Antimicrobial Drugs

 

10. List the antibiotic with the fewest side effects.
12. List the antibiotics used to treat tuberculosis.
13. List and describe the antibacterial drugs that work by inhibition of cell wall synthesis.
14. Define penicillinase and describe what it does.
15. List and describe the semisynthetic penicillins.
16. List and describe the monobactam antibiotics.
17. List and describe the cephalosporins.
18. List the other antibiotics that act by inhibition of cell wall synthesis.
19. Give the specific functions of isoniazid and ethambutol.

A Survey Of Commonly Used Antimicrobial Drugs

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis





All penicillins contain a B-lactam ring.

Natural Penicillins

Natural penicillins (Penicillin G, Penicillin V) produced by Penicillium are effective against gram-positive cocci and spirochetes.

Natural penicillins have a narrow spectrum activity and are susceptible to penicillinases (or B-lactimases) - bacterial enzymes that destroy natural penicillins.

 

Retention of Penicillin G

The Effect of Penicillinase

 

Semisynthetic Penicillins

Semisynthetic penicillins are made in the laboratory by adding different side chains onto the B-lactam ring after it is synthesized by a fungus.

Semisynthetic penicillins (oxacillin, ampicillin, amoxicillin, aztreonam, imipenem) are resistant to penicillinases and have a broader spectrum of activity than natural penicillins.

Pecillinase-Resistant Penicillins

The first penicillinase-resistant semisynthetic penicillin was methicillin.  We've got so much methicillin resistance that methicillin use has been discontinued in the U.S.

Oxacillin and nafcillin are replacements for methicillin.

Extended-Spectrum Penicillins

Ampicillin and amoxicillin are aminopenicillins, which are effective against both gram-positive bacteria and many gram-negative bacteria, but aren't penicillinase resistant.

The carboxypenicillins carbenicillin and ticarcillin were developed to fight aminopenicillin-resistant organisms and have better activity against gram-negative bacteria, including Pseudomonas aeruginosa.

Ureidopenicillins like mezlocillin and azlocillin are more recently developed extended spectrum penicillins.

Penicillins plus B-lactam Inhibitors

Potassium clavulanate is an inhibitor of penicillinase that can be combined with broad spectrum penicillins.

Augmentin is amoxicillin plus potassium clavulanate.

Carbapenems

Carbapenems are broad-spectrum B-lactam antibiotics that inhibit cell wall synthesis.

Primaxin is a combination of imipenem and cilastin (which inhibits degradation in the kidneys) and is active against 98% of all organisms isolated from hospital patients.

Monobactams

Monobactams are made resistant to penicillinase by using only a single ring rather than the B-lactam double ring.

Aztreonam affects only certain gram-negative bacteria, including pseudomonads and E. coli.

Cephalosporins

Cephalosporins inhibit cell wall synthesis like penicillins and have more activity against gram-negative organisms.

They are used against penicillin resistant strains but are susceptible to a different class of B-lactamases and also are contraindicated in people with penicillin allergy.

First generation cephalosporins include cephalothin, and cephalexin. Later generations of cephalosporins have greater activity against gram-negative organisms but sometimes don't work as well against gram-positive organisms (those beta-lactamases, damn it!). The goal is to be able to treat S. aureus, S. pneumoniae, Enterococcus, and Psuedomonas, and offer a reasonable dosing regimen (oral vs. parenteral, longer times between doses).

The third generation cephalosporins cefpodoxime (Vantin), cefdinir (Omnicef) and cefixime (Suprax) have been approved for oral administration. Third generation cephalosporins that require parenteral administration include cefotaxime (Claforan) and ceftriaxione (Rocephin).

Fourth generation? You bet - cefepime (Maxipime) - good against gram-positive cocci and Pseudomonas and is resistant to hydrolysis by many expanded spectrum beta-lactamases (ESBLs).

Comparison of Cephalosporin and Penicillin

 

Polypeptide Antibiotics

Bacitracin inhibits cell wall synthesis primarily in gram-positive bacteria. It is applied topically to treat superficial infections.

Vancomycin inhibits cell wall synthesis and may be used to kill penicillinase-producing staphylococci.

Antimycobacterial Antibiotics

Isoniazid (INH) inhibits mycolic acid synthesis in mycobacteria and is used to treat tuberculosis. INH is administered with rifampin or ethambutol to avoid resistance.

The antimetabolite ethambutol is only effective against mycobacteria.  Because it is weak it is used with other antitubercular drugs.