azlocillin and Drug-Hypersensitivity

The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 21 patients with cystic fibrosis (CF) (aged 5 to 39 years) with well-documented histories of allergic systemic reactions (SRs) to penicillin and/or cephalosporin antipseudomonal beta-lactam antibiotics (BLAs). Skin tests (STs) with penicilloyl-polylysine (PPL), penicillin minor determinant mixture, and antipseudomonal BLA were positive in 19 patients (90%). The BLA causing the most recent allergic reaction, minor determinant mixture, or PPL, was positive in 89%, 53%, and 32% of ST-positive patients, respectively. Serum PPL-specific IgE antibodies were not detectable, although PPL-specific IgG antibodies were found in 64% of patients tested. STs to aztreonam reagents were performed and were initially negative in 20 patients. One patient was ST positive to the polylysine conjugate of hydrolyzed aztreonam (SQ 27629), despite no prior exposure to aztreonam, and was not treated. Of 20 patients treated with aztreonam, four were demonstrated to be sensitized by exposure (one had an SR during initial treatment course, two had SRs on reexposure, and one patient was asymptomatic after intravenous desensitization) by positive aztreonam reagent skin responses on repeat testing. Aztreonyl-specific IgE and IgG serum antibodies were not detected in any patients, including patients with allergic reactions to aztreonam. Thus, aztreonam is generally well tolerated in high-risk patients with CF allergic to other BLAs and appears to have reduced immunogenicity by serologic testing. However, caution should be exercised with aztreonam in BLA-allergic patients with CF in light of 5% preexisting ST cross-reactivity and 20% sensitization rates found in this study.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Anti-Idiotypic; Azlocillin; Aztreonam; Ceftazidime; Child; Child, Preschool; Cross Reactions; Cystic Fibrosis; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Immunoglobulin G; Male; Piperacillin; Skin Tests; Ticarcillin; Tobramycin

The safety of azlocillin was evaluated in 631 patients treated for urinary tract or systemic infections in U.S.A. clinical trials. The mean azlocillin dose was 260 mg/kg/day and the mean duration of treatment was 11.1 days. Twenty patients (3.2%) experienced adverse local reactions and 92 patients (14.6%) experienced adverse systemic reactions. In thirty-one instances (4.9%) they led to premature termination of therapy, but only 14 of 135 reactions were classified as severe. All adverse reactions were reversible if adequate follow-up was done. Hypersensitivity reactions, manifest by rash, fever or eosinophilia occurred in 4.4%, 0.3% and 1.1% respectively. Hypokalaemia was noted in only three instances (0.5%). Hepatotoxicity occurred in 1.7%, diarrhoea in 1.9% and leukopenia in 0.3%. Transient chest discomfort was seen on rapid infusion on three occasions. Overall, azlocillin appeared well tolerated, and had no evident unique toxicity.

Topics: Adolescent; Adult; Aged; Azlocillin; Bacterial Infections; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Hypersensitivity; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Kidney Diseases; Male; Middle Aged; Penicillins; Water-Electrolyte Imbalance