In an open clinical trial, aztreonam was administered repeatedly to 15 cystic fibrosis patients who were chronically infected with Pseudomonas aeruginosa and had previously had severe hypersensitivity reactions to other beta-lactam antibiotics, including anaphylactic shock, generalized urticaria, and drug-associated fever. After negative results in a skin-prick test and a lack of reaction to an intravenous test dose of aztreonam, the patients were treated with aztreonam (150 mg/[kg.d]) in combination with tobramycin (10-20 mg/[kg.d]) for 14-day periods at 3- to 4-month intervals. To date, a total of 56 course of aztreonam have been administered to these patients (three to six courses per patient), and no type 1 hypersensitivity reactions have occurred. However, as a result of drug-associated fever, the administration of aztreonam had to be discontinued in two of 15 cases. The remaining 13 patients have tolerated treatment well.

Adolescent↗

PubMedDate not supplied

Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses.

A total of 2,793 courses of treatment with seven beta-lactam antibiotics were administered to 121 cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, and the patients were evaluated with respect to clinical hypersensitivity reactions. Seventy-five patients (62%) experienced 125 reactions, for an overall frequency (based on the number of courses) of 4.5%. Immediate reactions occurred in 34 patients (28.1%) during 53 courses (1.9%). The highest rate of reactions involved piperacillin (50.9% of patients), and the lowest rate involved imipenem and aztreonam (4.0% and 6.5% of patients, respectively); intermediate reaction rates were noted for carbenicillin (23.6% of patients), azlocillin (20.8%), cefsulodin (17.1%), and ceftazidime (13.0%). Cross-reactivity did not appear to be a major problem. Reactions to aztreonam seemed to be restricted to a small group of patients with a high propensity for beta-lactam hypersensitivity.

Anti-Bacterial Agents↗

PubMedDate not supplied

Pharmacokinetic evaluation of imipenem combined with cilastatin in cystic fibrosis.

The pharmacokinetics of imipenem (MK-787) and cilastatin (MK-791) were studied in 30 patients with cystic fibrosis (CF) receiving the drug for therapeutic purposes at doses of 11 mg/kg given as a 30-min infusion. The serum concentrations and urine elimination were studied after the first dose and during steady state. The concentrations were assayed by high-pressure liquid chromatography. The total areas under the imipenem serum concentration curves (AUCs) to infinity were 30.4 +/- 6.8 mg.h/l after the first dose compared with 29.1 +/- 7.1 mg.h/l during steady state (NS). The cilastatin AUCs on the 2 days were 40.3 +/- 9.3 and 38.3 +/- 0.4 mg.h/l (NS), respectively. The urinary recovery of imipenem was 47.8 +/- 17.8% after the first dose and 57.8 +/- 24.2% during steady state (NS). The amounts of cilastatin eliminated in the urine during 6 h were 6/7.3 +/- 22.9% after the first dose and 60.5 +/- 17.0% of the dose during steady state (NS). The mean half-life of imipenem in these CF patients was 1.2 +/- 0.4 h on the first day of the examination and within the same range during steady state. The distribution volume (Vd beta) was in the range of 28 liters, the total body clearance was 16.3 liters/h (285 ml/min) on the first day. The t1/2 of cilastatin was 0.59 +/- 0.14 h after the first dose and 0.61 +/- 0.14 h during steady state. Thus patients with CF eliminated cilastatin more quickly than imipenem.

Adolescent↗