Antimicrobials 3

8/13/2019 Antimicrobials 3

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PROTEIN SYNTHESIS INHIBITORS

Work by targeting bacterial ribosome

Mammalian (eukaryotic) cells have 80S ribosomes composed of 60S and

40S subunits

Bacteria (prokaryotic) cells have 70S ribosomes composed or 50S and 30Ssubunits

AMINO-

GLYCOSIDES

TETRA-CYCLINES CHLORAM-

PHENICOL

MACROLIDES LINCOSAMIDES

Streptomycin

Gentamicin

Tobramycin

Amikacin

Netilmicin

Neomycin

Kanamycin

Tetracycline

Doxycycline

Minocycline

Demeclocycline

Oxytetracycline

Chloram-

phenicol

Erythromycin

Clarithromycin

Azithromycin

Clindamycin

Lincomycin

AMINOGLYCOSIDES

Bactericidal

Inhibit protein synthesis

All bind irreversibly to the 30S ribosomal subunit and interfere with protein

synthesis in susceptible bacteria

Used to treat infections caused by several aerobic gram-negative bacteriaGiven parenterally

Mechanisms of Resistance:

o Plasmid-mediated synthesis of aminoglycoside –inactivating

enzymes such as acetyltransferase, nucleotidyltransferase and

phosphotransferase which modify and inactivate these drugs

o Changes in the 30S ribosomal subunit resulting in decreased affinity

between the drug and 30S subunit

o Decreased membrane permeability



TETRACYCLINES

Large group of related agents

Effective against both aerobic and anaerobic gr (+) and (-) bacteria,

rickettsiae, mycoplasma and chlamydiae

Can cross placenta but have poor CNS penetration



Mechanisms of Resistance:

o Resistance usually results from acquisition of an R-factor which may

code for the following:

Active efflux mechanism that pumps drug out of themicroorganism

Loss of cytoplasmic transport proteins which are required for

entry into susceptible organisms

Changes in membrane permeability to the drug



CHLORAMPHENICOL

Broad spectrum antibiotic

Inhibits protein synthesis in bacteria by binding to the 50S ribosomal

subunit

Remains an important drug for life-threatening infections such as

meningitis, typhoid fever

Mechanism for Resistance

o Resistance to gram (-) bacteria to this drug is usually caused by

a plasmid acquired by conjugation which may code for the ff:

o R-factors coding for Acetyl-CoA transferase which inactivates

chloramphenicol

o Decreased ability to penetrate the organism

Side effects:

o Anemia

o Gray baby syndrome

o Nausea, vomiting, diarrhes and perineal irritation



MACROLIDES

Characterized by a macrocyclic lactone ring to which sugars are attached

Erythromycin – drug prototype

Mechanisms of Resistance: o Plasmids coding for specific enzymes (erythromycin esterases)

which inactivate these drugs

o Methylation of an adenine residue on the 23S rRNA binding site

leads to decreased affinity for the 50S ribosomal subunit

o Defective uptake of the drug by the microbe

CLINICAL USES:

• Spectrum: anaerobic gram (+) cocci and bacilli

• Pneumonia

• Legionnaires’ disease

• Pertusis

• Diphtheria

SIDE EFFECT:

• GI side effects: nausea, vomiting, diarrhea

• Cholestatic hepatitis

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Antimicrobials 3