without CF the risk of a peni- cillin-hypersensitive patient developing a reaction to ceftazidime, meropenem, or aztreonam is very low, as there is little structural similarity [27, 28]. There have been fewer studies of patients who initially developed hypersensitivity to cephalo- sporins than to penicillins. Romano et al. studied 106 patients with a history of immediate reaction to cephalosporins. Skin testing and drug provocation tests revealed that around 25% of patients were also therapeutic dose. A 30 to 60 minute obser- vation period is required between steps. Patients with a high risk (e.g. those with a previous anaphylactic reaction) should be referred to a specialist allergy center for assessment, where a risk/benefit analysis specific to the individual will be performed. If the provocation test is tolerated the medical record should be updated and the patient informed that they can receive it in future. In non-CF patients, a negative skin test result plus a negative provocation test result has more than a 99% negative predictive value for excluding IgE-me- diated reactions. In people with CF this value will be lower as tests are performed when the patient is clinically stable and additional co-factors, such as infection, are often necessary for the reaction to develop. To completely exclude non-imme- diate reactions some centers advocate a longer course of antibiotics. However, it is generally felt that the patient should not be unnecessarily exposed to antibiotics. 3 Management of hypersensitive patients 3.1. Use alternative antibiotic The basic structure of beta-lactams is a four-member beta-lactam ring ( Figure 2 ) . In penicillin this beta-lactam ring is connected to a five-member thiazolidine ring to form the so-called penicillin nucleus. In cephalo- sporins the beta-lactam ring is connected to a six-member dihydrothiazine ring. Penicillins have one side chain (R1) while cephalosporins have two (R1 and R2). These side chains determine the pharmaco-