Role of pharmacokinetics in the outcome of infections

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

“…However, the determination of concentrations of antibiotics in sputum is unreliable. Various studies demonstrated considerable variability in the absolute concentrations of antimicrobial agents in sputum, even when identical classes of antimicrobial agents were considered (6,9,28). Furthermore, although the determination of antibiotic concentrations in bronchial biopsy specimens is comparatively easy and shows better reproducibility than sputum analysis, it has limited clinical relevance, since it provides no information on the relative drug concentration in the interstitial fluid.…”

“…In cases of lower respiratory tract infections, chemical analysis of sputum (6,9,28) and analyses of tissue biopsy specimens and bronchoalveolar lavage fluid (15,32), epithelial lining fluid (4,35), and alveolar macrophages (12,13) have been performed to obtain information about the penetration of antibiotics into the lungs (3,16). However, the determination of concentrations of antibiotics in sputum is unreliable.…”

“…Concentrations of antibiotics have been measured in sputum samples (6,9,19,28), bronchoscopically harvested biopsy specimens, and bronchoalveolar lavage fluids (15,32). More sophisticated approaches include the determination of antibiotic concentrations in epithelial lining fluid (4,35) or in alveolar macrophages (12,13).…”

Recent advances in materials for extended-release antibiotic delivery system

“…2 For these agents, the time that therapeutic drug concentrations are above the MIC (T4MIC) is the primary parameter and should be kept for a minimum standard to achieve the desired clinical outcomes. 3 In addition, dosage under the threshold may promote the development of antibiotic resistance. 4 Therefore, continuous infusion has been proposed and its clinical advantage against antibiotic resistance over intermittent bolus for time-dependent antimicrobials has been confirmed.…”

Pharmacokinetic and pharmacodynamic requirements for antibiotic therapy of experimental endocarditis

“…Unfortunately, these last two parameters are difficult to measure without altering the physiologic characteristics of the infected vegetations. (21,57) that, in monotherapy, antibiotics with slow bactericidal killing rates (i.e., those with a time-dependent effect) and no PAE, such as 1-lactams, must be administered at short intervals in order to maintain local inhibitory levels throughout the entire dosing interval. In contrast, antibiotics with a rapid killing rate (i.e., with a concentration-dependent effect) and a PAE, such as aminoglycosides and fluoroquinolones have on some organisms, can be administered at longer dosing intervals.…”