[17][18] Its spectrum of activity is enhanced by co-administration of sulbactam, a drug that inhibits beta lactamase, an enzyme produced by bacteria to inactivate ampicillin and related antibiotics.

[7] Pregnancy increases the clearance of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels.

Hypersensitivity reactions can include frequent skin rashes and hives, exfoliative dermatitis, erythema multiforme, and a temporary decrease in both red and white blood cells.

[13] Ampicillin is comparatively less toxic than other antibiotics, and side effects are more likely in those who are sensitive to penicillins and those with a history of asthma or allergies.

[13] In very rare cases, it causes severe side effects such as angioedema, anaphylaxis, and C. difficile infection (that can range from mild diarrhea to serious pseudomembranous colitis).

The gastrointestinal effects, such as hairy tongue, nausea, vomiting, diarrhea, and colitis, are more common with the oral form of penicillin.

[7] Ampicillin overdose can cause behavioral changes, confusion, blackouts, and convulsions, as well as neuromuscular hypersensitivity, electrolyte imbalance, and kidney failure.

Large doses of ampicillin can increase the risk of bleeding with concurrent use of warfarin and other oral anticoagulants, possibly by inhibiting platelet aggregation.

Ampicillin is normally used to treat cholera and typhoid fever, lowering the immunological response that the body has to mount.

This amino group, present on both ampicillin and amoxicillin, helps these antibiotics pass through the pores of the outer membrane of gram-negative bacteria, such as Escherichia coli, Proteus mirabilis, Salmonella enterica, and Shigella.

[19][36] Ampicillin acts as an irreversible inhibitor of the enzyme transpeptidase, which is needed by bacteria to make the cell wall.

[7][37] Ampicillin is well-absorbed from the GI tract (though food reduces its absorption), and reaches peak concentrations in one to two hours.

[13] In the kidneys, it is filtered out mostly by tubular secretion; some also undergoes glomerular filtration, and the rest is excreted in the feces and bile.

[39] Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against gram-positive organisms such as staphylococci and streptococci.

[37] Ampicillin (originally branded as "Penbritin") also demonstrated activity against gram-negative organisms such as H. influenzae, coliforms, and Proteus spp.