Anti-infective agents - Chapter 12:
 

Since antimicrobials are some the most frequently used drugs in veterinary medicine today they will be covered at the beginning of the course.
Anti-infective agents kill or inhibit microbes: bacteria, fungi, viruses and protozoans.  Antibiotics are a type of anti-infective drug that were originally made from living organisms such as molds, now most antibiotics are semi-synthetic.  Although these drugs have saved millions of human and animal lives around the world they are a relatively new discovery.

A) Historic perspective: Primitive forms of anti-infective agents have been used for thousands of years, in China the use of moldy curd (undoubtedly a form of antibiotic)

to treat skin infections was recorded in 2500 BC.

But, it wasn’t until the late 1930’s (Sulfa drugs in 1936) and early 1940’s (Penicillin in 1941) that antimicrobials were mass produced and widely available.  Until that time many people and animals died of infection, especially if their health was impaired due to poor nutrition, over work or filth.  Until World War II more men died of infections as a result of their battle wounds than of the original wounds during war.

When first produced penicillin was considered so valuable that it was recovered in patient’s urine and “recycled”!

 

B) Classification of anti-infective agents:  There are several methods used to describe these drugs including:

1. mode of action/pharmacodynamics

2. spectrum of activity

3. type of activity: cidal (kill the microbe) or static (inhibit the microbe’s growth).

 a) Spectrum of activity: The spectrum of activity describes what type of microbe (usually bacteria) the drug primarily works against.  The type of microbe is determined by characteristics such as its’ ability to absorb Gram stain (see book for more detail and review microbiology from Vet 132).  Most bacteria are either Gram positive (G+) or Gram negative (G-). 

Some bacteria grow best without oxygen (anaerobic) while others thrive on oxygen (aerobic); some are round in shape (cocci) while others are rod shaped (bacilli). 

Thus an anti-infective agent might be described as primarily affecting Gram negative anaerobic bacilli.

Newer forms of anti-infective agents affect coccidian, fungi and viruses.

 

b) Mode or mechanism of action: The mode of action describes how the drug kills or inhibits the microbe.  Some mechanisms of action include inhibiting vital bacterial enzymes or destroying the cell wall of the bacteria.

 

c) Cidal or static action on microbes: Some anti-infective agents work by killing the microbe (cidal), others only inhibit the growth of the microbe (static).  Certain drugs are static at low doses and cidal at high doses.  If a drug’s mode of action is to inhibit microbe growth, then the final destruction of the infecting agent will depend on the body’s own defenses, i.e. the white blood cells and other parts of the immune system

 

C) The animal health care teams’ role.

 
1. The veterinarian is primarily concerned with the correct diagnosis of disease

(with the help of technicians in the laboratory) and determining an appropriate drug for the particular situation. A diagnosis is based on clinical signs, history, and lab evaluation, such as a microbiological culture of tissue or exudates. 

The purpose of a culture is to grow the microbe in the lab and through a series of test determine its identity. Since bacterial cultures are somewhat expensive and take time to run, they are saved for diagnosing refractory cases, that do not respond to normal treatment.  Usually a second lab test is performed with the culture, called sensitivity or susceptibility.  The purpose of this test is to determine which anti-infective agent inhibit the growth of the bacteria.

Often a “presumptive” diagnosis is made based on symptoms, history and clinical chemistry tests and a therapy plan is started immediately.  The veterinarian usually has a good idea which drug might be effective, through prior experience or by looking up what microbes usually cause a particular problem.

 

 

2. The technician is often responsible for administering ant microbial medication to hospitalized patients and demonstrating medication techniques to owners in the out patient setting. Technicians can also be responsible for client education, i.e. explaining the possible side effects to clients and recognizing the usual side effects of the commonly used medications if an owner calls and is worried about how their pet is acting. Also the technician might recognize a problem or mistake with dosing and should take the responsibility to alert the veterinarian.

 

D) Anti-infective agents: It is unnecessary for a technician to memorize the vast amount of information about each drug, the text provides basic and useful information about the most important anti infective agents, including common side effects that techs should be aware of. Technicians should realize that every medication can cause some type of side effect and many are contra-indicated in certain situations.


As a way to study the basic facts about some select drugs a chart similar to the following can be filled in:

 

medication

class 

primary use

side effects

Route(s) of administration

amoxicillin

 

 

 

 

gentocin

 

 

 

 

Baytril

 

 

 

 

Cefa-tabs

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

E) Targeted antimicrobial therapy.

In the past practitioners often took a “shotgun” approach in treating infectious diseases. They had a tendency to treat every infection with a broad spectrum or very  powerful antimicrobial drug. The theory was that by using the drug with the most chance of success the patient had the best chance of being cured. Theses days with the concern over resistant strains of bacteria emerging quickly that the new, usually stronger antimicrobials should be saved and used only when absolutely necessary.

The types of bacteria causing many of the common bacterial diseases in animals have been identified in recent years and there is a wide selection of antimicrobial drugs on the market today. This has lead to “targeted therapy” a term sometimes used by pharmacologists to describe the selection of a drug regimen based on knowledge of the spectrum of activity of the drug and the most common bacteria causing the infection.

 

Common pathogens found in external ear (From Clinician’s Update, supplement to NAVC clinician’s Brief, Nov. 2003) .

Approximate % of pathogens.

 

 

Ear pathogens
1 =.Pseudomonas spp.

2 = Staphlococcus spp

3 = Proteus spp.
4 = E.Coli

 


 

Common pathogens of the skin - approximate % distribution

1= Staphlococcus spp.

2 = E. Coli

3 = Psuedomonas spp.

4 = Proteus spp.

 

Antimicrobial spectrum of activity (summarized from Small Animal Clinical Pharmacology and Therapeutics by Boothe)
4+ =very effective 

 

Drug

G +

G -

Psuedomonas

Anarobic

Clostridium

 

Ticarcillin

4+

4+

4+

4+

4+

 

Amoxicillin

4+

2+

0

3+

3+

 

Tetracycline

2+

2+

0

2-3+

2-3+

 

Sulfonamide/

Trimethoprim/

ormetoprim

2-3+

2-3+

0

2-3+

2-3+

 

 

F) A current issue regarding antimicrobial drugs and veterinary medicine.

In recent years there has been a growing awareness that many bacteria have become resistant to common antibiotics, some experts have predicted a coming “plague of super bugs” emerging from previously innocuous bacteria. These resistant microbes might be unresponsive to all known anti infective medications and cause worldwide epidemics. 
How does bacterial resistance develop?  The overuse of antibiotics in human medicine and veterinary medicine is often cited as a cause, as is the use of antibiotic feed additives in food producing animals.  Below is a summary of the livestock feed additive controversy collected from current news sources.
Low doses of antibiotics such as tetracycline and penicillin are
 routinely added to animal feed or water because they result in better
growth and prevent infections that can occur when animals are raised
in close contact. (National Research Council)
Bacteria, single-cell microorganisms that have survived for billions of years, can multiply explosively within short generation spans. Their ability to swap genes makes their development unpredictable and dangerous. The big fear of many researchers is that resistance to an antibiotic called vancomycin could spread from enterococci, which are found in the human or animal gut, to another bacteria called staphylococcus aureus. If this happened, there would be no defense against an estimated 25 percent of staph infections, often acquired in hospitals, for which vancomycin is the only remedy. One animal antibiotic, avoparcin, was banned three years ago because experts considered that it could lead to the emergence of bacteria resistant to vancomycin. (Reuters)
Now, doctors and researchers point to the antibiotic a Michigan woman received--Synercid, an important drug-of-last-resort in fighting life-threatening infections--as a case study illustrating why they are so concerned.  While Synercid was approved for human use only last fall, a closely related drug called Virginiamycin has been used on livestock since 1974. Researchers have found Virginiamycin-resistant bacteria in as much as 50 percent of supermarket chicken, turkey and pork. That alone causes concern that the effectiveness of Synercid is already significantly reduced in humans  "We're not at all convinced, based on the data, that Virginiamycin is the cause of the Synercid resistance, however minimal, in the human population," said Carl Johnson of Pfizer Inc., which developed Virginiamycin and later sold the rights to Synercid to Aventis Pharmaceuticals. "We believe it is coming from hospital use."  In Europe, officials have already banned the farm use of Virginiamycin and three other growth-promoting antibiotics, following recommendations from the World Health Organization. Researchers agree that many aspects of antibiotic resistance remain unresolved. But they say that more precise methods of studying bacteria on the molecular level have recently allowed them to demonstrate that resistant forms of at least two common bacteria--campylobacter and salmonella--are being passed from animals to humans. These organisms have become increasingly resistant to antibiotics known as fluoroquinolones--which include the most widely used antibiotic to treat food-borne infections, Ciprofloxacin. (Washington Post)
The scale of antibiotic use in commercial farming is enormous. Livestock are given anywhere from 100 to 1,000 times the amount of antibiotics as the human population, about half of all antibiotics used in the U.S. are for animal husbandry, stated a report in the Canadian Medical Association Journal. They also reported that about half of all antibiotics used in the U.S. are for animal husbandry. Only 10 percent of these drugs are given to treat infectious disease, the rest are given to promote growth or prevent disease. The report said recommended levels of antibiotics in animal feeds have increased by 10 to 20 times since the 1950s. The manufacturers (of anti infective agents) stand to lose a market worth hundreds of millions of dollars. (Reuters) TORONTO
The (National Research Council) panel recommends increased monitoring of drug resistance, drug usage and drug residues in farm animals, as well as identifying
alternative agricultural methods to using such drugs in farm animals.
A total ban on antibiotic feed additives could increase public health risks and lead to higher demand for antibiotics to treat sick animals. A ban could also raise the
prices of meat, poultry, and fish by as much as an additional $9.72
per person per year.
 The National Research Council report is a landmark, because it is the
 first authoritative US report that explicitly acknowledges that
agricultural uses of antibiotics pose a risk to the public health. (From the National Research Council report as reported in Wash.Post)

Chapter 12-Review questions

*These questions are to get you to think about the information you just read. They do NOT need to be turned in.  We will use them as jumping off points for chats and review sessions*

1)      Does the broth dilution susceptibility test or the agar diffusion test give more information regarding the possible dosage of antibiotic to use for a patient?

2)      List 3 things that can be done by practitioners and clients to decrease the possibility of causing mutant strains (resistant) bacteria.

3)      What useful property does the antibiotic Clavamox have compared to similar antimicrobials?

4)      What type of infective agent does acyclovir and interferon work against?
Are these drugs approved in veterinary medicine?
What condition are they used to treat most often?

5)      What can be added to alcohol to increase the activity against spores and viruses?
(Alcohol used to disinfect thermometers)

6)      Match the medicines in column A with their mode of action and/or adverse reactions and side effects in column B. (all answers in column B are to be used)

A B

a. penicillin

1. binds with calcium, is contraindicated in growing animals

b. cephalosporin(s)

2. ototoxic and nephrotoxic

c. tetracycline(s)

3. fluoroquinolone

d. gentamicin

4. inhibits bacterial cell wall synthesis by binding with PBPs

e. Baytril

5. second generation of this drug is resistant to beta-lactamase II

f. Tribrissen

6. this drug inhibits bacterial enzyme which causes bacterial DNA to coil in the nucleus
(DNAgyrase)

 

7. Adverse reactions include canine keratoconjunctivitis sicca

 

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