Figure 21.6 Chemical Structures and Properties of Representative Members of the Penicillin Family The entire structure of penicillin G and the side chain of each of the other penicillins are shown.
b-lactamase inhibitors are chemicals that interfere with the activity of some types of b-lactamases. When a b-lactamase inhibitor is administered with one of the penicillins, the medication is protected against enzymatic destruction. An example is Augmentin®, a combination of amoxicillin and clavulanic acid.
21.3 Mechanisms of Action of Antibacterial Drugs 515
The Cephalosporins The cephalosporins are derived from an antibiotic produced by the fungus Acremonium cephalosporium (formerly called Cephalosporium acremonium). Generally included in this family of drugs are a closely related group of antibiotics that are made by members of a genus of filamentous bacteria related to Streptomyces. The chemical structure of the cephalosporins makes them resistant to inactivation by certain b-lactamases, but some have a low affinity for penicillin-binding proteins of Grampositive bacteria, thus limiting their effectiveness against these organisms. Like the penicillins, the cephalosporins have been chemically modified to produce a family ofvarious related antibiotics. They are grouped as the first-, second-, third-, and fourth-generation cephalosporins. These include cephalexin and cephradine (first generation), cefaclor and cefprozil (second generation), cefixime and cefibuten (third generation), and cefepime (fourth generation). The later generations are generally more effective against Gram-negative bacteria and are less susceptible to destruction by b-lactamases.
Other b-Lactam Antibiotics Two other groups of b-lactam drugs, carba-penems and monobactams, are very resistant to b -lactamases. The carbapenems are effective against a wide range of Gram-negative and Gram-positive bacteria. Two types are available, imipenem and meropenem. Imipenem is rapidly destroyed by a kidney enzyme and is therefore administered in combination with a drug that inhibits that enzyme. The only monobactam used therapeutically, aztre-onam, is primarily effective against members of the family Enterobacteriaceae, which are Gram-negative rods. Structurally, it is slightly different from other b-lactam drugs; this characteristic is important because aztreonam can be given to patients who have developed an allergy to penicillin. ■ Enterobacteriaceae, p. 282
Vancomycin binds to the terminal amino acids of the peptide side chain of NAM molecules that are being assembled to form glycan chains. By doing so, it blocks synthesis of peptidoglycan, resulting in weakening of the cell wall and, ultimately, cell lysis. Vancomycin does not cross the outer membrane of Gramnegative bacteria; consequently, these organisms are innately resistant. It is, however, a very important medication for treating infections caused by Gram-positive bacteria that are resistant to b-lactam drugs. In addition, it is sometimes the preferred drug for treating severe cases of antibiotic-associated colitis. Because vancomycin is poorly absorbed from the intestinal tract, it must be administered intravenously except when used to treat intestinal infections. Acquired resistance to vancomycin is most often due to an alteration in the peptide side chain of the NAM molecule that prevents vancomycin from binding.
Bacitracin inhibits cell wall biosynthesis by interfering with the transport of peptidoglycan precursors across the cytoplasmic membrane. Its toxicity limits its use to topical applications; however, it is a common ingredient in non-prescription first-aid ointments.
Antibacterial Medications that Inhibit Protein Synthesis
Several types of antibacterial drugs inhibit prokaryotic protein synthesis (figure 21.7). While all cells synthesize proteins, the
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