Aminopenicillins

Aminopenicillins are a subclass of beta-lactam antibiotics belonging to the broader penicillin family. They are characterized by the presence of an amino group (-NH2) on the benzyl side chain, which improves their hydrophilicity and expands their antimicrobial spectrum compared to natural penicillins. This modification allows them to penetrate the outer membrane of certain Gram-negative bacteria, making them more versatile in clinical use. However, they remain susceptible to beta-lactamase enzymes, which limits their effectiveness unless combined with beta-lactamase inhibitors.

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Mechanism of Action

• Aminopenicillins exert a bactericidal effect by inhibiting bacterial cell wall synthesis.

• They bind to penicillin-binding proteins (PBPs), which are enzymes essential for cross-linking peptidoglycan chains in the bacterial cell wall.

• Inhibition of PBPs weakens the cell wall, leading to cell lysis and bacterial death.

• They are most effective against actively dividing bacteria.

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Spectrum of Activity

Aminopenicillins cover a broader range of bacteria compared to natural penicillins, but resistance remains a concern.

• Gram-positive bacteria: Streptococcus spp., Enterococcus faecalis, Listeria monocytogenes.

• Gram-negative bacteria: Escherichia coli, Haemophilus influenzae, Proteus mirabilis, Salmonella spp., Shigella spp..

• Limited activity against Pseudomonas aeruginosa and beta-lactamase–producing strains.

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Common Drugs and Doses

1. Amoxicillin

   • Oral bioavailability is high (better than ampicillin).

   • Adult dose: 250–500 mg every 8 hours or 500–875 mg every 12 hours orally.

   • Pediatric dose: 20–40 mg/kg/day divided every 8 hours.

   • Often combined with clavulanic acid (as Amoxicillin/Clavulanate) to resist beta-lactamases.

2. Ampicillin

   • Less well absorbed orally, often used IV or IM.

   • Adult dose: 250–500 mg orally every 6 hours or 1–2 g IV every 4–6 hours.

   • Pediatric dose: 50–250 mg/kg/day divided every 6 hours.

   • Often combined with sulbactam (as Ampicillin/Sulbactam).

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Clinical Uses

• Respiratory tract infections: Otitis media, sinusitis, bronchitis, pneumonia.

• Urinary tract infections (UTIs) caused by susceptible strains.

• Gastrointestinal infections: Salmonella, Shigella.

• Listeria meningitis: Ampicillin is the drug of choice, often combined with gentamicin.

• Endocarditis prophylaxis: Amoxicillin before dental or surgical procedures in high-risk patients.

• Helicobacter pylori eradication: Amoxicillin in triple or quadruple therapy regimens.

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Contraindications

• History of hypersensitivity to penicillins, cephalosporins, or other beta-lactams.

• Use with caution in patients with renal impairment, requiring dose adjustment.

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Side Effects

• Hypersensitivity reactions: Rash, urticaria, anaphylaxis.

• Gastrointestinal effects: Diarrhea, nausea, antibiotic-associated colitis (including C. difficile).

• Superinfections: Overgrowth of resistant organisms or fungi (e.g., Candida).

• Hematologic effects: Rare—neutropenia, thrombocytopenia.

• Hepatic effects: Mild, reversible transaminase elevations.

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Precautions

• Adjust dose in renal impairment.

• High doses may cause seizures in patients with renal dysfunction or meningitis.

• Use with caution in infectious mononucleosis, as ampicillin/amoxicillin can cause a non-allergic rash.

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Drug Interactions

• Allopurinol: Increases risk of rash with ampicillin or amoxicillin.

• Oral anticoagulants (warfarin): May enhance anticoagulant effect due to alteration of gut flora.

• Methotrexate: Aminopenicillins reduce clearance, increasing toxicity.

• Oral contraceptives: Possible reduced efficacy due to altered gut flora.

• Probenecid: Increases plasma concentration by decreasing renal excretion.