Those who treat children are well aware of the toxicities of tetracycline antibiotics, leading to a general contraindication for their use in children less than 8 years of age. However, as with any antibiotic, the benefits of therapy may outweigh the risks in certain situations. Tigecycline is a tetracycline derivative, administered intravenously, with a broader spectrum of activity than seen with most previously available agents in this class. The mechanism of action and the toxicities, including staining of bones in experimental animals, is present with tigecycline as with other tetracyclines. The antibiotic is not being actively pursued in children at this time, but was recently approved for use in adults for complicated skin and skin structure infections, and complicated intraabdominal infections. Tigecycline has activity against most Gram-positive cocci, including methicillin-resistant Staphylococcus aureus and enterococcus, in addition to demonstrating activity against Pseudomonas aeruginosa. The structure of the antibiotic is very similar to minocycline, with the addition of a glycylamido moiety (see Figure 13.8). The antibiotic is bacterio-static, with relatively high protein binding (80%) and relatively long serum elimination half-life of 30 hours, being excreted primarily into bile (60%), but with significant renal excretion (35%). Dosing every 12 hours was investigated in clinical trials. As with other tetracyclines, it inhibits protein synthesis in bacteria by binding to the 30S ribosomal subunit, blocking entry of amino-acyl tRNA molecules into
Figure 13.8. Tigecycline.
the ribosome. For the child with a life-threatening infection whose organism is resistant to alternative therapy, or in the child who cannot tolerate alternative therapy, tigecycline should provide a reasonable option (Babinchak et al., 2005; Ellis-Grosse et al., 2005; Hoban et al., 2004; Livermore, 2005; Meagher et al., 2005; Noskin, 2005).
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