Pharmacokinetics and pharmacodynamics of aztreonam and tobramycin in hospitalized patients

Abstract

Background: Pharmacokinetic/pharmacodynamic (PK/PD) optimization of antibiotic therapy has been shown to improve outcomes in several antibiotic classes. Despite the frequent use of beta-lactams, clinical data in humans remain limited. Objective: This study evaluated the relationship between serum pharmacokinetics, pharmacodynamics, pathogen susceptibility, and clinical outcomes in patients receiving aztreonam or tobramycin monotherapy. Methods: The case-report forms of hospitalized patients who received either aztreonam or tobramycin for a bacterial infection in 3 clinical trials conducted between 1982 and 1984 were reviewed for the present study. A pathogen was identified for all included patients, and susceptibility testing was performed to determine the minimum inhibitory concentration (MIC) for each agent. Pharmacokinetic parameters for each antibiotic were determined using population modeling, and variables potentially related to outcomes were evaluated using tree-based modeling, logistic regression, and nonlinear regression methods. Results: Data from 91 patients were analyzed, 68 treated with aztreonam monotherapy and 23 treated with tobramycin monotherapy. Of the types of infections treated, 39 were intra-abdominal, 42 involved the lower respiratory tract, and 10 involved the skin and skin structures. The pharmacodynamic ratio of the 24-hour area under the curve (AUC 24) to the MIC was associated with clinical outcome for both antibiotics: aztreonam and tobramycin patients with ratios meeting or exceeding the respective 24-hour inverse serum inhibitory titer breakpoints of 184 and 110 were significantly more likely to achieve a successful outcome than were those with ratios not meeting these values ( P < 0.01). The probabilities of clinical success in patients at or above and below the AUC 24/MIC break-points were a respective 85% and 53% for aztreonam and 80% and 47% for tobramycin (both, P < 0.01). When all patients were considered, the likelihood of achieving cure was 5.1 times greater in patients exceeding the target ratios ( P < 0.01). Conclusion: PK/PD optimization of both aztreonam and tobramycin is associated with improved patient outcomes.