Of the lincosamides, lincomycin (R = H) and clindamycin (R = Cl) (Supplementary Table ) are the only two lincosamides in clinical use. Lincosamides are bacteriostatic against Gram-positive cocci, Staphylococcus, group A and B Streptococcus, Clostridium species, Corynebacterium diphtheriae, Bacillus anthracis, and Gram-positive anaerobes but are not effective against Neisseria species, enterococci, Haemophilus influenzae, or Moraxella catarrhalis. Clindamycin also inhibits the growth of Plasmodium berghei and Toxoplasma gondii. Lincomycin is thus used for Gram-positive skin, skin structure, and bone infections, while clindamycin is used for anaerobic bacterial infections, particularly intestinal and vaginal infections. The lincosamides are administered intravenously but are incompatible with ampicillin, magnesium sulfate, calcium gluconate, phenytoin, B vitamins, and barbiturates. Lincosamides bind to the peptidyltransferase center of the 50S subunit of the bacterial ribosome to prevent peptide transfer and thus inhibit bacterial protein synthesis (a mechanism common to multiple antibiotic classes because of its conservation). However, bacteria have multiple pathways to resist lincosamide-mediated toxicity. The cell walls of Gram-negative bacteria reduce passive diffusion of antibiotics, which can be further reduced if efflux pumps are also present (a mechanism also available to Gram-positive bacteria). Methylation of the 23S rRNA by the methyltransferase produced by the CFR gene reduces the ability of lincosamides to bind to the ribosome, as it does for streptogramins and macrolides. In Staphylococcus aureus, an O-nucleotidyltransferase mediates the adenosine monophosphorylation of the 4'-hydroxyl group of lincosamides to ablate binding. Finally, alterations of membrane permeability in Gram-positive bacteria can reduce the cellular concentrations of lincosamides and thus their effectiveness.