Antimicrobials

Bacteriostatic

Inhibits bacterial growth

• Targets bacterial protein synthesis and metabolic pathways

What changes a drug’s properties

• Pathogen type

• Dose

• Length of the drug regimen

• Pathogen load

• Route of administration

Bactericidal

Kills bacterial growth

• Targets bacterial cell wall/cell membranes and nucleic acids

Is bacteriostatic or bactericidal more effective

Bactericidal is more effective, but it kills normal microbiota and can lead to deadly bacterial toxin release (e.g. LPS)

What is S. Griseus effective against

Tuberculosis (TB)

What drug changed modern medicine

Alexander Fleming’s penicillin.

• He studied S. Aureus and noticed a plate was contaminated w/mold

• S. Aureus were NOT able to grow near the mold

• Mold excreted a compound called Penicillin

Broad spectrum

Effective against both Gram-negative and Gram-positive bacteria

Narrow spectrum

Target a limited range of bacteria

• Better than broad because they present fewer disruptions to the normal microbiota

Antimicrobial drugs

Therapeutic compounds that kill microbes or inhibit their growth

Antibiotics

Naturally occurring antimicrobial compounds (compounds that kill or inhibit their growth)

Synthetic antimicrobials

Manufactured by chemical processes

Semisynthetic antimicrobials

Chemical modification of naturally occurring antibiotics

• Can be modified by chemical means, such as adding R groups

First-generation drugs

Result from a first round of chemical modification

Second-generation drugs

Drugs resulting from a second round of chemical modification

What happens to drugs after second generation

• Drugs in later generations have expanded capabilities over their predecessor such as an extended spectrum, increased stability, and the ability to circumvent resistance mechanisms

How is the therapeutic index defined?

Ratio of the maximum tolerated (safe dose) to the minimum effective (therapeutic dose)

Difference between a high and a low TI?

A high therapeutic index is safer than a drug w/narrow therapeutic index as it shows a greater gap in case of an overdose

Therapeutic drug monitoring (TDM)

• Used to ensure well-being and/or assess the therapeutic benefit of a drug

  • Measuring drug concentrations in blood

  • Monitoring patient parameters

2 antibiotics associated w/superinfection

Superinfection

What is selective toxicity

An antimicrobial drug inhibits or kills the targeted microbe without damaging host cells

• Toxic to pathogens but harmless to the patient’s own cells

2 organs most affected by antimicrobials?

Kidneys and the liver

How are they affected

They metabolize and eliminate drugs

• Susceptible to damage by certain drugs

• If damaged, nephrotoxicity and hepatotoxicity may occur

Nephrotoxicity

Kidney-toxic

• Antimicrobials may cause drug-associated nephropathy

  • Aminoglycosides and nonsteroidal anti-inflammatory drugs (NSAIDs)

Hepatotoxic

Liver damage/toxic

• Antimicrobials may be the leading agents of drug- induced liver injury (DILI)

• Liver recovers after the drug regimen stops

• DILI is the leading reason for removing a drug or discontinuing drug development

Oral administration

Stable in the acidic environment of the stomach

Sufficiently absorbed in the intestines

Parenteral administration (injection or infusion)

Injected through IV, IM, or SUBQ

What is the half-life for an antimicrobial drug?

The time it takes for half of a dose to be eliminated or deactivated by the body

How does half-life affect drug usage?

• Half-life determines the frequency of administration

Half-life of penicillin

30 minutes

• Take every 4 hours for 7-10 days

Half-life of azithromycin

68 hours

• Take every 24 hours for 3-5 days

Penicillin/ ampicillin/ amoxicillin (penicillins)

Natural→ Narrow spectrum

Semisynthetic→ broad spectrum

Beta-lactam superfamily

• Target cell wall synthesis/ bactericidal

Cephalosporin (cephalosporins)

Broad spectrum

Beta-lactam superfamily

• Targets cell wall synthesis/bactericidal

Bacitracin (Miscellaneous non-beta-lactam antimicrobials)

Narrow spectrum

• Target cell wall synthesis

• Bactericidal

• DOES NOT TARGET mycobacterium

Vancomycin (glycopeptides)

Narrow spectrum

• Target cell wall synthesis

• Bactericidal

• Glycopeptides

Isoniazid/ethambutol (miscellaneous non-beta lactam antimicrobials)

Narrow spectrum

• Different from Bacitracin as they DO target mycobacteria

• Target cell wall synthesis

• Bactericidal

Chloramphenicol (phenicols)

Broad spectrum

• Target ribosome (protein synthesis)

• Bacteriostatic

Streptomycin/ neomycin/ gentamicin (aminoglycosides)

• Narrow spectrum

• Target ribosome (protein synthesis)

• Bacteriostatic

Tetracycline (tetracyclines)

• Not recommended during pregnancy for nursing mothers

• Broad spectrum

• Target ribosome (protein synthesis)

• Bacteriostatic

tigecycline

Erythromycin/ azithromycin. clarithromycin (macrolides)

• Broad spectrum

• Macrolides

Daptomycin

Rifampin (Rifamycins)

Broad spectrum

• Inactivates oral contraceptives

• Target nucleic acids

• Bactericidal

Ciprofloxacin (quinolones)

• Targets nucleic acids

• Bactericidal

• Levofloxacin is an example

• Broad spectrum

Sulfa/TMP

Natural penicillin

Narrow spectrum

Semisynthetic derivatives

Broad spectrum

What is a beta-lactam ring

A four-sided ring that is part of the active chemical structure of beta-lactam antimicrobials

beta-lactam antimicrobials

• Penicillins

• Cephalosporins

• Carbapenems

• Monobactams

  • All antimicrobials above work against bacteria by blocking cell wall construction

How do beta-lactam antibiotics work

They bind to transpeptidase enzymes (builders of peptidoglycan), preventing the formation of protein cross-links that bind peptidoglycan’s carbohydrate chains together

What are beta-lactamases

Enzymes produced by bacteria that inactivate beta-lactam drugs.

• Beta-lactamase inhibitors can be administered w/beta-lactam antibiotics to prevent inactivation of the drug and its effects

• Inhibitors include: Clavulanate, sulbactam, or tazobactam

What is MRSA

Methicillin-resistant Staphylococcus aureus strains (MRSA)

• Alter their transpeptidase enzymes so that beta-lactam drugs cannot target it, making the bacteria resistant to beta-lactam antibiotics.

3 antibiotics used against MRSA

1. Polymyxin E

2. Tigecycline

3. Ceftaroline

3 antimycobacterial antibiotics

What are the antimycobacterial mode of action

Name an antibiotic associated w/superinfection and teeth discoloration

What antibiotics make up the triple ointment (neosporin)

Why do sulfa drugs adversely impact only bacteria cells