Bacterial Protein Synthesis Inhibitors: A Guide to Common Antibiotic Classes

Bacterial Protein Synthesis Inhibitors: A Guide to Common Antibiotic Classes

This article will explore several groups of antibiotics that inhibit bacterial protein synthesis, focusing on their mechanisms of action, characteristics, indications, adverse effects, and drug interactions.

# 1. Macrolides

Characteristics:

• Narrow spectrum: Primarily active against Gram-positive bacteria and intracellular organisms.

• Bacteriostatic: Inhibit bacterial growth, but can exert bactericidal effects at high concentrations or in tissues with high drug accumulation.

• Favorable safety profile: Generally well-tolerated.

• Good tissue penetration: Reach therapeutic concentrations in various tissues.

• Elimination via bile: Excreted in the bile, leading to high concentrations in the gut.

• Primarily oral administration (PO): Most commonly taken by mouth.

Macrolide Antibiotics:

• Erythromycin: Can be degraded in gastric acid, often formulated as enteric-coated tablets. Associated with cholestatic hepatitis.

• Troleandomycin: Can cause cholestatic hepatitis.

• Roxithromycin: May inhibit hepatic enzymes.

• Clarithromycin: Specific indications include Helicobacter pylori infection and prophylaxis/treatment of Mycobacterium avium complex (MAC) infection in individuals with HIV/AIDS. May inhibit hepatic enzymes.

• Azithromycin: Once-daily dosing for 5 days. Long half-life (48 hours). Does not inhibit hepatic enzymes.

• Josamycin: May inhibit hepatic enzymes.

• Spiramycin: Eliminated via bile. Can reduce the efficacy of Levodopa/Carbidopa. Often combined with Metronidazole for treating anaerobic infections of the mouth. Treatment for Toxoplasma encephalitis. Does not inhibit hepatic enzymes.

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 50S subunit of bacterial ribosomes, blocking protein synthesis.

Adverse Effects:

• Relatively few: Generally well-tolerated.

• Hepatic enzyme inhibition: Some macrolides can inhibit hepatic enzymes, potentially leading to elevated levels of other medications.

Drug Interactions:

• Astemizole, Terfenadine: Combination may cause Torsades de pointes (a type of heart arrhythmia).

• Warfarin: May increase the risk of bleeding.

• Ergotamine: Can lead to anemia and gangrene in extremities.

# 2. Ketolides

Characteristics:

• Enhanced activity against respiratory pathogens: Particularly effective against bacteria causing respiratory infections.

• Elimination via bile: Excreted in the bile.

Ketolide Antibiotics:

• Telithromycin: Important indication in community-acquired pneumonia.

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis.

# 3. Aminoglycosides

Characteristics:

• Hydrophilic structure: Water-soluble.

• Poor oral absorption: Not absorbed well when taken by mouth.

• Limited tissue distribution: Poorly distributed to tissues.

• Bactericidal: Kill bacteria directly.

• Post-antibiotic effect: Continued suppression of bacterial growth even after drug levels decline.

• Spectrum of activity: Primarily against Gram-negative and aerobic bacteria.

• Variable potency: Amikacin is the most potent, followed by Streptomycin as the least potent.

• Narrow therapeutic window: Difference between effective and toxic doses is small.

Aminoglycoside Antibiotics:

• Naturally occurring: Streptomycin, Gentamicin, Tobramycin, Kanamycin, Sisomycin, Neomycin, Paromomycin.

• Semi-synthetic: Amikacin, Dibekacin, Netilmicin, Framycetin.

• Similar structure: Spectinomycin (Effective against Neisseria gonorrhoeae).

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 30S subunit of bacterial ribosomes, interfering with protein synthesis.

Adverse Effects:

• Ototoxicity: Irreversible hearing loss.

• Nephrotoxicity: Reversible kidney damage.

• Neuromuscular blockade: Muscle weakness.

Indications:

• Serious infections caused by Gram-negative bacteria: Often used for severe infections.

Administration:

• Intravenous (IV) slow infusion: Typically administered intravenously over a prolonged period once daily.

• Intramuscular (IM) administration: May lead to variability in absorption rates, making therapeutic monitoring challenging.

• Once-daily dosing (OD): May increase efficacy, speed of action, peak concentration, and reduce toxicity.

• Subcutaneous (SC) administration: Can cause tissue necrosis at the injection site.

# 4. Tetracyclines

Characteristics:

• Broad spectrum: Active against both Gram-positive and Gram-negative bacteria, as well as certain parasites like malaria.

• Bacteriostatic: Inhibit bacterial growth, except Minocycline (bactericidal).

• Notable adverse effects: Dental discoloration (yellowing) and photosensitivity.

Tetracycline Antibiotics:

• First generation: Oxytetracycline, Chlortetracycline, Tetracycline, Demeclocycline.

• Second generation: Doxycycline, Minocycline.

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 30S subunit of bacterial ribosomes, interfering with protein synthesis.

Adverse Effects:

• Dental staining: Can cause permanent discoloration of teeth in children.

• Photosensitivity: Increased sensitivity to sunlight, leading to skin reactions.

• Minocycline: May cause intracranial hypertension (increased pressure in the skull), limiting its use.

Administration:

• Food interactions: Food can interfere with the absorption of first-generation tetracyclines, but has a lesser effect on second-generation drugs.

• Potency: Oxytetracycline < Tetracycline < Doxycycline < Minocycline.

• Absorption: Best absorbed in acidic environments.

• Interactions with metals: Form complexes with heavy metals.

• Elimination: Excreted via the kidneys (except Doxycycline, eliminated via bile).

• Enterohepatic circulation: Circulate between the gut and liver.

• Doxycycline: May cause esophagitis (inflammation of the esophagus), so patients should remain upright for at least 30 minutes after taking the medication.

Indications:

• Traveler’s diarrhea: Often used to prevent and treat diarrhea acquired during travel.

• Acne vulgaris: Used to treat acne.

• Malaria prophylaxis: Can help prevent malaria.

• Helicobacter pylori infection: Tetracycline is used for treating H. pylori infection.

# 5. Phenicols

Characteristics:

• Broad spectrum: Active against both Gram-positive and Gram-negative bacteria, including intracellular and anaerobic organisms.

• Good tissue penetration: Reach therapeutic levels in various tissues.

• Crosses the blood-brain barrier: Can enter the brain.

• Limited use due to toxicity: Use is restricted due to potential adverse effects on blood-forming organs.

• Bacteriostatic: Inhibits bacterial growth, but bactericidal against H. influenzae.

Phenicol Antibiotics:

• Chloramphenicol: Eliminated via the liver.

• Thiamphenicol: Eliminated via the kidneys.

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis.

Adverse Effects:

• Aplastic anemia: A serious blood disorder characterized by bone marrow failure.

• Gray baby syndrome: Occurs in newborns and infants, causing gray skin discoloration, respiratory distress, and low blood sugar.

• Jarisch-Herxheimer reaction: An acute reaction that can occur during treatment of certain infections, causing fever, chills, and muscle aches.

Indications:

• Typhoid fever: Treatment for typhoid fever.

• Meningitis: Used to treat bacterial meningitis.

Contraindications:

• Infants less than 6 months old: Not recommended in this age group.

• Bone marrow suppression: Not used in individuals with bone marrow suppression.

• Pregnancy: Not recommended during pregnancy.

Drug Interactions:

• Hepatic enzyme inhibition: May increase the levels of other medications due to inhibition of hepatic enzymes.

# 6. Streptogramins

Characteristics:

• Activity against Gram-positive bacteria: Primarily active against Gram-positive organisms.

• MRSA activity: Can be effective against methicillin-resistant Staphylococcus aureus (MRSA).

• Bactericidal: Kill bacteria directly, but bacteriostatic against Enterococcus faecium.

Streptogramin Antibiotics:

• Quinupristin/Dalfopristin: A combination of quinupristin and dalfopristin in a 30:70 ratio.

Mechanism of Action:

• Ribosomal subunit binding: Bind to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis.

Administration:

• Intravenous (IV): Administered intravenously.

# 7. Oxazolidinones

Characteristics:

• Narrow spectrum against Gram-positive bacteria: Primarily active against Gram-positive bacteria.

• No cross-resistance: Does not exhibit cross-resistance with other antibiotic classes.

Oxazolidinone Antibiotics:

• Linezolid: Available in both intravenous and oral formulations.

Mechanism of Action:

• Ribosomal subunit binding: Binds to the 23S rRNA of the 50S ribosomal subunit, inhibiting protein synthesis.

Indications:

• MRSA: Used to treat MRSA infections.

• VRE: Effective against vancomycin-resistant Enterococci (VRE).

Drug Interactions:

• Serotonin syndrome: Can cause serotonin syndrome when co-administered with monoamine oxidase inhibitors (MAOIs) or selective serotonin reuptake inhibitors (SSRIs).

# 8. Lincosamides

Characteristics:

• Ineffective against Clostridium difficile: Not effective against Clostridium difficile infections.

• Distinctive adverse effect: Associated with pseudomembranous colitis (inflammation of the colon).

Lincosamide Antibiotics:

• Lincomycin.

• Clindamycin.

Contraindications:

• Hypersensitivity: Not used in individuals with an allergy to lincosamides.

• Colitis: Contraindicated in patients with colitis (inflammation of the colon).

• Hepatic and renal impairment: Not used in individuals with severe liver or kidney disease.

Note:

• This article is for informational purposes only and should not be considered a substitute for professional medical advice.

• Always consult with a physician before using any antibiotic medication.

• Improper use of antibiotics can lead to drug resistance and serious side effects.