3. Example of a desensitisation regimen
The ideal choice for intravenous therapy in respiratory exacerbations comprises a combination of two antibiotics to which the pseudomonas isolates are sensitive and which have synergistic activity i.e. a ß-lactam plus an aminoglycoside. However, patients with CF are at risk of developing allergic reactions to antibiotics because of repeated high dose intravenous drug administration. The choice of antibiotics may be limited by a history of previous allergic reaction and patients may thus be denied optimal treatment.
Hypersensitivity reactions are reported with most of the antibiotics in regular use for patients with CF including aminoglycosides (Schretlen-Doherty & Troutman, 1995), semisynthetic penicillins (Moss et al, 1986), ß-lactams (Koch et al, 1991) and quinolones (Lantner, 1995). In one study of 121 CF patients 75 (62%) experienced 125 reactions, those to piperacillin being most frequent (50.9%) and aztreonam the least common (Koch et al, 1991). In another series, 18 of 53 CF patients experienced a reaction including 33% of patients treated intravenously and 9.5% of all IV courses: once again piperacillin was the most allergenic antibiotic (Wills et al, 1999). Seventy one of 196 (36%) adults with CF experienced one or more antibiotic hypersensitivity reaction (Etherington et al, 1998).
The idea of using a desensitisation method to prevent recurrence of allergic reaction in patients with CF is well established (Moss et al, 1984). The regimen involves administration of a 106-times dilution of the drug followed by six 10-fold increases in the concentration until the therapeutic dose is given. Each dilution in infused consecutively over 20 minutes. During the desensitisation procedure, which takes about 2-3 hours, the patient is observed for signs of allergy. If seven infusions are tolerated the therapeutic dose is continued until the course is completed. In one series, 54/61 desensitisation procedures were successful (Etherington et al, 1998). Desensitisation must be repeated in full for each course of treatment, and during any course of therapy, if more than one day's doses are omitted. If any of the escalating desensitisation doses is not tolerated the process is abandoned and not repeated on that occasion.
3 Example of a desensitisation regimen
ceftazidime 0.004 mg in 50 ml sodium chloride 0.9% [NaCl]
ceftazidime 0.04 mg in 50 ml NaCl ceftazidime 0.4mg in 50 ml NaCl
ceftazidime 4 mg in 50 ml NaCl
ceftazidime 40 mg in 50 ml NaCl
ceftazidime 400 mg in 50 NaCl
ceftazidime 4000mg in 50 ml NaCl
Each dose is infused consecutively over twenty minutes. If there is no adverse reaction the next dose follows at once.
Adrenaline, hydrocortisone and an antihistamine should be readily available and the appropriate doses for the patient known before starting the procedure.
Facilities for full resuscitation should be close at hand. Desensitisation for hypersensitivity to other antibiotics has been carried out successfully. Successful desensitisation to tobramycin is reported where, interestingly, the tolerance was later maintained by the use of long-term nebulised tobramycin (Schretlen-Doherty & Troutman, 1995). Other reports of desensitisation include ciprofloxacin (Lantner, 1995) and patients with multiple allergic reactions to both ß-lactams and aminoglycosides (Earl & Sullivan, 1987).
For more details see CF (UK) Trust antibiotic consensus section
Earl HS, Sullivan TJ. Acute desensitisation of a patient with cystic fibrosis to both beta-lactam and aminoglycoside antibiotics. J Allergy Clin Immunol 1987; 79:477-483.
Etherington C, Whitehead A, Conway SP, Bradbury H. Incidence of antibiotic related allergies in an adult cystic fibrosis unit and the success rate of a desensitisation regimen. Pediatr Pulmonol 1998; Suppl 17; 324. Abstract 427.
Ghosal S, Taylor CJ. Intravenous desensitisation to ceftazidime in cystic fibrosis patients. J Antimicrob Chemother 1997; 39:556-557.
Koch C, Hjelt K, Pedersen SS et al. Retrospective clinical study of hypersensitivity reactions to aztreonam and six other ß-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses. Rev Infect Dis 1991;13(Suppl 7):S608-611.
Lantner RR. Ciprofloxacin desensitisation in a patient with cystic fibrosis. J Allergy Clin Immunol 1995; 96:1001-1002.
Moss RB, Babin S, Yao-Pi H. Allergy to semi-synthetic penicillins in cystic fibrosis. J Pediatr 1984; 104:460-466.
Schretlen-Doherty JS, Troutman WG. Tobramycin induced hypersensitivity reaction. Ann Pharmacother 1995; 29:704-706.
Wills R, Henry RL, Francis JL. Antibiotic hypersensitivity reactions in cystic fibrosis. J Paediatr Child Health 1998; 34:325-329.
