Spectrum of Antimicrobial Activity

• Narrow spectrum antibiotics

  • Targets specifically gram-negative only or gram-positive only

• Broad-spectrum antibiotics

  • Targets both gram positive and gram-negative

• Superinfection - overgrowth of normal microbiota that is resistant to antibiotics

  • Antibiotics affect normal microbiota which then allows other bacteria or viruses that are not affected by the antibiotics to proliferate and cause an infection.

Action of Antimicrobial drugs

• Bactericidal → Kill microbes directly

• Bacteriostatic → prevent microbes from growing

Major Action Modes of Antibacterial Drugs

• Inhibition of cell wall synthesis

  • Penicillins prevent the synthesis of peptidoglycan

• Inhibition of protein synthesis

  • Target bacterial 70S ribosomes

  • Chloramphenicol, erythromycin, streptomycin, tetracyclines

• Inhibition of nucleic acid synthesis

  • interfere with DNA replication and transcription

  • Rifamycin, quinolones (nalidixic acid) & fluoroquinolones

• Injury to plasma membrane

  • Polypeptide antibiotics change membrane permeability

  • Ionophore antibiotics: allow for uncontrolled movement of cations

• Inhibition to essential metabolite synthesis

  • inhibits the creation for nucleotides

  • Anti-metabolites compete with normal substrates for an enzyme

  • Sulfanilamide competes with para-aminobenzoic acid (PABA), stopping the synthesis for folic acid

Antiviral drugs

• Entry and fusion inhibitors

  • Block the receptors on the host cell that bind to the virus

  • Block fusion of the virus and cell

• Uncoating, genome integration, and nucleic acid synthesis inhibitors

  • Prevent viral uncoating

  • Inhibit viral DNA integration into the host genome

  • Nucleoside analogs inhibit RNA/DNA synthesis

• Assembly and exit inhibitors

  • Protease inhibitor - block the cleavage of protein precursors

  • Exit inhibitors - inhibit neuraminidase, an enzyme required for some viruses to bud from the host cell

• Interferons

  • Produced by viral-infected cells to inhibit further spread of the infection

    • Imiquimod - promotes interferon production

• Antiretrovirals for Treating HIV/AIDS (RNA virus)

  • Antiretroviral drugs is used to treat HIV infections

    • AZT - interferes with reverse transcriptase

Resistance to Antimicrobial Drugs

• Persister cells - microbes with genetic characteristics allowing for their survival when exposed to an antibiotic

• Superbugs - bacteria that are resistant to a large number of antibiotics

Mechanisms of Resistance

• Enzymatic destruction or inactivation of the drug

• Prevention of penetration to the target site within the microbe

• Alteration of the drug’s target site

• Rapid efflux (ejection) of the antibiotic

• Variations of the mechanisms of resistance

Antibiotic Misuse

• Misuse of antibiotics selects for resistance mutants

• Misuse includes:

  • using outdated or weakened antibiotics

  • Using antibiotics for the common cold and other inappropriate conditions

  • Using antibiotics in animal feed

  • Failing to complete the prescribed regimen

  • Using someone else’s leftover prescription

Effects of Combination of Drugs

• Synergism - the effect of two drugs together is greater than the effect of either alone

  • Streptomycin & Penicillin

• Antagonism - the effect of two drugs together is less than the effect of either alone

  • Penicillin & Tetracycline