Ampicillin

Usage

Ampicillin is a broad-spectrum, penicillinase-susceptible, semisynthetic penicillin antibiotic used to treat a wide range of bacterial infections. It is effective against gram-positive and gram-negative bacteria, including Listeria monocytogenes, Streptococcus pneumoniae, Escherichia coli, Salmonella, Shigella, Haemophilus influenzae, and Neisseria gonorrhoeae (excluding penicillinase-producing strains).

Pharmacological Classification: β-Lactam antibiotic.

Mechanism of Action: Ampicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bacterial cell lysis and death.

Alternate Names

Ampicillin sodium, ampicillin trihydrate

Brand Names: Principen, Omnipen, Polycillin, Totacillin (Note: Brand names can vary regionally.)

How It Works

Pharmacodynamics: Ampicillin exerts a bactericidal effect by disrupting bacterial cell wall synthesis. It binds to and inhibits PBPs, crucial enzymes involved in peptidoglycan cross-linking, a key component of the bacterial cell wall. This inhibition weakens the cell wall, making the bacteria susceptible to osmotic lysis.

Pharmacokinetics:

• Absorption: Well-absorbed orally but bioavailability varies (30-70%). Parenteral administration (IV/IM) provides near-complete bioavailability. Food can delay absorption.
• Distribution: Widely distributed into tissues and body fluids, including cerebrospinal fluid (with inflamed meninges).
• Metabolism: Minimal hepatic metabolism.
• Elimination: Primarily excreted unchanged in urine via glomerular filtration and tubular secretion. Elimination half-life is approximately 1-2 hours, prolonged in renal impairment.

Mode of Action: Ampicillin, like other β-lactam antibiotics, targets the bacterial cell wall. It competitively binds to the transpeptidase active site of PBPs. These enzymes are involved in the final stages of peptidoglycan synthesis, forming the essential cross-links that provide rigidity to the cell wall. By inhibiting transpeptidation, ampicillin weakens the cell wall and ultimately causes bacterial lysis and death.

Elimination Pathways: Primarily renal excretion, with minor biliary excretion.

Dosage

Standard Dosage

Adults:

• Oral: 250-500 mg every 6 hours.
• IV/IM: 1-2 g every 4-6 hours (up to 12 g/day).

Children:

• Oral: 50-100 mg/kg/day divided every 6 hours.
• IV/IM: 50-200 mg/kg/day divided every 6 hours (up to 12 g/day).
• Neonates: Dosage depends on gestational age and postnatal age (consult neonatal dosing guidelines).

Special Cases:

• Elderly Patients: Dose adjustment may be necessary in renal impairment.
• Patients with Renal Impairment: Dose reduction and/or interval prolongation are based on creatinine clearance.
• Patients with Hepatic Dysfunction: Usually no adjustment necessary, but monitor closely.
• Patients with Comorbid Conditions: Adjust dose if interacting medications are used concurrently.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Higher doses (e.g., 2 g IV every 4-6 hours) are often used for severe infections.
• Emergency Situations: Administer high IV doses as indicated by clinical situation.

Dosage Adjustments:

Adjustments are required for patients with renal impairment based on creatinine clearance. Monitor drug levels if possible. For hepatic dysfunction, no specific dosage adjustment is generally recommended, but careful clinical monitoring is necessary.

Side Effects

Common Side Effects:

• Nausea, vomiting, diarrhea
• Rash, urticaria, pruritus
• Oral or vaginal candidiasis (thrush)

Rare but Serious Side Effects:

• Clostridium difficile-associated diarrhea (CDAD)
• Anaphylaxis
• Seizures (especially with high doses or renal impairment)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Leukopenia, thrombocytopenia, anemia

Long-Term Effects: Superinfection with resistant organisms may develop with prolonged use.

Adverse Drug Reactions (ADR): Anaphylaxis, CDAD, severe skin reactions require immediate attention.

Contraindications

• Hypersensitivity to penicillins or cephalosporins
• History of anaphylaxis or severe allergic reaction to any penicillin

Drug Interactions

• Allopurinol: Increased risk of rash.
• Probenecid: Decreased ampicillin elimination, potentially increasing ampicillin levels.
• Oral contraceptives: May reduce efficacy of hormonal contraceptives.
• Methotrexate: Increased methotrexate toxicity.
• Tetracyclines: Antagonistic effect, reducing ampicillin’s efficacy.
• Aminoglycosides: Synergistic effect when used in combination (administer separately).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (generally considered safe, but use only if clearly needed). Crosses the placenta, possibly requiring higher maternal dosage.
• Breastfeeding: Small amounts are excreted in breast milk. Generally considered safe, but monitor infant for diarrhea, rash, and candidiasis.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins.
• Side Effects: Nausea, vomiting, diarrhea, rash, anaphylaxis (rare).
• Contraindications: Hypersensitivity to penicillins.
• Drug Interactions: Allopurinol, probenecid, oral contraceptives, methotrexate.
• Pregnancy & Breastfeeding: Generally safe, monitor infant.
• Dosage: Adults: 250-500 mg PO q6h or 1-2 g IV q4-6h. Children: 50-200 mg/kg/day divided.
• Monitoring Parameters: Renal function, signs of infection, complete blood count (CBC) if prolonged use.

Popular Combinations

• Ampicillin/Sulbactam (Unasyn): Sulbactam is a beta-lactamase inhibitor, extending ampicillin’s activity against bacteria producing beta-lactamases.

Precautions

• General Precautions: Assess for penicillin allergy, renal function, other drug interactions.
• Specific Populations: As outlined above.
• Lifestyle Considerations: None specifically, but advise patients to complete the full course of therapy.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ampicillin?

A: Adults: 250-500 mg PO every 6 hours or 1-2 g IV every 4-6 hours. Children: 50-100 mg/kg/day PO divided every 6 hours or 50-200 mg/kg/day IV divided every 6 hours.

Q2: How should Ampicillin be administered?

A: Ampicillin can be administered orally (capsules, suspension), intravenously (IV), or intramuscularly (IM).

Q3: What are the most common side effects of Ampicillin?

A: Common side effects include nausea, vomiting, diarrhea, and rash.

Q4: What are the serious side effects of Ampicillin?

A: Serious side effects include Clostridium difficile infection, anaphylaxis, and seizures.

Q5: Can Ampicillin be used in pregnant women?

A: Ampicillin is generally considered safe in pregnancy (Category B) but should only be used if clearly needed. Higher doses may be needed to achieve therapeutic levels in pregnant patients.

Q6: Is Ampicillin compatible with breastfeeding?

A: Ampicillin is generally considered compatible with breastfeeding, though trace amounts are present in breast milk. Monitor infants for potential side effects like rash, diarrhea, or thrush.

Q7: What are the contraindications to Ampicillin use?

A: The main contraindication is a known hypersensitivity to penicillin or cephalosporins.

Q8: How does renal impairment affect Ampicillin dosing?

A: Dose reduction and/or increased dosing intervals are necessary in patients with renal impairment. Dosing should be adjusted based on creatinine clearance.

Q9: What are important drug interactions to consider with Ampicillin?

A: Significant drug interactions include allopurinol, probenecid, oral contraceptives, methotrexate, and tetracyclines.

Q10: What should patients be counseled on when prescribed Ampicillin?

A: Patients should be advised to complete the entire course of therapy, even if feeling better. Report any signs of allergic reaction (rash, hives, breathing difficulties) immediately. They should also be informed about the potential for gastrointestinal side effects and drug interactions.