Other Agents That Inhibit Bacterial Protein Synthesis

Other Agents That Inhibit Bacterial Protein Synthesis 

Chloramphenicol. Chloramphenicol (Chloromycetin) is a synthetically produced agent that exerts antibacterial effects similar to those of erythromycin that is, it binds to the 50S subunit of bacterial ribosomes and inhibits peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic that is active against many gram-negative and gram-positive bacteria. This drug is administered systemically to treat serious infections such as typhoid fever, Haemophilus infections such as osteomyelitis, rickettsial infections such as Rocky Mountain spotted fever, and certain forms of meningitis. Chloramphenicol may also be administered topically to treat various skin, eye, and ear infections. 

The most serious problem associated with chloramphenicol is the potential for bone marrow aplasia, which can lead to aplastic anemia and possibly death.16,83 Chloramphenicol is also associated with other blood dyscrasias such as agranulocytosis and thrombocytopenia. Because of these risks, chloram- 

Lincomycin. Lincomycin (Lincocin, Lincorex) is similar in mechanism of action, clinical indications, and adverse side effects to clindamycin (see previously in this section). 

Quinupristin and Dalfopristin. Quinupristin and Dalfopristin are combined in the same product (Syn- 

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The mechanism of toxicity for aminoglycosides has not been fully explained and is therefore unclear. It is known that the drug attaches to a bacterial cell wall and is drawn into the cell via channels made up of a protein, porin. Once inside the cell, the aminoglycoside attaches to the 30S bacterial ribosomes. Ribosomes are the intracellular structures responsible for manufacturing proteins. This attachment either inhibits protein biosynthesis or causes the cell to produce abnormal, ineffective proteins. The bacterial cell cannot survive with this impediment. This explanation, however, does not account for the potent bactericidal properties of these agents, since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not bactericidal. Recent experimental studies show that the initial site of action is the outer bacterial membrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer membrane probably accounts for most of the bactericidal activity. 

The mechanism of protein synthesis inhibition exhibited by aminoglycosides other than SM differ in particular details. It was shown that KM, NM, and GM have multiple ribosomal binding sites rather than the single site to which SM binds. Translocation on bacterial ribosomes is also inhibited by these agents. 

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