Ampicillin

1. Drug Name

• Generic Name: Ampicillin

• Brand Names: Omnipen, Principen, Ampicin, and others.

2. Drug Classification

• Class: Antibiotic, Penicillin (Beta-lactam)

• Subclass: Aminopenicillin

3. Mechanism of Action

• Primary Action: Ampicillin works by inhibiting bacterial cell wall synthesis. It binds to and inactivates penicillin-binding proteins (PBPs) that are essential for the formation of the bacterial cell wall. This leads to the disruption of cell wall integrity and eventual bacterial lysis, especially in rapidly dividing bacteria.

• Spectrum of Activity: Ampicillin is a broad-spectrum antibiotic effective against a variety of gram-positive and some gram-negative bacteria. It is especially effective against Streptococcus, Enterococcus, Haemophilus influenzae, and Escherichia coli, although it is more susceptible to beta-lactamase hydrolysis compared to some other penicillins (e.g., amoxicillin).

• Resistance: Ampicillin’s effectiveness is reduced against beta-lactamase-producing organisms. Therefore, it is often combined with beta-lactamase inhibitors (e.g., sulbactam) to broaden its spectrum.

4. Pharmacokinetics

• Absorption: Ampicillin is well absorbed from the gastrointestinal tract, with oral bioavailability around 40–60%. Food may reduce the absorption slightly, so it is generally recommended to take it on an empty stomach for optimal absorption.

• Distribution: Ampicillin is widely distributed in the body, reaching therapeutic concentrations in blood, urine, cerebrospinal fluid (CSF), and other tissues. It crosses the placenta and is excreted in breast milk.

• Metabolism: Ampicillin undergoes minimal metabolism in the liver. The parent drug remains largely unchanged in the bloodstream.

• Excretion: Ampicillin is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. The half-life of ampicillin is approximately 1–1.5 hours in individuals with normal renal function.

• Special Considerations: Dose adjustments are required for patients with renal insufficiency, as renal clearance is the primary route of elimination for ampicillin.

5. Indications

• Primary Indications:

  • Respiratory tract infections (e.g., pneumonia, bronchitis).

  • Urinary tract infections (UTIs) caused by susceptible organisms (e.g., Escherichia coli).

  • Meningitis caused by susceptible organisms like Listeria monocytogenes.

  • Endocarditis prophylaxis in certain at-risk patients (e.g., patients with heart valve disease undergoing dental procedures).

  • Skin and soft tissue infections caused by Streptococcus and Staphylococcus (non-resistant strains).

  • Gastrointestinal infections (e.g., Salmonella and Shigella).

• Off-label Uses:

  • Treatment of Helicobacter pylori infections when used in combination with other agents like clarithromycin or metronidazole.

  • Listeria infections in neonates and immunocompromised individuals.

• Specific Populations: Safe for use in pregnant women (Category B) and children. Adjustments may be necessary in patients with renal impairment.

6. Dosage and Administration

• Adult Dosing:

  • Infections (e.g., respiratory, UTI, skin infections): 250–500 mg every 6 hours or 500–1000 mg every 8 hours, depending on infection severity.

  • Endocarditis prophylaxis: 2 grams orally 1 hour before the procedure.

• Pediatric Dosing:

  • Infections: 50–100 mg/kg/day divided into 3–4 doses.

  • Maximum dose: The usual maximum dose is 12 grams per day in children, but it may be adjusted for specific infections and age.

• Renal/Hepatic Adjustments: Dose adjustments are required in patients with renal impairment (CrCl <30 mL/min) due to decreased renal clearance.

• Route of Administration: Oral (capsules, suspension), intramuscular (IM), or intravenous (IV) administration.

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity to ampicillin, penicillins, or any components of the formulation.

  • History of a severe allergic reaction to any beta-lactam antibiotics (e.g., penicillins or cephalosporins).

• Relative Contraindications:

  • Use with caution in patients with a history of gastrointestinal diseases such as colitis.

  • Caution in patients with renal impairment as ampicillin is renally excreted.

8. Warnings and Precautions

• Allergic Reactions: Anaphylactic reactions, urticaria, and angioedema can occur in sensitive individuals. Discontinue ampicillin immediately if signs of a serious allergic reaction are noted.

• Clostridium difficile-associated Diarrhea (CDAD): Antibiotic-associated diarrhea, including life-threatening colitis, may occur during or after therapy.

• Renal Function: Dose adjustments are necessary in patients with impaired renal function. Renal function should be monitored in patients on prolonged therapy.

• Pregnancy and Lactation: Ampicillin is classified as Pregnancy Category B. It is considered safe for use in pregnant women but should be used only when necessary. It is also excreted into breast milk, but the amount is small and considered safe for nursing infants.

9. Adverse Effects

• Common Adverse Effects (≥10%):

  • Diarrhea

  • Rash

  • Nausea

  • Vomiting

  • Abdominal pain

• Less Common but Clinically Significant:

  • Hypersensitivity reactions: urticaria, angioedema, anaphylaxis

  • Pseudomembranous colitis (due to Clostridium difficile infection)

  • Oral and vaginal candidiasis (yeast infections)

• Serious Adverse Reactions:

  • Hematologic: eosinophilia, thrombocytopenia, leukopenia, agranulocytosis

  • Hepatic: cholestatic jaundice, liver toxicity

  • Renal: interstitial nephritis, acute renal failure

  • Severe allergic reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis

10. Drug Interactions

• Major Drug Interactions:

  • Probenecid: Probenecid inhibits renal tubular secretion of ampicillin, increasing its serum concentration and prolonging its action.

  • Methotrexate: Ampicillin may interfere with renal excretion of methotrexate, increasing the risk of toxicity.

  • Oral Contraceptives: Although the effect is minimal, there is some evidence suggesting antibiotics like ampicillin could reduce the efficacy of oral contraceptives, so alternative contraception may be advised.

• Food-Drug Interactions: Food may delay the absorption of ampicillin, but it is not a major concern. It is often recommended to take ampicillin on an empty stomach to maximize absorption.

• Lab Test Interference: Ampicillin can cause false-positive results in tests for urinary glucose (non-enzyme-based methods) and in some cases, liver enzyme tests.

11. Clinical Pharmacology

• Pharmacodynamics: Ampicillin is bactericidal, meaning it kills bacteria rather than merely inhibiting their growth. It is most effective during the growth phase of bacterial replication due to its action on the cell wall synthesis.

• Additional Effects: Ampicillin has a moderate to broad spectrum of activity against a variety of pathogens. However, it is less effective against beta-lactamase-producing organisms, requiring combination therapy or alternative antibiotics in such cases.

12. Special Populations

• Pregnancy: Category B – No evidence of risk to the fetus in human studies. Ampicillin is considered safe during pregnancy and is commonly prescribed for infections in pregnant women.

• Lactation: Ampicillin is excreted into breast milk in small amounts but is generally considered safe for use while breastfeeding.

• Pediatrics: Safe for use in pediatric patients. Dosing is based on weight and clinical indication, and care should be taken in neonates and infants.

• Geriatrics: Older adults, particularly those with renal insufficiency, may require dose adjustments. Use with caution and monitor renal function.

13. Therapeutic Uses

• First-Line Use:

  • Ampicillin is commonly used to treat mild to moderate infections of the respiratory tract, urinary tract, skin, and soft tissues.

  • First-line therapy for Listeria monocytogenes meningitis and certain Enterococcus infections.

• Combination Therapy:

  • Ampicillin is often used in combination with other antibiotics (e.g., sulbactam) to treat infections caused by beta-lactamase-producing organisms.

• Clinical Trials and Efficacy:

  • Ampicillin has shown efficacy in clinical trials for a wide range of infections, including respiratory, urinary, and gastrointestinal infections. Its role in the treatment of Listeria infections and meningitis has been well-documented.

14. Monitoring and Follow-Up

• Lab Tests: Regular monitoring of liver and renal function is recommended during prolonged therapy. A complete blood count (CBC) should also be monitored in patients receiving long-term therapy.

• Symptom Monitoring: Watch for signs of allergic reactions, gastrointestinal distress, or changes in mental status.

• Therapeutic and Toxic Level Monitoring: Therapeutic drug monitoring is not routinely required, but dose adjustments may be necessary for renal dysfunction.

15. Overdose Management

• Symptoms of Overdose: Symptoms may include nausea, vomiting, diarrhea, and gastrointestinal distress.

• Treatment Protocols: In cases of overdose, activated charcoal may be administered if ingestion occurred within a few hours. Symptomatic treatment is supportive.

• Supportive Measures: There is no specific antidote for ampicillin overdose, and treatment is generally symptomatic and supportive.

16. Patient Counseling Information

• Key Points to Discuss with Patients:

  • Complete the entire course of therapy, even if symptoms improve.

  • Take the medication on an empty stomach for better absorption, unless otherwise instructed.

  • Report any signs of an allergic reaction, such as skin rash, difficulty breathing, or swelling.

• Signs/Symptoms to Watch For:

  • Seek immediate medical attention if you experience severe allergic reactions like anaphylaxis.

  • Notify the healthcare provider if diarrhea, abdominal pain, or blood in stools develops, which may indicate a serious gastrointestinal infection.