Pharm tutoring: Antimicrobials 1

Based on condensed slides

What is an antimicrobial?

Any drug that acts on ANY microorganisms.

-kills or inhibits a microbe (bacteria, fungi, viruses, protozoa)

What is an antibiotic?

“against life”, technically from another organism to act on another microorganism

What does -cidal mean?

Kills bacteria

What does bacteriostatic mean?

Inhibits bacterial growth and relies on host immunity to clear the infection.

What are narrow-spectrum antimicrobials?

They act against a limited group, primarily either gram-positive or gram-negative bacteria

(ONLY) 1 or 2 quadrants

What are broad-spectrum antimicrobials?

They act against both gram-positive and gram-negative bacteria.

-belonging to at least 2 quadrants

What are the three goals of antimicrobial therapy?

• The pathogen is susceptible

• the drug reaches the infection site at an effective concentration

• the host tolerates the drug

What does MIC stand for?

Minimum inhibitory concentration to inhibit/stop growth.

(the minimum concentration of antimicrobial needed to inhibit bacterial growth)

What does MBC stand for?

Minimum concentration to kill bacteria

(the minimum concentration of antimicrobial needed to kill bacteria)

What does MTD stand for?

Maximum tolerated dose by the host

If bacteria is susceptible to the drug, where are MIC and MBC in relation to MTD?

Both MIC and MBC are below the MTD, meaning the drug can inhibit or kill the bacteria at levels that the patient can safely tolerate.

-they would all be far apart on the chart

In the lecture's simplified model, what makes a drug only bacteriostatic at tolerated exposure?

The MBC would be above the MTD → meaning you can’t safely give enough of the drug to kill the bacteria.

In the lecture's simplified model, what happens when the bacteria is resistant to the drug?

The MTD would be below the MIC and MBC, meaning it would reach the maximum dose before inhibiting or killing the bacteria.

(in layman’s terms) The host cannot safely receive enough drug to inhibit or kill the bacteria; the bacteria are resistant in this model.

Why does susceptibility not always guarantee treatment success?

the drug may not reach the infection site at an effective concentration

Why might bacteria on an airway surface survive despite drug in the bloodstream?

bacteria on airway will survive because drugs in blood don’t reach bacteria on surface.

(meaning that a drug circulating in the blood MUST move into the airway secretions to reach bacteria on the airway surface. if too little drug gets there, the bacteria may survive - even though they are susceptible)

Why may hydrophilic antimicrobials fail to treat bacteria in the brain?

They generally do not penetrate the blood-brain barrier.

(hydrophilic → poor lipid penetration → poor BBB penetration)

What does partial antibiotic treatment remove?

Susceptible bacteria are removed while resistant bacteria survive and repopulate.

What is selection pressure in antibiotic resistance?

Antibiotic exposure favors survival and multiplication of resistant bacteria over susceptible bacteria.

What do you do to reduce antibiotic selection pressure?

• Use the correct prescribed dose and full course of antibiotics (client education!)

• reserve antibiotic use for bacterial infections only

• consider the patient's immune status

Why should the patient's immune status be considered when choosing an antimicrobial?

Host defenses contribute to clearing infection, especially when treatment inhibits growth rather than killing bacteria.

What are antimicrobial residues?

Drug remaining in animal products such as meat, milk, or eggs.

What concerns are associated with antimicrobial residues?

• Allergic reactions

• continued low exposure that can lead to selection pressure and resistance

  • kills weakest bacteria and allows more naturally resistant bacteria to survive

Why must withdrawal times be followed in food-producing animals?

To allow drug residues to fall to acceptable levels before animal products enter the food supply.

What are the five antimicrobial targets?

• Bacterial cell wall

• bacterial cell membranes

• bacterial protein synthesis

• bacterial nucleic acids

• bacterial metabolic pathways

_______ cells don’t have cell walls.

Mammalian

Which antimicrobial groups inhibit bacterial cell wall formation?

Penicillins, cephalosporins, and bacitracin attack cell wall synthesis

-results in formation of weak cell wall (readily breaks apart)

When do cell wall synthesis inhibitors work?

When bacteria are actively dividing and forming cell walls.

What is an example of an antimicrobial that targets bacterial cell membranes?

Topical drugs like Polymyxin B

-disruption of the membrane can result in leakage of cell contents and cell death

Which antimicrobial groups inhibit bacterial protein synthesis?

Aminoglycosides, macrolides, tetracyclines, and lincosamides.

What bacterial structure is targeted by protein synthesis inhibitors?

• Ribosomes

  • either the 30S (small) or 50S (large) unit

  • interferes with making essential proteins

Which antimicrobials are listed as targeting nucleic acids?

Quinolones and metronidazole.

What processes are affected by antimicrobials that target nucleic acids?

• They affect DNA/RNA replication and transcription

  • drugs bind to the enzymes needed for DNA replication (quinolones)

Which antimicrobials interfere with folic acid synthesis?

Sulfonamides and trimethoprim.

Why does inhibiting folic acid synthesis affect bacteria?

Bacteria need folic acid synthesis to grow

Are sulfonamides alone generally bacteriostatic or bactericidal?

Bacteriostatic.

-they are bactericidal when combined with trimethoprim

To which antimicrobial family do penicillins belong?

Beta-lactams.

The four types of penicillins

• natural penicillins

  • penicillin G

• aminopenicillins

  • amoxicillin, ampicillin

• penicillinase-resistant penicillins

  • oxacillin, cloxacillin, dicloxacillin, methicillin

  • naturally resistant to beta lactamase enzyme

• extended spectrum penicillins

  • piperacillin, ticarcillin, carbenicillin

Are penicillins bactericidal or bacteriostatic?

Bactericidal, against anaerobic gram positive bacteria, and some gram negative

How do penicillins act on bacterial cell walls?

They block the transpeptidase enzyme that weakens cell wall and the cell bursts

How is penicillin G administered?

by injection only, because it is inactivated by gastric acid

What veterinary use is listed for penicillinase-resistant penicillins?

Staphylococcal mastitis treatment using intramammary teat infusions.

Do penicillins penetrate barriers?

No; they do not penetrate BBB, prostate, or globe of the eye. (meaning they are not effective in those infection sites)

Which infection sites do penicillins work best in?

• The bloodstream and urinary tract

  • effective against most bacteria in urine: drug has much higher concentration in urine (exceeds MIC for most bacteria in urine)

  • commonly used to treat bacterial cystitis

How can bacteria resist penicillins, using beta-lactamase?

• They make beta-lactamase enzymes that destroy the drug and make it resistant

  • combining penicillin with clavulanic acid will block that enzyme

Are penicillins effective against Pseudomonas?

• No; they’re completely ineffective against it.

  • they have an outer capsule that surrounds the bacteria and prevents drugs from accessing the wall

What adverse effects of penicillins are listed?

• Allergic reactions

• gastrointestinal upset

• potentially severe diarrhea and death in guinea pigs, ferrets, rabbits and hamsters

  • don’t give oral penicillins to these animals

What are the three basic forms of natural penicillins?

1. aqueous solution

   1. complexed with sodium or potassium

   2. only form that can be given IV

2. suspension combined with procaine

   1. slow absorption over 24 hours

3. suspension combined with benzathine

   1. 3-5 days

How are cephalosporins related to penicillins?

• Both are beta-lactams

  • target cell wall formation

  • susceptible to bacteria’s beta-lactamase enzyme

What first-generation cephalosporins are listed?

Cefadroxil, cephapirin, cephalexin (human- Keflex), and cefazolin (human- Kefzol).

-generally more gram positive

What third-generation cephalosporins are listed?

Cefovecin (Convenia), cefpodoxime (Simplicef), and ceftiofur (Naxcel).

-generally more gram negative (like pseudomonas)

How does third-generation cephalosporin coverage generally compare with first-generation coverage?

The activity against gram negative bacteria increases

-third gen drugs are often selected for empirical treatment

Why do many cephalosporins have limited penetration into the brain?

They are hydrophilic at body pH and generally cross the blood-brain barrier poorly.

-they are actively secreted into the renal tubules (urine)

What are the adverse effects with oral cephalosporins?

Vomiting and diarrhea (high doses)

Cephalosporins are prohibited from extra label use in what animals?

cattle, swine, chickens, and turkeys

Name 4 microbes

bacteria, viruses, fungi, protozoa

fungicidal

kills fungi (mycotic agents)

virucidal

kills viruses