Antibiotics

Definition

Antibiotics are used for treatment or prevention of bacterial infection. They may be informally defined as the subgroup of anti-infectives that are derived from bacterial sources and are used to treat bacterial infections. Other classes of drugs, most notably the sulfonamides , may be effective antibacterials. Similarly, some antibiotics may have secondary uses, such as the use of demeclocycline (Declomycin, a tetracycline derivative) to treat the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Other antibiotics may be useful in treating protozoal infections.

Description

Classifications

Although there are several classification schemes for antibiotics, based on bacterial spectrum (broad versus narrow) or route of administration (injectable versus oral versus topical), or type of activity (bactericidal versus bacteriostatic), the most useful is based on chemical structure. Antibiotics within a structural class will generally show similar patterns of effectiveness, toxicity, and allergic potential.

PENICILLINS The penicillins are the oldest class of antibiotics and have a common chemical structure that they share with the cephalosporins. Classed as the betalactam antibiotics, the two groups are generally bacteriocidal, which means that they kill bacteria rather than simply inhibit its growth. The penicillins can be further subdivided. The natural penicillins are based on the original penicillin G structure; penicillinase-resistant penicillins, notably methicillin and oxacillin, are active even in the presence of the bacterial enzyme that inactivates most natural penicillins. Aminopenicillins such as ampicillin and amoxicillin have an extended spectrum of action compared with the natural penicillins; extended spectrum penicillins are effective against a wider range of bacteria. These generally include coverage for Pseudomonas aeruginosa.

CEPHALOSPORINS Cephalosporins and the closely related cephamycins and carbapenems, like the penicillins, contain a beta-lactam chemical structure. Consequently, there are patterns of cross-resistance and cross-allergenicity among the drugs in these classes. The "cepha" drugs are among the most diverse classes of antibiotics and are themselves subdivided into first, second, and third generations. Each generation has a broader spectrum of activity than the one before. In addition, cefoxitin, a cephamycin, is highly active against anaerobic bacteria, which offers utility in treatment of abdominal infections. The third generation drugs, cefotaxime, ceftizoxime, ceftriaxone, and others, cross the blood-brain barrier and may be used to treat meningitis and encephalitis . Cephalosporins are the usually preferred agents for surgical prophylaxis.

FLUOROQUINOLONES The fluoroquinolones are synthetic antibacterial agents and not derived from bacteria. They are included here because they can be readily interchanged with traditional antibiotics. An earlier, related class of antibacterial agents, the quinolones, drugs that were not well absorbed, could be used only to treat urinary tract infections. The fluoroquinolones, which are based on the older group, are broad-spectrum bacteriocidal drugs that are chemically unrelated to the penicillins or the cephalosporins. They are well distributed into bone tissue and so well absorbed that in general they are as effective by the oral route as by intravenous infusion.

TETRACYCLINES Tetracyclines got their name from the fact that they share a chemical structure that has four rings. They are derived from a species of Streptomyces bacteria. Broad-spectrum bacteriostatic agents, the tetracyclines may be effective against a wide variety of microorganisms, including rickettsia and amoebic parasites.

MACROLIDES The macrolide antibiotics are derived from Streptomyces bacteria. Erythromycin, the prototype of this class, has a spectrum and use similar to penicillin. Newer members of the group, azithromycin and clarithromycin, are particularly useful for their high level of lung penetration. Clarithromycin has been widely used to treat Helicobacter pylori infections, the cause of stomach ulcers.

OTHERS Other classes of antibiotics include the aminoglycosides, which are particularly useful for their effectiveness in treating Pseudomonas aeruginosa infections, and the lincosamide drugs clindamycin and lincomycin, which are highly active against anaerobic pathogens. There are other, individual drugs which may have utility in specific infections.

General use

Antibiotics are used for treatment or prevention of bacterial infections. In most cases, they are prescribed for a short period of time to treat a specific infection. This period may range from three days to 10 days or more. More serious infections may require longer periods of treatment, up to several months or longer. Lower doses may be used over a long period of time to prevent the return of a serious infection.

Precautions

All antibiotics should be used as prescribed. These drugs will degrade over time and lose their potency. Not completing a prescribed course of treatment increases the probability that drug-resistant strains of organisms will develop.

Side effects

All antibiotics cause risk of overgrowth by non-susceptible bacteria. Manufacturers list other major hazards by class; however, the healthcare provider should review each drug individually to assess the degree of risk. Generally, breastfeeding may be continued while taking antibiotics, but nursing mothers should always check with their physician first. Excessive or inappropriate use may promote growth of resistant pathogens.

Hypersensitivity to penicillins may be common, and cross allergenicity with cephalosporins has been reported. (That is, those who are allergic to penicillin may also be allergic to cephalosporins.) Penicillins are classed as category B during pregnancy.

Several cephalosporins and related compounds have been associated with seizures. Cefmetazole, cefoperazone, cefotetan, and ceftriaxone may be associated with problems in poor blood clotting. Pseudomembranous colitis (an intestinal disorder) has been reported with cephalosporins and other broad spectrum antibiotics. Some drugs in this class may cause kidney toxicity. Cephalosporins are classed as category B during pregnancy.

Regarding fluoroquinolones, lomefloxacin has been associated with increased sensitivity to light. All drugs in this class have been associated with convulsions. Fluoroquinolones are classed as category C during pregnancy.

Of the tetracyclines, demeclocycline may cause increased photosensitivity. Minocycline may cause dizziness . Healthcare providers do not prescribe tetracyclines in children under the age of eight, and they specifically avoid doing so during periods of tooth development. Oral tetracyclines bind to anions such as calcium and iron. Although doxycycline and minocycline may be taken with meals, people must be advised to take other tetracycline antibiotics on an empty stomach and not to take the drugs with milk or other calcium-rich foods. Expired tetracycline should never be administered. These drugs have a pregnancy category D. Use during pregnancy may cause alterations in fetal bone development.

Of the macrolides, erythromycin may aggravate the weakness of people with myasthenia gravis. Azithromycin has, rarely, been associated with allergic reactions, including angioedema (swelling), anaphylaxis, and severe skin reactions. Oral erythromycin may be highly irritating to the stomach and when given by injection may cause severe phlebitis (inflammation of the veins). These drugs should be used with caution in people with liver dysfunction. Azithromycin and erythromycin are pregnancy category B. Clarithromycin, dirithromycin, and troleandomycin are pregnancy category C.

The aminoglycosides class of drugs causes kidney and ear problems. These problems can occur even with normal doses. Dosing should be based on kidney function, with periodic testing of both kidney function and hearing. These drugs are pregnancy category D.

Parental concerns

Parents should be sure to follow all dosage and label directions. This includes using all of a prescription at the time it is prescribed. Parents should also ensure that children cannot ingest any prescription medications by accident.

KEY TERMS

Bacteria —Singular, bacterium; tiny, one-celled forms of life that cause many diseases and infections.

Bacterial spectrum —The number of bacteria an antibiotic is effective against. Broad-spectrum antibiotics treat many different kinds of bacteria. Narrow-spectrum antibiotics treat fewer kinds.

Inflammation —Pain, redness, swelling, and heat that develop in response to tissue irritation or injury. It usually is caused by the immune system's response to the body's contact with a foreign substance, such as an allergen or pathogen.

Meningitis —An infection or inflammation of the membranes that cover the brain and spinal cord. It is usually caused by bacteria or a virus.

Microorganism —An organism that is too small to be seen with the naked eye, such as a bacterium, virus, or fungus.

Organism —A single, independent unit of life, such as a bacterium, a plant, or an animal.

Pregnancy category —A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies, or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies, or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Resources

BOOKS

Antibiotics: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: ICON Health Publications, 2003.

Archer, Gordon, and Ronald E. Polk. "Treatment and Prophylaxis of Bacterial Infections." In Harrison's Principles of Internal Medicine, 15th ed. Edited by Eugene Braunwald, et al. New York: McGraw-Hill, 2001, pp. 867-81.

Diasio, Robert B. "Principles of Drug Therapy." In Cecil Textbook of Medicine, 22nd ed. Edited by Lee Goldman, et al. Philadelphia: Saunders, 2003, pp. 124-34.

Scott, Geoffrey M. Handbook of Essential Antibiotics. New York: Gordon & Breach Publishing Group, 2004.

Sherman, Josepha. War against Germs. New York: Rosen Publishing Group, 2004.

PERIODICALS

Ashworth, M., et al. "Why has antibiotic prescribing for respiratory illness declined in primary care?" Journal of Public Health (Oxford) 26, no. 3 (2004): 268–74.

Carrat, F., et al. "Antibiotic treatment for influenza does not affect resolution of illness, secondary visits or lost workdays." European Journal of Epidemiology 19, no. 7 (2004): 703-5.

Dancer, S. J. "How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chemotherapy." Lancet Infectious Diseases 4, no. 10 (2004): 611–9.

Simoes, J. A., et al. "Antibiotic resistance patterns of group B streptococcal clinical isolates." Infectious Diseases in Obstetrics and Gynecology 12, no. 1 (2004): 1–8.

ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Web site: http://www.aafp.org/.

American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. Web site: http://www.aap.org/.

American College of Emergency Physicians. PO Box 619911, Dallas, TX 75261-9911. Web site: http://www.acep.org/.

WEB SITES

"Antibiotic Guide." Johns Hopkins Point of Care Information Technology. Available online at http://hopkinsabxguide.org/ (accessed December 19, 2004).

"Antibiotics: When They Can and Can't Help." American Academy of Family Physicians. Available online at http://familydoctor.org/x2250.xml (accessed December 19, 2004).

L. Fleming Fallon, Jr., MD, DrPH