Antibiotics - What, How, Where, When, and Why

Antibiotics 101

Paul Dorr

NCSU College of Veterinary Medicine

Population Health and Pathobiology

North Carolina State University

Introduction:

Antibiotics and antimicrobials are very important in the treatment of bacterial

infections in both humans and animals. Of equal importance is the judicious use of these

substances. In today’s swine industry, producers must be very aware as to what exactly they

are treating their animals with, and what they are treating their animals for. One cannot

judiciously use antimicrobials without a basic understanding of what they are, how they

work, where and when one uses them, and why they are used. Furthermore, the recognition

of certain antimicrobials and other therapeutic agents that should never be found on any

swine farm is essential knowledge that producers must have.

So, what is an antibiotic, and what is the difference between an antibiotic and an

antimicrobial? According to the FDA an antibiotic is defined as, “A chemical substance

produced by a microorganism. It has the capacity, in dilute solutions, to inhibit the growth

of or to kill other microorganisms.” (1) So, essentially antibiotics are produced by various

types of bacteria and fungi. The following is an example of some common antibiotics and

their bacterial/fungal origins.

–Tetracycline - Streptomyces aureofaciens

–Neomycin - Streptomyces fradiae

–Lincomycin - Streptomyces lincolnensis

–Ceftiofur - Cephalosporium acremonium

–Gentamicin - Micromonaspora purpurea (2)

An antimicrobial may be defined as a compound that inhibits the growth or kills

microorganisms. This includes antibiotics in addition to various compounds that are not of

microorganism origin.(1) This definition would include synthetic products such as sulfas,

quinolones, and nitrofurans.

This leaves us with the next question, how do these substances work? Antibiotics are

usually grouped according to their method of action and their spectrum of activity. There are

5 general methods of action (MOA) that antibiotics exhibit. These include inhibition of

ribosomal protein synthesis, inhibition of DNA replication, alteration of metabolism,

disruption of cell membrane function, and disruption of cell wall synthesis. (2,3) Also,

antibiotics may have either a broad or narrow spectrum of activity. Simply put, a broad

spectrum antibiotic is an antibiotic that is effective against both gram positive and gram

negative bacteria. A narrow spectrum antibiotic is an antibiotic that is effective only for a

limited or specific type of bacteria.(1) The different classes of antibiotics, their spectrum of

activity, and various general methods of action are summarized in Table 1.

Antibiotic class Antibiotic name examples Spectrum Method of action

Penicillins Potassium Pen G, Ampicillin, Amoxicillin

Narrow to broad disruption of cell wall synthesis

Cephalosporins Ceftiofur Broad disruption of cell wall synthesis

Aminoglycosides Streptomycin, Neomycin, Gentamycin Narrow inhibition of ribosomal protein synthesis

Spectinomycin Spectinomycin Broad inhibition of ribosomal protein synthesis

Chloramphenicol Florfenicol Broad inhibition of ribosomal protein synthesis

Tetracyclines Tetracyline, Oxytetracycline, Chlorteteracycline Broad inhibition of ribosomal protein synthesis

Macrolides Erythromycin, Tylosin, Tilmicosin Narrow inhibition of ribosomal protein synthesis

Lincosamides Lincomycin Narrow inhibition of ribosomal protein synthesis

Polymyxin Polymyxin B Narrow disruption of cell membrane function

Bacitracin Bacitracin Narrow disruption of cell wall synthesis

Tiamulin Tiamulin Narrow alteration of metabolism

Sulfas Sulfathiazole, Sulfamethazine, Sulfadiazine Broad alteration of metabolism

Table 1. Summary of antibiotic class, name, spectrum of activity and method of action of

antibiotics commonly used in swine production. (2,4,5)

Where then, do we use these substances, or more succinctly, how are they

administered? To answer this question, a few things must be considered. First, WHAT

DOES THE LABEL SAY! This is by far the most important consideration when

administering antibiotics. Various antibiotics may be administered a number of different

ways and have different withdrawal times which are indicated on the label. The various

routes of administration that may be listed on the labels of different products include oral

(dosing pump, water, feed), intravenous, intramuscular, and subcutaneous. The second

aspect that must be considered is the bioavailability of the antibiotic given the route of

administration and antibiotic type. For example, potassium penicillin G has a bioavailability

of approximately 5% when administered orally (i.e. 5% is absorbed into the blood and the

rest is excreted in the feces). So this would not be a good choice of antibiotic when trying to

treat a systemic infection like Strep. even though the bacteria may be susceptible.

When do we use these substances? Obviously when the pigs are sick. As with the

label information, there are some important points to consider. First, antibiotics are not

virusidial, i.e. they will have no direct effect on killing viral agents like PRRS, SIV, and

TGE. Second, they are not a silver bullet for general illness or disease of unknown etiology.

You have to know what you are up against. Third, culture and sensitivity data must be

utilized. You have to know what works. Fourth, what kind of infection is it, respiratory,

enteric, or systemic? All of these factors play a part when considering when to use

antibiotics and which ones to use.

Now we must consider why the label must be followed. A lot of research has been

done to determine the optimal blood concentration or bioavailability at the site of infection

that these antibiotics must obtain in order to be effective against the bacteria they are labeled

to protect against. The effects of underdosing and overdosing will both have a detrimental

effect on the health on the pig. Underdosing may provide an opportunity for bacterial

proliferation when blood concentrations of the antibiotic are low, as seen in Figure 1.

Figure 1. Relative antibiotic blood levels when patient is under dosed.

Figure 2. Relative antibiotic blood levels with a correct dosing schedule.

Some possible ramifications of underdosing include, but are not limited to: having

to treat the animal longer, persistence of infection (resulting in decreased ADG and FE), and

selection and proliferation of resistant subpopulations of bacteria. Overdosing may result in

toxicity which will affect various body systems depending on the agent. If the bacterial

infection that is being treated is persisting beyond the scheduled treatment period, many

things must be considered. First, the animal(s) may have a superinfection in which the

bacteria overwhelm the antibiotic at the given dose and bodies own defenses cannot fight off

the bacteria. Along these same lines the animal may be immunocompromised as is the case

with PRRS infection. Other reasons include failure of the antibiotic to reach the site of

infection, the pH of the tissues is to high or to low, the bacteria is resistant to the current

therapy, an incorrect dose was used, the antibiotic is outdated, an incorrect route of

administration was used, or the dosing schedule was altered. (3).

Blood level of antibiotic

Minimum blood level of antibiotic where bacteria are killed

Antib io tic B lood Levels

0

2

4

6

8

4 12 20 28 36 44 52 60 68Hours

Relative Blood

Level

Bacterial growth will occur here

Antib io tic B lood Levels

0

2

4

6

8

10

4 12 20 28 36 44 52 60 68Hours

Relative blood

levels

Minimum blood level of antibiotic where bacteria are killed

Blood level of antibiotic

Part of using antimicrobials judiciously includes knowing which ones not to use

and being able to identify substances on the farm that are currently illegal for use in

animals. Many of these substances have adverse human and animal health implications.

Furthermore, a few products, which are listed below, are legal for use in some animals,

but not in swine. Table 2 contains a list of products that should never be found on a

swine farm.

Substances That Should Never Be Found On A Swine Farm

Chloramphenicol – aplastic anemia in humans

Clenbuterol

Diethylstilbesterol - (DES) carcinogenic

Nitroimidazoles - (dimetridazole, ipromidazole) carcinogenic

Nitrofurans - (nitrofurazone) carcinogenic, mutagenic

Sulfonamides – There are some approved ones, check label

Fluoroquinolones - (enrofloxacin - Baytril 100)

Dipyrone!!!

Glycopeptides - (Vancomycin) human Staph. aureus resistance concern

Table 2. Substances that should never be found on a swine farm.(6) Judicious use of antimicrobials is of great importance in today’s production systems.

Un-judicious use of these substances has both human and animal health implications and

legal ramifications. The most important take home message is: Be Responsible! Treat the

animals that need to be treated. Follow the directions on the label/prescription paying

special attention to withdrawal time, dose, dosing schedule, spectrum of activity, and route

of administration. Furthermore, always be aware of what is on your farm with regards to

outdated product and products not approved for use in swine. Always consult your

veterinarian with any questions regarding these issues. Following these simple guidelines

concerning antimicrobial use will help to ensure a healthier hog out the door.

Sources

1. Judicious Use of Antimicrobials for Pork Producers. Department of Health and Human

Services, Public Health Service, Food and Drug Administration Center for Veterinary

Medicine. Aug. 2001.

2. Plumb, DC. Veterinary Drug Handbook. Third Edition. Iowa State University Press.

Ames, IA.

3. Berg, J. Pathogenic Bacteriology and Mycology in Veterinary Medicine. VM553

note set. University of Missouri – Columbia. Fall 2000.

4. Butaye, P, et. al. Influence of different medium components on the in vitro activity of

the growth promoting antibiotic flavomycin against enterococci. Journal of Antimicrobial

Chemotherapy (2000) 46, 713-716.

5. Compendium of Veterinary Products. 7th

Ed. Bayer. North American Compendiums,

Ltd. 2003.

6. Drugs Prohibited From Extralabel Use In Food Animals.

http://www.saanendoah.com/prohibiteddrugs.html. 2003