Antibiotics

Antibiotics inhibit or kill bacteria. Source: NIH.

The term "antibiotic" strictly refers only to substances produced by microorganisms that affect bacteria; however, most people understand that synthetic molecules (such as sulfonamides and quinolones) can be antibiotics as well. The term "antimicrobial" is sometimes used to include agents that inhibit or kill non-bacterial microorganisms such as fungi and protozoa. Hundreds of antibiotics and antimicrobials have been identified and characterized, and their appropriate use is a cornerstone of the medical specialty of infectious disease.

Types

There are several classes of antibiotics, some of which are shown in the following table.

Uses

Antibiotics are used to treat infections caused by bacteria; they are different from other drug classes that inhibit [[viruses]], fungi, and parasites. Different bacteria have different susceptibilities to the various antibiotics; as well antibiotics have different routes of administration, solubilities, absorption rates, and toxicities once in the body. The particular antibiotic used to treat a bacterial infection is a complex decision involving the bacterial cause, site of infection, and other health issues the patient may have.

Antibiotics can also be used to prevent infection from occurring (antibiotic prophylaxis). Common prophylactic uses for antibiotics include the following:

• Prevention of spread of group B Streptococcus from mother to baby during birth.^[1]
• After a splenectomy (removal of the spleen), particularly in children.^[2]
• After exposure to Sexually Transmitted Diseases (STDs)^[3] including sexual assault.^[4]
• In children with sickle cell disease.^[5]
• In some cases of surgery of the cardiovascular system,^[6] gastrointestinal tract, brain, joints, and other organ systems.

How Antibiotics Work

A paper disk impregnanted with an antibiotic is able to stop nearby bacterial growth. Source: NOAA

Each antibiotic works only against a specific type of bacteria. It is, therefore, important to try and isolate the bacteria in a clinical specimen such as a blood or stool culture in someone who has an infectious disease. Bacteria can take several hours or days to grow in culture, and until the culture results are available, health care professionals will often make a best guess as to which antibiotic will be the most effective in a particular infection.

Most antibiotics inhibit or kill bacteria in one of the following methods:

• Preventing bacteria from making cell walls: Many antibiotics, such as penicillins and cephalosporins, prevent bacteria from constructing cell walls. All bacteria have complex cell walls that protect them from the environment. If a bacterium is unable to build a cell wall it cannot reproduce to make new bacteria.
• Stopping the production of bacterial proteins: Other antibiotics, such as aminoglycosides and erythromycin, prevent bacteria from making proteins that are essential for the bacteria's growth.
• Some antibiotics use other methods to inhibit or kill bacteria, including damaging internal structures of the bacteria, making the cell membrane more permeable, or preventing the production of DNA (a form of genetic material passed on to new bacteria).

How the Body Affects Antibiotics

There are many different types of antibiotics, and some are metabolized in the liver. If a patient with liver disease is given these antibiotics, the liver may not be able to effectively metabolize the drug, resulting in increased concentration of the antibiotic. Commonly prescribed antibiotics than can affect the liver include: tetracyclines, erythromycin, and chloramphenicol.

Many antibiotics are excreted by the kidneys. Patients with decreased kidney function may not be able to excrete the antibiotic properly. This can lead to increased concentrations of the drug in the body, possibly causing further damage. Some medicines can also damage the kidney, especially if not excreted properly. Common antibiotics that can cause kidney problems include the aminoglycosides, nitrofurantoin, penicillins, cephalosporins, quinolones, sulphonamides, and tetracyclines.

Benefits

If used appropriately, antibiotics can prevent and treat infections before they become serious. Untreated infections can lead to sepsis (blood poisoning) or bacteria in the bloodstream, which can ultimately lead to organ failure, profound low blood pressure, and ultimately death.

Side Effects

Many antibiotics produce side effects (unwanted effects of a drug). The more common side effects include the following:

• Nausea
• Diarrhea
• Upset stomach
• Loss of appetite
• Allergic reactions including rash, hives, and itching

Antibiotics can also kill healthy bacteria in the body leading to the uncontrolled growth of harmful microbes. This can result in illnesses such as antibiotic associated colitis and vaginal yeast infection.

Side effects of antibiotics and other drugs can contribute to increased medical costs, length of hospitalization, and risk of death in people who are hospitalized.^[7]

Risks

Antibiotic resistance

With the widespread use and misuse of antibiotics in modern medicine, bacteria are often exposed to these drugs. Many bacteria are killed when exposed to antibiotics, but many bacteria can develop resistance to the drugs' effects. Furthermore, bacteria which develop resistance can spread the genes (genetic code) for resistance to other bacteria.

The result has been an increase in antibiotic resistant bacteria that have developed increasingly complex ways to escape the killing power of today's antibiotics.^[8] Antibiotic-resistant bacteria (notably methicillin-resistant Staph. aureus MRSA) can cause severe and life-threatening diseases which are difficult to treat. Researchers are continually working to develop new drugs that are effective against resistant strains.^[9] Many of these new antibiotics are effective for a few years, but bacteria often develop new methods of resistance against these drugs.

One way to help limit the development of antibiotic resistant strains of bacteria is to take antibiotics only for bacterial infections (not for viral infections such as the common cold or the flu) and for the full amount of time prescribed by a doctor. Health care providers are also studying ways to reduce the use of antibiotics in certain infections.^[10]

History

Compounds with anti-infective activity have been used for medical purposes for thousands of years. The Chinese knew of the healing properties of moldy soybean curd applied to boils and other infections more than 2,500 years ago.^[11] Hippocrates routinely used substances with antimicrobial activity including wine, myrrh, and inorganic salts.

Although the antimicrobial properties of a fungus, Penicillium, was first described by Ernest Duchesne in 1897 ^[12] and penicillin, a product of this fungus was described in 1928 by Alexander Fleming ^[13] it was not the first antibiotic used in clinical practice. That honor goes to the sulfonamides which were discovered in 1936.^[11] It wasn't until 1941 that Florey and Chain had demonstrated the antibacterial effects of penicillin in mice and had produced enough of the drug to treat a few patients. Fleming, Florey, and Chain received the nobel prize in medicine in 1945 for their work on penicillin.^[14]

Other classes of antibiotics were soon discovered including the cephalosporins ^[15] and streptomycin, an aminoglycoside.^[16]

Controversy

Misuse of antibiotics

Antibiotics came into general medical use about 60 years ago. Over the years, the increasing use and misuse of these medications has led to a dramatic increase in antibiotic resistance. Misuse of antibiotics refers to the inappropriate use of an antibiotic in either humans or animals.

Misuse in humans. Inappropriate use of antibiotics in humans can be attributed to over-prescribing of antibiotics by health care workers^{[17] [18]} and to failure of the patient to take the medication as prescribed.^{[19] [20]} Doctors may prescribe antibiotics for common illnesses such as colds and the flu, because of the belief that the patient expects to receive an antibiotic.^[21] Attempts are being made to educate both health care workers and the public on the appropriate use of antibiotics.^{[22] [23]}

Misuse in animals. The debate regarding the use of antibiotics in human food animals and the effects on human health have been going on for a number of years.^[24] Although the use of antibiotics in food animal production has been associated with improved animal health, higher food production, and in some cases, a reduction in food borne pathogens, antimicrobial use has been shown to contribute to the increase in antibiotic resistant bacteria that cause human disease.^[25] Reasons for this include the fact that antibiotic use in food animals is the largest use of antimicrobials worldwide; much of this use results in bacteria being exposed to low levels of antibiotics which contributes to the formation of resistance; drugs of important clinical classes are used in animals; and people are exposed to resistant bacteria by consuming animal products and through widespread release of resistant bacteria into the environment.^[26]

Alternatives

There are a number of compounds that have been proposed as anti-infectives. Some have been studied for efficacy, while others have not. Some substances which may have antibiotic properties include:

• Garlic (effective against intestinal pathogens in clinical studies)^{[27] [28]}
• Oregano (the oil may be effective against Camphylobacter jejuni ^[29] and Escherichia coli ^[30])
• Thyme (may be effective in combination with marjoram, basil and oregano against intestinal pathogens) ^[31]
• Pau d'arco (may be effective against Helicobacter pylori) ^[32]
• Goldenseal (against oral pathogens) ^[33]
• Myrrh ^[34] (abstract claims antimicrobial properties but no statistics available).
• Turmeric (Curcuma longa) shows efficacy against Pseudomonas aeruginosa. ^[35]

While many substances have been shown to kill bacteria in vitro (outside the body), it is difficult to demonstrate how effective a anti-microbial is in sick people because most minor bacterial infections, in healthy people, will be cleared by the immune system without antibiotics or any treatment whatsoever. ^[36]

Research

Recent discoveries

Recently concluded studies relating to antibiotics include:

• To evaluate the impact of a multidimensional (patient, system, clinician) intervention on appropriate antibiotic use for adults with acute respiratory tract infections-- identifying factors that influence successful translation across VA hospital and non-VA hospital acute care and to evaluate the impact of a rapid diagnostic test for c-reactive protein on antibiotic use for adults with acute cough illness when added to a multidimensional intervention. ^[37]
• Using computers to aid in decision-making about the use of antibiotics in the impatient setting. ^[38]
• Evaluating the outcome of patients who did not respond to antibiotics in the outpatient setting. ^[39]
• Evaluating the efficacy and cost of switching from intravenous to oral antibiotics in the treatment of community-aquired pneumonia. ^[40]

Clinical Trials

For a list of open studies involving antibiotic research, please go here

Other Resources

The Centers for Disease Control and Prevention (CDC) offers a number of brochures related to antibiotic use.

• Cold or Flu. Antibiotics Don't Work For You. (For adults 18 to 49 years of age.)
• Snort. Sniffle. Sneeze. No Antibiotics Please. (For parents of young children.)
• A Veces, el Remedio es Peor que la Enfermedad. (For Spanish speakers 18 to 49 years of age.)
• Be Smart. Antibiotics Will Not Help a Cold of the Flu. (For American Indian/Alaska Native adults 18 to 49 years of age.)
• Get Smart. Know When Antibiotics Work. Virus Bacteria Chart. (For parents of young children and adults 18 to 49 years of age.)
• Fluid in the Middle Ear (Otitis Media with Effusion): Questions and Answers. (For parents of young children.)

References

1. ↑ CDC. Prevention of perinatal group B streptococcal disease. MMWR. 2002 Aug 16;51(RR11):1-22. Full Text | PDF
2. ↑ Price VE, Blanchette VS, Ford-Jones EL. The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am. 2007 Sep;21(3):697-710, viii-ix. Abstract
3. ↑ CDC:Sexually transmitted diseases treatment guidelines, 2006. MMWR. 2006 Aug 4;55(RR-11):1-94.Full Text | PDF
4. ↑ Hampton HL. Care of the woman who has been raped. N Engl J Med. 1995 Jan 26;332(4):234-7. Abstract. Published correction appears in N Engl J Med. 1997;337(1):56. Full Text.
5. ↑ Overturf GD. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics. 2000 Aug;106(2 Pt 1):367-76. Abstract | Full Text | PDF
6. ↑ Källman J, Friberg O. Antibiotic prophylaxis in cardiac surgery--general principles. APMIS. 2007 Sep;115(9):1012-5. Abstract
7. ↑ Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1997 Jan 22-29;277(4):301-6. Abstract
8. ↑ Chastre J. Evolving problems with resistant pathogens. Clin Microbiol Infect. 2008 Apr;14 Suppl 3:3-14. Abstract
9. ↑ National Institute of General Medical Sciences. New strategies take on antibiotic resistance. Press Release
10. ↑ Johnson NC, Holger JS. Pediatric acute otitis media: the case for delayed antibiotic treatment. J Emerg Med. 2007 Apr;32(3):279-84. Abstract
11. ↑ ^{11.0 11.1} Weinstein L. General considerations. In: Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. New York: Mcmillan; 1970:1154.
12. ↑ Pouillard J. A forgotten discovery: doctor of medicine Ernest Duchesne's thesis (1874-1912. Hist Sci Med.2002 Jan-Mar;36(1):11-20. Abstract
13. ↑ Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol. 1929;10:226.
14. ↑ NobelPrize.org The Nobel Prize in Physiology or Medicine 1945.
15. ↑ Abraham EP. Cephalosporins 1945-1986. Drugs. 1987;34 Suppl 2:1-14. Abstract
16. ↑ Waksman SA, Schatz AI. Present status of streptomycin therapy. Lancet. 1946;66:77-8.
17. ↑ Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA. 1997 Sep 17;278(11):901-4. Abstract
18. ↑ Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic treatment of children with sore throat. JAMA. 2005 Nov 9;294(18):2315-22. Abstract | Full Text | PDF
19. ↑ Edwards DJ, Richman PB, Bradley K, Eskin B, Mandell M. Parental use and misuse of antibiotics: are there differences in urban vs. suburban settings? Acad Emerg Med. 2002 Jan;9(1):22-6. Abstract
20. ↑ Richman PB, Garra G, Eskin B, Nashed AH, Cody R. Oral antibiotic use without consulting a physician: a survey of ED patients. Am J Emerg Med. 2001 Jan;19(1):57-60. Abstract
21. ↑ Ong S, Nakase J, Moran GJ, Karras DJ, Kuehnert MJ, Talan DA; EMERGEncy ID NET Study Group. Antibiotic use for emergency department patients with upper respiratory infections: prescribing practices, patient expectations, and patient satisfaction. Ann Emerg Med. 2007 Sep;50(3):213-20. Abstract
22. ↑ Harris RH, MacKenzie TD, Leeman-Castillo B, et al. Optimizing antibiotic prescribing for acute respiratory tract infections in an urban urgent care clinic. J Gen Intern Med. 2003 May;18(5):326-34. Abstract | Full Text | PDF
23. ↑ Razon Y, Ashkenazi S, Cohen A, et al. Effect of educational intervention on antibiotic prescription practices for upper respiratory infections in children: a multicentre study. J Antimicrob Chemother. 2005 Nov;56(5):937-40. Abstract | Full Text | PDF
24. ↑ McDermott PF, Zhao S, Wagner DD, Simjee S, Walker RD, White DG. The food safety perspective of antibiotic resistance. Anim Biotechnol. 2002 May;13(1):71-84. Abstract
25. ↑ Mathew AG, Cissell R, Liamthong S. Antibiotic resistance in bacteria associated with food animals: a United States perspective of livestock production. Foodborne Pathog Dis. 2007 Summer;4(2):115-33. Abstract
26. ↑ Silbergeld EK, Graham J, Price LB. Industrial food animal production, antimicrobial resistance, and human health. Annu Rev Public Health. 2008;29:151-69. Abstract
27. ↑ Sasaki J, Kita T, Ishita K, Uchisawa H, Matsue H. Antibacterial activity of garlic powder against Escherichia coli O-157. J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):785-90. Abstract
28. ↑ Sasaki J, Kita J. Bacteriocidal activity of garlic powder against Bacillus anthracis. J Nutr Sci Vitaminol (Tokyo). 2003 Aug;49(4):297-9. Abstract
29. ↑ Ravishankar S, Zhu L, Law B, Joens L, Friedman M. Plant-derived compounds inactivate antibiotic-resistant Campylobacter jejuni strains. J Food Prot. 2008 Jun;71(6):1145-9. Abstract
30. ↑ Si H, Hu J, Liu Z, Zeng ZL. Antibacterial effect of oregano essential oil alone and in combination with antibiotics against extended-spectrum beta-lactamase-producing Escherichia coli. FEMS Immunol Med Microbiol. 2008 Jul;53(2):190-4. Epub 2008 Apr 23.Abstract
31. ↑ Gutierrez J, Barry-Ryan C, Bourke P. The antimicrobial efficacy of plant essential oil combinations and interactions with food ingredients. Int J Food Microbiol. 2008 May 10;124(1):91-7. Epub 2008 Mar 4. Abstract
32. ↑ Park BS, Kim JR, Lee SE, et al. Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria. J Agric Food Chem. 2005 Feb 23;53(4):1152-7. Abstract
33. ↑ Hwang BY, Roberts SK, Chadwick LR, Wu CD, Kinghorn AD. Antimicrobial constituents from goldenseal (the Rhizomes of Hydrastis canadensis) against selected oral pathogens. Planta Med. 2003 Jul;69(7):623-7. Abstract
34. ↑ El Ashry ES, Rashed N, Salama ON, Saleh A. Components, therapeutic value and uses of myrrh. Pharamzie. 2003 Mar;58(3):163-8. Abstract
35. ↑ Rudrappa T, Bais HP. Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem. 2008 Mar 26;56(6):1955-62. Epub 2008 Feb 20. Abstract
36. ↑ Morton, P., Should we treat strep throat with antibiotics? Can Fam Physician. 2007 August; 53(8): 1299. Abstract | Full Text
37. ↑ ClinicalTrials.gov. Improving Antibiotic Use in Acute Care Treatment (IMPAACT)
38. ↑ ClinicalTrials.gov. Computerized Decision Support System for Antibiotic Treatment
39. ↑ ClinicalTrials.gov. Outcomes of Patients Not Responding to Antibiotics in the Community
40. ↑ ClinicalTrials.gov. Study on Costs and Safety of Early Conversion From Intravenous to Oral Antibiotic Treatment in Patients With Severe Community-Acquired Pneumonia

External Links

Medline Plus: Antibiotics