Antibiotics

Various families of antibiotics are used for various types of microorganisms to achieve control and assist body defenses during times of infection. Antibiotics are products of microorganisms that react with and inhibit the growth of other microorganisms. An antibiotic should be selectively toxic to pathogenic microorganisms, should not incite an allergic response in the body, should not upset the normal microbial population of various body sites, and should not foster the development of drug resistance.

Penicillin. Penicillin prevents Gram-positive bacteria from forming peptidoglycan, the major component of the cell wall. Without peptidoglycan, internal pressures cause the bacterium to swell and burst.

Penicillin is not one antibiotic, but a family of antibiotics. The family includes penicillin F, penicillin G, and penicillin X, as well as ampicillin, amoxicillin, nafcillin, and ticarcillin. The first penicillin was derived from the green mold Penicillium, but most penicillins are now produced by synthetic means. A few are used against Gram-negative bacteria.

People allergic to penicillin may suffer localized allergy reactions or whole body reactions known as anaphylaxis. Long-term use of penicillin encourages the emergence of penicillin-resistant bacteria because these bacteria produce penicillinase, an enzyme that converts penicillin to penicilloic acid.

Cephalosporin antibiotics. Cephalosporin antibiotics include cefazolin, cefoxitin, cefotaxime, cefuroxime, and moxalactam. The antibiotics were first produced by the mold Cephalosporium. They prevent synthesis of bacterial cell walls, and most are useful against Gram-positive bacteria; the newer cephalosporin antibiotics are also effective against Gram-negative bacteria. Cephalosporins are especially useful against penicillin-resistant bacteria and are often used as substitutes for penicillin.

Aminoglycoside antibiotics. The aminoglycoside antibiotics inhibit protein synthesis in Gram-negative bacteria. Members of this antibiotic group include gentamicin, kanamycin, tobramycin, and streptomycin. Originally isolated from members of the bacterial genus Streptomyces, the aminoglycosides are now produced synthetically or semisynthetically. Streptomycin is effective against the tuberculosis bacterium. Unfortunately, many aminoglycosides have a deleterious effect on the ear and impair hearing.

Tetracycline antibiotics. Tetracycline antibiotics are broadspectrum drugs that inhibit the growth of Gram-negative bacteria, rickettsiae, chlamydiae, and certain Gram-positive bacteria. They accomplish this by inhibiting protein synthesis. Compared to other antibiotics, tetracyclines have relatively mild side effects, but they are known to destroy helpful bacteria in the body. Also, they interfere with calcium deposit in the body, so they should not be used in very young children. Originally isolated from members of the genus Streptomyces, the tetracyclines include such antibiotics as minocycline, doxycycline, and tetracycline.

Other antibacterial antibiotics. The antibiotic erythromycin may be used as a substitute for penicillin when penicillin sensitivity or penicillin allergy exists. Erythromycin is useful against Gram-positive bacteria and has been found effective against the organisms that cause Legionnaires' disease and mycoplasmal pneumonia. It inhibits protein synthesis.

Tuberculosis is a difficult disease to treat because the etiologic agent is the extremely resistant bacterium Mycobacterium tuberculosis. Five drugs are currently useful for treating tuberculosis: rifampin, ethambutol, streptomycin, para-aminosalicylic acid, and isoniazid. Rifampin is also used to treat bacterial meningitis.

Bacitracin is used for the treatment of skin infections due to Gram-positive bacteria. This antibiotic inhibits cell wall synthesis in bacteria and can be used internally, but it may cause kidney damage.

Vancomycin is currently used against bacteria displaying resistance to penicillin, cephalosporin, and other antibiotics. Vancomycin is a very expensive antibiotic with numerous side effects, and it is used only in life-threatening situations. It interferes with cell wall formation in bacteria.

Chloramphenicol is effective against a broad range of bacteria including Gram-positive and Gram-negative bacteria, rickettsiae, and chlamydiae. However, it has serious side effects such as aplastic anemia (blood cells without hemoglobin), and it may induce the gray syndrome (a type of cardiovascular collapse) in babies. Therefore, it is used for only the most serious bacterial infections such as typhoid fever and meningitis.

Sulfa drugs such as sulfamethoxazole and sulfisoxazole are effective against Gram-positive bacteria. These bacteria produce folic acid, and the sulfa drugs interfere with its production by replacing para-aminobenzoic acid (PABA) in the folic acid molecule. This action typifies how an antibiotic can interfere with a metabolic pathway in bacteria.

Antifungal drugs. Several antifungal antibiotics are currently available for treating infectious disease. One example is griseofulvin, which is used against the fungi of ringworm and athlete's foot. Other examples are nystatin, clotrimazole, ketoconazole, and miconazole, all of which are used against vaginal infections due toCandida albicans. For systemic fungal infections, the antibiotic amphotericin B is available, although it has serious side effects.

Antiviral drugs. Antiviral drugs are not widely available because viruses have few functions or structures with which drugs can interfere. Nevertheless, certain drugs are available to interfere with viral replication. One example is azidothymidine (AZT), which is used to interrupt the replication of human immunodeficiency virus. Other examples are acyclovir, which is used against herpes viruses and chickenpox viruses;ganciclovir, which is used against cytomega-lovirus; amantadine, which is prescribed against influenza viruses; and interferon, which has been used against rabies viruses and certain cancer viruses.

Antiprotozoal drugs. Many antibiotics used against bacteria, for example, tetracycline, are also useful against protozoa. Among the drugs used widely as antiprotozoal agents are metronidazole (Flagyl), which is used against Trichomonas vaginalis; quinine, which is used against malaria; and pentamidine isethionate, which is valuable againstPneumocystis carinii.


Drug resistance. Over the past decades, drug-resistant strains have developed in bacteria. These strains probably existed in the microbial population, but their resistance mechanisms were not needed because the organisms were not confronted with the antibiotic. With widespread antibiotic use, the susceptible bacteria died off, and the resistant bacteria emerged. They multiplied to form populations of drug-resistant microorganisms.

Microorganisms can exhibit their resistance in various ways. For example, they can release enzymes (such as penicillinase) to inactivate the antibiotic before the antibiotic kills the microorganism; or they can stop producing the drug-sensitive structure or modify the structure so that it is no longer sensitive to the drug; or they can change the structure of the plasma membrane so that the antibiotic cannot pass to the cytoplasm.