Chapter 14: Antimicrobial Drugs

Antibacterial Drugs

Aka antibiotics

• natural

• Semisynthetic Drugs

• Synthetic Drugs

Antifungal, Antiprotozoal, Antiviral drugs

Antibiotics

naturally occurring antimicrobials

• Metabolic products of bacteria and fungi

• Reduce competition for nutrients and space

Bacteria: Streptomyces and Bacillus

Molds: Penicillium and Cephalosporium

Selective Toxicity

The drug kills pathogens without damaging the host.

• Becomes more difficult to achieve, and more side effects are seen when the infectious agent becomes more similar to the vertebrate host cell.

Antimicrobial Drugs

• Disrupt the cellular processes or structures of bacteria, fungi, and protozoa.

• Inhibit virus replication.

Cell Wall

Penicillin

DNA Synthesis

Fluoroquinolones

RNA Synthesis

Rifamycin

Plasma Membrane

Polymyxin B and Lipopeptide

Ribosomes

30S Subunit, 50S subunit

Metabolic Pathways

Folic Acid, Sulfonamides

Narrow-spectrum

Affects only a select group of microbes

Broad-spectrum

affects a more diverse range microbes.

• Can kill good bacteria as well

• Quick

B-lactams

Block the synthesis of peptidoglycan, causing the cell wall to lyse.

• All contain a highly reactive 3-C, 1-N ring

• E.g. Penicillin and Cephalosporin

Penicillin

Semisynthetic ______

• B-lactam antibacterial that was the first cell wall synthesis inhibitor developed

Cephalosporin

Semisynthetic ______

• A group of cell wall synthesis inhibitors within the class of B-lactams

Monobactam

Semisynthetic ______

• Interact directly with PBPs and inhibit transpeptidase activity

• Inhibit the synthesis of bacterial cell walls by binding to penicillin-binding proteins.

Carbapenem

Semisynthetic ______

• Interact directly with PBPs and inhibit transpeptidase activity

• Broad-spectrum antibiotics used to treat severe bacterial infections, particularly those resistant to other antibiotics

Methicillin

Interact directly with PBPs and inhibit transpeptidase activity

• Narrow spectrum against gram positive bacteria only, including strains producing penillinase

Folic Acid synthesis

Inhibits the enzyme involved in production of dihydrofolic acid.

• Sulfonamides

• Sulfones

Broad Spectrum

Drug that targets many different types of microbes

Antiviral Drugs

• Selective toxicity is almost impossible in viruses

  • Obligate intracellular parasites

• Block Penetration into the host

• Prevent Maturation of Viral Particles

• Block replication, transcription, or translation or viral genetic material, viral uncoating.

Nucleotide analog

Synthetic compounds that resemble natural nucleotides, the building blocks of DNA and RNA.

• Acyclovir

  • Herpesviruses

• Ribavirin

  • A guanine analog

  • RSV, hemorrhagic fevers

• Azidothymidine (AZT)

  • Thymine analog

  • HIV

Adaptive response to drugs

• Due to genetic versatility or variation

• Intrinsic and acquired through vertical gene transfer

Acquired Resistance

• Spontaneous mutations in critical chromosomal genes

• Acquisition of new genes or sets of genes via transfer from another species.

Superbugs

Group of pathogens that carry one or more resistance mechanisms, making them resistant to multiple antimicrobials.

Superinfection

Secondary infection that may develop as a result of long-term, broad-spectrum antimicrobial use.

Efflux Pump

Membrane proteins that help bacteria resist antibiotics by pumping them out of the cell

• Fluoroquinolones

• Aminoglycosides

• Tetracyclines

• B-lactams

• Macrolides

Blocked Penetration

Occurs when bacteria become less permeable to antibiotics. This can happen when bacteria alter their outer membrane proteins or pump antibiotics out of the cell.

• B-lactams

• Tetracyclines

• Fluoroquinolones

Inactivation of Enzymes

A mechanism that bacteria use to develop resistance to antibiotics. This can occur when bacteria evolve enzymes that modify or destroy the structure of antibiotics.

• B-lactams

• Aminoglycosides

• Macrolids

• Rifamycins

Target Modification

It occurs when the bacterial target protein that an antibiotic binds to is altered, preventing the antibiotic from effectively inhibiting bacterial growth.

• Fluoroquinolones

• Rifamycins

• Vancomycin

• B-lactams

• Macrolides

• Aminoglycosides

Antimicrobial Resistance

Misuse of antibiotics selects for resistant mutants

• Using outdated or weakened antibiotics

• Using antibiotics for the common cold and other inappropriate conditions

• Using antibiotics in animal feed

• Failing complete the prescribed regimen

• Using someone else’s leftover prescription

Side Effects of Drugs

• Direct damage to tissue due to toxicity of a drug.

• Allergic reactions

• Disruption in the balance of normal flora-superinfections possible.

Considerations in selecting an antimicrobial drug

• Identify the microorganism causing the infection

• Test the microorganism’s susceptibility (sensitivity) to various drugs in vitro when indicated.

• The overall medical condition of the patient.

Kirby-Bauer Disk Diffusion Test

Simple, rapid method for determining susceptibility and resistance of a bacterial pathogen to antibacterial drugs. The test involves drug-impregnated disks placed on an agar plate inoculated with a bacterial lawn.

• Essential for groups of bacteria commonly showing resistance.

E-Test Diffusion Test

A quantitative method that measures how susceptible bacteria are to antimicrobial agents. Uses a plastic strip with a gradient of an antimicrobial agent to determine the minimum inhibitory concentration (MIC) of the drug.

Minimum Inhibitory Concentration

The lowest concentration of an antimicrobial that prevents the growth of bacteria or fungi.

• Smallest concentration of drug that visibly inhibits growth.