Ampicillin !

An intravenous aminopenicillin, key against Listeria and enterococci; with an aminoglycoside it is used in newborn sepsis and meningitis.

Updated 2026-11-01

Class: Beta-lactams
Enzyme: Penicillin-binding proteins (bacterial transpeptidases)
ATC code: J01CA01
WHO Model List of Essential Medicines

Penicillin-binding proteins (bacterial transpeptidases)Ampicillin

The figure shows PBP4 from Listeria monocytogenes with ampicillin bonded to the active-site serine (β-lactam ring already opened).

Target in 3D: Penicillin-binding proteins (bacterial transpeptidases). PDB structure 3ZG8 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Ampicillin is an aminopenicillin: its amino group helps it pass through the porins of some gram-negatives and widens penicillin G's spectrum. It acylates the PBPs and blocks the last step of wall synthesis. It is active against Listeria monocytogenes and most enterococci, where cephalosporins fail, but penicillinases destroy it.

Crosses the wall, including the porins of some gram-negatives
Acylates the PBPs of Listeria, enterococci and streptococci
Peptidoglycan cross-linking stops
The wall weakens and the bacterium lyses

Pharmacokinetics

Absorption: Used mainly by the intravenous or intramuscular route.
Distribution: The least protein-bound penicillin; it reaches the cerebrospinal fluid only when the meninges are inflamed and concentrates in bile.
Elimination: Mainly by the kidney, unchanged.

Indications

Bacterial meningitis; added to empirical therapy when Listeria is suspected (newborns, older adults, immunocompromised). Bacterial meningitis →
Enterococcal or streptococcal endocarditis, together with an aminoglycoside. Infective endocarditis →
Sepsis, including neonatal sepsis, with an aminoglycoside to widen gram-negative cover. Sepsis and septic shock →
Urinary tract infections by susceptible E. coli or Proteus mirabilis. Urinary tract infection (acute cystitis) →
Typhoid fever and other infections by susceptible Salmonella or Shigella.

Adverse effects

Common

Maculopapular rash, very common in infectious mononucleosis
Diarrhoea, nausea
Pain or phlebitis at the injection site

Contraindications

History of a hypersensitivity reaction to any penicillin

Key interactions

Allopurinol: Raises the rate of rash with aminopenicillins.
Probenecid: Reduces tubular secretion: higher and longer-lasting β-lactam levels.
Aminoglycosides (in the same mixture): Ampicillin inactivates them in vitro: they are prepared and given separately, although in the patient they act synergistically.
Tetracyclines and chloramphenicol: Bacteriostatic drugs can antagonise the bactericidal effect.

What is monitored

Clinical response and cultures
Kidney function and blood count in long courses

Administration and safety

Intravenous or intramuscular; the reconstituted solution loses stability quickly, so it is prepared just before use.
Do not mix in the same bag or syringe with aminoglycosides.
Too rapid intravenous injection can cause seizures; the prescribed administration time is respected.

Nursing care

Before the first dose: ask about allergy to penicillins, cephalosporins and other β-lactams, and what the reaction was.
After the first dose, watch for hives, wheeze, low blood pressure or swelling of lips and tongue, with anaphylaxis equipment at hand.
Check the IV site for phlebitis.
In newborns, watch urine output and kidney function, which govern elimination.
Teach the patient to report watery or bloody diarrhoea, even weeks after the course ends.

Pregnancy and breastfeeding

Animal studies showed no harm; there are no controlled studies in pregnant women and it is used when clearly needed.

Test yourself

Think of the answer, then tap the question to see it.

Why is ampicillin added to ceftriaxone for meningitis in an older adult?

To cover Listeria monocytogenes, which does not respond to cephalosporins and is more common in older adults, newborns and immunocompromised people.

Why are ampicillin and gentamicin not mixed in the same bag?

Because ampicillin inactivates the aminoglycoside in vitro; they are given separately, and in the patient they do act synergistically.

What does ampicillin's amino group add compared with penicillin G?

It helps the drug pass through the porins of some gram-negatives (E. coli, Proteus, H. influenzae), widening its spectrum.

Add to my cards (3)

← Back to the class: Beta-lactams

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Ampicillin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - AMPICILLIN SODIUM injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); RCSB PDB - 3ZG8: Crystal Structure of Penicillin Binding Protein 4 from Listeria monocytogenes in the Ampicillin bound form (RCSB Protein Data Bank, 2026); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.