Chapter 20 Antimicrobial drugs

Spectrum of Antimicrobial Activity:

• Narrow spectrum antibiotics

• Broad-spectrum antibiotics

Spectrum of Antimicrobial Activity-

Superinfection:

overgrowth of normal microbiota that is resistant to antibiotics

The Action of Antimicrobial Drugs

Bactericidal:

kill microbes directly

Bacteriostatic:

prevent microbes from growing

Inhibiting cell wall synthesis

Penicillins prevent the synthesis of peptidoglycan

Injuring the plasma membrane

Polypeptide antibiotics change membrane permeability.

Injuring the plasma membrane

Ionophore antibiotics:

allow for uncontrolled movement of cations.

Inhibiting protein synthesis

‒ Target bacterial 70S ribosomes

‒ Chloramphenicol, erythromycin, streptomycin, tetracyclines

The Action of Antimicrobial Drugs

Inhibiting nucleic acid synthesis:

interfere with DNA replication and transcription

Rifamycin; quinolones (nalidixic acid) & fluoroquinolones

inhibiting the synthesis of essential metabolites

• Anti-metabolites compete with normal substrates for an enzyme.

• Sulfanilamide competes with para-aminobenzoic acid (PABA), stopping the synthesis of 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 inhibitors:

block the cleavage of protein precursors

Assembly and exit inhibitors

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:

drug is used to treat HIV infections

AZT:

interferes with reverse transcriptase

Persister cells:

microbes with genetic characteristics allowing for their survival when exposed to an antibiotic

Superbugs:

bacteria that are resistant to large numbers of antibiotics

Resistance to Antimicrobial Drugs

Resistance genes are often spread horizontally among bacteria on plasmids or transposons via conjugation or transduction

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 mechanisms of resistance

Antibiotic Misuse

Misuse of antibiotics selected 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 Combinations of Drugs

Synergism:

the effect of two drugs together is greater than the effect of either alone

Effects of Combinations of Drugs

Antagonism:

the effect of two drugs together is less than the effect of either alone