Clarithromycin, a 14-membered ring macrolide, is antimicrobially active against a broad range of gram-positive and certain gram-negative pathogens frequently isolated from softtissue infections and bite wounds (11). Clarithromycin is considered a therapeutic alternative in special cases of minor softtissue infections and penicillin allergy or in cases of nontuberculous mycobacterial skin infections (19,20). High tissue concentrations of the class of the macrolides have been reported previously in the literature (10,13,21). Indeed, intracellular accumulation of macrolides in isolated peripheral blood phagocytes, alveolar macrophages, and tissue culture cells of human origin has been demonstrated previously (9, 16). To date, investigations of in vivo tissue pharmacokinetics (PK) of clarithromycin have been confined to concentrations derived from homogenized biopsy samples of the upper and lower respiratory tract and epithelial lining fluid collection obtained by bronchoalveolar lavage (10, 13, 21). The results derived from homogenized biopsy samples, as frequently used in previous studies, represent an average concentration of all tissue components extracted, including blood cells, intracellular fluid, interstitial fluid, and structural tissue components, and may therefore cause confusion with regard to the actual concentration of an antimicrobial agent in a defined compartment. These data, thus, provide only limited insight into the time course of concentration at the relevant site of most bacterial infections, namely, the extracellular-space fluid. Hence, we used the microdialysis technique, which is capable of the continuous assessment of unbound, i.e., microbiologically active concentrations of clarithromycin in the interstitial-space fluid of soft tissues (15).Knowledge about the concentration-time profiles of free clarithromycin in the interstitial-space fluid of soft tissues can be considered a prerequisite for dosage recommendations in the treatment of extracellularly proliferating bacteria causing soft-tissue infections. Hence, the aim of the present study was to determine free interstitial concentrations of clarithromycin in subcutaneous adipose tissue and skeletal muscle after oral single-and multiple-dose administration to healthy male volunteers. MATERIALS AND METHODSThe study took place at the Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. The study protocol was approved by the local Ethics Committee, and the study was performed in accordance with the Declaration of Helsinki 1964 (including current revisions), the Austrian Drug Law, and the Good Clinical Practice Guidelines.Healthy volunteers. Seven healthy male volunteers between the ages of 25 and 37 years were enrolled into the study. Written informed consent was obtained from each volunteer prior to any study-related investigation or intervention. Each volunteer underwent a screening examination consisting of the following: medical history, physical examination, routine laboratory tests, heart rate, blood pres...

By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens.

Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC 0-10 ) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC 0-10 for tissue to the AUC 0-10 for free gemifloxacin in plasma were 1.7 ؎ 0.7 (mean ؎ standard deviation) for skeletal muscle and 2.4 ؎ 1.0 for adipose tissue. The AUC 0-24 ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections.