Intrapulmonary Pharmacokinetics of Antibacterial Agents
The idea of studying the pharmacokinetics and pharmacodynamics of antibacterials in order to predict their efficacy has long been of interest. Traditionally, serum drug concentrations have been evaluated against the minimum inhibitory concentration (MIC) of a given pathogen; however, infection site-specific data continue to gain interest from clinicians. Despite methodological limitations, progress in techniques has improved the clinical significance of data generated. Rather than using tissue homogenates which fail to differentiate between interstitial and intracellular concentrations, newer collection techniques focus on sampling of matrices that allow for this differentiation. These collection techniques now allow one to accurately describe β-lactam and aminoglycoside interstitial penetrations, as well as, the interstitial and phagocytic concentrations of macrolides and fluoroquinolones. By using these specific data and the MICs of infecting pathogens, it is hoped that conclusions can be drawn by a clinician as to the appropriateness of the choice of an antibacterial.
KeywordsMinimum Inhibitory Concentration Alveolar Macrophage Azithromycin Macrolides Cefixime
The authors have received no funding for the preparation of this manuscript and have no conflicts of interest that are directly relevant to it.
- 9.Ogren S, Cars O. Importance of drug-protein interactions and protein concentrations for antibiotic levels in serum and tissue fluid. Scand J Infect Dis 1985; Suppl. 44: 34–40Google Scholar
- 21.Rodvold KA, Danziger LH. Intrapulmonary concentrations of clarithromycin and azithromycin: impact of differences in methodology on the variability of results [abstract]. Proceedings of the Sixth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2002 Jan 23–25; Bologna, 129. Atlanta (GA): Wallace Communications Inc., 2002Google Scholar
- 31.Yao JDC, Moellering RC. Antimicrobial agents: glycopeptides and lipopeptides. In: Balows A, Hausler WJ, Herrmann KL, et al., editors. Manual of clinical microbiology. 5th ed. Washington, DC: American Society for Microbiology, 1991: 1076–7Google Scholar
- 39.Andrews JM, Honeybourne D, Brenwald NP, et al. Concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum after administrations of single or multiple oral doses to patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1997; 39: 797–802PubMedCrossRefGoogle Scholar
- 41.Kashuba ADM, Bertino Jr JS, Nafziger AN. Dosing of aminoglycosides to rapidly attain pharmacodynamic goals and hasten therapeutic response by using individualized pharmacokinetic monitoring of patients with pneumonia caused by Gram-negative organisms. Antimicrob Agents Chemother 1998; 42: 1842–4PubMedGoogle Scholar