Pharmacokinetics and pharmacodynamics of aztreonam and tobramycin in hospitalized patients

Background: Pharmacokinetic/pharmacodynamic (PK/PD) optimization of antibio tic therapy has been shown to improve outcomes in several antibiotic classe s. Despite the frequent use of beta-lactams, clinical data in humans remain limited. Objective: This study evaluated the relationship between serum pharmacokine tics, pharmacodynamics, pathogen susceptibility, and clinical outcomes in p atients 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 con ducted between 1982 and 1984 were reviewed for the present study. A pathoge n 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 deter-mined usin g population modeling, and variables potentially related to outcomes were e valuated using tree-based modeling, logistic regression, and nonlinear regr ession methods. Results: Data from 91 patients were analyzed, 68 treated with aztreonam mon otherapy and 23 treated with tobramycin monotherapy. Of the types of infect ions treated, 39 were intra-abdominal, 42 involved the lower respiratory tr act, and 10 involved the skin and skin structures. The pharmacodynamic rati o of the 24-hour area under the curve (AUC(24)) to the MIC was associated w ith clinical outcome for both antibiotics: aztreonam and tobramycin patient s with ratios meeting or exceeding the respective 24-hour inverse serum inh ibitory 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 pat ients were considered. the likelihood of achieving cure was 5.1 times great er in patients exceeding the target ratios (P < 0.01). Conclusion: PK/PD optimization of both aztreonam and tobramycin is associat ed with improved patient outcomes.