ECFS 2020 - Optimizing pharmaceutical care in cystic fibrosis

European Cystic Fibrosis Society   175  OPTIMIZING PHARMACEUTICAL CARE IN CYSTIC FIBROSIS EVALUATION AND MANAGEMENT OF BETA-LACTAM ANTIBIOTIC DRUG REACTIONS CHAPTER 10 3.4. Desensitization While alternative regimens can be devised for most patients, there are some for whom all options have been exhausted. In this difficult scenario, drug desensitization represents a safe method of reintroducing a drug to which a patient has been proven hypersensitive. As with provocation tests this approach should be avoided in patients with severe T-cell-mediated reactions. Desensitization results in a temporary state of immune tolerance to the culprit drug by administering gradually increasing subop- timal doses prior to the full therapeutic dose. This is an established procedure in people with CF who have immediate antibiotic reactions [31, 32]. Legere et al. reported 52 successful desensitization procedures in 15 patients with immediate reactions [32]. The procedure involves a rapid protocol consisting of either 12 or 16 increments performed in less than six hours ( Figure 3 ). Protocols have also been designed for desensitization to oral antibi- otics such as flucloxacillin, co-trimoxazole, and oral ciprofloxacin. When undertaking rapid intravenous desen- sitization the patient must be kept in a monitored area with 1:1 nurse supervision. In patients in whom the original reaction was anaphylaxis the procedure should be performed in an intensive care setting. The patient must provide full consent, and accept the risk that a further reaction could occur. There is no clear consensus as to whether pre-medication with anti-his- tamines and steroids should be adminis- tered empirically. Once desensitization is completed, the patient should remain in penicillin-allergic, but only 3% reacted to aztreonam and only 1% to meropenem [29]. 3.2. Treating through In some patients who experience a mild reaction it may be possible to “treat through” the reaction without suspending treatment. The reaction can be made more tolerable with the addition of anti-hista- mines and steroids. In others, the symp- toms appear to worsen after administra- tion of high-dose antibiotics over a short infusion time. In this situation, initiation of continuous antibiotic infusion can help to combat the severity of reaction symptoms, and in some patients the reaction may even resolve. 3.3. Alternative routes of administration The intravenous route of administration appears to be the most immunogenic. It is reported that in mild non-immediate reac- tions the patient will often tolerate the drug when it is given in nebulized form [30]. This is an important option. Moreover, nebulized aztreonam can be used alongside an intra- venous antibiotic in patients with multiple drug reactions. The careful use of intrave- nous antibiotics is important to prevent the development of hypersensitivity. Given the overall improvements in the routine management of CF care there is less of a need for frequent intravenous antibiotics to maintain stability. Indeed, mild exacer- bations can be effectively treated with a combination of oral antibiotics and intensi- fied inhaled treatment.