Tetracyclines,Macrolides,Clindamycin,Chloramphenicol,Streptogramins Henry F.Chambers,MD INTRODUCTION The drugs described in this chapter inhibit bacterial protein synthesis by binding to and interfering with ribosomes. TETRACYCLINES Introduction All of the tetracyclines have the basic structure shown below: Free tetracyclines are crystalline amphoteric substances of low solubility.They are available as hydrochlorides,which are more soluble.Such solutions are acid and,with the exception of chlortetracycline,fairly stable.Tetracyclines chelate divalent metal ions,which can interfere with their absorption and activity.A newly approved tetracycline analog,tigecycline,is a glycylcycline and a semisynthetic derivative of minocycline. Antimicrobial Activity Tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis.They are active against many gram-positive and gram-negative bacteria, including anaerobes,rickettsiae,chlamydiae,mycoplasmas,and L forms;and against some protozoa,eg,amebas.The antibacterial activities of most tetracyclines are similar except that tetracycline-resistant strains may be susceptible to doxycycline, minocycline,and tigecycline,all of which are poor substrates for the efflux pump that mediates resistance.Differences in clinical efficacy for susceptible organisms are minor and attributable largely to features of absorption,distribution,and excretion of individual drugs. Tetracyclines enter microorganisms in part by passive diffusion and in part by an energy-dependent process of active transport.Susceptible cells concentrate the drug intracellularly.Once inside the cell,tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome,blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex (Figure 44-1).This prevents addition of amino acids to the growing peptide.Tetracyclines, Macrolides, Clindamycin, Chloramphenicol, & Streptogramins Henry F. Chambers, MD INTRODUCTION The drugs described in this chapter inhibit bacterial protein synthesis by binding to and interfering with ribosomes. TETRACYCLINES Introduction All of the tetracyclines have the basic structure shown below: Free tetracyclines are crystalline amphoteric substances of low solubility. They are available as hydrochlorides, which are more soluble. Such solutions are acid and, with the exception of chlortetracycline, fairly stable. Tetracyclines chelate divalent metal ions, which can interfere with their absorption and activity. A newly approved tetracycline analog, tigecycline, is a glycylcycline and a semisynthetic derivative of minocycline. Antimicrobial Activity Tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis. They are active against many gram-positive and gram-negative bacteria, including anaerobes, rickettsiae, chlamydiae, mycoplasmas, and L forms; and against some protozoa, eg, amebas. The antibacterial activities of most tetracyclines are similar except that tetracycline-resistant strains may be susceptible to doxycycline, minocycline, and tigecycline, all of which are poor substrates for the efflux pump that mediates resistance. Differences in clinical efficacy for susceptible organisms are minor and attributable largely to features of absorption, distribution, and excretion of individual drugs. Tetracyclines enter microorganisms in part by passive diffusion and in part by an energy-dependent process of active transport. Susceptible cells concentrate the drug intracellularly. Once inside the cell, tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex (Figure 44-1). This prevents addition of amino acids to the growing peptide