Antimicrobial Therapy: Mechanism and Resistance

• Microorganisms are widespread, and some can cause disease.
• Antimicrobial drugs have been developed since the early 1900s, with the earliest being sulfa drugs used in World War II.
• Bacteria can be classified as either Gram-positive, staining dark blue to purple, or Gram-negative, staining pink to red.
• Bacteria that stain similarly usually respond to the same antimicrobial therapy

Mechanism of Action

• Bactericidal agents kill bacteria, important for severe cases, such as sepsis.
• Bacteriostatic agents inhibit bacterial growth, allowing the body to eliminate them.
• Bacteria can develop resistance, making treatment difficult and indiscriminate use of antimicrobials accelerates this process.
• Bacterial identification and sensitivity testing guide correct antimicrobial therapy
• In vitro tests show efficacy, but this may not translate to in vivo.
• Sensitivity tests determine the minimum inhibitory concentration (MIC), which determines if the drug will have maximal inhibition of growth

Considerations

• Antimicrobials should be reserved for at-risk individuals to avoid resistance.
• Asepsis should not be compromised.
• Use antimicrobials based on definitive diagnosis, selecting the most specific antibiotic; caution should be used in food animals to avoid drug residue.

How Antibiotics Work

• Inhibition of cell wall synthesis prevents bacteria from forming cell wall.
• Damage to the cell membrane alters cell permeability, causing cell rupture.
• Inhibition of protein synthesis is required for cell maintenance and division, and is done so at the ribosomes.
• Interference with metabolism blocks enzyme action or nutrient usage like with sulfa drugs; impairs nucleic acid production, preventing cell division

Bacterial Resistance

• Antibiotic resistance occurs when bacteria change, reducing or eliminating antibiotic effectiveness.
• Drug misuse, viral infections, wrong dosage, or inadequate duration can promote resistance.
• Mutations allow bacteria to resist antibiotics, leading to a predominant resistant population.
• Resistance genes can transfer plasmids from a resistant bacterium to a nonresistant one.
• Cross resistance occurs when unrelated antibiotics share similar resistance mechanisms.
• Hospitals spread infections with resistant bacteria.
• Hand washing and preventing close contact help limiting spread
• Antibiotic choice should be based on culture results.

Penicillins (Beta Lactams)

• Discovered in 1928 by Sir Alexander Fleming, penicillins are bactericidal.
• Many formulations require shaking before use, must be mixed appropriately to prevent dilution.
• Oral preparations are only stable for 7-14 days and most penicillins need refrigeration.
• Drugs in this class can be recognized with the -cillin suffix

Pharmacokinetics

• Orally administered penicillin is absorbed in the stomach and small intestine.
• Injectable penicillin is rapidly absorbed at the injection site.
• Kidneys are the primary organs of excretion through milk

Pharmacodynamics

• Penicillins bind reversibly to penicillin-binding proteins (PBPs) outside the bacterial membrane.
• The binding to PBPs increases internal osmotic pressure and bursts the cell.
• Some bacteria produce beta-lactamase (penicillinase) that increases penicillin resistance by converting penicillin to inactive penicillin acid.
• Some penicillins are beta-lactamase resistant.
• Penicillins are usually most effective against Gram-positive bacteria; gram-negatives have a PBP coating which reduces the drugs effectiveness

Frequently Used Formulations

• Procaine penicillin G is injectable IM in horses and cattle, SQ in dogs and cats, and inactivated by stomach acid.
• Oral amoxicillin comes in suspension, tablets, and capsules.
• Ampicillin IV and SQ forms come in forms.
• Benzathine penicillin is long acting, but it is not absorbed by horses.
• Ticarcillin is often used intrauterine in horses.
• Amoxicillin-clavulanate combines a beta-lactam with a beta-lactamase inhibitor.
• A potentiated drug is chemically combined with another drug to enhance the effects of both

Uses

• Treating infections caused by penicillin-susceptible organisms, such as Streptococcus sp. and Staphylococcus sp.
• It can be used in combination with other antibiotics to increase gram-negative and anaerobic spectrum.

Adverse Effects

• Anaphylactic reactions with injectable medications can cause hives, respiratory distress, collapse, and death and require immediate epinephrine administration.
• Procaine reactions result in excitement, ataxia, and vocalization
• This may occur as a result of procaine entering the microvasculature at the injection site
• Superinfections in hind-gut fermentors may cause severe, life-threatening diarrhea
• Use with caution in rabbits with Pastuerella

Learn about antimicrobial drugs developed since the early 1900s. Explore how these drugs work, distinguishing between bactericidal and bacteriostatic agents. Understand bacterial classification, resistance, sensitivity testing, and determining minimum inhibitory concentration (MIC).