Search

The direct effect of clarithromycin and azithromycin on human polymorphonuclear leukocyte (PMN) functions and their intracellular activity against Staphylococcus aureus, phagocytosed by human monocytes, were studied. The presence of both antibiotics, in the range of concentrations from 0.25 to 20 micrograms/ml, did not affect chemotaxis, opsonized-zymosan phagocytosis, respiratory burst measured by nitroblue tetrazolium reduction and phorbol myristate acetate-induced superoxide production, or the microbicidal activity of human PMNs against Candida albicans. Both macrolides were bactericidal against staphylococci in the monocyte system, while bacteriostatic activity was found in cell free system. At concentrations equal to the minimum inhibitory concentrations (MICs) (0.75 and 0.1 respectively for azithromycin and clarithromycin) more than 99% of intraphagocytic S. aureus were killed after 24 h incubation. Increasing the concentrations of each drug above the MICs (5 and 10 MICs) did not alter the killing rate of intracellular bacteria. Moreover, no differences between the intracellular bioactivity of these antibiotics were demonstrated, despite their different uptake kinetics.

The Author provides a review of clinical experience with tobramycin as therapy for lower respiratory tract infections, in comparison to other aminoglycosides, including the pharmacokinetics and toxicity, dwelling on oto- and nephrotoxicity. The article includes a discussion of various dosing regimens of the aminoglycosides, focussing on efficacy and toxicity arising from once-daily administration. The Author then provides a more detailed description of tobramycin's pharmacokinetics, indications for its use, and the possibilities of once-daily dosing, concluding that toxicity is favorably influenced by a single daily administration as well as efficacy, and that patient compliance and reduced hospital costs are other advantages of this regimen.